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Biomedical subjects

M Bertini

Publications and source records attributed to M Bertini.

At least 19 recordsLinked to original sources
PubMed2000

The spontaneous K-complex during stage 2 sleep: is it the 'forerunner' of delta waves?

The hypothesis that K-complexes (KCs) contribute to the process of synchronization leading to Slow-Wave Sleep (SWS) was evaluated by measuring their dynamic evolution across sleep cycles and before transitions to rapid eye movement (REM) or to SWS. KC density and inter-KC intervals respectively decreased and increased across the sleep cycles, revealing linear trends. Comparisons among transitions from stage 2 to SWS or to REM sleep showed a prevalence of KCs before the shift to SWS as compared to REM. Changes in KC density before the shift to SWS were fitted by a linear regression, at variance with the transition to REM sleep. Intra-night variations of KCs, paralleling the well-known decrease of slow waves across sleep cycles, and intracycle variations before shifting to SWS, both converge to indicate that KCs can be considered as the forerunner of delta waves.

Adult↗
PubMed2000

A complementary relationship between wake and REM sleep in the auditory system: a pre-sleep increase of middle-ear muscle activity (MEMA) causes a decrease of MEMA during sleep.

Since some evidence has supported a complementary relationship between waking and REM-sleep eye movement (variations in frequency, amplitude, or direction of waking saccades have been found to inversely affect the corresponding parameters of rapid eye movements), the present study assessed whether this relationship can also be shown for other phasic components of REM sleep, such as middle-ear muscle activity (MEMA), as a consequence of an increase of middle-ear reflex frequency during pre-sleep wake. Ten subjects were studied in three consecutive nights (one adaptation, one baseline, one experimental). In the experimental night, subjects underwent a 2-h pure-tone (1000 Hz, 90 dB SPL) auditory stimulation and MEMA was monitored every 15 min; noise exposure during daytime was also controlled. Results show that MEMA frequency during REM sleep significantly decreased during the experimental nights compared with baseline nights, while each sleep variable as well as mean daily auditory input did not present any significant difference between baseline and experimental nights. Results suggest that the complementary relationship between wake and REM sleep is not bounded to oculomotor activity, but it may also be extended at least to middle-ear muscle phasic activity.

Acoustic Stimulation↗
PubMed2000

The relationship between frequency of rapid eye movements in REM sleep and SWS rebound.

Previous studies have shown a decrease in rapid eye movement (REM) frequency during desynchronized sleep in recovery nights following total or partial sleep deprivation. This effect has been ascribed to an increase in sleep need or sleep depth consequent to sleep length manipulations. The aims of this study were to assess REM frequency variations in the recovery night after two consecutive nights of selective slow-wave sleep (SWS) deprivation, and to evaluate the relationships between REM frequency and SWS amount and auditory arousal thresholds (AAT), as an independent index of sleep depth. Ten normal males slept for six consecutive nights in the laboratory: one adaptation, two baseline, two selective SWS deprivation and one recovery night. SWS deprivation allowed us to set the SWS amount during both deprivation nights close to zero, without any shortening of total sleep time. In the ensuing recovery night a significant SWS rebound was found, accompanied by an increase in AAT. In addition, REM frequency decreased significantly compared with baseline. This effect cannot be attributed to a variation in prior sleep duration, since there was no sleep loss during the selective SWS deprivation nights. Stepwise regression also showed that the decrease in REM frequency is not correlated with the increase in AAT, the traditional index of sleep depth, but is correlated with SWS rebound.

Adult↗
PubMed2000

Time-course of sleep inertia upon awakening from nighttime sleep with different sleep homeostasis conditions.

BACKGROUND: We assessed the time-course of sleep inertia during the first 75 min after morning awakening from regular nocturnal sleep, as well as from nighttime sleep episodes with altered sleep homeostasis conditions. METHODS: Ten normal males slept for 6 nights in the laboratory: 1 adaptation (AD), 2 baseline (BSL, BSL-A), 2 selective Slow-Wave Sleep (SWS) deprivation (DEP-1, DEP-2), and 1 recovery night (REC). On morning awakening, performance was assessed by means of: a) Descending Subtraction Task (DST); b) Auditory Reaction Time task (ART); and c) Finger Tapping Task (FTT). The test battery, lasting about 13 min, was repeated for 5 times. RESULTS: In regard to DST, the Correct Response ratio (CR/NR) showed a great increase of sleep inertia on the first testing session of REC. Regarding sleep inertia time-course, a significant linear decrease across the testing sessions during the BSL-A and the DEP-2 was present, whereas a significant quadratic trend during the AD, the DEP-1 and the REC was found. On the other hand, ART performance showed a significant quadratic trend across testing sessions, while FTT performance did not show any significant variation. CONCLUSIONS: A uniform pattern of variation of time-course of sleep inertia as a function of the different sleep homeostasis conditions was not recognized. Performance accuracy (CR/NR) on the DST showed the hypothesized increasing linear trend across testing sessions only during 2 out of 6 nights, while the unexpected quadratic trend of ART performance is probably due to a fatigue effect. During sleep inertia, cognitive performance reached the baseline level about 30 min after awakening, while motor performance was still below the baseline levels 75 min after awakening. The finding that cognitive performance recovery is greater and more rapid than motor performance recovery could be very important for operational settings and in sustained operations.

Adult↗
PubMed2000

Selective slow-wave sleep deprivation and time-of-night effects on cognitive performance upon awakening.

We evaluated the effects of selective slow-wave sleep (SWS) deprivation and time-of-night factors on cognitive performance upon awakening. Ten normal men slept for 6 consecutive nights in the laboratory: 1 adaptation, 2 baseline, 2 selective SWS deprivation, and 1 recovery night. Cognitive performance was assessed by means of a Descending Subtraction Task after 2, 5, and 7.5 h of sleep. There was an almost complete selective SWS suppression during both deprivation nights, and a significant SWS rebound during the recovery sleep. Regarding cognitive performance, a progressive linear decrease of sleep inertia upon successive awakenings was found during all experimental nights except for the recovery night. In addition, a significant decrease of sleep inertia was observed upon the morning awakening of the second deprivation night for the measure of performance speed, and a significant increase of sleep inertia upon the morning awakening of the recovery night for the measure of performance accuracy. The results show that cognitive performance upon awakening is adversely affected by sleep depth and that, during the sleep-wake transition, cognitive performance accuracy is more impaired than performance speed.

Adult↗
PubMed1999

Effects of different sleep reductions on daytime sleepiness.

This study evaluated the effects of different amounts of sleep and SWS restriction on the ensuing day-time sleepiness. Six healthy selected males, after one adaptation night and an initial 8-hr baseline night, were allowed to sleep 5, 4, 3, 2, and 1 hr with a 1-week interval between conditions. The following day, 4 sleep onset MSLT trials and 2 Wilkinson Auditory Vigilance Task (WAVT) were administered. Before each MSLT, self evaluations of sleepiness and activation on a visual analogue scale (ADAS) were assessed. Each restriction night was followed by an 8-hr recovery night, and a final 8-hr baseline night was recorded. The day after each night the same diurnal tests were repeated. Results indicated a linear increase in the propensity to sleep (MSLT) and of subjective sleepiness as a function of the increase in sleep restrictions. Performance scores (WAVT) showed that vigilance is partially affected by sleep restrictions. For each measure, regression analyses showed that the effect of sleep reduction is better predicted by the total duration of sleep than by the amount of SWS. Correlations between measures were negligible with the exception of those between performance and subjective sleepiness measures.

Adult↗
PubMed1999

Auditory arousal thresholds after selective slow-wave sleep deprivation.

OBJECTIVES: The aim of this study is to assess Auditory Arousal Thresholds (AATs) three times during an undisturbed baseline night and to compare them to AATs during the recovery night that follows two consecutive nights of selective SWS deprivation. The presence of a time-of-night effect on AATs will also be assessed. METHODS: Ten male Ss slept in the laboratory for 6 consecutive nights. The first two nights were undisturbed. The 3rd night was considered as baseline. During the 4th and 5th nights, selective SWS deprivation was obtained by means of acoustic stimulation. The 6th night was a recovery. In the last 4 nights Ss were awakened three times, after 2, 5 and 7.5 h of sleep, respectively. All the awakenings were carried out from stage 2 (after at least 5 consecutive min of stage 2), by means of 1000 Hz ascending tone series. The AAT determination was based on EEG-EMG criteria: at least 10-s of clear alpha rhythm and/or a 10 s movement arousal. RESULTS: During both deprivation nights, SWS amount was close to zero. In the ensuing recovery night a significant SWS rebound was found, accompanied by a significant increase of AATs with respect to the baseline. Furthermore, there was a significant linear decrease of AATs during the night. Finally, the individual correlations between AATs and SWS amount were significant in 4 out of 10 Ss. CONCLUSIONS: These results confirm that AATs are a reliable index of sleep depth by showing that the SWS rebound following selective SWS deprivation is paralleled by a significant AAT enhancement. The experimental paradigm also allows us to claim that AATs show a decreasing linear trend during the night, having excluded any procedural bias. Finally, AATs can be directly related to SWS amount that preceded the awakening, although the individual correlations between AATs and SWS have to be considered with caution, given the high inter-subject variability and the small number of observations.

Acoustic Stimulation↗
PubMed1999

Stage-modified international prognostic index effectively predicts clinical outcome of localized primary gastric diffuse large B-cell lymphoma. International Extranodal Lymphoma Study Group (IELSG)

BACKGROUND: The definition of prognostic parameters in early stages of gastric lymphoma is still controversial. The aim of this retrospective analysis was to assess the value of the stage-modified international prognostic index (IPI) in predicting the outcome of a large, consecutive series of patients with PGL of diffuse large B-cell histology (DLCL). PATIENTS AND METHODS: Three hundred twelve consecutive, newly-diagnosed, patients with localized PGL (stages I-IIE according to the 'Lugano staging system for GI lymphomas') referred from April 1972 to December 1997 to eight Italian and one Swiss centers were reviewed and their outcomes updated to June 1998. One hundred three patients were treated with single-modality therapy, while two hundred four received combined-modality treatment, most of which included surgery and short-term chemotherapy. RESULTS: After a median follow-up of 66 months (range 0.6-300 months), 195 (64%) were alive in first continuous complete remission (CCR). The five-year estimates of overall survival (OS) and event-free survival (EFS) were 75% and 67%, respectively. OS and EFS varied according to IPI, from, respectively, 90% and 82% for patients with 0-1 risk factors, to 40% and 35% for patients with > or = 3 risk factors (P = 0.00001). Cox regression analysis showed that IPI was the strongest predictor of survival. CONCLUSIONS: This study shows that stage-modified IPI is an effective predictive model in patients with primary DLCL of the stomach, enabling identification of patients with significantly different outcomes.

Adolescent↗
PubMed1998

A peptide fraction from factor VIII reduces PKC activity in cultured endothelial cells.

A peptide fraction of low molecular weight (Vueffe) prepared from bovine Factor VIII by enzymatic hydrolysis with trypsin, reduces significantly (p<0.05) membrane bound protein kinase C (PKC) activity in cultured bovine pulmonary artery endothelial cells grown with enhanced glucose levels (22.2 mM) or stimulated by phorbol 12-myristate 13-acetate (PMA). The activation of PKC is a common pathway by which mediators increase transendothelial permeability during tissue inflammation and in the development of diabetic vascular complications. Our results suggest that the antihaemorrhagic properties of Vueffe could be related to a decrease in endothelial permeability mediated by PKC.

Animals↗
PubMed1998

Rearrangements of bcl-6, bcl-2, c-myc and 6q deletion in B-diffuse large-cell lymphoma: clinical relevance in 71 patients.

BACKGROUND: B-diffuse large-cell lymphomas (DLCL) have been associated with some molecular lesions, but the role of such lesions as prognostic markers is still controversial. This report concerns an investigation of the frequency and clinical correlation of bcl-6, bcl-2, c-myc rearrangements and 6(q) deletions in B-DLCL. PATIENTS AND METHODS: The presence of these genetic lesions was analyzed in samples of lymph nodes or bone marrow collected at diagnosis in 71 patients with B-DLCL, all treated with an anthracycline-containing chemotherapy regimen. RESULTS: Rearrangement of bcl-6 was found in 11 patients (15%), rearranged bcl-2 in 12 (17%), 6(q) deletions in 10 patients (14%) and c-myc rearrangement in four (6%). Patients with rearranged bcl-6 tended to have a more aggressive disease than patients with germ-line bcl-6 (intermediate-high/high risk according to IPI criteria: 73% vs. 43%), but there were no differences in three-year survival rates (62% vs. 42%) between the two groups. The numbers of involved extranodal sites were similar in patients with rearranged and those with germ-line bcl-6. Patients with bcl-2 rearrangement appeared to have a less aggressive disease than those with germ-line bcl-2 (low/ low-intermediate risk 75% vs. 47%) and a slightly better three-year survival rate (70% vs. 41%) but again the difference was not significant. Both groups with or without 6(q) deletion had similar clinical characteristics and outcomes. The four patients with c-myc rearrangement had aggressive disease and did poorly. CONCLUSIONS: The analysis of molecular lesions in B-DLCL may be useful for a better diagnostic definition; however, in this study we were unable to show that the evaluated genetic lesions had a significant impact on clinical outcome.

Adolescent↗
PubMed1998

Colonic disease in cirrhotic patients with portal hypertension: an endoscopic and clinical evaluation.

Fifty cirrhotic patients with portal hypertension but without colonic or systemic disease underwent lower gastrointestinal endoscopy in order to investigate the effects, if any, of portal hypertension on the colon. Fifty patients without liver or systemic disease, examined by colonoscopy because of irritable bowel syndrome in the same period served as controls. Rectosigmoid varices were observed in 34% of the cirrhotic patients and 2% of the controls. Hemorrhoids were observed in 70% of the cirrhotic patients and 48% of the controls. Multiple vascular-appearing lesions were found in 16% of the cirrhotic patients and 6% of the controls. Nonspecific inflammatory changes were noted in 10% of the cirrhotic patients and 4% of the controls. Simultaneous presence, in the same patient, of rectosigmoid varices, hemorrhoids, multiple vascular-appearing lesions, and nonspecific inflammatory changes, was observed in only five (10%) of the cirrhotic patients. We found polyps in 12% of the cirrhotic patients and 14% of the controls, and a malignant tumor in 4% of the cirrhotic patients. The patients with normal colonoscopic findings were 8% of the cirrhotic patients and 36% of the controls. All patients and controls were followed up for 1 year; there was no gastrointestinal hemorrhage among controls, whereas 34% of the cirrhotic patients had an upper gastrointestinal hemorrhage (88% from esophageal varices, 12% from the stomach) and 4% had a lower gastrointestinal hemorrhage (one from rectosigmoid varices and one from nonspecific inflammatory lesions). Colonic lesions were significantly more frequent in the cirrhotic patients (92%) than in the control group (64%); however, such lesions did not seem specific to the disease and were not statistically correlated with the degree of esophageal varices by Child's grading, the etiology of cirrhosis, or the bleeding risk from the lower gastrointestinal tract.

Adult↗
PubMed1998

Ultrastructural lesions in the small bowel of patients with cystic fibrosis.

In the small bowel of patients with cystic fibrosis, primary defects involving both chloride transport and mucus secretion have been demonstrated, but there is no general consensus about the morphologic counterpart of functional and biochemical abnormalities. We have studied the intestinal mucosa in a group of patients with cystic fibrosis and gastrointestinal symptoms with the aim of evaluating whether the intestinal mucosa is normal as previously described. The results showed that the small bowel involvement is characterized by a typical pattern of lesions with preservation of the mucosal architecture and abundant mucus at the surface. In the villi, the absorbing cells were generally well preserved, but unusual features were found in the apical portion of the goblet cells, which formed sacks containing mucus droplets. Similar sacks were also found detached from the goblet cells. Aspects of degeneration were present in the upper portion of the crypts where elements with an extensive vacuolization of the cytoplasm and swelling were detectable. This study demonstrates that in patients with cystic fibrosis the ultrastructure of the small bowel mucosa is not normal as previously described, but that an ultrastructurally detectable enteropathy exists. This enteropathy seems to be localized mainly in sites where molecular biology studies described the highest expression of cystic fibrosis transmembrane conductance regulator.

Child↗
PubMed1998

Mantle cell lymphoma: a retrospective study on 27 patients. Clinical features and natural history.

BACKGROUND AND OBJECTIVE: Mantle cell lymphoma (MCL) is a separate histological and clinical entity recently recognized in the new revised European-American Lymphoma Classification. Little information exists regarding its therapy. We report the results of a retrospective study of 27 patients affected by MCL evaluating the clinical characteristics and the results of different therapeutical options used during the period of observation. DESIGN AND METHODS: From 1983 to 1993, we observed 27 patients affected by MCL according to the criteria proposed by European Lymphoma Task Force in a revision of 55 cases classified as NHL E according to Working Formulation (WF) criteria. We analyzed the clinical characteristics, the prognostic factors and the O.S. of these patients. RESULTS: The clinical characteristics of our patients (pts) are similar to those observed in other series: male prevalence, median age 62 years, B symptoms in 9 cases, P.S. > 2 in 11 cases, 3 pts were in stage I and II, 4 in stage III, 20 in stage IV; 18 pts had a bone marrow involvement, 13 pts had spleen enlargement and 14 had extranodal localization; 8 pts had bulky tumor and 5 had LDH above normal. The CR rate was 51.8%, the median O.S. was 43 months, and DFS was 18 months; the pts without bulky disease and with localized disease had a better CR rate. The inclusion of an anthracycline in the regimen did not affect the results. INTERPRETATION AND CONCLUSIONS: Our results were not divergent from those present in literature. The mantle cell lymphoma is an incurable and highly aggressive disease. Autologous bone marrow transplantation as support of high dose chemotherapy or allogenic bone marrow transplantation may be a chance for some patients, but not for the majority of patients, which are older than 65 years. Studies of a larger series and different therapeutical approaches, i.e. using biological modifiers in association or as maintenance after chemotherapy are essential.

Adult↗
PubMed1997

Hepatotropic conjugate of adenine arabinoside monophosphate with lactosaminated poly-L-lysine. Synthesis of the carrier and pharmacological properties of the conjugate.

BACKGROUND/AIMS: The hepatotropic conjugate of adenine arabinoside monophosphate with lactosaminated poly-L-lysine (L-Poly(Lys)) must have a high solubility in order to be injected in a small volume compatible with the intramuscular route. In this paper the molecular weights of Poly(Lys) which allowed the synthesis of conjugates with the properties of high solubility and limited loss by the kidney were determined and a procedure for obtaining Poly(Lys) preparations with the required range of polymerization has been described. METHODS: Conjugates were prepared using Poly(Lys) of different molecular weights obtained by the procedure described here or purchased from a commercial source. Their solubility and renal loss in mice was determined. RESULTS: Poly(Lys) with molecular weights ranging from 45,000 and 65,000 Da guarantees high solubility and low renal elimination of the conjugates. Conjugate preparations with these properties, intramuscularly administered to woodchuck hepatitis virus-infected woodchucks for 37 days at a daily dose of 5.8 mg/kg exerted a strong antiviral activity. These preparations were devoid of acute toxicity in rat and caused no toxic effects when injected intramuscularly daily for 28 days at a dose ten times higher than that active in woodchucks. CONCLUSIONS: The results support the possibility of a clinical use of L-Poly(Lys) to obtain liver targeting of adenine arabinoside monophosphate for the treatment of chronic hepatitis B virus infection.

Amino Sugars↗
PubMed1997

Liver targeting of antiviral nucleoside analogues through the asialoglycoprotein receptor.

In order to reduce the extrahepatic side-effects of antiviral nucleoside analogues in the treatment of chronic viral hepatitis, these drugs are conjugated with galactosyl-terminating macromolecules. The conjugates selectively enter hepatocytes after interaction of the carrier galactose residues with the asialoglycoprotein receptor present in large amounts and high affinity only on these cells. Within hepatocytes the conjugates are delivered to lysosomes where enzymes split the bond between the carrier and the drug, allowing the latter to become concentrated in the liver. The validity of this chemotherapeutic strategy has been endorsed by a clinical study. Adenine arabinoside monophosphate (ara-AMP), conjugated with lactosaminated human serum albumin (L-HSA) and administered to hepatitis B virus (HBV)-infected patients for 28 days, exerted an antiviral activity to the same extent as the free drug without producing any clinical side-effects, including the severe neurotoxicity caused by the free drug. Preclinical studies are now underway with conjugates obtained using lactosaminated poly-L-lysine (Lac-poly(Lys)) as the hepatotropic carrier. These new conjugates have some advantages over those prepared with L-HSA: they can be administered by the intramuscular route; they are obtained entirely by chemical synthesis, thus eliminating the problems involved in the use of haemoderivatives; they have a heavy drug load, which permits administration of smaller quantities of conjugate that are more easily digested in lysosomes; and they enable higher quantities of drug to be introduced into hepatocytes. The results of the experiments with two Lac-poly(Lys) conjugates, one with ara-AMP and one with ribavirin, are reported in this review.

Animals↗
PubMed1997

Assessing vigilance through a brief pencil and paper letter cancellation task (LCT): effects of one night of sleep deprivation and of the time of day.

Behavioural effects of the lack of sleep in normal subjects have been investigated mostly by experimenter-paced choice reaction times in prolonged stimulus detection tasks. However, length and procedure complexity of these tasks limit their use in research on larger numbers of subjects. The aim of the present study was to assess the effectiveness of a brief subject-paced pencil and paper performance task, i.e. letter cancellation task (LCT) in revealing the effects of one night of sleep deprivation. In addition, the authors evaluated sleep loss and time of day effects on six Visual Analogue Scales (VAS) measuring subjective activation-deactivation. Results show that a LCT is sensitive in revealing the effects of time of day and of 24 h of sleep deprivation. Effects of sleep deprivation were also revealed by VAS data. Sleepiness, tiredness and energy scales on the VAS were also affected by time of day. Despite the sensitivity of both the LCT and VAS, there was little correspondence between performance and subjective measures.

Adult↗
PubMed1997

A finger-tapping task and a reaction time task as behavioral measures of the transition from wakefulness to sleep: which task interferes less with the sleep onset process.

The aim of this study was to assess whether a finger-tapping task (FTT), in which normal subjects repeatedly tap on a button while falling asleep, could be less disturbing and provide comparable information on the sleep onset period (SOP) with respect to a reaction-time task (RTT) to acoustic stimuli, in which the onset of sleep can be delayed by the arousing effect of the acoustic stimuli. Twelve subjects slept at their homes and six slept in a sleep laboratory for four consecutive nights. After one adaptation night and one baseline night, subjects were required to fall asleep in the third and fourth nights, bimanually performing either a RTT or a FTT. The results indicate that the FTT interfaces less with the SOP compared to the RTT and suggest that the FTT provides further advantages as a behavioral measure of the transition from wakefulness to sleep. In fact, the tapping task is associated with significantly shorter behavioral and polysomnographic sleep onset latencies and with a greater proportion of slow-wave sleep (SWS) during the transition from wakefulness to sleep compared with the RTT. Furthermore, correlations among subjective, behavioral, and electroencephalograph (EEG) latencies confirm the validity of the finger-tapping task as a behavioral measure of sleep onset.

Acoustic Stimulation↗