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Background . Alzheimer's cognitive-behavioral syndrome is the result of impaired connectivity between nerve cells, due to misfolded proteins, which accumulate and disrupt specific brain networks. Electroencephalography, because of its excellent temporal resolution, is an optimal approach for assessing the communication between functionally related brain regions. O bjective . To detect and compare EEG resting-state networks (RSNs) in patients with amnesic mild cognitive impairment (aMCI), and healthy elderly (HE). Methods . We recruited 125 aMCI patients and 70 healthy elderly subjects. One hundred and twenty seconds of artifact-free EEG data were selected and compared between patients with aMCI and HE. We applied standard low-resolution brain electromagnetic tomography (sLORETA)-independent component analysis (ICA) to assess resting-state networks. Each network consisted of a set of images, one for each frequency (delta, theta, alpha1/2, beta1/2). Results . The functional ICA analysis revealed 17 networks common to groups. The statistical procedure demonstrated that aMCI used some networks differently than HE. The most relevant findings were as follows. Amnesic-MCI had: i) increased delta/beta activity in the superior frontal gyrus and decreased alpha1 activity in the paracentral lobule (ie, default mode network); ii) greater delta/theta/alpha/beta in the superior frontal gyrus (i.e, attention network); iii) lower alpha in the left superior parietal lobe, as well as a lower delta/theta and beta, respectively in post-central, and in superior frontal gyrus(ie, attention network). Conclusions . Our study confirms sLORETA-ICA method is effective in detecting functional resting-state networks, as well as between-groups connectivity differences. The findings provide support to the Alzheimer's network disconnection hypothesis.

Purpose: Minimally invasive surgery has been universally accepted as a valid option for the treatment of diverticular disease, provided specific expertise is available. Over the last decade, there has been a growing interest in the application of robotic approaches for diverticular disease. We aimed at evaluating whether robotic colectomy may offer some advantages over the laparoscopic approach for surgical treatment of diverticular disease by meta-analyzing the available data from the medical literature., Methods: The PubMed/Medline, EMBASE, and Web Of Sciences electronic databases were searched for literature up to December 2020. Inclusion criteria considered all comparative studies evaluating robotic versus laparoscopic colectomy for diverticulitis eligible. The conversion rate to the open approach was evaluated as the primary outcome., Results: The data of 4177 patients from nine studies were included in the analysis. There were no significant differences in the baseline characteristics. Patients undergoing laparoscopic colectomy compared to those who underwent surgery with a robotic approach had a significantly higher risk of conversion into an open procedure (12.5% vs. 7.4%, p < 0.00001) and abbreviated hospital stay (p < 0.0001) at the price of a longer operating time (p < 0.00001)., Conclusion: Compared with conventional laparoscopic surgery, the robotic approach offers significant advantages in terms of conversion rate and shortened hospital stay for the treatment of diverticular disease. However, because of the lack of available evidence, it is impossible to draw definitive conclusions., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Recent studies demonstrated that beta oscillations are elicited during cognitive processes. To investigate their potential as electrophysiological markers of amnestic mild cognitive impairment (aMCI), we recorded beta EEG activity during resting and during an omitted tone task in patients and healthy elderly. Thirty participants were enrolled (15 patients, 15 healthy controls). In particular, we investigated event-related spectral perturbation and intertrial coherence indices. Analyses showed that ( a) healthy elderly presented greater beta power at rest than patients with aMCI patients; ( b) during the task, healthy elderly were more accurate than aMCI patients and presented greater beta power than aMCI patients; ( c) both groups showed qualitatively similar spectral perturbation responses during the task, but different spatiotemporal response patterns; and ( d) aMCI patients presented greater beta phase locking than healthy elderly during the task. Results indicate that beta activity in healthy elderly differs from that of patients with aMCI. Furthermore, the analysis of task-related EEG activity extends evidences obtained during resting and suggests that during the prodromal phase of Alzheimer's disease there is a reduced efficiency in information exchange by large-scale neural networks. The study for the first time shows the potential of task-related beta responses as early markers of aMCI impairments.

There are several evidences indicating that an impairment in attention-executive functions is present in prodromal Alzheimer's disease and predict future global cognitive decline. In particular, the issue of temporal orienting of attention in patients with mild cognitive impairment (MCI) due to Alzheimer's disease has been overlooked. The present research aimed to explore whether subtle deficits of cortical activation are present in these patients early in the course of the disease. We studied the upper-alpha event-related synchronization/desynchronization phenomenon during a paradigm of temporal orientation of attention. MCI patients (n = 27) and healthy elderly controls (n = 15) performed a task in which periodically omitted tones had to be predicted and their virtual onset time had to be marked by pressing a button. Single-trial responses were measured, respectively, before and after the motor response. Then, upper-alpha responses were compared to upper-alpha power during eyes-closed resting state. The time course of the task was characterized by two different behavioral conditions: (1) a pre-event epoch, in which the subject awaited the virtual onset of the omitted tone, (2) a post-event epoch (after button pressing), in which the subject was in a post-motor response condition. The principal findings are: (1) during the waiting epoch, only healthy elderly had an upper-alpha ERD at the level of both temporal and posterior brain regions; (2) during the post-motor epoch, the aMCI patients had a weaker upper-alpha ERS on prefrontal regions; (3) only healthy elderly showed a laterality effect: (a) during the waiting epoch, the upper-alpha ERD was greater at the level of the right posterior-temporal lead; during the post-motor epoch, the upper alpha ERS was greater on the left prefrontal lead. The relevance of these findings is that the weaker upper-alpha response observed in aMCI patients is evident even if the accuracy of the behavioral performance (i.e., button pressing) is still spared. This abnormal upper-alpha response might represent an early biomarker of the attention-executive network impairment in MCI due to Alzheimer's disease.

In recent years, newer tools have been developed and used in thyroid surgery. This study compared patients with multinodular goiter undergoing thyroidectomy using the Harmonic FOCUS™ with patients undergoing the clamp-and-tie technique. Medical records of 268 patients with multinodular goiter undergoing thyroidectomy from December 2006 to July 2011 in two centers in Italy, the Department of Surgery of Pisa and the General Surgery Unit of Grosseto, were prospectively evaluated. Patients were divided into group A (Harmonic FOCUS™ Shear), and group B (clamp-and-tie technique). Patient demographics and specific end points analyzed included age, sex, diagnosis, thyroid gland volume, operative time, complications, need for clips and hemostatic agents, need for suction balloon, postoperative blood loss, and postoperative hospital length of stay. 141 patients were included in group A, and 127 patients were included in group B. The two groups were similar in age, sex ratio, indication for surgery, and thyroid volume. Mean operative time was significantly shorter with the Harmonic FOCUS™ Shear (51.8 min) than with the clamp-and-tie technique (70.9 min). The mean postoperative amount obtained from the suction balloon was similar. Vascular clips were needed significantly more frequently in group A (26.2 %) than in group B (12.5 %), whereas the need for hemostatic agents was significantly reduced in group A (4.2 %) compared with group B (14.9 %). The decision to leave a suction drain at the end of the operation occurred significantly more frequently in group B (96 %) than in group A (78 %). Mean postoperative hospital length of stay was 2.02 days in group A compared with 3.1 days in group B, which was significant. No definitive postoperative complications were documented in either group, except a higher rate, but not statistically significant, of permanent hypoparathyroidism in group B versus Group A. Transient laryngeal nerve injury was similar in both groups, whereas transient hypoparathyroidism occurred more frequently in Group B (4.7 %) than in Group A (2.4 %). Harmonic FOCUS device was significantly associated with lower rate of postoperative transient hypocalcemia, decreased operative time, shorter hospitalization, and lesser need for hemostatic agents and postoperative drain balloon. These results might be considered "indirect" money-saving factors, despite the cost of the device, especially in countries where the cost of thyroidectomy is influenced also by the hospital length of stay.

We examined the hypothesis that the attention/executive deficits in mild cognitive impairment (MCI) due to Alzheimer's disease is associated to an abnormal cortical activation, revealed by the method of event-related synchronization/desynchronization (ERS/ERD) in the theta band during a paradigm of temporal orienting of attention. MCI patients (n = 25) and healthy elderly (HE) matched controls (n = 15) performed a task in which periodically omitted tones had to be predicted and their virtual onset time had to be marked by pressing a button. Single-trial theta responses were measured, respectively, before and after the motor response. Then, theta responses were compared to theta power during eyes closed resting state (ERD/ERS method).The temporal course of the task was characterized by two different behavioural conditions: (1) a pre-event epoch, in which the subject awaited the virtual onset of the omitted tone, (2) a post-event (after button pressing) epoch, in which the subject was in a post-motor response condition. The most important findings are summarized as follows: (1) in both groups, the pre-event epoch was characterized by theta ERS on temporal electrodes, but HE had a greater theta ERS compared to that of MCI group; (2) in both groups, during the post-motor condition, there was a theta ERS on prefrontal regions, and, also in this case, HE showed a greater theta enhancement compared to that of MCI patients; (3) HE showed evidence of lateralization: during the waiting epoch, theta ERS was dominant on the right posterior temporal lead (T6), whilst, during the post-motor epoch, theta ERS was greater on the left, as well as the midline prefrontal leads. Compared to the traditional neuropsychological measures for the episodic memory, these theta ERS indicators were less accurate in differentiating MCI patients from healthy elderly. The clinical relevance of these findings is that the weaker theta reactivity in MCI would indicate an early impairment in the temporal orienting of attention in the early stage of the clinical course of this neurodegenerative disease.

Background: The robotic approach is an interesting option for overcoming the limitations of laparoscopic adrenalectomy. We aimed to report our technique and outcomes of robot-assisted adrenalectomy (RAA)., Methods: From November 2000 to February 2010, all consecutive patients who underwent a RAA by the same surgeon were prospectively entered into a dedicated database. The data were reviewed retrospectively., Results: During the study period, 21 right (50%), 20 left (47.6%) and 1 bilateral (2.4%) RAA were performed. Mean lesion size was 5.5 cm (max. 10 cm). Mean operative time was 118 ± 46 min and median blood loss was 27 ml. There were no conversions. The postoperative morbidity rate was 2.4%; mortality rate, 2.4%; median hospital stay, 4 days., Conclusions: RAA achieves good short-term outcomes and could be considered a valid option for the treatment of adrenal masses, with the potential to expand the limits of minimally invasive surgery., (Copyright © 2010 John Wiley & Sons, Ltd.)

Robotic surgery has gained acceptance for surgical use but few data exist regarding its value in thoracic procedures. The aim of this study is to report our experience with totally robotic thoracic resections. From June 2001 to June 2009, 38 consecutive totally robotic lung resections were performed in two different hospitals by a single surgeon. All data was prospectively collected in a dedicated database, and reviewed retrospectively. A total of 32 lobectomies, three bilobectomies, and three pneumonectomies were performed. The indication was a malignant tumor in 28 cases. There were nine cases with benign pathology. Mean operating time was 209 min (range: 105-380 min). Six conversions were required (15.8%) and there was one postoperative death (2.6%). Four postoperative complications occurred (10.5%). Median hospital stay was 10 days (range: 3-24 days). After a median follow-up of 42 months, 80% of patients with stage I disease are alive without recurrence. Advanced thoracic procedures can be performed safely using the robotic system. In this heterogeneous series of lung resections, we report low mortality and morbidity. The robotic approach can achieve a good dissection in difficult to reach areas, making it particularly useful for oncologic resections.

There is evidence that theta responses reflect cognitive performance: good performances are associated with a decrease in tonic theta power as well as an increase in phasic theta power. In the present study, both tonic and phasic theta activity were analysed in 22 patients with mild Alzheimer's disease (AD), and 16 healthy elderly controls. Single-trial theta power responses were evaluated by an active auditory oddball paradigm along an early poststimulus window (0-250 ms) and a late time window (250-500 ms), and then compared to prestimulus theta power during both target tone and standard tone processing. The main findings were: (1) in AD patients, there was an increased prestimulus theta power, as well as no significant poststimulus theta power increase upon both target and non-target stimulus processing; (2) in healthy aged controls, only during target tone processing, an enhancement of both early and late theta responses relative to the prestimulus baseline was found. Moreover, healthy controls had a frontal dominance of theta power. The results might indicate that, during target processing, theta response is not functionally sensitive in AD and cannot be involved in processing demands as efficiently as in healthy controls. From a psychophysiological point of view, this might suggest an impairment of attentional allocation resources. The psychological implications might be related to selective attention/working-memory impairment from the early stage of the disease. Our data confirm that both tonic and phasic theta are relevant indicators of cognitive performance: the lack of a phasic theta and an increase in tonic theta are congruous findings in cognitive decline. Another factor worth noting is that in AD patients theta response is not dominant at the frontal site (as observed in healthy controls), indicating a weaker frontal lobe network reactivity during stimulus processing.

Background: Use of robotic surgery has gained increasing acceptance over the last few years. There are few reports, however, on advanced pancreatic robotic surgery. In fact, the indication for robotic surgery in pancreatic disease has been controversial. This paper retrospectively reviews one surgeon's experience with robotic surgery to treat pancreatic disease, and analyzes its indications and outcomes, as well as the controversy that exists., Methods: A retrospective review of the charts of all patients who underwent robotic surgery for pancreatic disease by a single surgeon at two different institutions was carried out., Results: From October 2000 to January 2009, 134 patients underwent robotic-assisted surgery for different pancreatic pathologies. All procedures were performed using the da Vinci robotic system. Of the 134 patients, 83 were female. The average age of all patients was 57 years (range 24-86 years). Mean operating room (OR) time was 331 min (75-660 min). There were 14 conversions to open surgery. Mean length of stay was 9.3 days (3-85 days). Length of stay for patients with no complications was 7.9 days (3-15 days). The postoperative morbidity rate was 26% and the mortality rate was 2.23% (three patients). Among the procedures performed were 60 pancreaticoduodenectomies, 23 spleen-preserving distal pancreatectomies, 23 splenopancreatectomies, 3 middle pancreatectomies, 1 total pancreatectomy, and 3 enucleations. Another 21 patients underwent different surgical procedures for treatment of acute and chronic pancreatitis. Two cases of pancreaticoduodenectomy were performed in outside institutions and are not included in this series., Conclusions: This is the largest series of robotic pancreatic surgery presented to date. Robotic surgery enables difficult technical maneuvers to be performed that facilitate the success of pancreatic minimally invasive surgery. The results in this series demonstrate that it is feasible and safe. Complication and mortality rates are comparable to those of open surgery but with the advantages of minimally invasive surgery.

Background: Middle pancreatectomy has been accepted as a valid surgical alternative to more extensive standard resections for the treatment of benign central pancreatic tumors. In this article, we describe a new minimally invasive approach to this procedure, using a robot-assisted laparoscopic technique., Materials and Methods: From May 2004 to October 2005, 3 patients (2 female and 1 male), with a mean age of 52 years (range, 44-68), underwent robot-assisted laparoscopic middle pancreatectomies at the Department of General Surgery of Misericordia Hospital in Grosseto, Italy. Two of the patients had symptomatic serous cystadenomas, and 1 patient had a mucinous cystadenoma, which was discovered incidentally. The da Vinci((R)) Surgical System (Intuitive Surgical, Sunnyvale, CA) was used to perform the main steps of the intervention. All patients underwent a pancreaticogastrostomy for pancreaticoenteric reconstruction to the distal stump., Results: The mean operative time was 320 minutes (range, 270-380). Mean blood loss was 233 mL (range, 100-400). There were no mortalities. One patient developed a postoperative pancreatic fistula, which was managed conservatively. The postoperative hospital stay was 9 days for 2 patients and 27 days for the third patient. No endocrine or exocrine deficiencies were observed in the patients during a mean follow-up of 44 months (range, 38-48)., Conclusions: Robot-assisted laparoscopic middle pancreatectomy presents an interesting, less-invasive option for resection of benign tumors of the neck and proximal body of the pancreas. In benign disease, it allows for the preservation of functional pancreatic parenchyma and, subsequently, reduced operative trauma.

The present study assessed auditory event-related potentials in patients with Alzheimer's disease (AD). Delta responses of 21 mild probable AD subjects according to NINCDS-ADRDA criteria, and 16 healthy elderly controls were evaluated by an active oddball paradigm. Averaged and single sweep potentials were analyzed during target tone processing. As far as time domain averaged event-related potentials (ERPs) are concerned, no significant group differences were observed for N100 and P200 components (both latency and amplitude); also, N200 and P300 amplitude did not differ between groups, whilst N200 and P300 latency were significantly prolonged in AD patients. Concerning delta frequency component of the averaged ERPs, no significant differences between groups were obtained for delta response amplitude as well as delta response topography (Fz, Cz, Pz). Analysis of delta responses was performed for single sweep maximal peak-to-peak amplitude. Significant between groups differences were revealed at the level of single sweep amplitude at the 3 midline sites (Fz, Cz, Pz), during target tone processing. In particular, the difference between healthy controls and AD subjects was at the level of stimulus-related delta amplitude changes: in all locations a significant enhancement of the delta response is recorded in healthy subjects (especially at the frontal location), whilst this delta reactivity was not detectable in AD patients. From a clinical point of view, the lack of delta reactivity might relate to a decision-making function impairment since mild Alzheimer's disease.

Background: Few studies exist on ERPs and patients with subcortical vascular cognitive impairment (SVCI). This latter is a quite homogeneous subtype of vascular dementia whose cognitive profile is quite different from that of Alzheimer disease (AD)., Aims: The present study aims at comparing the ERPs profile both in patients with SVCI and in patients with AD., Subjects and Methods: ERPs and psychometric tests were collected from 39 healthy elderly controls, 51 patients with SVCI and 43 patients with AD. Subjects mentally count high pitched target tones that were randomly intermixed with low pitched frequent tones. We measured ERPs latencies (N1, P2, N2 and P3), and interpeak latencies (N1-P3, N1-P2, N1-N2)., Results: Grand averaged potentials in SVCI showed a significant increase of P3 latency. AD patients showed a prolongation of N1, P2, N2, P3 latencies. As far as interpeak latencies are concerned, SVCI patients showed a significant prolongation of N1-P3, AD patients had a significant increase of N1-N2, and N1-P3 intervals. When all patients were considered as a single group, correlation of neuropsychological tests scores showed a significant negative relationship between P300 latency and, respectively, Mini Mental Status Examination, auditive and visual span forward. In both groups, ERPs latency sensitivity, was low, whilst specificity values were quite high., Conclusions: Our finding suggest that these two dementing diseases have different electrophysiologic features that may be related to their specific underlying pathogenetic mechanism; in particular, we hypothesise that, differently from AD, P300 latency prolongation characterizes the early stage of SVCI. So, this ERPs approach could be helpful to detect early alterations of the attentional/working-memory functions in patients with subcortical ischaemic vascular disease.

Hypothesis: Robotic technology is the most advanced development of minimally invasive surgery, but there are still some unresolved issues concerning its use in a clinical setting., Design: The study describes the clinical experience of the Department of General Surgery, Misericordia Hospital, Grosseto, Italy, in robot-assisted surgery using the da Vinci Surgical System., Results: Between October 2000 and November 2002, 193 patients underwent a minimally invasive robotic procedure (74 men and 119 women; mean age, 55.9 years [range, 16-91 years]). A total of 207 robotic surgical operations, including abdominal, thoracic and vascular procedures, were performed; 179 were single procedures, and 14 were double (2 operations on the same patient). There were 4 conversions to open surgery and 3 to conventional laparoscopy (conversion rate, 3.6%; 7 of 193 patients). The perioperative morbidity rate was 9.3% (18 of 193 patients), and 6 patients (3.1%) required a reoperation. The postoperative mortality rate was 1.5% (3 of 193 patients)., Conclusions: Our preliminary experience at a large community hospital suggests that robotic surgery is feasible in a clinical setting. Its daily use is safe and easily managed, and it expands the applications of minimally invasive surgery. However, the best indications still have to be defined, and the cost-benefit ratio must be evaluated. This report could serve as a basis for a future prospective, randomized trial.

Stroke is frequently followed by electrocardiographic (ECG) changes. The aim of the present study was to evaluate the global incidence of these changes after ischemic or hemorrhagic strokes, but it focused on cardiac arrhythmias. In ischemic strokes, these were correlated with the side of the lesion(s). The study was retrospective, and 450 patients (out of 971 examined) were entered in the study based on the following inclusion criteria: (1) "completed" stroke (352 ischemic and 98 hemorrhagic), (2) ECG on admission, and (3) at least 1 previous ECG. We also examined 71 patients with carotid or vertebro-basilar transient ischemic attacks (TIA). As controls, 71 patients suffering from nonvascular neurologic diseases were examined. The results were as follows: In stroke patients, new-onset ECG abnormalities were present in 75% of cases, and cardiac arrhythmias accounted for 28.7%. Cardiac arrhythmias were observed in 21.9% of ischemic strokes (26.8% of patients with right hemispheric lesion and 14.3% of those with left hemispheric lesion) and in 20.4% of hemorrhagic strokes, with the highest incidence in subarachnoid hemorrhage (37.5%). The mechanisms of genesis of cardiac arrhythmias occurring after stroke are still not well understood. Some evidence supports the hypothesis of a "cardiac cortical rhythm control site," probably lying within the middle cerebral artery territory. Vascular damage to this area could be followed by cardiac arrhythmias related to a disinhibition of the right insular cortex with resulting increased sympathetic tone. Our data seem to indicate that ischemic involvement of the right hemisphere induces a higher risk for cardiac arrhythmia occurrence than that of the left hemisphere.

Objectives: To evaluate the efficacy of gabapentin in the treatment of hemifacial spasm., Material and Methods: Twenty-three patients with hemifacial spasm not suitable for surgery or therapy with botulinum toxin were treated with gabapentin. The main efficacy parameter was the percentage of spasm reduction., Results: A clinically significant reduction of spasms was obtained by 16 patients., Conclusion: Gabapentin was effective and safe in reducing hemifacial spasm in 16 out 23 (69.6%) patients.

Auditory event-related potentials (AERPs) were recorded during an auditory oddball paradigm in 108 epileptics and in 32 healthy controls. P300 latency varied in relationship with age only in controls. Symptomatic epileptics had significantly prolonged P300 mean latency compared to those without detectable brain lesion(s) on MR scan. Moreover, these latter patients were compared on the basis of epilepsy duration, type of seizure, seizure frequency and antiepileptic treatment; the application of a multiple regression model showed a significant relationship between P300 latency prolongation and epilepsy duration, seizure frequency and polytherapy.

A neurophysiological (SEP, VEP) follow-up study was carried out in 30 diabetic patients with type I diabetes mellitus of ten or more years duration. This in order to investigate whether one year of improved glucoregulation may influence the progression of central damage. In our series, patients showed a significant decrement of HbA1C levels (p < 0.05) in the one-year follow-up. In the same period the frequency of SEP and VEP abnormalities varied from 10/30 (33%) to 16/30 (53%) and from 8/30 (26%) to 5/30 (16%) respectively. This finding would suggest that prevailing glycaemic control would be a major determinant for the outcome of VEP measurements. SEP alterations, in contrast, tend to progress in a 12 months period despite a considerable improvement in glycaemic control. However, by dividing patients in two groups according mean one year HbA1C less than 8% and more than 8%, the latter group only showed a significant increasing of absolute latencies of each median and tibial SEP components. Our results suggest that VEP abnormalities are still reversible in diabetic patients with improved metabolic control. The acquired abnormalities of somatosensory pathways persist longer, but a strict glycaemic control may influence and retard the progression of central conduction involvement.

We performed clinical, radiological (MRI) and neurophysiological (NCV, SEPs, and BAEPs) investigations in 36 unselected patients affected by Systemic Lupus Erythematosus (SLE). Fifteen patients (42%) presented clear neurological events and were considered as definite neuropsychiatric lupus (NPLE); 21 (58%) presented minor subjective complaints or no neurological problems referable to SLE and were considered as no-NPLE. Twenty-three patients (64%) showed neurophysiological abnormalities: 21 (58%) presented central abnormal neurophysiological measurements (including SEP and BAEP values), while 17 (47%) has slowed peripheral nerve conduction. Twenty-six out of 36 patients executed brain MRI examination. High intensity spots (HIS) in deep or subcortical white matter were the most common abnormalities and were present in 19 of the 26 patients (73%). We found that the incidence of neurophysiological and radiological abnormalities did not significantly differ in neurologically symptomatic and asymptomatic patients. Central nervous system impairment evidenced by abnormal N13-20 interpeak intervals (p = 0.05) and HIS (p = 0.01) findings was significantly associated with the presence of cutaneous vasculitis; while peripheral nerve involvement was significantly more frequent in patients with renal failure (p = 0.006).

Background and Aim: The aim of this study is to assess the clinical usefulness of the serum assay for CAR-3 in the diagnosis and follow-up of pancreatic cancer., Materials and Methods: Serum levels of tumor markers (CAR-3, Ca 19.9, Ca 195 and CEA) were measured in a total of 238 patients with various diseases of the gastrointestinal (GI) tract, including 61 pancreatic cancers. Cut-off levels were calculated on the basis of a non-parametric estimate of 90% specificity. After surgery, patients with pancreatic cancer underwent a combined serological and radiological (CT-scan) follow-up., Results: At the cut-off level of 6.15 U/L, the sensitivity of CAR-3 was 62.3% (CA 19.9: 77%; Ca 195: 75.4%; CEA: 24.5%). In the differential diagnosis between pancreatic cancer and other GI diseases, significant differences were found. No association was discovered either between serum level of tumor markers and tumor stage or between short- and long-term survivors. In the follow-up, CT-scan was superior to serologic tests (sensitivity: 94.2%). Among tumor markers, CAR-3 achieved a sensitivity of 62.5% (Ca 19.9: 83.3%; Ca 195: 75%)., Discussion: CAR-3 is shed in the circulating stream in a much lower proportion of cases than that observed for antigen expression at immunohistochemistry. During the follow-up CT-scan was the most accurate diagnostic tool. However, the meagre therapeutical options for recurrent pancreatic cancer, do not justify such an aggressive follow-up., Conclusions: Ca 19.9 remains the tumor marker of choice for either the pre-operative work-up or the post-surgical follow-up of patients with pancreatic cancer.

In previous experimental studies, carried out on cats, we demonstrated that electrical stimulation of lateral habenula (LH) at 0.5-3.0 Hz or 5-20 Hz had a double effect (low frequency-excitation; high frequency-inhibition) on the spontaneous firing rate of single hippocampal neurones. Our results, in agreement with similar case studies, allowed us to hypothesise that in the habenular modulation of the hippocampus the raphe nucleus is probably involved. In fact, all the effects of LH stimulation were antagonised by the iontophoretic intrahippocampal application of methysergide. In the present series of experiments, performed on rats, it was possible to demonstrate that LH stimulation at 1-10 Hz causes an excitation of a progressively major number of hippocampal neurones depending upon the increase of frequency stimulation. The absence of habenulo-induced effects after a iontophoretic application of methysergide on single hippocampal units suggests the involvement of the raphe nucleus. Furthermore, in consideration of recent anatomical evidences demonstrating an excitatory projection between LH and raphe nucleus, intraraphal N-methyl-D-aspartate (NMDA) application, performed through a Hamilton microsyringe, induces an inhibitory effect. All the results suggest that in the raphe context it is possible to hypothesise the presence of an intrinsic interneurone, directly activated by the excitatory projection arising from the LH; this interneurone is likely inhibitory on the serotonergic raphe-hippocampus efferent neurone. This functional organization is responsible for the effect of LH stimulation at different frequencies as well as for the effects of intraraphal NMDA application.

Many experimental observations have demonstrated the modulatory role exerted by several neural structures and neurotransmitters on spontaneous and paroxysmal bioelectric activity of the hippocampus. Recently, the control exerted by locus coeruleus (LC) and its noradrenergic (NA) efferent pathway on different experimental models of epilepsy (e.g. cortical cobalt chronic epilepsy, amygdaloid and hippocampal kindling) was emphasised. On this basis, a series of experiments was performed to elucidate the functional role of LC-NA system on the hippocampal penicillin (PCN) focus and the type of adrenergic receptor involved. The experiments were carried out on 25 rats in which an epileptiform hippocampal focus was obtained through intrahippocampal PCN administration (100-200 I.U.). In these conditions, LC, ipsilateral to PCN hippocampal focus, was stimulated before and after intraperitoneal (i.p.) administration of a beta-adrenergic receptor antagonist propranolol (2 mg/kg). Results showed a significant reduction of hippocampal spiking frequency during LC stimulation; after i.p. propranolol injection, LC stimulation, at the same parameters, failed to induce any sort of modification of PCN hippocampal spiking frequency. Furthermore, intrahippocampal application of a beta-selective agonist 2-fluoro-noradrenaline (2-FNA) mimics the inhibitory effects of LC stimulation. All data suggest that the LC-NA system is able to induce a net reduction of hippocampal epileptiform focus and the inhibitory NA control involves the activation of adrenergic beta receptors.

The H reflex of flexor carpi radialis and radial-induced reciprocal inhibition were recorded in normal subjects during conditioning stimulation of the contralateral median or radial nerves. It was found that stimulation of the contralateral median nerve enhanced the degree of reciprocal inhibition exerted by the radial nerve on the median nerve, while contralateral radial nerve stimulation reduced the reciprocal inhibition exerted by the extensor on the flexor. In two subjects in which a pure extensor H reflex was recorded specular features were observed following contralateral median and radial stimulation. These findings are considered to be the electrophysiological manifestation of contralateral modulation of reciprocal inhibition, which is likely to act at the level of the IA interneurone.

Hippocampal-based epileptiform activity may reach the basal ganglia via the nucleus accumbens. Previous data suggested that caudate nucleus is able to influence hippocampal epilepsy, probably sending a projection to the septum. In order to test the hypothesis of a retrograde activation of accumbens-caudate pathway in hippocampal regulation, we electrically stimulated both caudate nucleus and nucleus accumbens and studied modifications of hippocampal EEG in the feline focal epilepsy model. We also performed bilateral electrolytic lesion of nucleus accumbens and repeated caudate stimulation. Results showed that nucleus accumbens stimulation was ineffective in modifying hippocampal epilepsy; on the contrary, caudate stimulation caused a statistically significant decrease of hippocampal spike frequency and amplitude. On the other hand, in accumbens-lesioned animals caudate activation consistently reduced hippocampal epilepsy to a significant degree. As the caudate nucleus influences hippocampal activity and the septum may constitute a relay station of this functional relation, a possibility was tested concerning a GABAergic mediation. To this end, after a stable caudate-induced effect was reached, an intraseptal microinjection of picrotoxin (GABA receptor antagonist) was made and caudate stimulation repeated at the same parameters. Such a study showed that after intraseptal picrotoxin, caudate stimulation failed to elicit any type of modification of hippocampal activity. Experimental findings support the notion that the striatal modulation on hippocampus is mediated by an anterograde rather than a retrograde pathway, and underline the possibility of a GABAergic caudate-septal influence.

The role of contralateral movement on both H reflex and reciprocal inhibition was studied. In normal men H reflex was induced by median nerve stimulation. Reciprocal inhibition was achieved through stimulation of the antagonist radial nerve. On this basis the effects of contralateral arm movement were analyzed. Furthermore the putative influence of exteroceptive origin was also verified by means of digit stimulation. Results showed that contralateral arm movement did not affect H reflex amplitude; on the contrary, it was able to enhance reciprocal inhibition induced by extensors on flexors. Study of cutaneous afferents demonstrated that contralateral digit stimulation failed to elicit modifications on both H reflex and reciprocal inhibition. On the other hand, ipsilateral digit stimulation lowered H reflex amplitude and increased the degree of reciprocal inhibition. Experimental findings underline the possibility that an informational array reaches the contralateral IA interneuron: therefore a mutual (bilateral) interaction among IA interneurones may accordingly be hypothesised.

In the cat, the effects of lateral habenula stimulation, at different ranges of frequency, on hippocampal units were studied. Habenular stimulation at low frequency excited, while at high frequency inhibited the greater part of hippocampal units. Moreover, in order to clarify the possible pathway involved in the habenulo-hippocampal circuit, the effects of iontophoretic acetylcholine and serotonin on hippocampal units were compared with those of habenular stimulation. Iontophoretic acetylcholine induced both excitatory and inhibitory responses while serotonin induced only inhibitory responses. Iontophoretic atropine blocked the effects of acetylcholine ejection but did not antagonize stimulation effects; ion-tophoretic methysergide induced an increase of basal firing of hippocampal units and antagonized both serotonin and habenular stimulation inhibition. The results suggest an influence of lateral habenula to the hippocampus which does not appear to be cholinergically-mediated. A possible involvement of the raphe as a relay station in the habenulo-hippocampal pathway is discussed.

Substantia nigra is a mesencephalic structure inserted along several circuits which appear to play a key role in epilepsy. In previous researches we postulated that substantia nigra pars compacta (SNpc) may be the site of a precise control of hippocampal epilepsy while substantia nigra pars reticulata (SNpr) may exert a modulation of both neocortical epilepsy and spreading of hyperactivity toward a motor target. In order to better understand mechanisms subserving nigral action in feline hippocampal epilepsy we electrically stimulated SNpc (dopaminergic), before and after sulpiride (dopamine receptor-antagonist) intravenous injection. Furthermore we compared hippocampal epileptiform activity prior to and after apomorphine (dopamine receptor-agonist) intrahippocampal injection as well as prior to and after SNpc electrolytic destruction. Results showed that SNpc is able to regulate hippocampal epilepsy. This effect is selectively antagonized by sulpiride while apomorphine exerts, synergically with SNpc stimulation, inhibitory effects. On the contrary SNpc lesions induces a significant enhancement of hippocampal epileptiform spikes. Experimental findings suggest that SNpc represents a strategic region for the control of hippocampal excitability and that this regulation appears to be dopaminergic in nature.

Previous experimental evidences showed that the caudate nucleus has a modulatory effect on hippocampal epilepsy. The caudate's regulating action might reach the hippocampus either via the septal region or, retrogradely, via the accumbens nucleus. In order to obtain new data about the pathway involved in caudate hippocampal influence the spreading of abnormal activity towards the nucleus accumbens was studied. Furthermore the effects of caudate stimulation in animals with electrolytic lesions of the nucleus accumbens were analyzed. It was observed that abnormal penicillin-induced activity spreaded from the hippocampus to the nucleus accumbens in about 30 minutes. In animals with and without lesions of nucleus accumbens, caudate stimulation brought about a significant decrease in the frequency and amplitude of hippocampal activity. The results suggest that the nucleus accumbens is reached by the spreading of hippocampal epilepsy but does not participate in the control exerted by the caudate nucleus on the hippocampus. Thus the caudate-induced inhibition takes place through an anterograde caudate-hippocampal circuit, while at the same time excluding retrograde activation by way of a caudate-accumbens-hippocampal pathway.