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Biomedical subjects

M Bertini

Publications and source records attributed to M Bertini.

At least 19 recordsLinked to original sources

Point mutations of the BCL-6 gene: clinical and prognostic correlation in B-diffuse large cell lymphoma.

Although point mutations of the 5' noncoding regions of the BCL-6 proto-oncogene are frequently detected in B-diffuse large cell lymphoma (B-DLCL), a thorough analysis of the clinical correlation of these mutations has not been performed to date. In this study, BCL-6 mutations were examined by DNA direct sequencing in 103 patients with B-DLCL. BCL-6 mutations were found in 53/103 patients, including 38/76 treated with standard chemotherapy and 15/27 treated with autologous stem cell transplantation (ASCT) up front. The presence of BCL-6 mutations was correlated with clinical features at diagnosis and outcome. Mutated patients had a significantly higher LDH level (66% vs 38%, P < 0.05), and bulky disease (51% vs 32%, P = 0.05). In the whole series of patients BCL-6 mutations did not affect CR and OS. Patients with BCL-6 mutations tended to have a prolonged 5-years DFS and FFS compared to those without mutations (DFS 82% vs 63%, FFS 63% vs 49%). Among B-DLCL treated with standard chemotherapy, mutated patients showed a significantly improved 5-year DFS (85% vs 61%, P < 0.05) and, notably, the only four relapses observed among mutated patients occurred in less than 8 months. The multivariate regression analysis (P < 0.01) with DFS as endpoint confirmed the independent prognostic value of BCL-6 mutations. There was a trend for 5-year failure-free survival to be better for patients with BCL-6 mutations (63% vs 43%, P = 0.09). In the 27 patients treated with ASCT, BCL-6 mutations did not correlate with outcome. These results suggest that BCL-6 mutations may predict a higher chance of being free of disease in B-DLCL treated with standard chemotherapy. Larger series of patients need to be analyzed to evaluate the clinical relevance of BCL-6 mutations properly.

Adolescent↗

Early bronchopulmonary involvement in Crohn disease: a case report.

BACKGROUND: Bronchopulmonary manifestations of Crohn disease have been rarely described in children, including both subclinical pulmonary involvement and severe lung disease. CASE PRESENTATION: A 6.5-year-old girl is described with early recurrent bronchopulmonary symptoms both at presentation and in the quiescent phase of Crohn disease. Pulmonary function tests (lung volumes and flows, bronchial reactivity and carbon monoxide diffusing capacity) were normal. Bronchoalveolar cytology showed increased (30%) lymphocyte counts and bronchial biopsy revealed thickening of basal membrane and active chronic inflammation. CONCLUSIONS: Clinical and histological findings in our young patient suggest involvement of both distal and central airways in an early phase of lung disease. The pathogenesis of Crohn disease-associated lung disorders is discussed with reference to the available literature. A low threshold for pulmonary evaluation seems to be advisable in all children with CD.

Biopsy↗

EEG arousals in normal sleep: variations induced by total and selective slow-wave sleep deprivation.

STUDY OBJECTIVES: Aim of the present study was to assess changes in arousal rates after selective slow-wave (SWS) and total sleep deprivations. DESIGN: Two-way mixed design comparing the arousal index (Al), as expressed by the number of EEG arousals divided by sleep duration, in totally or selectively sleep deprived subjects. SETTING: Sleep laboratory. PATIENTS OR PARTICIPANTS: Nineteen normal male subjects [mean age=23.3 years (S.E.M.=0.55)]. INTERVENTIONS: Al was measured in baseline nights and after selective SWS (N=10) and total sleep deprivation (N=9). MEASUREMENTS AND RESULTS: During the baseline nights AI values changed across sleep stages as follows: stage 1 > stage 2 and REM > SWS, but did not present any significant variations as a function of time elapsed from sleep onset. The recovery after deprivation showed a reduction in EEG arousals, more pronounced after total sleep deprivation; this decrease affected NREM but not REM sleep. During the baseline nights Al showed a close-to-significance negative correlation with REM duration, while during the recovery nights a significant positive relation with stage 1 duration was found. CONCLUSIONS: The present results suggest that recuperative processes after sleep deprivation are also associated with a higher sleep continuity as defined by the reduction of EEG arousals.

Adult↗

Auditory evoked responses upon awakening from sleep in human subjects.

The hypothesis that a state of hypoarousal upon awakening should lead to a decrease in amplitude and an increase in latency of the N1-P2 components of the Auditory Evoked Potentials (AEPs) as compared to presleep wakefulness levels, was evaluated after two nocturnal awakenings and after the final morning awakening from a 7.5-h night of sleep. The amplitude of the N1-P2 complex was reduced upon awakening as compared to presleep wakefulness levels, but only following the first nocturnal awakening, scheduled after the first 2 h of sleep. This result is interpreted as indicating a link between slow wave sleep amount, mainly present during the first part of the night, and lowered levels of brain activation upon awakening. The reaction times, recorded concomitantly to AEPs, were more sensitive to the negative effects of sleep inertia.

Adult↗

Sleepiness: evaluating and quantifying methods.

The aim of this literature review is to analyze the methods mainly used for evaluating and quantifying the complex phenomenon of sleepiness. The most common distinction is between subjective measures or self-evaluations, performance decrement measures, measures for evaluating sleep propensity and measures of arousal decrease. Techniques mainly used in specialized literature will be briefly presented and commented upon, evaluating their sensitivity, advantages and limitations. We conclude that: (a) different measures inevitably are differently sensitive to sleepiness fluctuations; (b) the amount of prior sleep is strongly relevant in quantifying sleepiness levels; (c) subjective and behavioral measures show a higher level of vulnerability to external and motivational factors.

Attention↗

The boundary between wakefulness and sleep: quantitative electroencephalographic changes during the sleep onset period.

Microstructural electroencephalographic changes during the wakefulness-sleep transition have been investigated by comparing two definitions of sleep onset: the first occurrence of stage 1 and of stage 2. Power values were calculated across a 1-28-Hz frequency range in a 1-Hz bin resolution in the sleep recordings of 26 normal subjects. Quantitative changes were assessed after averaging individual time series, aligned with respect to the first occurrence of stage 1 or of stage 2. The time course of the single-Hz activity revealed a linear increase of power in the 1-6-Hz range and a linear decrease in the 9-12- and 16-28-Hz ranges during the stage 1 transition. During the stage 2 transition, electroencephalogram power linearly increased in the 1-7- and 14-15-Hz ranges and decreased in the 18-28-Hz range, while the 8-12-Hz range fitted a second-order polynomial curve. The two 'switch' points were also compared in their ability to differentiate Hz by Hz wakefulness from sleep: a lower mean power was found after stage 1 onset in the 9-11-Hz and 20-28-Hz bins and a higher one in the 1-5-Hz bins, while a higher power was found in the 1-8-Hz and 12-16-Hz bins and a lower one in 18-28-Hz bins after stage 2 onset. The time course of three electroencephalographic frequency ranges [delta/theta/sigma (1-7 and 12-16 Hz); beta (17-28 Hz); alpha (8-11 Hz)], grouped on the basis of a principal component analysis, fitted a first-order polynomial curve for the first two ranges, and a second-order polynomial curve for the last, with a progressive decrease during wakefulness, a minimum point during stage 1, and a subsequent increase during stage 2. The uniformly increasing electroencephalographic power across the 1-16-Hz frequency range during stage 2 and the shift of functional meaning for the alpha power during stage 1 point to the start of stage 2 as a more reliable boundary between wakefulness and sleep.

Adult↗

A brief survey of the modifications in sensory-secretory organs of the neonatal rat tongue.

Recent data obtained on rats suggest that in the days immediately following birth several events take place in the circumvallate papillae of the oral cavity. A phylogenetically primitive system of solitary chemosensory cells develops and is rapidly replaced by taste buds. The lipase-secreting von Ebner gland, which is associated with taste organs, begins to develop by forming short tubules. The intrinsic nervous system of the gustatory organs rapidly completes its maturation showing fast proliferation of fibers and immunocytochemical maturation. Intraepithelial lipid accumulation is visible in the non-receptorial mucosa of the tongue, showing aspects which suggest an active lipid secretion. These data demonstrate that in the rat the structure of the sensory-secretory organs of the newborn's tongue shows a typical conformation with respect to the adult and rapidly changes its organization in the first week after the birth. At the present level of knowledge, it is difficult to link the anatomical structures to peculiar functional roles but the rather simple organization of the neonatal gustatory epithelium could be in relation to the dietary regimen. The data obtained in laboratory animals underline the necessity of studies on human newborns to update the anatomical knowledge of the oral chemoceptive system.

Animals↗

The Influence of advanced age on the treatment and prognosis of diffuse large-cell lymphoma (DLCL).

The incidence of non-Hodgkin's lymphoma (NHL) in elderly patients has increased in recent years. Approximately 36% of elderly patients with NHL are diagnosed with diffuse large-cell lymphoma (DLCL), an aggressive lymphoma subtype. Some authors have suggested that lymphoma in the elderly is intrinsically different from that seen in younger patients. Diffuse large-cell lymphoma, for example, is curable in about 50% of patients younger than 65 years of age but has a significantly lower cure rate in older subjects. Elderly patients with DLCL represent a group that is difficult to treat because of comorbidity, diminished organ functions, altered drug metabolism, and irregular drug clearance rates. These factors must be carefully considered when evaluating treatment options for older patients. The quality of life (QOL) associated with various regimens should obviously be evaluated, though QOL has so far received little attention in clinical trials. Analyses of the results from numerous phase II and phase III trials in patients with advanced aggressive NHL have demonstrated that overall survival is reduced when chemotherapy regimens more toxic than CHOP (cyclophosphamide/doxorubicin/ vincristine/prednisone) are employed, whereas therapeutic regimens that are less toxic are often less effective. CHOP, therefore, may be regarded as the current gold standard of therapy for elderly patients with DLCL. The addition of granulocyte colony-stimulating factors to CHOP chemotherapy is recommended to limit myelosuppression. Intensive chemotherapy followed by autologous stem cell transplantation has recently been extended to patients older than 60 years, with encouraging results, albeit in a highly selected groups of patients. Other promising lymphoma treatments with improved toxicity profiles are being developed. Clinical trials are recommended to determine if these new therapies are safe and active in elderly patients with DLCL.

Age Factors↗

Insomnia is associated with systolic hypertension in uremic patients on hemodialysis.

A newly developed questionnaire was administered to 140 hemodialyzed patients (82 M and 58 F) who have achieved adequate anemia correction according to the best guidelines with the aim: to evaluate the prevalence of clinical/subclinical dyssomnias in these patients; to study the influence of the dialytic shift (morning versus afternoon schedules) on sleep duration and disturbancies; and to evaluate the relationship between clinical sleep disorders and blood pressure values in uremic patients. Results indicated that 85% of uremic patients undergoing hemodialysis complain of clinical insomnia (frequent, persistent and associated with daytime consequences) or sub-clinical sleep disorders; patients dialyzing in the morning sleep significantly less during the night preceding the treatment, than those dialyzing in the afternoon; older patients complaining of clinical insomnia have a higher risk of failure to achieve target-optimal values in systolic blood pressure.

Adult↗

Effect of slow-wave sleep deprivation on topographical distribution of spindles.

Spindle activity, visually scored in the 12-15 Hz range over antero-posterior midline derivations, has been assessed in ten normal subjects during a baseline and a recovery sleep after 2 nights of selective slow-wave sleep (SWS) deprivation. The recovery sleep, characterized by a significant increase of stage 4 and SWS as compared to the baseline, revealed that sleep spindles are reduced in the first NREM sleep cycle. The size of this reduction in spindle density progressively decreased in the course of the night, paralleling the depletion of SWS rebound. Topographical distribution of spindle activity showed a global linear increase over consecutive NREM-REM sleep cycles, regarding to the whole antero-posterior midline EEG derivations except the occipital one. It is concluded that the SWS rebound after 2 nights of selective SWS deprivation is associated with a reduction of spindles during stage 2.

Adult↗

Voluntary oculomotor performance upon awakening after total sleep deprivation.

The potential impact of sleep inertia on measures of voluntary oculomotor control have been surprisingly neglected. The present study examined the effects of 40 hours of sleep deprivation on saccadic (SAC) and smooth pursuit (SP) performance, attentional/visual search performance (Letter Cancellation Task, LCT) and subjective sleepiness (Sleepiness Visual Analog Scale, SVAS) recorded immediately after awakening. Standard polysomnography of nine normal subjects was recorded for 3 nights (1 adaptation, AD; 1 baseline, BSL; 1 recovery, REC); BSL and REC were separated by a period of 40 h of continuous wakefulness, during which subjects were tested every two hours. Within 30 s of each morning awakening, a test battery (SAC, SP, LCT, SVAS) was administered to subjects in bed. For data analysis, mean performance obtained during the day preceding the sleep deprivation night was considered as "Diurnal Baseline" and compared to performance upon awakening from nocturnal sleep. As a consequence of sleep deprivation, SWS percentage was doubled during REC. Saccade latency increased and velocity decreased significantly upon awakening from REC as compared to the other three conditions (Diurnal baseline, AD awakening, BSL awakening); accuracy was unaffected. As regards SP, phase did not show any impairment upon awakening, while velocity gain upon awakening from REC was significantly lower as compared to the other conditions. Finally, number of hits on LCT upon awakening from REC was significantly lower and subjective sleepiness higher as compared to Diurnal Baseline. It is concluded that 40 h of sleep deprivation significantly impaired performance to SAC and SP tasks recorded upon awakening from recovery sleep. This performance worsening is limited to the measures of speed, while both SAC accuracy and SP phase do not show a significant decrease upon awakening. Since saccadic velocity has recently been found to negatively correlate with simulator vehicle crash rates, it is suggested that the adverse effects of sleep deprivation on sleep inertia magnitude should be avoided by any personnel who may have to perform critical tasks involving high oculomotor control immediately after awakening.

Adult↗

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↗

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↗

Percutaneous treatment with amphotericin B of mycotic lung lesions from invasive aspergillosis: results in 10 immunocompromised patients.

The aim of this study was to evaluate the efficacy of percutaneous treatment of pulmonary lesions from invasive aspergillosis in immunocompromised patients. From 1992 to 1998, ten patients (seven men and three women; mean age 56 years) affected by hematological neoplasms (8 acute myeloid leukemias, 2 non-Hodgkin's lymphomas) and post-chemotherapy prolonged neutropenia developed pulmonary lesions from invasive aspergillosis. A total of 13 lesions (diameter 2-7 cm, median 5 cm) were treated percutaneously due to insufficiency of the high-dose i.v. therapy; under CT guidance, a median of 10 cm3 per session of a 1 mg/cm3 diluted solution of amphotericin B was injected through a fine needle (21-22 G); 45 sessions overall were performed (one to five per lesion, median four), according to the volume of the nodules, tolerance, and complications. The results were retrospectively evaluated either radiologically or clinically. Complications were cough, mild hemoptysis, and small pneumothorax and/or pleural effusion. No major complications occurred. One month after the beginning of treatment, 8 lesions completely resolved, 4 greatly improved, and 1 was not significantly reduced. In all ten patients symptoms improved (eight of ten could restart chemotherapy as scheduled). After antiblastic retreatment, 1 patient had mycotic recurrence. In our experience transthoracic topical treatment with amphotericin B of single or few lung lesions from invasive aspergillosis was effective, affording a rapid improvement of the lesions and symptoms, and allowing continuation of chemotherapy as scheduled, thereby reducing the risk of recurrences.

Amphotericin B↗

Oculomotor impairment after 1 night of total sleep deprivation: a dissociation between measures of speed and accuracy.

OBJECTIVES: The present study examined the effects of 40 h of sleep deprivation and of time-of-day on saccadic and smooth pursuit oculomotor performance. METHODS: Nine normal subjects slept for 3 consecutive nights in the laboratory (one adaptation, one baseline, one recovery). Baseline and recovery were separated by a period of 40 h of continuous wakefulness, during which subjects were tested every 2 h. Oculomotor performance assessed at the following hours: 10:00, 12:00, 14:00, 16:00, 18:00, 20:00, 22:00, of both the days preceding and following the sleep deprivation night, as well as at 24:00, 02:00, 04:00, 06:00 and 08:00 h during the deprivation period. RESULTS: Saccade latency increased and peak velocity decreased significantly during the post-deprivation day; saccadic accuracy was unaffected. As regards smooth pursuit performance, phase (a measure of accuracy) was not affected by sleep loss, while velocity gain significantly decreased during the day that followed the sleep deprivation night. Significant time-of-day effects on the considered oculomotor variables except saccadic accuracy were also found, indicating an overall performance impairment during the night. CONCLUSIONS: It is concluded that 40 h of sleep deprivation significantly impaired diurnal performance in pursuit and saccadic tasks. This performance worsening is limited to the measures of speed, while accuracy is not affected by sleep loss. A significant operational relevance of these results is suggested, since saccadic velocity has recently been found to be negatively correlated with simulator vehicle crash rates.

Adult↗

Slow eye movements and EEG power spectra during wake-sleep transition.

OBJECTIVE: The aim of the present study was to assess the relationship between slow eye movements (SEMs) and quantitative EEG measures during the wake-sleep transition. METHODS: Individual distributions were aligned with respect to the onset of stage 2 to provide an unequivocal hallmark of the beginning of sleep and to reduce the sources of variability in this transition. The relationship between EEG spectral powers and EOG changes was assessed by means of product-moment correlations and bootstrap analyses for individual time series, and by means of a multiple regression analysis for the entire sample. RESULTS: Results on the individual distributions as well as on averaged data showed a tight relationship between SEMs and EEG changes, negative across the 1-14 Hz frequency range and positive across the 15-30 Hz one. Spectral power in the sigma EEG band, that corresponds to the frequency at the phasic sleep spindles, resulted as the best predictor of SEM variations, being negatively correlated to the EOG changes. With respect to the other EEG frequency bands, the split half of the distributions with respect to stage 2 onset indicated a positive correlation of delta power with the increase of SEM activity before sleep onset, and of beta power with the decrease of SEMs after sleep onset. CONCLUSIONS: These results seem to suggest that sleep spindles could trigger the reduction and the final disappearance of slow eye movements in the late part of the wake-sleep transition.

Adult↗

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↗