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Biomedical subjects

M Bertini

Publications and source records attributed to M Bertini.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1997

NADPH-diaphorase in antral gastritis of childhood.

BACKGROUND: Nitric oxide has an important role in the pathophysiology of the gastric mucosa. However, to date, it is not clear if nitric oxide plays a cytoprotective or cytotoxic role in the pathogenesis of mucosal lesion. METHODS: We have used the NADPH-diaphorase histochemistry that selectively stains cells containing nitric oxide synthase, the enzyme that catalyzes the production of nitric oxide on the antral gastric mucosa of children with antral gastritis. RESULTS: In the lamina propria of the mucosa, the presence of the enzymatic activity was found in perivascular round cells and nerve fibers. In the epithelium, focal positivity to NADPH-diaphorase was found in superficial cells, mainly located in the extrusive zones. The epithelial cells in the pits and glands were negative, in the mucous layer, Helicobacter pylori were also stained by NADPH-diaphorase. A single H. pylori-infected child who was also examined after eradication of the H. pylori showed during the control examination absence of microorganisms and reduction of the NADPH-diaphorase-positive cells in the mucosa. CONCLUSIONS: Our results demonstrate that, in gastric mucosa, endogenous and exogenous structures express a NADPH-diaphorase activity.

Animals↗
PubMed1997

Effects of different sleep duration on delta sleep in recovery nights.

The study assessed the effects of different amounts of sleep restriction on slow wave sleep (SWS) in the ensuing recovery nights. After one adaptation night and an 8-hr baseline night, six healthy men were individually studied during and following five nights in which sleep was reduced to 5, 4, 3, 2, and 1 hr with a 1-week interval between conditions. Each sleep reduction was followed by an 8-hr recovery night. Finally, a second 8-hr baseline night was recorded. A trend analysis revealed that SWS amount in recovery nights increases with decreasing previous sleep duration. Regression analyses showed that, within each participant, the rebound of SWS after a sleep reduction is predicted better by the total duration of sleep than by the specific amount of SWS lost.

Adult↗
PubMed1997

Intensified and high-dose chemotherapy with granulocyte colony-stimulating factor and autologous stem-cell transplantation support as first-line therapy in high-risk diffuse large-cell lymphoma.

PURPOSE: In our previous study with MACOPB, we identified a high-risk group of patients with a poor 3-year survival rate of 29%. These patients were defined as having at diagnosis advanced-stage disease with high tumor burden (TB) and elevated lactate dehydrogenase (LDH) level or bone marrow (BM) involvement. A novel therapeutic scheme was investigated to improve the outcome of these patients. PATIENTS AND METHODS: Fifty patients with high-risk diffuse large-cell lymphoma (DLCL) were enrolled. The therapeutic scheme includes three phases: induction with 8 weeks of MACOPB; intensification with a 3-day course of mitoxantrone 8 mg/m2 plus high-dose cytarabine (HDARA-C) 2 g/m2 every 12 hours plus dexamethasone 4 mg/m2 every 12 hours (MAD protocol) and granulocyte colony-stimulating factor (G-CSF) 5 microg/kg on days 4 to 17 to harvest peripheral-blood progenitor cells (PBPC); consolidation with carmustine (BCNU), etoposide, ARA-C, and melphalan (BEAM) regimen; plus autologous stem-cell transplantation (ASCT) with PBPC, marrow, or both. RESULTS: Thirty-six patients (72%) achieved a complete response (CR), 11 (22%) showed no response (NR), and three (6%) died of toxicity. Among the 22 PRs or NRs after the induction phase, 56% of patients achieved a CR with subsequent intensified therapy. With a median follow-up duration of 32 months, the overall survival and failure-free survival rates were 56% and 50%, respectively. The disease-free survival rate is 69% at 32 months. Leukapheresis after MAD and G-CSF yielded a median of 32 x 10(6)/kg CD34+ cells and 80 x 10(4)/kg granulocyte-macrophage colony-forming units (CFU-GM). Thirty-nine patients were autografted and 11 did not undergo ASCT: six because of disease progression, four due to toxicity, and one because of patient refusal. The median times to achieve engrafment were 11 days (range, 7 to 19) to a neutrophil count greater than 0.5 x 10(9)/L and 12 days (range, 8 to 60) to a platelet count greater than 50 x 10(9)/L. CONCLUSION: This sequential scheme with intensified and high-dose chemotherapy with ASCT is feasible with moderate toxicity and may improve the outcome in high-risk DLCL.

Adult↗
PubMed1996

Molecular heterogeneity of B-lineage diffuse large cell lymphoma.

B-lineage diffuse large cell lymphoma (B-DLCL) arising de novo is characterized by a marked degree of clinical heterogeneity. To determine whether or not the clinical heterogeneity of de novo B-DLCL is reflected by heterogeneity in the molecular features of these tumors, we investigated the pattern of distribution of several genetic lesions in 70 cases of de novo B-DLCL at diagnosis. The panel of genetic lesions tested comprised the molecular alterations most frequently detected in B-DLCL, including rearrangements of BCL2, BCL6, and MYC as well as deletions of 6q and mutations of TP53. One or more genetic lesions were detected in 39/70 cases of B-DLCL. Isolated structural alterations of BCL2, BCL6, 6q or TPS3 were detected in 8/70, 10/70, 11/70, and 3/70 cases, respectively. No isolated MYC lesions were detected. Six cases carried different combinations of two genetic lesions, including lesions of BCL2 + BCL6 (1 case), BCL2 + MYC (1 case), BCL2 + 6q (2 cases), or BCL6 + 6q (2 cases). One case had accumulated three genetic lesions, namely a rearrangement of BCL2 and BCL6 and a mutation of TPS3. Overall, these data show that multiple distinct patterns of genetic lesions may associate with de novo B-DLCL, indicating that the molecular pathogenesis of this group of lymphomas is characterized by a high degree of molecular heterogeneity.

Chromosome Deletion↗
PubMed1996

Rapid eye movements density as a measure of sleep need: REM density decreases linearly with the reduction of prior sleep duration.

In the recovery nights from total and partial sleep deprivation there is a reduction of oculomotor activity during paradoxical sleep as compared to baseline nights. Aims of the present within-subjects study are to contribute in understanding the nature of the relationship between REM density and sleep need and to evaluate whether an inverse relationship exists between REM density and slow wave sleep (SWS) amount. Six healthy subjects were studied for 7 consecutive weeks with standard polysomnographic recordings. Variations in REM density were assessed in the recovery nights following a gradual sleep restriction, obtained by postponing the sleep onset time while maintaining the final awakening time constant. Results indicate that sleep curtailment decreases REM density in the ensuing recovery nights; the decrease is linearly related to the amount of sleep curtailment. The decrease in REM density parallels an increase in SWS, while no corresponding variation was found neither in the duration of paradoxical sleep nor in the latency of any other sleep stage. These results suggest that REM density could be used as a measure of sleep need.

Adult↗
PubMed1996

Combined modality treatment with a weekly brief chemotherapy (ACOP-B) followed by locoregional radiotherapy in localized-stage intermediate- to high-grade non-Hodgkin's lymphoma.

BACKGROUND: A cooperative study was undertaken to evaluate the efficacy and toxicity of a very brief course of chemotherapy followed by locoregional radiotherapy in patients with localized-stage intermediate- to high-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHOD: From January 1988 to November 1994, 84 patients with localized stages IA and IIA intermediate- to high-grade NHL underwent a combined modality treatment. All patients underwent a six-week chemotherapy regimen, ACOP-B (doxorubicin 50 mg/sqm and cyclophosphamide 350 mg/sqm on weeks 1, 3, 5; vincristine 1.4 mg/sqm and bleomycin 10 mg/sqm on weeks 2, 4, 6; prednisone 50 mg p.o. daily throughout the first two weeks and thereafter every other day), followed by locoregional radiotherapy (36 Gy). RESULTS: The median age was 58 years, with 35% older than 65 years; 52 patients had stage I and 32 stage II; 39 patients had extranodal +/- nodal involvement, and 4 had testicular involvement. Treatment was well tolerated, with only 38% suffering from mild mucositis and no toxic deaths. Seventy-nine patients achieved CR after ACOP-B and 83 at the end of the program. With a median follow-up of four years, relapse-free survival was 79% with 15 relapses (93% disseminated). Two patients with testis lymphoma had CNS relapses. Overall survival was 90% at four years. CONCLUSION: This combined program is effective and probably curative in localized stage intermediate- to high-grade NHL, with low toxicity, also in elderly people. Patients with NHL of the testis, as primary site, require CNS prophylaxis due to the high likelihood of CNS relapse.

Adult↗
PubMed1996

Variations in sleep mentation as a function of time of night.

Mentation reports collected from sleep onset, Stage 2 and REM Stage awakenings, in the first part and in the second part of the night were analyzed both with systematic psycholinguistic and global measures. Results confirm the relationship between activation and the length of sleep mentation report shown by Antrobus. Length of the report increases with sleep time, but time does not modulate qualitative inter-stage differences. By partialling out the length of the report, many inter-stage differences disappeared; however significant differences remain in the global measure of bizarreness and in the psycholinguistic measure of visual imagery. These results cannot be explained entirely by differences in attention and memory and point to more basic differences in mental activity.

Adult↗
PubMed1996

The treatment of elderly patients with aggressive non-Hodgkin's lymphomas: feasibility and efficacy of an intensive multidrug regimen.

The results of a prospective trial of an 8 week treatment for elderly patients with advanced intermediate-high grade NHL are reported. Our aim was to reduce general toxicity without losing an antilymphoma effect. For this reason the use of growth factor was studied. We also analysed the behavior of different histological groups (E + F vs G + H). From November 1991 to November 1993 100 patients older than 65 years with combination intermediate-high grade advanced stage NHL were treated with the P-VEBEC regimen, an original including epirubicin 50 mg/sqm, cyclophosphamide 300 mg/sqm and etoposide 100 mg/sqm on weeks 1, 3, 5, 7; vinblastine 5 mg/sqm and bleomycin 5 mg/sqm on weeks 2, 4, 6, 8; prednisone 50 mg/sqm/day per os in the first two weeks and thereafter every other day .46 pts received rG-CSF 5 micrograms/Kg/day throughout the treatment starting on day 2 of every week for 4 consecutive days. Twenty eight pts had B symptoms, 41 had bulky disease, 37 LDH levels above normal, 50 stage IV patients and 30 had bone marrow involvement. Sixty two percent achieved a complete remission (CR). Adverse prognostic factors for CR were E and F histology, stage IV disease, bone marrow infiltration, serum LDH levels above normal, international Prognostic Index (I.I.) intermediate-high and high risk categories and relative dose intensity (RDI) less than 0.80. Severe toxicity was rarely recorded and only one toxic death was observed. With a median follow-up of 33 months OS, DFS and EFS were 44%, 60% and 30% respectively. EFS was influenced by stage, BM involvement, level of LDH and I.I. intermediate-high and high risks. The 52 patients with DLCL (diffuse large cell lymphomas--G + H according to WF) did better with a higher CR, OS, DFS and EFS rates, than the other WF subtypes. In conclusion P-VEBEC is a feasible combination to use in elderly patients, mainly in DLCL. The use of rG-CSF improves the RDI. A RDI > 0.80 could play a role in improving the outcome, especially in patients with adverse prognostic factors. For other subgroups another schedule is probably justified.

Aged↗
PubMed1996

Tannic acid supplemented fixation improves ultrastructural evaluation of respiratory epithelium in children with recurrent respiratory tract infections.

Samples of the respiratory mucosa of children with recurrent respiratory infections suspected of having primary ciliary dyskinesia are routinely fixed with glutaraldehyde before ultrastructural examination. This standard technique, however, may not be optimal for visualizing ciliary components or for preserving several cellular and extracellular structures during dehydration and embedding procedures. In this study, brushes of nasal (28 samples) and/or tracheal (9 samples) mucosa from 32 children with recurrent respiratory tract infections were examined. Twenty-nine samples were fixed with glutaraldehyde supplemented with tannic acid to determine if the ultrastructural analysis of respiratory epithelium and bronchial secretions could be improved. Eight samples were conventionally fixed with glutaraldehyde alone. Lesions of the cellular membrane and damaged cells were easily visualized using tannic acid supplemented fixation. Internal ciliary structures including individual microtubules and dynein arms were also more clearly observed. In addition, the internal structure of microvilli of the respiratory epithelium could be studied and the presence of phospholipid-rich surfactant-like material within nasal and tracheal secretions were visualized after tannic acid supplemented fixation. We suggest that addition of tannic acid during fixation is useful for accurate ultrastructural evaluation of respiratory mucosa in both clinical and experimental situations.

Adolescent↗
PubMed1996

[Clinical assessment of a new oral bacterial treatment for children with acute diarrhea].

This study was carried out to evaluate the efficacy of a new oral bacteriotherapeutic drug in 63 children under 4 years old affected by infective diarrhoea or by extraintestinal infective pathology caused by oral antibiotic therapy. The patients were divided into three groups: the first and the second included subjects affected by acute diarrhoea enrolled in a comparative and controlled study; the third included subjects in chemotherapeutic treatment because suffering from infective extraintestinal pathologies, these patients were enrolled in a not controlled study. The first group underwent the rehydratant treatment for the acute enteritis together with the therapy with inactivated Lactobacillus acidophilus LB to value its antidiarrheic activity. To the second group (control group) was administered a no bacteriotherapeutic drug, while to the third group was administered the antibiotic therapy for extra-intestinal pathologies together with inactivated Lactobacillus acidophilus to avoid possible phenomena due to intestinal dysmicrobism. For all the patients included in the study, were reported; the number, the characteristics, the consistency of the motions and the description of the symptomatology during the treatment and daily. The greater part of the patients affected by the intestinal infective pathology subdued bacteriologic tests by coproculture. The obtained results showed a statistically significant clinical improvement of the first group patients compared with those of the second group, while those of the third group showed that the drug activity prevents the intestinal dysmicrobism affections due to the antibiotic therapy.

Acute Disease↗
PubMed1995

Changes in cognitive asymmetries from waking to REM and NREM sleep.

In previous studies, a right hemisphere superiority was shown during REM sleep with respect to Wake and NREM states for right hemisphere tasks. The question can be raised whether the increasing right hemisphere performance during REM is related to right hemisphere tasks only, or whether it is of more general nature. This hypothesis was tested by giving the lateralized Consonant Recognition Task to 16 subjects during waking and upon awakenings from REM and NREM sleep. Results support the hypothesis that right hemisphere superiority in REM sleep is not restricted to right hemisphere tasks.

Adult↗
PubMed1995

The complementary relationship between waking and REM sleep in the oculomotor system: an increase of rightward saccades during waking causes a decrease of rightward eye movements during REM sleep.

Since an inverse relationship between waking and REM sleep eye movements (EMs) has been found with respect to frequency, amplitude and direction of EMs, we evaluated variations in the percentages of horizontal rapid eye movements (REMs) during REM sleep after having increased rightward saccades during waking by means of a unilateral tachistoscopic visual test administered prior to sleep. In another condition subjects were given the same 4 h testing condition prior to sleep, the only difference being that they were instructed not to move their gaze; therefore only "attentional movements" were possible. This condition served as a control for the role of oculomotor activity in the complementary relationship between waking and REM sleep eye movements. The actual increase of rightward saccades during waking resulted in a significant decrease of rightward REMs. This effect has been observed only in the condition in which rightward eye movements were increased and it is specific for REMs of amplitude similar to those which were increased during waking by the lateralized test.

Adult↗
PubMed1995

Which hemisphere falls asleep first?

Behavioral tasks (reaction times to acoustic stimuli and finger tapping tasks) performed by normal subjects when sleepy or attempting to fall asleep have been used as indices of hemispheric asymmetries during the sleep onset period. Results show a stronger impairment of the left hemisphere (right hand) both in reacting to external stimuli and in sustaining endogenous motor programs. The left hemisphere seems to fall asleep earlier than the right hemisphere.

Acoustic Stimulation↗
PubMed1995

Increase of REM duration and decrease of REM latency after a prolonged test of visual attention.

Following one adaptation night, the nocturnal sleep of nine female college students was recorded for two baseline and two experimental nights. In both experimental nights, prior to sleep the subjects performed a 4 hour long visual task requiring the recognition of letters tachistoscopically presented in the right visual hemifield. In the first experimental night eye movements were permitted, while in the second subjects were allowed only covert movements of attention while keeping their gaze on a fixation point. Results show that, as a consequence of the experimental manipulation, there is an increase of REM duration and a shortening of REM latency without any concomitant significant change in REM density and in the duration and latency of the other sleep stages. The increase of REM duration was greater in the night in which only attentional "movements" were permitted (i.e., when there is a covert orienting of attention), suggesting that a load of spatial attention might have a role in increasing REM pressure.

Adult↗