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Biomedical subjects

M Pagani

Publications and source records attributed to M Pagani.

At least 19 recordsLinked to original sources
PubMed2006

Global versus local linear beat-to-beat analysis of the relationship between arterial pressure and pulse transit time during dynamic exercise.

Global linear analysis has been traditionally performed to verify the relationship between pulse transit time (PTT) and systolic arterial pressure (SAP) at the level of their spontaneous beat-to-beat variabilities: PTT and SAP have been plotted in the plane (PTT,SAP) and a significant linear correlation has been found. However, this relationship is weak and in specific individuals cannot be found. This result prevents the utilization of the SAP-PTT relationship to derive arterial pressure changes from PTT measures on an individual basis. We propose a local linear approach to study the SAP-PTT relationship. This approach is based on the definition of short SAP-PTT sequences characterized by SAP increase (decrease) and PTT decrease (increase) and on their search in the SAP and PTT beat-to-beat series. This local approach was applied to PTT and SAP series derived from 13 healthy humans during incremental supine dynamic exercise (at 10, 20 and 30% of the nominal individual maximum effort) and compared to the global approach. While global approach failed in some subjects, local analysis allowed the extraction of the gain of the SAP-PTT relationship in all subjects both at rest and during exercise. When both local and global analyses were successful, the local SAP-PTT gain is more negative than the global one as a likely result of noise reduction.

Arteries↗
PubMed2006

Outbreak of vancomycin-resistant Enterococcus spp. in an Italian general intensive care unit.

Following the identification of two clinical isolates of vancomycin-resistant enterococci (VRE) from intensive care unit (ICU) patients, a surveillance programme detected that six of eight ICU patients were colonised by VRE. Standard epidemic control measures were instituted in the ICU. During a 16-month period, 13 (2.5%) of 509 ICU patients had VRE-positive swabs upon admission, and 43 (8.7%) of 496 VRE-negative patients were colonised by VRE in the ICU. Patients who acquired VRE in the ICU had a longer ICU stay (p < 0.0001). No other statistically significant differences were demonstrated. Two patients had documented infection (infection/colonisation index, 3.6%; overall VRE infection frequency, 0.4%), but both recovered and were discharged. VRE colonisation did not increase the mortality rate. Automated ribotyping identified three clusters containing, respectively, the first 52 Enterococcus faecium isolates, two Enterococcus faecalis isolates, and two further isolates of E. faecium. Multilocus sequence typing demonstrated that two E. faecium isolates representative of the two ribotypes belonged to sequence types 78 and 18, and that these two isolates belonged to the epidemic lineage C1, which includes isolates with a wide circulation in northern Italy. The outbreak was controlled by continuous implementation of the infection control programme, and by the opening of a new unit with an improved structural design and hand-washing facilities.

Adult↗
PubMed2006

Autonomic and psychological adaptations in Olympic rowers.

AIM: Power spectral analysis of heart rate variability has been used to assess the time course of neurovegetative adaptations to training. This study was undertaken: 1) to evaluate whether and which indicator(s) of autonomic cardiac regulation and psychophysical stress can identify successful athletes during a training season culminating with the Olympic Games and 2) to evaluate the feasibility of a quasi-on-line assessment of autonomic cardiac regulation from training field, by a telematic approach. METHODS: This study was conducted on the group of male athletes composing the Italian national team of rowing (n=34), in the season preceding the 2004 Olympic Games. Complete results are from 18 subjects (age 25.3+/-0.5 years), who were selected to participate to the Athens' Olympic games. Athletes were studied while partially detrained, at mid-training season and close to the games. The RR interval was obtained through a miniature transtelephonic-ECG recorder in the supine and standing posture, thus allowing the evaluation of cardiovascular responses to a sympathetic challenge. Data were downloaded through a telephone line, to the referral center where RR-interval variability data were analyzed with the autoregressive method. Also, in each study sessions, athletes filled a self-administered questionnaire of stress perception and somatic symptoms (4S-Q). RESULTS: All ECG recordings were transmitted successfully by phone to the referral center. No significant difference was detected in any marker of autonomic cardiac regulation between athletes who won a medal at the Olympic Games and those who did not. However, respiratory rate was faster in medal winners (P=0.02), while the questionnaire addressing stress (4S-Q) provided greater scores in the group that did not win a medal (F=5.55, P<0.022) at mid-training season and close to the Olympic Games. CONCLUSIONS: The results of this study would suggest the possibility of an early detection of psychosomatic symptoms resulting from long duration and elevated stress of preparing for top level competitions, whose better handling might identify the most successful athletes. In addition, it indicates the feasibility of a quasi-on-line assessment of autonomic cardiac adaptations to strenuous training directly from field to be possibly used for improving individual training programs, allowing athletes evaluation in their natural environment.

Adaptation, Physiological↗
PubMed2003

Non-invasive model-based estimation of the sinus node dynamic properties from spontaneous cardiovascular variability series.

A non-invasive model-based approach to the estimation of sinus node dynamic properties is proposed. The model exploits the spontaneous beat-to-beat variability of heart period and systolic arterial pressure and the sampled respiration, thus surrogating the information from direct measures of neural activity. The residual heart period variability not related to baroreflex, to direct effects of respiration and to low frequency influences independent of baroreflex, is interpreted as the effect of the dynamic properties of the sinus node and modelled as a regression of the RR interval over its previous value. Therefore the sinus node transfer function is modelled by means of a filter with a real pole z = mu (and a zero in the origin). It was found that: first, in young healthy subjects the nodal tissue responded as a low-pass filter with mu = 0.76 +/- 0.12 (mean +/- SD); secondly, ageing did not significantly modify either its shape or gain at 0 Hz; thirdly, in heart transplant recipients, the dynamic transduction properties were lost (all-pass filter, p = 0.06 +/- 0.16, p < 0.001); fourthly, low-dose atropine left the sinus node dynamic properties unmodified; fifthly, high-dose atropine affected the dynamic transduction properties by increasing the gain at 0 Hz and rendering steeper its roll-off (the percent increase of mu with respect to baseline was 18.3 +/- 22.3, p < 0.05).

Adult↗
PubMed2003

Alterations of rCBF and mitochondrial dysfunction in major depressive disorder: a case report.

OBJECTIVE: A mitochondrial disease might be considered when depressive disorder is associated with diabetes mellitus or other symptoms commonly found in mitochondrial disease. Scattered regional cerebral blood flow (rCBF) decreases and increases have been reported in depressive and mitochondrial disorders. A 61-year-old male patient with early adult onset of depressive disorder and a slowly developing multiorgan syndrome including diabetes mellitus was investigated. METHOD: 99mTc-HMPAO rCBF SPECT and muscle biopsy to assess mitochondrial functions were performed in the patient. RESULTS: Alterations of rCBF were found in the patient, with the most pronounced decreases in the left dorsolateral frontal and inferior parietal lobes, and the most pronounced increases in the bilateral superior parietal lobes. Muscle biopsy revealed myopathy and decrease of mitochondrial adenosine triphosphate production rates (MAPRs). CONCLUSION: The MAPRs decreases support the suspicion of mitochondrial dysfunction in the patient. A subgroup of depressed patients may have mitochondrial dysfunctions.

Brain↗
PubMed2003

Barrett's esophagus: combined treatment using argon plasma coagulation and laparoscopic antireflux surgery.

The treatment of Barrett's esophagus is still controversial. Actually, the only method to prevent the development to cancer is endoscopic surveillance, which ensures good results in terms of long-term survival. An ideal treatment capable of destroying columnar metaplasia, followed by squamous epithelium regeneration could potentially result in a decrease of the incidence of adenocarcinoma. Recently most ablative techniques were used, such as photodynamic therapy, ablation therapy with Nd-YAG laser or argon plasma coagulation and endoscopic mucosal resection. We started a prospective study in January 1998, enrolling 94 patients affected by Barrett's esophagus and candidates for antireflux repair in order to assess the effectiveness and the results of endoscopic coagulation with argon plasma combined with surgery in the treatment of uncomplicated Barrett's esophagus. All patients underwent endoscopic treatment with argon plasma; we observed complete response in 68 patients (72.34%), 27 of them (39.7%) underwent antireflux surgery and the other 41 continued medical therapy. Post-operatively 19 patients (70%) underwent regular surveillance endoscopies and in two cases metaplasia recurred. The final objective of these combined treatments should be the complete eradication of metaplastic mucosa. Our experience was that argon plasma coagulation combined with antireflux surgery or proton pump inhibitor therapy gave satisfactory results, even if follow-up is too short to evaluate the potential evolution of metaplasia to cancer. For this reason, we recommend that this technique should be done only in specialized centres and that these patients continue their endoscopic surveillance program.

Adolescent↗
PubMed2003

The stress of competition dissociates neural and cortisol homeostasis in elite athletes.

AIM: Stressful situations affect autonomic nervous system activity and hormonal responses. This study aimed to investigate the effects of the stress of sports competition on both endocrine system functioning and neurovegetative control of heart rate (HR) in elite athletes. METHODS: In 7 top-level pentathletes salivary cortisol levels and autoregressive power spectral analysis of HR variability (HRV) were assessed in the morning and in the afternoon on a regular training day (control) and on the day of a competitive selection trial, held 4 weeks apart. RESULTS: HR, as well as low (LF) and high (HF) frequency components of HRV did not differ significantly both between and within the control and the trial days. On the selection day, morning cortisol levels were significant and markedly greater than on the control day and increased further in the afternoon in contrast to the control day, when cortisol levels decreased in the afternoon as expected from the normal diurnal variation. CONCLUSION: These results would indicate a dissociation of the neural and hypothalamic-pituitary-adrenal axis functioning in response to the stress of competition in elite athletes, and the considerable extent to which competition may alter selectively the physiology of stress-related hormones while sparing autonomic cardiac regulation.

Adult↗
PubMed2002

Analysis of cardiac left-ventricular volume based on time warping averaging.

The cardiac left-ventricular (LV) volume signal, obtained by acoustic quantification, is affected by noise and respiratory modulation, resulting in a large beat-to-beat variability that affects the computation of LV function indices. A new method is proposed to improve the evaluation of LV indices by applying a signal averaging technique based on dynamic time warping to consecutive LV volume waveforms. Volume signals obtained from ten normal young (NY) subjects (mean age +/- SD: 25+/-5 years) were used to evaluate the performance of this algorithm. To evaluate its clinical utility, the effects of ageing and pharmacologically induced changes on LV function were assessed by studying, respectively, ten normal (N) adult subjects (age 64+/-8 years) and ten patients with dilated cardiomyopathy during a control and low-dose dobutamine (10 microg kg(-1) min(-1)) study. Indices of LV function were highly consistent, with a variability of less than 8%, even when only 16 beats were averaged, independently of their selection inside the whole recording. When compared with beat-to-beat measures, the averaging of 16 beats significantly reduced (by more than 50%) the interbeat variability of all indexes. Expected alterations in both diastolic and systolic function were evidenced both with ageing (peak filling atrial contraction and ejection rates: from 275+/-77 mls(-1), 76+/-30 ml s(-1) 230+/-70 mls(-1), respectively, in NY, to 160+/-33 mls(-1), 125+/-39 mls(-1), 163+/-54 mls(-1) in N) and with dobutamine (peak filling and ejection rates from 160+/-72 mls(-1) and 183+/-86 mls(-1) respectively, in control, to 253+/-75 mls(-1) and 251+/-105 mls(-1) with dobutamine). Signal averaging with time warping allows fast and improved assessment of LV function.

Aging↗
PubMed2002

Quantifying the strength of the linear causal coupling in closed loop interacting cardiovascular variability signals.

The coherence function measures the amount of correlation between two signals x and y as a function of the frequency, independently of their causal relationships. Therefore, the coherence function is not useful in deciding whether an open-loop relationship between x and y is set (x acts on y, but the reverse relationship is prevented) or x and y interact in a closed loop (x affects y, and vice versa). This study proposes a method based on a bivariate autoregressive model to derive the strength of the causal coupling on both arms of a closed loop. The method exploits the definition of causal coherence. After the closed-loop identification of the model coefficients, the causal coherence is calculated by switching off separately the feedback or the feedforward path, thus opening the closed loop and fixing causality. The method was tested in simulations and applied to evaluate the degree of the causal coupling between two variables known to interact in a closed loop mainly at a low frequency (LF, around 0.1 Hz) and at a high frequency (HF, at the respiratory rate): the heart period (RR interval) and systolic arterial pressure (SAP). In dogs at control, the RR interval and the SAP are highly correlated at HF. This coupling occurs in the causal direction from the RR interval to the SAP (the mechanical path), while the coupling on the reverse causal direction (the baroreflex path) is not significant, thus pointing out the importance of the direct effects of respiration on the RR interval. Total baroreceptive denervation, by opening the closed loop at the level of the influences of SAP on RR interval, does not change these results. In elderly healthy men at rest, the RR interval and SAP are highly correlated at the LF and the HF. At the HF, a significant coupling in both causal directions is found, even though closed-loop interactions are detected in few cases. At the LF, the link on the baroreflex pathway is negligible with respect to that on the reverse mechanical one. In heart transplant recipients, in which SAP variations do not cause RR interval changes as a result of the cardiac denervation, the method correctly detects a significant coupling only on the pathway from the RR interval to the SAP.

Animals↗
PubMed2002

Differences in resting state regional cerebral blood flow assessed with 99mTc-HMPAO SPECT and brain atlas matching between depressed patients with and without tinnitus.

An increased occurrence of major depressive disorder has been reported in tinnitus patients, and of tinnitus in depressive patients. Involvement of several Brodmann areas (BAs) has been reported in tinnitus perception. The aim of this study was to assess the regional cerebral blood flow (rCBF) changes in depressed patients with and without tinnitus. The rCBF distribution at rest was compared among 45 patients with a lifetime prevalence of major depressive disorder, of whom 27 had severe tinnitus, and 26 normal healthy subjects. 99mTc-hexamethylenepropylene amine oxime (99mTc-HMPAO) single photon emission computed tomography (SPECT), using a three-headed gamma camera, was performed and the uptake in 34 functional sub-volumes of the brain bilaterally was assessed by a computerized brain atlas. Decreased rCBF in right frontal lobe BA 45 (P<0.05), the left parietal lobe BA 39 (P<0.00) and the left visual association cortex BA 18 (P<0.05) was found in tinnitus patients compared with non-tinnitus patients. The proportion of tinnitus patients with pronounced rCBF alterations in one or more of the temporal lobe BAs 41+21+22 was increased compared to gender matched controls (P<0.00) and patients without tinnitus (P<0.05). Positive correlations were found between trait anxiety scales from the Karolinska Scales of Personality and rCBF in tinnitus patients only in three limbic BAs (P<0.01), and inverse correlations in non-tinnitus patients only in five BAs subserving auditory perception and processing (P<0.05). rCBF differences between healthy controls and depressed patients with and without tinnitus were found in this study. The rCBF alterations were distributed in the cortex and were particularly specific in the auditory cortex. These findings suggest that taking audiological symptoms into account may yield more consistent results between rCBF studies of depression.

Age Factors↗
PubMed2001

The C-terminal domain of yeast Ero1p mediates membrane localization and is essential for function.

In eukaryotes, members of the Ero1 family control oxidative protein folding in the endoplasmic reticulum (ER). Yeast Ero1p is tightly associated with the ER membrane, despite cleavage of the leader peptide, the only hydrophobic sequence that could mediate lipid insertion. In contrast, human Ero1-Lalpha and a yeast mutant (Ero1pDeltaC) lacking the 127 C-terminal amino acids are soluble when expressed in yeast. Neither Ero1-Lalpha nor Ero1pDeltaC complements an ERO1 disrupted strain. Appending the yeast C-terminal tail to human Ero1-Lalpha restores membrane association and allows growth of ERO1 disrupted cells. Therefore, the tail of Ero1p mediates membrane association and is crucial for function.

Endoplasmic Reticulum↗
PubMed2001

Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability.

Histone H3 lysine 9 methylation has been proposed to provide a major "switch" for the functional organization of chromosomal subdomains. Here, we show that the murine Suv39h histone methyltransferases (HMTases) govern H3-K9 methylation at pericentric heterochromatin and induce a specialized histone methylation pattern that differs from the broad H3-K9 methylation present at other chromosomal regions. Suv39h-deficient mice display severely impaired viability and chromosomal instabilities that are associated with an increased tumor risk and perturbed chromosome interactions during male meiosis. These in vivo data assign a crucial role for pericentric H3-K9 methylation in protecting genome stability, and define the Suv39h HMTases as important epigenetic regulators for mammalian development.

Aneuploidy↗
PubMed2001

Selective impairment of excitatory pressor responses after prolonged simulated microgravity in humans.

The haemodynamic and autonomic effects of prolonged exposure to simulated microgravity were assessed non-invasively in seven healthy volunteers completing a 42-day -6 degrees head down tilt. Before, during and after head down tilt, subjects were exposed to moderate excitatory stimuli (mental arithmetic and static handgrip) to gauge possible progressive impairment of pressor responses. Before and after head down tilt, subjects were also exposed to orthostatic stress, to assess influences of simulated microgravity on orthostatic defence. Simple haemodynamics (heart rate and systolic arterial blood pressure), linear (i.e., oscillatory) components of beat-by-beat variability, non-linear properties (i.e., corrected conditional entropy (CCE)) of RR interval variability, and baroreflex slope furnished a non-invasive evaluation of autonomic regulatory mechanisms. Pressor responses to mental arithmetic and to handgrip were markedly impaired after 42 days head down tilt, whereas responses in markers of autonomic regulation were not modified. Standing, performed 8 days after head down tilt to limit the risk of syncope, still induced a variable degree of hypotension, with signs of progressively greater sympathetic activation than before head down tilt. Simulated microgravity-induced reduction of pressor responses, in spite of largely maintained autonomic activation, favours the hypothesis of a peripheral impairment of cardiovascular homeostasis. rights reserved.

Autonomic Nervous System↗
PubMed2001

RR-arterial pressure variability relationships.

Methodological aspects of a causal black-box model of heart period/arterial pressure interaction, arterial pressure closed-loop regulation and respiration effects on both heart period and arterial pressure are revisited in the "time" (more exactly heart beat count) domain. Parameters are estimated from experimental data (model identification) by means of multiple linear regressions of actual samples over the past ones. The elements composing either heart period or systolic arterial pressure variability are visualised as beat-by-beat series. Indexes describing the signal interactions, the loop properties and the spectral components of the variability series are consequently summarised. In 17 normal young volunteers, the analysis was carried out during active standing, rest, mild clinostatic pedalling exercise at 10%, 20%, and 30% of the maximum effort, and recovery. A negative effect of heart period changes on systolic arterial pressure of - 13.3 mm Hg/s was found at rest. This effect, though augmented by exercise, appeared insignificant in explaining arterial pressure variability. Arterial baroreflex was assessed by alphaart index which had a value of 5.18 mm Hg/ms at rest, 3.78 mm Hg/ms during active standing, and decreased progressively with exercise down to 0.55 mmHg/ms. The pressure regulation loop displayed a tendency to amplify disturbances at low frequency (around 0.1 Hz) 5.94 times at rest, augmented to 8.88 times during standing, 7.55 at 30% exercise. The first parameter of the pressure auto-regression was slightly higher than 1 at rest and even more augmented during standing, thus, indicating a tendency of arterial pressure perturbations to persist from one beat to the next. These mechanisms appear important in the genesis of low-frequency pressure waves. Nonetheless, the trace of different sources was evident in the regression residuals. Noticeably, during exercise it explained 10.16% of total heart period variability compared to 12.49% related to the low-frequency oscillations of closed-loops. The origin of high-frequency waves synchronous with respiration appeared miscellaneous as well. Arterial pressure appeared negligibly affected by heart period changes. Conversely, a limited effect of arterial pressure waves was found on heart period superimposed to a large effect of cardiopulmonary reflexes directly modulating the sinus node. In conclusion, both high-frequency and low-frequency waves are composite phenomena and a multi-channel analysis comparing heart period and arterial pressure variability yields a variety of figures assessing cardiovascular regulation and cardiorespiratory coupling.

Adult↗
PubMed2001

Autonomic dysregulation in essential hypertension: insight from heart rate and arterial pressure variability.

Essential hypertension is the most prevalent cardiovascular disorder, affecting more than 50 million people in the USA. Hypertension-related mortality and morbidity figures have been greatly improved over the last three decades by major advances in prevention. Detection and operative suggestions for practicing physicians are available from several guideline treatments derived from grouped data obtained in numerous well-conducted studies on large numbers of patients. However, the disappointing results of some forms of antihypertensive therapies, particularly in preventing coronary artery disease, has shed some doubts on traditional approaches to managing hypertensive patients. At present, in spite of extensive investigations, the exact causal mechanism(s) are far from being fully understood, and consequently, essential hypertension is still managed using a heuristic approach. Persistent elevations in arterial pressure imply some disturbances in the complex and multifactorial cardiovascular control mechanisms. In this context, neurohumoral disturbances might play a special role, in view of the demonstration that an elevated sympathetic drive seems essential in hypertensive patients. In this review, we follow the hypothesis that other allied methods capable of quantitatively assessing some aspects of the regulatory system might support and integrate the usual dichotomous diagnostic procedure based on arterial pressure determinations. In prior studies, we reported that parameters obtained by spectral analysis of heart rate variability (HRV) might furnish useful information on autonomic normal and abnormal nervous system regulation. In the foregoing, we summarize our experience using this approach in the clinical management of hypertensive patients. It is our tenet that spectral analysis of mono or multivariate cardiovascular beat-by-beat variabilities provides potentially important information on alterations in neural control of the circulation accompanying essential hypertension. In spite of an ongoing debate on the interpretation of specific aspects of HRV spectral components, overall, it appears that the available evidence supports the hypothesis that in essential hypertension, there is an increased sympathetic and reduced vagal cardiac drive coupled with an enhancement of vasomotor sympathetic modulation. Prospective studies on large populations, rendered more easy to perform, thanks to improvements in technology and telemedicine applications, might provide an answer to the still open question of how to apply spectral analysis of HRV to a better mechanistic understanding of essential hypertension, and to more satisfactory individually tailored antihypertensive treatments.

Autonomic Nervous System↗
PubMed2001

Trends, rhythms, and aberrations in global climate 65 Ma to present.

Since 65 million years ago (Ma), Earth's climate has undergone a significant and complex evolution, the finer details of which are now coming to light through investigations of deep-sea sediment cores. This evolution includes gradual trends of warming and cooling driven by tectonic processes on time scales of 10(5) to 10(7) years, rhythmic or periodic cycles driven by orbital processes with 10(4)- to 10(6)-year cyclicity, and rare rapid aberrant shifts and extreme climate transients with durations of 10(3) to 10(5) years. Here, recent progress in defining the evolution of global climate over the Cenozoic Era is reviewed. We focus primarily on the periodic and anomalous components of variability over the early portion of this era, as constrained by the latest generation of deep-sea isotope records. We also consider how this improved perspective has led to the recognition of previously unforeseen mechanisms for altering climate.

Animals↗