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Biomedical subjects

R Nicoletti

Publications and source records attributed to R Nicoletti.

At least 37 records · Page 2Linked to original sources

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↗

Antiviral activity of natural and semisynthetic polysaccharides on the early steps of rubella virus infection.

The natural and semisynthetic carbohydrates scleroglucan, locust bean gum, tamarind gum (glyloid) and its three sulphate derivatives (GP4311, GP4327 and GP4324), glycogen and its two sulphate derivatives (GP4427 and GP4435), alginic acid and dextran sulphate, were investigated for their inhibitory effect on rubella virus (RV) infection of Vero cells. The neutral polymer scleroglucan and two highly negatively charged compounds, glyloid sulphate 4324 and dextran sulphate, had the highest inhibitory effect on RV antigen synthesis. The antiviral properties of active molecules appears to be dependent on the shape of the macromolecule and/or on the electric charge, while saccharide units play a minor role. The results indicated that polysaccharides blocked a step in virus replication subsequent to virus attachment, such as internalization and/or uncoating. Confirmation that the inhibitory activity of the compounds was directed at the early steps of RV multiplication, was that none of the polysaccharides had any effect on infection initiated by transfection of cells with RVRNA.

Animals↗

Parathyroid scintigraphy: comparison of technetium-99m methoxyisobutylisonitrile and technetium-99m tetrofosmin studies.

We report the preliminary results of a prospective study demonstrating tetrofosmin uptake in surgically and histologically proven parathyroid adenomas. In ten patients with primary chronic hyperparathyroidism, parathyroid imaging was performed using (1) technetium-99m methoxyisobutylisonitrile (MIBI) and (2) 99mTc-1, 2-bis(bis(2-ethoxyethyl)phosphino)ethane (tetrofosmin) within a time interval of 3-5 days. Both tracers correctly identified the parathyroid adenomas by focal prolonged tracer retention. On visual inspection image contrast was generally higher with MIBI than with tetrofosmin in all the patients studied. Tetrofosmin showed a slower elimination from the parathyroid adenomas than MIBI in six of the ten cases. Our preliminary results show that tetrofosmin, like MIBI, as a feasible, sensitive tracer for parathyroid scintigraphy. For routine use, the rapid kit preparation without heating and the lower radiation dose to the patient make tetrofosmin an alternative tracer for parathyroid scintigraphy. Further evaluation is needed to determine which of the two tracers is the more sensitive for the detection of parathyroid adenomas, and which tracer properties better reflect the degree of endocrine activity.

Adenoma↗

Antiviral effect of a polysaccharide from Sclerotium glucanicum towards herpes simplex virus type 1 infection.

Among different neutral polysaccharides from natural sources, scleroglucan from Sclerotium glucanicum significantly inhibits the replication of herpes simplex virus type 1 on Vero cells. Scleroglucan belongs to a class of exopolymers, expressed by members of genus Sclerotium and consists of a linear beta-1,3-linked glucopyranose with side chains of single glucopyranose residues linked through beta-1,6 glycosidic bonds. The effective antiviral concentration of this polysaccharide is far from the cytotoxicity threshold and consequently this natural product possesses a good selectivity index. Results obtained in experiments carried out in order to clarify the mechanism of action of this carbohydrate indicate that the block of infection occurs during the very early phases of the viral mutliplication cycle since the highest inhibitory effect took place when it was added during the attachment step. The antiviral effect of scleroglucan seems to be related to its binding with membrane glycoproteins of HSV-1 particles which impedes the complex interactions of the virus with the cell plasma membrane.

Animals↗

Semi-quantitative scintigraphic follow-up studies of cerebral arteriovenous malformations after radiosurgical treatment.

An evaluation of semi-quantitative 99Tcm-red blood cell scintigraphy (RBCS) was undertaken in patients with cerebral arteriovenous malformations (AVM) during follow-up after radiosurgical treatment. Twenty-seven patients were studied with an initial dynamic imaging sequence of 32 frames each lasting 2 s, planar images in four projections beginning 15 min post-injection and single photon emission tomography immediately following the planar imaging. A 2 ml cubital vein blood sample was imaged to obtain an extracorporeal equivalent of the intravascular activity. The counts within the AVM on a planar image were divided by the counts obtained from the image of the blood sample (corrected for the same acquisition time and radioactive decay). This value yielded the 'volume index' (VI), which was proportional to the volume of the AVM. The VI obtained from the first RBCS served as the initial reference value and was set at 100%. The VIs obtained from the follow-up investigations of the same patient in the same projection were expressed as the percentage of the initial VI. We found RBCS identified the AVM in all patients. The VIs obtained from the follow-up studies demonstrated a decrease in blood volume at different time intervals after radiosurgical treatment. RBCS provides a sensitive, relatively non-invasive, semi-quantitative method for measuring the relative volume and follow-up of the degree of obliteration of AVMs after radiosurgical treatment.

Cerebral Arteries↗

Dynamic and static scintigraphic evaluation of cerebral arteriovenous malformations to evaluate radiosurgical treatment.

The radiobiologic changes induced by cobalt-60 gamma irradiation in cerebral arteriovenous malformations (AVMs) is a torpid process. Complete obliteration may take 1 or 2 years or even longer. Neuroradiological modalities like magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) do not provide sufficient information to comprehend this process. Digital subtraction angiography represents an invasive method and is therefore most often performed when complete obliteration is expected. The purpose of this study was to investigate the value of blood pool scintigraphy and functional imaging, such as single photon emission computed tomography (SPECT), to gain more knowledge about the volumetric changes of AVMs treated by radiosurgery. Twenty consecutive candidates for Gamma Knife treatment were selected for comparative MRI/ MRA and scintigraphic studies. All lesions ranging from 0.6 to 18.6 cm3 could be identified on blood pool and SPECT images. Seven patients had repetitive examinations at 3-month intervals to compare the relative volumetric change of the lesion. In 5 cases, a marked decrease in blood pooling was noticed after 3 months, and in 2 patients no significant change was evident. In contrast, MRI/MRA scans done at the same time did not similarly indicate progressive obliteration changes. This preliminary result indicates that scintigraphic evaluation using the blood pool technique is a very sensitive method to describe the relative volumetric change of radiosurgically treated AVMs.

Adolescent↗

Inhibition of herpes simplex virus infection by negatively charged and neutral carbohydrate polymers.

Different natural and semisynthetic polysaccharides were evaluated for their inhibitory effect on in vitro replication of herpes simplex virus (HSV) types 1 and 2. Some neutral and negatively charged carbohydrates were able to inhibit viral infection by interfering mainly with the adsorption process showing a dose-dependent relationship. Their effect was shown within the concentration range of 200-0.8 micrograms/ml, and the inhibiting compounds were in order of action: dextran sulfate = scleroglucan = lambda carrageenan > glyloid sulfate 4324 > locust beam gum towards HSV-1 and dextran sulfate = glyloid sulfate 4324 = lambda carrageenan > scleroglucan > glycogen sulfate 4435 towards HSV-2. The data obtained indicate that the antiviral activity of polysaccharides was not only related to their electric charge. Other characteristics of the molecules such as the polymeric backbone, the carbohydrate moieties and the degree of polymerization could play a role in influencing their antiviral properties.

Animals↗

SPET quality control: a comprehensive test procedure for evaluating the rotation system parameters COR-offset, y-shift and detector tilt.

This paper describes a method for SPET quality control that facilitates the determination of COR-offset, parallel y-shift and detector tilt by means of a single, comprehensive test using a special phantom consisting of three point sources. The evaluation of the method was performed by a series of measurements utilizing manually adjusted detector tilts and a simulation of y-shift by moving the phantom. The results show that y-shift and detector tilt are measured with reasonable accuracy, and that y-shift caused by variations in detector tilt can be differentiated from y-shift caused by other factors.

Evaluation Studies as Topic↗

[A new concept in imaging pelvic recurrence of curatively operated rectal carcinoma--image fusion of nuclear magnetic resonance tomography and anti-CEA immunoscintigraphy (SPECT): technique and clinical example].

We present a new technique of image fusion (IF) of magnetic resonance imaging (MRT) and anti-CEA-immunoscintigraphy (Behring 431/26) and single photon emission computed tomography (SPECT). We performed SPECT and MRT within 8 hours on the same day. Glucagon intravenously was used to reduce artefacts due to intestinal motility. Before image fusion we analysed the SPECT and MRT images independently of each other. The MRT and SPECT were connected by a local area network (LAN) to a Gateway computer, which is also used as a picture archive. There a program automatically starts, translates the MRT data from the ACR/NEMA format to the Elscint one and these data are sent for image fusion to the nuclear medicine computer Elscint SP1. By means of a clinical example we present anatomic concordant superimposition and explain the findings and the clinical value of our technique. This system and technique are equally applicable to other digital imaging investigations. By IF, on the basis of the certain evidence of the tracer depot of a pathological lesion diagnosed by MRT and the reliability of the anatomical assignment of a focal lesion diagnosed by SPECT, early detection of local recurrence after surgical treatment of rectal cancer, the correct localisation of recurrent disease and its distinction from non-malignant tissue becomes possible. This enables planning of further therapeutical strategies.

Adenocarcinoma↗

Left-right asymmetry of callosal transfer in normal human subjects.

Interhemispheric transfer (IT) of visuomotor information can be assessed by measuring the crossed-uncrossed difference (CUD) in the Poffenberger paradigm [14]. We report a series of experiments aimed at casting light on two aspects of IT: the importance of motor response variables and the nature of the left-right asymmetries found in a recent meta-analysis of studies using the Poffenberger paradigm [10]. In Experiments 1 and 2 we found no effect of varying the finger used for response while there was a larger CUD when using the left hand in comparison to the right hand. In Experiment 3, which employed visual stimuli different from the two preceding experiments, CUD asymmetries were related to hemifields rather than to hands with a CUD larger for the right than for the left visual hemifield. These findings suggests that both motor and visual variables are important for CUD asymmetries to occur and are in keeping with a horse race model according to which overall speed of IT is determined by whichever signal (visual or pre-motor) is more rapid in crossing from one side to the other. As to the issue of lateral asymmetries in the CUD, the results of Expt. 3 have also shown that asymmetries arise only in tasks requiring an IT and therefore cannot depend upon additive hemispheric effects.

Adult↗

Analysis of a bioactive synthetic analogue of tuftsin by tandem mass spectrometry: anomalous fast atom bombardment activated processes.

Fast atom bombardment (FAB) tandem mass spectrometry has been used to analyse the biologically potent, partially modified retro-inverso (PMRI) synthetic isomer of tuftsin: this compound represents the active peptide of the fraction of gamma-globulin (leukokinin) which binds specifically to blood neutrophilic leukocytes and monocytes. Protonated molecules and fragment ions were collisionally dissociated at low energies in a triple-quadrupole mass spectrometer to yield a complete picture of the reactions that occur in the condensed and in the gas phase. The study shows that, when retro-inversion is within the N-terminal amino acid, charge localization at the basic sites (possibly at the N-terminus) induces a marked decomposition of the molecule, the loss of ammonia being the most favourable fragmentation process. Also, artifacts are formed in the liquid phase via bimolecular reactions promoted by the high-energy beam. The findings indicate that despite the fact that PMRI isomers of this type are stable against exo-peptidases and also stable under acidic conditions, they appear to be labile under conditions where the energy deposition, due to FAB is necessarily high.

Amino Acid Sequence↗

Attention shifts produce spatial stimulus codes.

In the Simon task the spatial position of the stimulus, though task irrelevant, influences speed of response. We (Umiltà & Nicoletti, 1992) proposed that the orienting of attention to the imperative stimulus produces a Stroop-like interference. This paper reports the results of three experiments that provide empirical support for two predictions of this hypothesis. One is that the stimulus spatial code is formed with relation to the position to which attention is directed. The other prediction is that the Simon effect is obtained on condition that attention can orient to the stimulus.

Adult↗

Scintigraphy and sonography in reflux nephropathy: a comparison.

The evaluation of reflux nephropathy (RNP) is a major task in the following up of children with vesicoureteral reflux (VUR). Adequate monitoring of RNP development depends on the frequent use of sonographical and scintigraphical examinations. In order to evaluate the accuracy of sonography in monitoring RNP 63 patients suffering from VUR (mean age: 8.8 years, range: newborn to 18 years, male:female = 19:44) were examined prospectively. We calculated renal size sonographically and compared our data to static and dynamic renographic findings. Our results showed a good correlation between relative DMSA uptake and sonographically estimated relative renal size (r = 0.95, P < 0.001), whereas not unexpectedly the correlation between relative kidney function and sonographically estimated renal size was poor (r = 0.83, P < 0.01). We therefore believe, that in monitoring children with VUR, sonography can offer accurate information on questions about renal size and renal parenchymal structure as well as pelvic distention. With very small kidneys as well as with kidneys showing severe dilatation and above all for evaluating renal function, scintigraphy proved to be the better method.

Adolescent↗