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Biomedical subjects

R Nicoletti

Publications and source records attributed to R Nicoletti.

At least 19 recordsLinked to original sources

Ketamine increases human motor cortex excitability to transcranial magnetic stimulation.

Subanaesthetic doses of the N-methyl-D-aspartate (NMDA) antagonist ketamine have been shown to determine a dual modulating effect on glutamatergic transmission in experimental animals, blocking NMDA receptor activity and enhancing non-NMDA transmission through an increase in the release of endogenous glutamate. Little is known about the effects of ketamine on the excitability of the human central nervous system. The effects of subanaesthetic, graded incremental doses of ketamine (0.01, 0.02 and 0.04 mg kg-1 min-1, I.V.) on the excitability of cortical networks of the human motor cortex were examined with a range of transcranial magnetic and electric stimulation protocols in seven normal subjects. Administration of ketamine at increasing doses produced a progressive reduction in the mean resting motor threshold (RMT) (F(3, 18) = 22.33, P < 0.001) and active motor threshold (AMT) (F(3, 18) = 12.17, P < 0.001). Before ketamine administration, mean RMT +/- S.D. was 49 +/- 3.3 % of maximum stimulator output and at the highest infusion level it was 42.6 +/- 2.6 % (P < 0.001). Before ketamine administration, AMT +/- S.D. was 38 +/- 3.3 % of maximum stimulator output and at the highest infusion level it was 33 +/- 4.4 % (P < 0.002). Ketamine also led to an increase in the amplitude of EMG responses evoked by magnetic stimulation at rest; this increase was a function of ketamine dosage (F(3, 18) = 5.29, P = 0.009). In contrast to responses evoked by magnetic stimulation, responses evoked by electric stimulation were not modified by ketamine. The differential effect of ketamine on responses evoked by magnetic and electric stimulation demonstrates that subanaesthetic doses of ketamine enhance the recruitment of excitatory cortical networks in motor cortex. Transcranial magnetic stimulation produces a high-frequency repetitive discharge of pyramidal neurones and for this reason probably depends mostly on short-lasting AMPA transmission. An increase in this transmission might facilitate the repetitive discharge of pyramidal cells after transcranial magnetic stimulation which, in turn, results in larger motor responses and lower thresholds. We suggest that the enhancement of human motor cortex excitability to transcranial magnetic stimulation is the effect of an increase in glutamatergic transmission at non-NMDA receptors similar to that described in experimental studies.

Adult↗

Diabetic patients and retinal proliferation: an evaluation of the role of vascular endothelial growth factor (VEGF).

Vascular endothelial growth factor (VEGF) has been shown to play a major role in intraocular neovascularisation in ischaemic retinal diseases. The aim of this study was to evaluate the concentration of VEGF in vitreous, aqueous and epiretinal membranes of diabetic and non-diabetic patients, with other pathological conditions requiring surgical intervention. Higher VEGF concentration were found in samples from the eyes of diabetic patients versus other pathologies as well as in epiretinal membranes versus the other eye compartments in diabetic patients. However, high VEGF levels were also found in retinal detachment and proliferative vitreoretinopathy of non-diabetic patients. We concluded that VEGF is produced locally and plays a fundamental, but not specific, role in diabetic retinal neovascularisation and proliferation.

Aqueous Humor↗

Vitreous polyamines spermidine, putrescine, and spermine in human proliferative disorders of the retina.

BACKGROUND/AIMS: Many cytokines are involved in the pathogenesis of retinal proliferative diseases, but none has been shown to be related to a specific disorder. The aim of this study was to provide a selective marker of diabetes induced proliferative retinopathies. METHODS: 10 vitreous samples from 10 subjects affected by quiescent proliferative diabetic retinopathy (PDR), 20 vitreous samples from 20 subjects affected by active PDR, and 15 samples from 15 patients with proliferative vitreoretinopathy (PVR) were studied. Samples from 18 patients with a macular hole (n = 8) or pucker (n = 10) served as controls. Vitreous samples were obtained via pars plana vitrectomy. The polyamines spermidine, putrescine, and spermine, vascular endothelial growth factor (VEGF), interleukin 8 (IL-8), and transforming growth factor 1beta (TGF-1beta) were measured by high performance liquid chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA), and the correlation coefficients between the vitreous polyamine content and VEGF, IL-8, and TGF-1beta levels were determined. RESULTS: Spermidine and putrescine were expressed in normal vitreous, but spermine was not detectable. In all the test groups spermidine was 3-4 times higher than in control vitreous and putrescine was similarly lower. The spermine content was up to 15 times higher only in vitreous from patients affected by PDR. Correlation coefficients showed that the spermidine and putrescine level variations correlated with the VEGF and IL-8 content in the active PDR and PVR groups, but not in those with quiescent PDR patients, while spermine was correlated to these cytokines in PDR, but not in PVR groups. CONCLUSIONS: These data suggest a significant role for spermidine and putrescine as markers of proliferative diseases of the retina. The increase in spermine, restricted to diabetic states, may indicate that this polyamine is a unique and specific index of PDR.

Adult↗

[Diagnosis of metastasis of malignant melanoma in the thyroid gland with f18-FDG PET scan].

Metastases in the thyroid gland are very rare. When they occur, long-term survival is dismal; thus an early diagnosis is critical. Malignant melanoma is one of the tumors which may metastasize to the thyroid gland. Therefore we wanted to demonstrate F18-Fluorodeoxyglucose-Positron emission tomography (F18-FDG-PET) is a sensitive and reliable method to identify such metastases. We report about a 51-year-old man, who had an inguinal lymph node metastasis of a malignant melanoma with unknown primary tumor site. He came to us for an a follow-up F18-FDG-PET investigation. In the PET there was a pathologic FDG-uptake in the left lobe of the thyroid gland. The nodule was removed and showed a malignant melanoma metastasis. This unusual scenario underscores the value of the PET in the oncologic follow-up of patients with malignant melanoma.

Diagnosis, Differential↗

Definitive results of a phase II trial of cisplatin, epirubicin, continuous-infusion fluorouracil, and gemcitabine in stage IV pancreatic adenocarcinoma.

PURPOSE: To evaluate the efficacy and toxicity of a cisplatin, epirubicin, gemcitabine, and fluorouracil (PEF-G) schedule on stage IV pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients < or = 70 years, with no prior chemotherapy and with bidimensionally measurable stage IV pancreatic adenocarcinoma, Eastern Cooperative Oncology Group performance status < or = 2, and adequate bone marrow, kidney, and liver function were eligible for this trial. Eligibility criteria for clinical benefit assessment were pain with at least a daily analgesic consumption of two nonsteroidal anti-inflammatory drugs or Karnofsky performance status between 50 and 70. Treatment consisted of 40 mg/m2 each of cisplatin and epirubicin day 1, gemcitabine 600 mg/m2 on days 1 and 8 every 4 weeks, and fluorouracil 200 mg/m2/d as a protracted venous infusion. RESULTS: Between April 1997 and April 1999, 49 patients from a single institution were eligible for the study. Altogether, 203 cycles (median, four cycles) of PEF-G were delivered. The objective response rate was 58% in 43 assessable patients and 51% in the intent-to-treat population. Fourteen patients had stable disease. Grade 3 or 4 World Health Organization neutropenia occurred in 51% of cycles, thrombocytopenia in 28%, anemia in 7%, stomatitis in 5%, and diarrhea, and nausea, and vomiting in 2%. The median duration of response was 8.5 months. The median time to tumor progression was 7.5 months. The median survival was 11 months in the assessable population and 10 months in the intent-to-treat population. Clinical benefit was achieved in 22 (78%) of 28 assessable patients. CONCLUSION: PEF-G is a well-tolerated and safe regimen; it obtained a very high rate of durable responses and deserves further evaluation in a phase III trial.

Adenocarcinoma↗

Explicit and incidental facial expression processing: an fMRI study.

Considerable evidence indicates that processing facial expression involves both subcortical (amygdala and basal ganglia) and cortical (occipito-temporal, orbitofrontal, and prefrontal cortex) structures. However, the specificity of these regions for single types of emotions and for the cognitive demands of expression processing, is still unclear. This functional magnetic resonance imaging (fMRI) study investigated the neural correlates of incidental and explicit processing of the emotional content of faces expressing either disgust or happiness. Subjects were examined while they were viewing neutral, disgusted, or happy faces. The incidental task required subjects to decide about face gender, the explicit task to decide about face expression. In the control task subjects were requested to detect a white square in a greyscale mosaic stimulus. Results showed that the left inferior frontal cortex and the bilateral occipito-temporal junction responded equally to all face conditions. Several cortical and subcortical regions were modulated by task type, and by facial expression. Right neostriatum and left amygdala were activated when subjects made explicit judgements of disgust, bilateral orbitofrontal cortex when they made judgement of happiness, and right frontal and insular cortex when they made judgements about any emotion.

Adult↗

Focusing attention on overlapping and non-overlapping figures with subjective contours.

In a series of five experiments we investigated whether observers could focus attention on a restricted visual area that was demarcated by Kanizsa-like subjective contours, and whether this effect also occurred in the case of overlapping figures. The task was a simple reaction time to a luminance increment and the basic finding was that reaction time was faster when the imperative stimulus fell inside the focus of attention than when it fell outside. The first two experiments showed that the extent of the attentional focus could be adapted to a region that was demarcated by subjective contours, thus extending the results of previous studies that used regions demarcated by real contours. The last three experiments showed that, regardless of the type of margins, focusing was more efficient for the figure that was perceived as lying in front in a pair of overlapping figures.

Analysis of Variance↗

Can expectancy influence hemispheric asymmetries?

We carried out three experiments with the aim of verifying a critical assumption of Kinsbourne's (Acta Psychol., 33 (1970), 193-201; Attention and Performance V, London: Academic press, (1975), pp. 81-96) 'dynamic' attentional hypothesis of hemispheric asymmetries, namely, that asymmetries arise only when subjects know in advance what type of stimulus and/or cognitive mode they are about to be engaged with. We used a paradigm modified from Posner (J. Exp. Psychol., 109 (1980), 160-174) to study the effects of non-spatial 'cognitive' cueing on hemispheric asymmetries using a lexical decision and a visuo-spatial discrimination task (acute vs. obtuse angles). While we did not find significant overall hemispheric asymmetries with the spatial material, we found a consistent advantage of the left hemisphere in the lexical decision task. In Experiment 2 where the cue was presented in central vision and only the stimuli were lateralised and in Experiment 3 where both cue and stimuli were lateralised to the same hemisphere, the left hemisphere advantage did not interact with the effect of cueing. In contrast, in Experiment 4, where only the cue was lateralised and the stimuli were centrally presented, the left hemisphere advantage in the lexical decision task emerged only following invalid cueing. While the results of Experiments 2 and 3 are not in keeping with Kinsbourne's hypothesis, the result of Experiment 4 shows that some pre-exposural mechanisms may indeed affect the emergence of hemispheric asymmetries. A differential susceptibility in 'disengaging' from the processing mode induced by an invalid cue might represent another interesting example of hemispheric difference.

Adult↗

Shifting attention between objects.

Experiment 1 used a modified spatial cueing paradigm that was introduced by Egly et al. [J. Exp. Psychol. Gen. 123 (1994) 161] to investigate the cost incurred in shifting attention within an object as opposed to shifting attention between objects. Subjects were presented with two outline rectangles and had to detect a target (a luminance increment) that could appear in the cued location (valid trials), in an uncued location inside the cued rectangle (inside-invalid trials), or in an uncued location inside the uncued rectangle (outside-invalid trials). Valid trials were faster than invalid trials, and inside-invalid trials were faster than outside-invalid trials. In Experiment 2, the two rectangles were joined to form a unitary object. Here, no difference was found between outside-invalid trials and inside-invalid trials. Experiment 3 showed that the delayed response on outside-invalid trials in Experiment 1 was not due to attention needing to cross the figural borders in order to re-orient to the uncued rectangle. The results were interpreted as showing that an extra cost is incurred for shifting attention between different objects.

Attention↗

Response strategies and the Simon effect.

The study investigated whether the Simon effect, and its facilitation and interference components, shows up in reaction time (RT) or in movement time (MT), depending on the response strategy. Experiment 1 replicated a study by Hietanen and Rämä. Subjects had to press one of two lateralised keys in response to one of two stimuli. The stimuli were presented in the center (neutral condition) or to the left or right side (corresponding or non-corresponding conditions). To press the response key, a reaching movement was necessary, and both RT and MT were recorded. One group of subjects showed an RT facilitation effect and an MT interference effect. Another group of subjects showed both MT facilitation and MT interference effects. It was hypothesized that the two groups used different response strategies. In Exps. 2 and 3, the subjects were explicitly instructed to use the two strategies that were hypothesized for Exp. 1. The results showed that whether facilitation and interference manifest themselves in RT or MT depends on the response strategy adopted by the subjects.

Humans↗

Endovascular treatment of a noninfected anastomotic juxtarenal aortic aneurysm.

An 82-year-old man underwent an endovascular procedure with a commercially available endovascular graft for an anastomotic juxtarenal abdominal aortic aneurysm. The anastomotic aneurysm, which showed no sign of infection, developed 4 years after implantation of an aortic end-to-end graft for an infrarenal aortic aneurysm. The aneurysm was diagnosed during routine ultrasonographic follow-up; there was no apparent infection of the graft. Aortography confirmed the diagnosis and also revealed a small pseudoaneurysm at the level of the distal aortic anastomosis. Endovascular surgery was performed in the operating room with the guidance of C-arm fluoroscopy and intravascular ultrasound. Two Vanguard Straight Endovascular Aortic Graft Cuffs (26 x 50 mm and 24 x 50 mm) were implanted, successfully excluding both the anastomotic juxtarenal aortic aneurysm and the distal pseudoaneurysm. The renal arteries were preserved and no early or late endoleaks were observed. The patient was discharged 2 days after the procedure. Sixteen months later, he was alive and well, with no endovascular leakage, no enlargement of the aortic aneurysms, and no sign of infection. In our opinion, this experience shows that commercially available endovascular grafts may be used successfully to treat anastomotic aortic aneurysms and pseudoaneurysms.

Aged↗

Age-related slowing of control processes: evidence from a response coordination task.

Normal aging is associated with slowing of performance mostly due to a slowed functioning of central response-related processes. In this paper we set out to discover whether slowing occurs also when the process controlling the coordination of responses is engaged by the task. To this end, we compared the mean-reaction time performance of two groups of subjects (young vs. elderly) in single- and dual-task experimental paradigm. The response coordination process is required only by the dual-task paradigm. The results indicate that, in the dual-task situation, the elderly are markedly slower than young subjects. The eventual relevance of information-processing speed in determining the cognitive performance of the elderly is considered in the discussion of the results.

Adult↗

Synthesis and biological evaluation of 2-methoxy- and 2-methylthio-6-[2'-alkylamino)ethyl]-4(3H)-pyrimidinones with anti-rubella virus activity.

The synthesis of a new family of antiviral compounds, 2-methoxy-, and 2-methylthio-6-[(2'-alkylamino)ethyl]-4(3H)-pyrimidinones, has been accomplished. The activity of these agents against positive strand (rubella virus and sindbis virus) and negative strand (vesicular stomatitis virus) RNA viruses is reported. Some of these compounds are efficient and selective inhibitors of rubella virus.

Animals↗

Facilitation and interference components in the Simon effect.

In four experiments we investigated whether the Simon effect consists of both facilitation and interference. In Experiment 1 subjects had to press one of two lateralized keys in response to one of two stimuli (a rectangle or a square). The stimuli were presented at fixation or to the right or left of it. The stimulus-response mappings could be corresponding (i.e., right key--rectangle or square on the right side), non-corresponding (i.e., right key--rectangle or square on the left side), or neutral (i.e., stimulus in the center). Results showed both facilitation and interference effects, but interference was three times greater than facilitation. To test whether the neutral position was favored by visual acuity, Experiments 2, 3 and 4 used slight different displays where visual acuity was the same at every stimulus position. Results indicated that the Simon effect is comprised of facilitation and interference components of the same magnitude. These findings were discussed with reference to dual-route models of the Simon effect.

Adult↗

Kinematic analysis of the reach to grasp movement in Parkinson's and Huntington's disease subjects.

This experiment investigates the kinematic characteristics of the reach to grasp movement of Parkinson's and Huntington's disease subjects under two different experimental conditions. In the first condition subjects were required to perform the movement at a normal speed, while in the second condition they were required to perform the movement as fast as possible. Results showed that the kinematic parameterization of movement in Parkinson's disease subjects did not differ from that of age-matched control subjects for both the normal and the fast condition. However, the performances of Huntington's disease subjects appeared to be different when compared to the other two groups. Differences were mainly related to Huntington's disease patients' inability to properly define the temporal features of the movements.

Adult↗

Renography before heart transplantation in patients with cardiomyopathy.

UNLABELLED: In patients with ischemic cardiomyopathy (CM), abnormal renograms may result not only from circulatory failure (which should reverse after transplantation) but also from intrinsic renal disease (which contraindicates heart transplantation). Here, the outcome of heart transplantation was related to preoperative renograms, and the differentiating and prognostic value of renography was analyzed. METHODS: The study population consisted of 50 patients with ischemic CM expecting heart transplantation. Anatomical renal pathology was excluded in all patients. Dynamic renal scintigraphy was performed with 99mTc-mercaptoacetyltriglycine. Background-subtracted renograms were inspected visually and characterized numerically. Mean parenchymal transit time (mPTT), renal tracer content at 15 min (RTC15) and retention index (RI) were determined. The parametric renogram values were related to a normal reference group of 64 patients. The preoperative renograms were matched with the postoperative outcome. RESULTS: Three characteristic types of symmetrical findings in the kidneys were found: no pathological findings, mildly delayed peak and excretion phase and severely delayed peak and excretion phase. Pathological renograms were observed in 36 of 50 (72%) patients. The mean parametric renogram values in ischemic CM were as follows: Group A (normal kidney function), mPTT = 142+/-26.6 sec, RTC15 = 22.3%+/-4.6% and RI = 24.7+/-11.9; Group B (mild dysfunction), mPTT = 210+/-44.0 sec, RTC15 = 42.6%+/-10.3% and RI = 101.4+/-50.5; Group C (severe dysfunction), mPTT = 320+/-94.2 sec, RTC15 = 79.6%+/-15.9% and RI = 347.7+/-194.7; and reference patients (normal kidney function), mPTT = 137+/-31.1 sec, RTC15 = 22.8%+/-3.8% and RI = 24.6+/-7.9. Postoperative serum creatinine levels were <1.5 mg/dl in all Group A patients, between 1.5 and 2.5 mg/dl in 78% of Group B patients and >2.5 mg/dl in 75% of Group C patients. CONCLUSION: Renography revealed abnormal kidney function when structural pathology was excluded. The renographic abnormalities in ischemic CM did not reflect simply the circulatory failure. The numerical grading of renograms allowed patient stratification, suggestive of possible renal insufficiency after cardiac transplantation and immunosuppressive therapy. With further experience, renography may become a useful tool for predicting postoperative outcome in ischemic CM.

Adult↗

Cholescintigraphy in the evaluation of bile flow after Roux-en-Y hepatico-jejunostomy and hepatico-antrostomy in infants with choledochal cysts.

BACKGROUND: The study tests the hypothesis that stasis of bile in the Roux-en-Y hepatico-jejunostomy (RYJS) loop might facilitate biliary reflux and cause cholangitis, whereas quicker transit times in hepatico-antrostomy (HAST) might prevent cholangitis. MATERIALS AND METHODS: Cholescintigraphy was performed using Tc99m-trimethyl-Br-IDA in seven RYJS patients and in five HAST patients. RESULTS: The time to peak (Tmax) within the RYJS loop occurred between 18 and 50 min postinjection in all patients and the mean transit time (MTT) ranged between 42 and 69 min in 5/7 patients. Prolonged clearance of the tracer from the liver was seen in 2/7 RYJS patients, in whom the MTT was 77 and 240 min, respectively. In the HAST group, the Tmax within the anastomosed antrum occurred between 5 and 33 min postinjection, and the MTT ranged between 42 and 44 min in 2/5 patients. Protracted tracer uptake in the liver in one patient and localised tracer retention in the left hepatic bile ducts in 2/5 patients caused prolonged MTTs. Recurrent cholangitis and diarrhoea occurred in 4/7 RYJS patients, but in none of the HAST patients. Elevated gastrin levels after RYJS contrasted sharply to normal gastrin levels after HAST. CONCLUSION: The findings on cholescintigraphy did not differ significantly between RYJS and HAST and provided no explanation for the distinctly different postoperative clinical course of both surgical methods. Nevertheless, we consider cholescintigraphy to be an efficient and cost-effective diagnostic modality for evaluation of the surgical outcome as regards biliary flow.

Anastomosis, Roux-en-Y↗

The Simon effect occurs relative to the direction of an attention shift.

We investigated whether the Simon effect depends on the orienting of attention. In Experiment 1, participants were required to execute left-right discriminative responses to 2 patterns that were presented to the left or right of fixation. The 2 patterns were similar, and the discrimination was difficult. A letter at fixation signaled whether the current trial was a catch trial. The results showed a reversal of the Simon effect. That is, spatially noncorresponding responses were faster than spatially corresponding responses. In Experiment 2, the discrimination of the relevant stimulus attribute was easy. In Experiment 3, the discrimination of the relevant stimulus attribute was difficult, but the stimulus exposure time was long. In either experiment, the regular Simon effect was reinstated. In Experiment 4, the letter that signaled a catch trial appeared to the left or right of the imperative stimulus. The Simon effect occurred relative to the position of the letter.

Adult↗