The web of laughter: frontal and limbic projections of the anterior cingulate cortex revealed by cortico-cortical evoked potential from sites eliciting laughter.

According to an evolutionist approach, laughter is a multifaceted behaviour affecting social, emotional, motor and speech functions. Albeit previous studies have suggested that high-frequency electrical stimulation (HF-ES) of the pregenual anterior cingulate cortex (pACC) may induce bursts of laughter-suggesting a crucial contribution of this region to the cortical control of this behaviour-the complex nature of laughter implies that outward connections from the pACC may reach and affect a complex network of frontal and limbic regions. Here, we studied the effective connectivity of the pACC by analysing the cortico-cortical evoked potentials elicited by single-pulse electrical stimulation of pACC sites whose HF-ES elicited laughter in 12 patients. Once these regions were identified, we studied their clinical response to HF-ES, to reveal the specific functional target of pACC representation of laughter. Results reveal that the neural representation of laughter in the pACC interacts with several frontal and limbic regions, including cingulate, orbitofrontal, medial prefrontal and anterior insular regions-involved in interoception, emotion, social reward and motor behaviour. These results offer neuroscientific support to the evolutionist approach to laughter, providing a possible mechanistic explanation of the interplay between this behaviour and emotion regulation, speech production and social interactions. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.

Simultaneous stereo-EEG and high-density scalp EEG recordings to study the effects of intracerebral stimulation parameters.

BACKGROUND: Cortico-cortical evoked potentials (CCEPs) recorded by stereo-electroencephalography (SEEG) are a valuable tool to investigate brain reactivity and effective connectivity. However, invasive recordings are spatially sparse since they depend on clinical needs. This sparsity hampers systematic comparisons across-subjects, the detection of the whole-brain effects of intracortical stimulation, as well as their relationships to the EEG responses evoked by non-invasive stimuli. OBJECTIVE: To demonstrate that CCEPs recorded by high-density electroencephalography (hd-EEG) provide additional information with respect SEEG alone and to provide an open, curated dataset to allow for further exploration of their potential. METHODS: The dataset encompasses SEEG and hd-EEG recordings simultaneously acquired during Single Pulse Electrical Stimulation (SPES) in drug-resistant epileptic patients (N = 36) in whom stimulations were delivered with different physical, geometrical, and topological parameters. Differences in CCEPs were assessed by amplitude, latency, and spectral measures. RESULTS: While invasively and non-invasively recorded CCEPs were generally correlated, differences in pulse duration, angle and stimulated cortical area were better captured by hd-EEG. Further, intracranial stimulation evoked site-specific hd-EEG responses that reproduced the spectral features of EEG responses to transcranial magnetic stimulation (TMS). Notably, SPES, albeit unperceived by subjects, elicited scalp responses that were up to one order of magnitude larger than the responses typically evoked by sensory stimulation in awake humans. CONCLUSIONS: CCEPs can be simultaneously recorded with SEEG and hd-EEG and the latter provides a reliable descriptor of the effects of SPES as well as a common reference to compare the whole-brain effects of intracortical stimulation to those of non-invasive transcranial or sensory stimulations in humans.

Multiple time courses of somatosensory responses in human cortex.

Here we show how anatomical and functional data recorded from patients undergoing stereo-EEG can be used to decompose the cortical processing following nerve stimulation in different stages characterized by specific topography and time course. Tibial, median and trigeminal nerves were stimulated in 96 patients, and the increase in gamma power was evaluated over 11878 cortical sites. All three nerve datasets exhibited similar clusters of time courses: phasic, delayed/prolonged and tonic, which differed in topography, temporal organization and degree of spatial overlap. Strong phasic responses of the three nerves followed the classical somatotopic organization of SI, with no overlap in either time or space. Delayed responses presented overlaps between pairs of body parts in both time and space, and were confined to the dorsal motor cortices. Finally, tonic responses occurred in the perisylvian region including posterior insular cortex and were evoked by the stimulation of all three nerves, lacking any spatial and temporal specificity. These data indicate that the somatosensory processing following nerve stimulation is a multi-stage hierarchical process common to all three nerves, with the different stages likely subserving different functions. While phasic responses represent the neural basis of tactile perception, multi-nerve tonic responses may represent the neural signature of processes sustaining the capacity to become aware of tactile stimuli.

Decomposing Tool-Action Observation: A Stereo-EEG Study.

A description of the spatiotemporal dynamics of human cortical activity during cognitive tasks is a fundamental goal of neuroscience. In the present study, we employed stereo-EEG in order to assess the neural activity during tool-action observation. We recorded from 49 epileptic patients (5502 leads) implanted with intracerebral electrodes, while they observed tool and hand actions. We deconstructed actions into 3 events-video onset, action onset, and tool-object contact-and assessed how different brain regions respond to these events. Video onset, with actions not yet visible, recruited only visual areas. Aligning the responses at action onset, yielded activity in the parietal-frontal manipulation circuit and, selectively for tool actions, in the left anterior supramarginal gyrus (aSMG). Finally, by aligning to the tool-object contact that signals the achievement of the main goal of the observed action, activations were found in SII and dorsal premotor cortex. In conclusion, our data show that during tool-action observation, in addition to the general action observation network there is a selective activation of aSMG, which exhibits internally different patterns of responsiveness. In addition, neural responses selective for the contact between the tool and the object were also observed.

Smile and laughter elicited by electrical stimulation of the frontal operculum.

Laughter and smile are typical expressions of mirth and fundamental means of social communication. Despite their general interest, the current knowledge about the brain regions involved in the production of these expressions is still very limited, and the principal insights come from electrical stimulation (ES) studies in patients, in which, nevertheless, laughter or smile have been elicited very rarely. Previous studies showed that laughter is evoked by the stimulation of nodes of an emotional network encompassing the anterior cingulate, the superior frontal and basal temporal cortex. A common feature of these stimulation studies is that the facial expression was always accompanied by motor awareness and often by mirth, in line with the affective functions attributed to these regions. Little is known, in contrast, on the neural basis of the voluntary motor control of this expression. The objective of this study was to investigate the effect of ES of the frontal operculum (FO), which is considered a crucial node for the linkage of the voluntary motor system for emotional expression and limbic emotional network. We report the case of ES applied to the frontal operculum (FO) in four patients with drug-resistant focal epilepsy undergoing stereo-electroencephalographic (SEEG) implantation of intracerebral electrodes. In all patients, ES applied to the FO produced laughter or smile. Interestingly, in one patient, the production of a smiling expression was also clearly accompanied by the lack of motor awareness. Since the lack of motor awareness has been previously observed only after the stimulation of the voluntary motor network, we speculate that FO is involved in the voluntary control of facial expressions, and is placed at the interface with the emotional network, gating limbic information to the motor system.

Development of simple equations for effective screening of spurious hemolysis in whole-blood specimens.

INTRODUCTION: We aimed to identify simple but reliable indices for effective screening of spurious hemolysis in whole-blood specimens. METHODS: Thirteen inpatient whole-blood samples were divided in two aliquots. The former was left untreated, whereas the latter was mechanically hemolyzed by forced aspiration with an insulin syringe. All aliquots were tested on Siemens Advia 2120 and Sysmex XE-2100. The hemolysis index (HI) was also assessed in centrifuged plasma. RESULTS: The mechanical hemolysis generated a 4-40% decrease in red blood cells (RBCs). A statistically significant decrease was observed for hematocrit (Ht) and mean corpuscular volume (MCV), whereas mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and platelet count were increased. The values of hemoglobin (Hb) and white blood cells remained substantially unchanged. Two specific equations ([Ht/Hb] × âˆšMCV and [Ht/Hb] × 100) were developed. Both equations displayed an area under the curve of ≥0.99 for identifying spurious hemolysis, much greater than that of both RBC ghosts and immature platelet fraction. A highly significant correlation was also observed between results of these equations and percentage reduction in RBCs or HI increase. CONCLUSION: Provided that these results will be confirmed in further studies, these equations may provide a reliable means for screening spurious hemolysis in whole-blood samples.

Influence of in vitro hemolysis on nucleated red blood cells and reticulocyte counts.

INTRODUCTION: Nucleated red blood cells (NRBCs) and reticulocytes are early and important measures of red blood cells' (RBCs) turnover, but little is known on how spurious hemolysis may affect the reliability of these parameters. MATERIALS AND METHODS: Ten EDTA-anticoagulated samples were divided into three aliquots. The first was immediately tested, where-as the others (defined A and B) were mechanically hemolyzed by aspiration 5 and 10 times through a small-gauge needle. RBC, NRBC, and reticulocyte counts were performed on Sysmex XE-2100. RESULTS: An increasing amount of hemolysis was produced in hemolyzed aliquots A and B. The RBC and reticulocyte counts progressively decreased from the nonhemolyzed sample to hemolyzed aliquots 'A' and 'B'. The NRBC count increased in 3 of the 10 samples and decreased in the remaining seven. CONCLUSIONS: Hemolysis of venous blood samples may seriously jeopardize NRBC and reticulocyte counts.

Incomplete filling of lithium heparin tubes affects the activity of creatine kinase and gamma-glutamyltransferase.

This study aims to assess whether or not incomplete filling of primary lithium heparin tubes may influence the activity of creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT). Blood was drawn from 20 healthy volunteer using an identical sequence of tubes. First, a 6 mL, 13 x 100 mm 14 unit/mL lithium heparin Vacuette was filled and discharged. Then, three identical lithium heparin Vacuette tubes were filled, one to the nominal volume (i.e., full-draw tube), another with half of the nominal volume (half-draw tube) and the last with one-third of the nominal volume (low-draw tube). The plasma was separated and tested for CK (non-activated by N-acetylcysteine), AST and ALT on a Beckman Coulter Unicel DxC 800. Tests for CK were performed with a different reagent on a Beckman Coulter AU5800 (activated by N-acetylcysteine). Although the concentrations of ASL and ALT measured on the Unicel DxC and that of CK measured on the AU5800 did not change significantly across the different specimens, those of CK and GGT measured on the Unicel DxC 800 were significantly increased in the half-draw and low-draw tubes. The percentage bias of CK on the Unicel DxC 800 (using Bland Altman plots) was 3.3% and 7.9% for the half-draw and low-draw tubes, respectively, whereas that of GGT was 10.3% and 16.6% for the half-draw and low-draw tubes, respectively. These results suggest that short-draw lithium heparin tubes might be unsuitable for testing GGT and CK using specific combinations of reagents and instrumentation.

Influence of in vitro hemolysis on hematological testing on Advia 2120.

INTRODUCTION: Although there is broad knowledge on the effect of several preanalytical errors on laboratory hematology, there is no information on the reliability of routine hematological testing on hemolyzed specimens. METHODS: K(2) EDTA-anticoagulated blood collected from 13 healthy volunteers was divided in three aliquots. Aliquot A did not undergo further manipulation, while the second and third aliquots (B and C, respectively) were passed 5 and 10 times through a small-gauge needle to produce scalar amounts of hemolysis. Hematological testing was first performed on Advia 2120. The plasma was then separated by centrifugation and tested for lactate dehydrogenase and hemolysis index (HI). RESULTS: As compared with the nonhemolyzed aliquot, analytically and clinically significant variations were recorded in both mildly and frankly hemolyzed specimens for lactate dehydrogenase, HI, red blood cells count, hematocrit, mean corpuscular volume, mean hemoglobin content, lymphocytes, basophils, and large unstained cells. Both the platelets count and the mean platelet volume were also dramatically affected. The other parameters tested (hemoglobin, red blood cell distribution width, neutrophils, and eosinophils) did not vary significantly. CONCLUSION: The results of routine hematological testing on mildly to frankly hemolyzed specimens might be unreliable.

Perceived parenting behavior in the childhood of cocaine users: relationship with genotype and personality traits.

Low parental care during childhood, a pattern characteristic of an "affectionless control" rearing style was frequently reported in the history of addicted individuals. Parents' childrearing regimes and children's genetic predispositions, with their own behavioral characteristics, have been seen to be closely interwoven, probably affecting children's development and addictive behavior susceptibility. In the present study, parents care perception, aggressive personality traits, and genotype (serotonin transporter promoter gene--5-HTTLPR) have been investigated in cocaine users and healthy control subjects. PBI scores (maternal and paternal care) were lower and BDHI scores (aggressiveness) higher in cocaine users in comparison with controls and significant differences in the perception of either paternal or maternal care were observed between cocaine users and non-users. The short-short (SS) genotype frequency was significantly higher among cocaine users compared with control subjects (P = 0.04). Logistic regression proves that persons bearing the SS genotype have a risk of becoming cocaine user almost three times higher than those having the LL genotype. Estimations of the effects of other factors potentially affecting the risk of being cocaine addicted clearly prove the significant impact of aggressiveness: the highest the score, the highest the risk of becoming cocaine user. Moreover, paternal and maternal care perception significantly improve the fit of the model (the log likelihood decreases passing from -105.9 to -89.8, LR test = 32.17, P-value = 0.0000). Each unit increase in the PBI score yields a significant 12% and 10% decrease of the risk of becoming cocaine user, respectively for paternal and maternal care. Interestingly, once controlled for the PBI score, the relative risk associated to the SS genotype drops strikingly and becomes no longer statistically significant. On the whole, our preliminary data suggest that the association between 5-HT transporter polymorphism and psycho-stimulant use may be mediated by mother-child relationship and parental attachment perception, both being environmental and genetic factors involved in the proneness to substance use disorders, particularly in aggressive-antisocial individuals.

[Sensitivity and accuracy of health databases in determining incidence of lymphoid malignancies in an Italian population]. / Sensibilità ed accuratezza diagnostica dei flussi informativi del Servizio Sanitario Nazionale nella rilevazione dell'incidenza delle patologie linfoproliferative in una popolazione italiana.

We examined the sensitivity and the accuracy of three health databases (hospital discharge data, death certificates and pathologic records) between 1997 and 2001 in an Italian community, to evaluate their accuracy for the diagnosis of lymphoid malignancies and their ability to detect newly diagnosed patients affected by these diseases. Hospital discharge data showed the best sensitivity among the examined databases, though they exhibited an unexpectedly high number of diagnostic errors, even when limiting the analysis to patients with repeated hospital admissions over time. Overall, the pathologic registry and the death certificate file showed a higher diagnostic accuracy, though their sensitivity was considerably lower than hospital discharge data.

[Pulmonary hyalinizing granuloma. Clinicopathologic study of 2 cases, with some original ultrastructural observations and review of the literature]. / Granuloma jalinizzante del polmone. Studio clinico-patologico di 2 casi, con alcune originali osservazioni ultrastrutturali e revisione della letteratura.

AIM: To report the clinical, histological, immunohistochemical and ultrastructural features of 2 new cases of pulmonary hyalinizing granuloma. RESULTS: Both patients were males: one, 72-year-old with retroperitoneal fibrosis, was asymptomatic, while the other, 67-year-old, presented with non productive cough. In both cases, a chest x-ray showed a solitary pulmonary nodule. Microscopically, the nodules were well circumscribed and composed of lamellae of hyalinized collagen. At the periphery, a more cellular rim consisting of lymphocytes, plasma cells and myofibroblasts was present. Immunohistochemical and ultrastructural examinations revealed myofibroblastic elements actively synthesizing collagen fibrils.

[Health databases to assess the incidence of lymphoid malignancies in Italian population]. / I flussi informativi del servizio sanitario nello studio dell'incidenza delle malattie linfoproliferative in una popolazione italiana.

We tested the usefulness of the National Health Service Databases for investigating the incidence of lymphoid malignancies in an Italian community. We analyzed hospital discharge data, drug prescription, pathologic records and death certificates to identify the new cases of Hodgkin's disease, non Hodgkin's lymphoma, multiple myeloma, and acute and chronic lymphocytic leukemia diagnosed in the municipal population of Reggio Emilia, northern Italy, 1991 through 1996. The completeness of Hospital discharge data was very high, and several incident cases could be identified only through this source. Completeness of the pathologic registry was satisfactory for Hodgkin's disease and non-Hodgkin's lymphoma, and this source independently yielded a few incident cases of lymphoid neoplasms. Analysis of death certificates and drug prescriptions appears to be of limited value in the epidemiology of lymphoproliferative diseases.

A variant of ProMACE-CytaBOM chemotherapy for non-Hodgkin's lymphoma with threefold higher drug dose size but identical cumulative dose intensity. A pilot study of the Italian lymphoma study group (GISL).

BACKGROUND AND OBJECTIVE: The positive results of high-dose chemotherapy followed by rescue with bone marrow progenitor cell transplantation are generally ascribed to the high dose size (DS) of the drugs given. However, a concomitant marked increase in dose intensity (DI) is always involved. With the aim of comparing the role of DS and DI in non-Hodgkin's lymphomas, a variant of Fisher's ProMACE-CytaBOM regimen was designed in which the projected cumulative drug DIs remained the same as in the original schedule but the DSs were tripled. DESIGN AND METHODS: Dosages in mg/m(2), route and days of administration were the following: cyclophosphamide 1,950 i.v. on days 1, 64; methotrexate 360 i.v. days 15, 78; vincristine 1.4 iv days 15, 78, 43, 106; etoposide 360 i.v. days 29, 92; epirubicin 120 i.v. days 29, 92; bleomycin 15 i.v. days 43, 106; cytarabine 900 i.v. days 50, 113. Thirty-six outpatients with intermediate- and high-grade non-Hodgkin's lymphomas entered the pilot study; 29 were untreated and 7 had relapse disease. Clinical stage was I in 1 patient, II in 7, III in 5 and IV in 23; 10 had B symptoms; the IPI score was 0-2 in 29 cases and > or =3 in the remaining 7. RESULTS: Of the 29 previously untreated patients, 16 achieved complete remission, 8 partial remission, 4 developed progressive disease and 1 was withdrawn early from the study because of acute viral hepatitis; subsequently 4 relapsed and 3 died (2 of disease progression, 1 of causes unrelated to the disease). In the pre-treated group 3 patients obtained complete remission, 2 partial remission and in 1 patient the disease progressed; 3 of these pre-treated patients died (1 of progressive disease, 1 of a new relapse, 1 of myocardial infarction during therapy). With a 20-month median follow-up, the 30-month overall and relapse-free survival were 0.58 and 0.70, respectively. G-CSF was administered to all but 2 patients, with median delivery throughout the whole regimen of 8, 400 microg per patient. Actual cumulative DI was 0.82+/-0.11. Grade 3-4 hematologic toxicity consisted of anemia in 3 cases, of leukopenia in 8 and of thrombocytopenia in 2; the same grade of non-hematologic toxicity involved the liver in 2 cases, the heart in 1 (the above mentioned death), the digestive mucosa in 2 and the peripheral nerves in 1 patient. INTERPRETATION AND CONCLUSIONS: The iso-DI sequential variant of the ProMACE-CytaBOM regimen can be considered feasibile, relatively non-toxic, and can be given on an out-patient basis. Limited use of G-CSF is required (about 3 vials after each drug administration). Thus, a randomized trial with the original ProMACE-CytaBOM regimen can be designed.

Neurotransmitters, neuroendocrine correlates of sensation-seeking temperament in normal humans.

Correlations between sensation-seeking (SS) personality dimension and plasma concentrations of norepinephrine (NE), epinephrine, and NE-dependent testosterone (T), cortisol and prolactin (PRL) were studied in 74 physically and psychologically healthy male volunteers, in order to see whether or not the noradrenergic system is involved in the modulation of this personality trait. Novelty-seeking scores by the Temperament and Character Inventory and SS scores on a Visual Analog Scale were positively correlated with plasma NE, T and PRL levels, suggesting that NE and the downstream cascade of NE-dependent hormones, together with other monoaminergic changes, might be responsible for the development and the degree of this temperamental character.

Retrospective analysis of mantle cell lymphoma: experience of the "Gruppo Italiano per lo Studio dei Linfomi" (GISL).

BACKGROUND AND OBJECTIVE: Mantle cell lymphoma is a recently recognized histologic entity with specific biological and clinical features. Clinically, the reported unfavorable outcome of these patients has focused attention on this category of non-Hodgkin's lymphoma (NHL). DESIGN AND METHODS: The slide specimens of 69 NHL patients, originally classified as Working Formulation (WF) group B and E, were reviewed. The clinical features at presentation, response to therapy, response duration and survival were analyzed in cases reclassified as MCL. The correlation between clinical and histologic characteristics and the final outcome was evaluated. RESULTS: Out of 69 cases, 34 specimens were reclassified as MCL; in 6 patients, previously classified as WF group B, the nodular pattern was confirmed; in 2 instances the blastoid form was recognized. After a median follow-up of 35.7 months, the entire series displayed a median overall survival of 41.2 months; a significantly longer survival was associated with the nodular histologic pattern, IPI score < 2, response achievement, and a higher Hb level. The vast majority of patients received anthracycline-containing combination chemotherapy. Complete remission rate was 38.8% and overall response rate was 67.6%; response achievement was significantly influenced only by Hb level. Median response duration was 23.3 months. INTERPRETATION AND CONCLUSIONS: The present study confirms the unfavorable clinical course of MCL and the possible need for an alternative therapeutic strategy for this NHL category. Therefore, the correct identification of MCL at diagnosis appears of relevance.

Efficacy of two different ProMACE-CytaBOM derived regimens in advanced aggressive non-Hodgkin's lymphoma. Final report of a multicenter trial conducted by GISL.

BACKGROUND AND OBJECTIVE: To compare the efficacy of ProME(Epidoxorubicin)CE-CytaBOM (PE-C) and ProMI(Idarubicin)CE-CytaBOM (PI-C) in the treatment of adult patients with aggressive non Hodgkin's lymphoma in a multicenter randomized controlled trial performed by 18 centers of the Italian Lymphoma Study Group (GISL). DESIGN AND METHODS: One hundred and twenty-eight and 122 patients were randomly assigned to receive either 6 courses of PE-C or PI-C, respectively. Some patients achieving complete remission with induction therapy participated in another randomized study comparing no further therapy versus maintenance therapy consisting of four blocks of two drugs. RESULTS: The rate of CRs was 62% and 64% for patients treated with PE-C and PI-C, respectively (p = 0.51). The 5-year relapse-free survival was 60% for PE-C and 53% for PI-C (p = 0.29). The estimated relapse-free disease survival rates at 4 years were 75% for patients in the consolidation group and 57% for those in the observation group (p = 0.11). Patients alive in first complete remission 4 years after study entry were estimated to be 39% in the PE-C arm and 38% in the PI-C arm (p = 0.90). The 3-year and 5-year estimated survival rates were 61% and 55% for the PE-C group and 56% and 47% for the PI-C group (p = 0.26). Fatal toxicities occurred in 7 patients (2.9%) with active disease and in 4 patients (1.7%) in complete remission. Stage (p = 0.04), bulky disease (p = 0.02), serum LDH (p = 0.0006), serum albumin (p = 0.0051), hemoglobin (p = 0.0011), performance status (p = 0.0001), International prognostic index (p < 0.0001) and the index proposed by the French group G.E.L.A. (p < 0.0001) were of prognostic value. In a multivariate analysis (Cox regression model) alternatively IPI alone or G.E.L.A. index plus performance status emerged as independent prognostic factors. INTERPRETATION AND CONCLUSIONS: The present study indicates that epirubicin and idarubicin in a combined chemotherapy regimen, have similar activities. The toxic profile also indicates the safety of both anthracyclines at the dosages employed, suggesting their possible dose escalation in a combined chemotherapy setting. PE-C and PI-C were both effective and feasible regimens in an outpatient setting, with acceptable cardiovascular toxicity. The trend toward a better outcome in patients undergoing consolidation therapy after the achievement of a complete remission, warrants further investigation.

Weekly administration of vincristine, cyclophosphamide, mitoxantrone and bleomycin (VEMB) in the treatment of elderly aggressive non Hodgkin's lymphoma. Gruppo Italiano per lo Studio dei Linfomi.

BACKGROUND AND OBJECTIVE: Aim of the study was to assess the efficacy of VEMB, a short-lasting therapeutic regimen (50 days) which alternates two myelotoxic drugs (cyclophosphamide and mitoxantrone) every week with two less hematologically toxic drugs (vincristine and bleomycin) in the treatment of aggressive NHL in the elderly (over 70). DESIGN AND METHODS: Between November 1994 and March 1996, 37 patients aged more than 70 years, with highly or moderately malignant NHL (according to the Working Formulation) have been enrolled into the study. The stage of the disease ranged between II and IV according to Ann Arbor. Mean age was 77 years; 14 patients (38%) had stage IV; 19 patients (51%) had LDH higher than normal; 26 patients (70%) had extranodal and 9 patients (24%) had bulky disease at time of diagnosis. RESULTS: Sixty-two percent of patients achieved a complete and 22% a partial remission. Non-responders amounted to 5%. Four patients (11%) died during the therapy. Nine patients (24%) experienced grade III-IV neutropenia. The most frequently observed event was mild neurotoxicity (43% of cases). The overall survival rate at 30 months was 55%. DFS at 24 months was 66%. INTERPRETATION AND CONCLUSIONS: VEMB is a therapeutic regimen whose efficacy is comparable to that of the other derived MACOP-B therapeutic regimens used in the elderly NHL. It has proved to have a good feasibility, though the number of toxic deaths should not be neglected.

Neurotransmitter-hormonal responses to psychological stress in peripubertal subjects: relationship to aggressive behavior.

The relationship between different degrees of normal aggressiveness (low, medium, high) and neurotransmitter-neuroendocrine responses to the administration of psychologically stressful tests (Mental Arithmetic, Stroop Color Word Interference task, Trial Social Stress test) was examined in thirty male peripubertal junior school adolescents. Plasma concentrations of norepinephrine (NE), epinephrine (EPI), ACTH, cortisol (CORT), growth hormone (GH), prolactin (PRL) and testosterone (T) were measured immediately before the beginning of the tests and at their end, 30 min later. High-normal aggressiveness have been found associated with significantly higher basal concentrations of NE, ACTH, PRL, and T and with a significant increase of GH responses to the stressful stimuli.