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Biomedical subjects

R Benti

Publications and source records attributed to R Benti.

At least 19 recordsLinked to original sources

Brain SPECT imaging in multiple system atrophy.

Clinical diagnosis of multiple system atrophy (MSA) relays on signs and symptoms that are often difficult to identify particularly at early stage. Indeed neuropathological studies have demonstrated that MSA is the first cause of misdiagnosis in a cohort of patients presenting with parkinsonian features. Dopamine transporter imaging (DAT) shows striatal decrements in both MSA and Parkinson's disease (PD) making it not sensitive for differential diagnosis. Studies of dopamine D2 receptors with IBZM may help revealing striatal degeneration but a large overlap exist particularly if PD patients with advanced disease are included. We have measured brain flow with technetium-99m ethyl cysteinate dimer (ECD-SPECT) in 36 MSA patients and compared it with 43 PD and 39 age-matched controls. Using Statistical Parametric Mapping (SPM99) we found areas of significant reduced perfusion in the striatum, brain stem and cerebellum in MSA compared to the other groups. We believe that ECD-SPECT imaging may offer significant advantages compared to other imaging techniques in the assessment of neuronal degeneration in MSA and may help the clinician in the diagnostic characterization of patients presenting with atypical parkinsonism.

Animals↗

123I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT) uptake in patients with Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy.

We used SPECT and the tracer (123)I-Ioflupane to measure dopamine transporter (DAT) binding in the caudate nucleus and the putamen of 70 patients with Parkinson's disease (PD), 10 with multiple system atrophy (MSA-P type), and 10 with progressive supranuclear palsy (PSP). Data were compared with 12 age-matched control subjects. We found significant reductions in mean striatal values in all three forms of parkinsonism. However, decrements were significantly greater in PSP (0.51+/-0.39, p<0.01) compared with MSA-P (0.70+/-0.33) and PD (0.95+/-0.38). No differences were found between MSA and PD. Putamen/caudate ratios were greater in PSP (0.83+/-0.12, p<0.01) than in PD (0.51+/-0.11), suggesting a more-uniform involvement of dopamine nerve terminals in both caudate nucleus and putamen. Our results confirm that DAT binding can provide an accurate and highly sensitive measure of dopamine degeneration. PSP patients may show a different pattern of neuronal loss compared with MSA and PD.

Aged↗

Brain flow changes before and after deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) markedly improves motor symptoms and reduces medication needs in Parkinson's disease (PD) patients. However, its effect on brain function has remained unclear. We used SPECT and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the STN in 22 PD patients and 13 healthy controls. PD patients were divided into good and poor responders to DBS, if changes in "off" UPDRS motor scores after surgery were >60% or <40%, respectively. Statistical analysis was performed using the SPM99 software. At baseline, all PD patients showed significant perfusion reductions in cortical areas (premotor frontal, parietal, and occipital). After DBS, changes were normalized only in the good responders, while cortical defects in the poor responders were unchanged. No flow decrements were detected in basal ganglia and thalamus in both groups, suggesting that DBS does not have a "lesion-like" effect. We conclude that good surgery outcome is associated with normalization of cortical flow abnormalities in PD.

Case-Control Studies↗

Functional neuroimaging (PET and SPECT) in the selection and assessment of patients with Parkinson's disease undergoing deep brain stimulation.

Deep brain Stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor complications who can no longer be improved by adjustment of medical therapy. Selection of surgery candidates and follow-up after surgery are critical for good outcome. Functional neuroimaging can help in the clinical assessment of these patients. We have used single photon emission computed tomography (SPECT) and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the subthalamic nucleus (STN) in 20 patients with advanced PD. We found a significant increase in the anterior cingulate/supplementary motor cortex in the 12 good responders (change in off unified UPDRS >50%). Conversely, patients with poor response (n=8; change in off UPDRS-III <50% following DBS) revealed a significant worsening of cortical hypoperfusion particularly in the prefrontal areas. No flow decrements were detected in the basal ganglia and in the thalamus in both groups during DBS stimulation suggesting that DBS does not have a "lesion like" effect. If DBS stimulates and does not inactivate STN projection neurons, flow reduction in the poor responders may be secondary to increased inhibitory basal ganglia output.

Cerebrovascular Circulation↗

Perfusion ECD/SPECT in the characterization of cognitive deficits in Parkinson's disease.

Cognitive abnormalities have been reported in a large percentage of patients with Parkinson's disease (PD). Often cognitive changes are sub-clinical and involve frontal lobe function. In other occasions they develop into full dementia. Functional neuroimaging may help characterize these abnormalities. We have studied brain perfusion with SPECT and the tracer ECD in 44 PD patients, 22 presenting with normal cognitive function and 22 with clinical and neuropsychological signs of dementia. Compared with 21 healthy controls, demented PD patients showed significant perfusion decrements in all cortical areas, particularly temporal and parietal regions; in the non-demented cohort reductions were limited to the frontal lobe area. These results suggest that brain perfusion abnormalities are present in PD patients. It is speculated that different pathological mechanisms underlie perfusion differences.

Aged↗

Biodistribution studies of 99mTc-labeled myoblasts in a murine model of muscular dystrophy.

The purpose of this study was twofold: first, to evaluate the myoblast labeling of various 99mTc complexes and to select the complex that best accomplishes this labeling, and second to evaluate the biodistribution of myoblasts labeled with this complex using mice with MDX muscular dystrophy (the murine homologue of Duchenne's muscular dystrophy). The following ligands were used to prepare the corresponding 99mTc complexes: hexakis-methoxy-isobutyl-isonitrile (MIBI), bis(2-ethoxyethyl)diphosphinoethane (Tf), (RR,SS)-4,8-diaza-3,6,6,9-tetramethyl-undecane-2,10-dione-bisoxime (HM-PAO), bis(N-ethyl)dithiocarbamate (NEt), and bis(N-ethoxy, N-ethyl)dithiocarbamate (NOEt). One million murine myoblasts were incubated for 30-60 minutes with 5 mCi of each of the 99mTc complexes prepared from the above ligands. Viability was assessed by microscopic counting after trypan blue staining, and the radioactivity absorbed in the cells was measured after centrifugation. The compound with the highest uptake in cellular pellets was [99mTc]N-NOEt. The biodistribution of myoblasts labeled with this complex was evaluated after intraaortic injection in dystrophic mice. Such an approach has the potential of effecting widespread gene transfer through the bloodstream to muscles lacking dystrophin.

Animals↗

Usefulness and limits of distal echo-Doppler velocimetric indices for assessing renal hemodynamics in stenotic and non-stenotic kidneys.

BACKGROUND: Distal echo-Doppler velocimetric indices are widely used for revealing the presence of a renal artery stenosis but there is scarce information as to whether they reflect the renal hemodynamics in stenotic and nonstenotic kidneys. OBJECTIVES AND METHODS: We evaluated the pulsatility and resistive indices (PI and RI), acceleration (A) and acceleration time (At) and correlated their values with those of effective renal plasma flow (ERPF), glomerular filtration rate (GFR), renal vascular resistance (RVR) and filtration fraction (FF) estimated by single kidney scintigraphy in 24 kidneys with 70-95% renal artery stenosis (atherosclerotic n = 17, fibromuscular n = 7) and in 27 non-stenotic kidneys (11 contralateral to renal artery stenosis and 16 of patients with essential hypertension). In patients with stenotic kidneys, these measurements were repeated within 7 days after a successful percutaneous transluminal renal angioplasty (PTRA) (in 11 arteries performed in combination with stent implantation). RESULTS: Prior to dilation we found that the stenotic kidneys had significantly lower values of ERPF, GFR and higher RVR than the non-stenotic kidneys and that these hemodynamic alterations were associated with those, also statistically significant, of the four velocimetric indices. In non-stenotic kidneys, there were highly significant relationships between PI and ERPF, and RVR (r = -0.68 and 0.81 respectively P < 0.01); similar relationships were found for RI (r = -0.67 and 0.78 P < 0.01) whereas no such correlations were found between these two velocimetric indices and GFR and FF; also no correlations were found between A and Atand ERPF, GFR, RVR and FF. In stenotic kidneys no significant correlations were found between any of the velocimetric and the hemodynamic indices. Renal artery dilation induced clear cut increments in ERPF, GFR and reduction in RVR in post-stenotic kidneys, which were associated with normalization of all four velocimetric indices. No relationships were observed between the renal hemodynamic and the velocimetric changes induced by dilation; however in post-stenotic kidneys the relationships between PI and RI, ERPF and RVR were restored as in nonstenotic kidneys. CONCLUSIONS: These data indicate that PI and RI can be used to assess ERPF and RVR both in non-stenotic and post-stenotic kidneys; however, none of the velocimetric indices examined in this study can provide valid informations on the renal hemodynamics of stenotic kidneys and on their changes induced by PTRA.

Adolescent↗

Angioplasty of atherosclerotic and fibromuscular renal artery stenosis: time course and predicting factors of the effects on renal function.

The effects of percutaneous transluminal renal angioplasty (PTRA) on the renal function of stenotic kidneys are usually assessed by evaluating the changes in serum creatinine, which is quite a rough indicator of glomerular filtration rate (GFR). In 27 hypertensive patients with 19 atherosclerotic and 11 fibromuscular significant renal artery stenoses, we investigated with renal scintigraphy the short-term (5 days) and long-term (10 months) effects of a technically successful PTRA (in seven cases combined with a stent implantation) on GFR of the stenotic and contralateral kidneys; these measurements were combined with those of plasma renin activity (PRA) and of angiotensin II (AII). We found that in short-term studies after PTRA GFR rose from 29.7 +/- 3.5 to 34.6 +/- 3.1 mL/min and from 36.9 +/- 4.0 to 45.1 +/- 4.3 mL/min, respectively, in atherosclerotic and fibromuscular poststenotic kidneys. In long-term studies GFR further and significantly increased, to 37.8 +/- 3.2 mL/min in the former group, whereas it stabilized in the latter group (46.0 +/- 3.6 mL/min). In patients with fibromuscular stenosis these changes in GFR were associated with clear-cut reductions in blood pressure (BP), PRA, and AII; these decrements also occurred in patients with atherosclerotic stenosis but to a much lesser extent. We also found that in short- and long-term studies the percent of PTRA-induced increments of GFR in the poststenotic kidneys were inversely correlated with the baseline values of GFR. In addition, the absolute and percent increments of GFR were positively correlated with the basal levels of AII. Thus the time course of the improvement in GFR after angioplasty may differ in kidneys, depending on the etiology of the stenosis, in that in those with fibromuscular stenosis it was entirely apparent within a few days whereas in those with atherosclerotic stenosis it required several months to be fully expressed. Also, it appears that the more compromised kidneys are those that benefit most from the dilatation and that AII levels are useful indicators of the possibility that the stenotic kidney will have a favorable functional outcome in terms of restoration of renal blood flow.

Adolescent↗

Unilateral periventricular nodular heterotopia associated with diffuse areas of cerebral functional abnormalities.

A 17-year-old boy with polymorphic simple and complex partial seizures is described. Magnetic resonance imaging revealed a unilateral periventricular nodular heterotopia near the occipital ventricular right horn. Interictal and ictal electroencephalographic recordings showed bilateral specific epileptiform anomalies in the occipital region and asynchronous slow waves in frontal areas. Single photon emission computed tomography documented a reduction in regional cerebral blood flow in an area of the left occipital cortex and a symmetric increase in tracer uptake in the frontal lobes. The neuropsychologic assessment revealed a dysfunction of the frontal associative areas. Data collected led the authors to suspect a more diffuse cortical dysfunction than the nodular heterotopia revealed on magnetic resonance imaging.

Adolescent↗

Focal cognitive impairment in mitochondrial encephalomyopathies: a neuropsychological and neuroimaging study.

Mitochondrial encephalomyopathies (ME) are a multisystemic group of diseases characterized by a wide range of biochemical and genetic mitochondrial defects with a variable mode of inheritance. We studied the neuropsychological profile, magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) data in a group of ME patients in order to look for common or specific cognitive defects and a possible correlation with related brain areas. Three main cognitive areas were assessed: general intelligence, memory functions and visuo-perceptual skills. Our sample included 16 ME patients (nine males, seven females) aged 25-68 years (mean age 45.2, SD 13.0). No sign of mental deterioration was found in the group of elderly subjects. Despite subjects showing no global cognitive impairment they scored lower in nonverbal versus verbal tasks. Visuo-spatial skills and short-term memory were selectively impaired. There was no correlation between neuropsychological results and age, illness duration, age of onset, clinical phenotypes, genetic mitochondrial alterations and pharmacological therapy. The most frequent SPECT pattern observed was the hypoperfusion of temporal lobes, with a direct localization in the temporal cortex and with prevalent mesial involvement. The neuropsychological profile and SPECT imaging revealed similarities with focal defects.

Adult↗

Scintigraphic imaging and absorption of a 5-aminosalicylic acid enema in patients with ileorectal anastomosis.

UNLABELLED: Ileorectal anastomosis (IRA) is a possible surgical treatment for hyperacute and drug-unresponsive forms of ulcerative colitis (UC). UC relapses in the rectal remnant usually are prevented by chronic administration of 5-aminosalicylic acid (5-ASA) in topical formulations. The relationships between intestinal absorption and pattern of luminal spread of 5-ASA enemas are still unknown in patients with IRA. We correlated the absorption of a 5-ASA enema with its spread in the distal bowel of patients with IRA as assessed by 99mTc radioenema imaging. METHODS: Eight patients with UC in remission and previous IRA received a therapeutic 50-mL 5-ASA enema labeled with 99mTc-sulfer colloid. Absorbed 5-ASA and its major metabolite, acetyl 5-ASA, were measured in plasma, and dynamic images of radiolabeled enema were obtained for 6 h. The retrograde ileal spread (RIS) was determined and expressed as percentage of total enema radioactivity. Plasma levels of 5-ASA and acetyl 5-ASA were measured in six healthy volunteers after administration of the same enema volume with no radiolabeling. RESULTS: The mean 5-ASA plasma level was 0.70 microg/mL (range 0.37-0.95 microg/mL) in patients and 0.96 microg/mL (range 0.78-1.16 microg/mL) in healthy volunteers (P = not significant), and the mean acetyl 5-ASA plasma levels were 0.89 microg/mL (range 0.44-1.19 microg/mL) and 0.84 microg/mL (range 0.51-1.02 microg/mL), respectively (P = not significant). Radioenema imaging allows RIS assessment of patients with IRA. The mean value was 8.5% (range 2%-19.3%) of administered radioactivity, which correlated significantly with the total absorption of 5-ASA in the IRA group (P = 0.033, linear correlation test). Rectal wall contractions recognized by dynamic radioenema imaging were defined as a common cause of RIS episodes. CONCLUSION: In IRA patients, 5-ASA plasma levels were similar to those in healthy volunteers after administration in enema. Only part of a 50-mL 5-ASA enema reaches the ileum, and radiolabeled imaging shows the degree and number of these RIS episodes. The absorption of 5-ASA can increase in patients compared with healthy volunteers, in the presence of either occasional but significant ileal spread associated with postural factors and abdominal wall contraction or multiple moderate episodes of radioenema backdiffusion related to rectal wall motility.

Adult↗

High cerebral perfusion pressure improves low values of local brain tissue O2 tension (PtiO2) in focal lesions.

Arterial hypertension is widely applied to improve regional cerebral blood flow (rCBF). We measured local brain tissue O2 pressure (PtiO2) in low density lesions at computerized tomography (CT) of the head before and after manipulation of mean arterial pressure (MAP) in order to increase cerebral perfusion pressure (CPP). Nine patients, 7 subarachnoid hemorrhage (SAH), 1 severe head injury, 1 meningeoma, were included in our study. A flexible polarographic microcatheter for PtiO2 measurement was placed at the border of the low density area found at CT. PtiO2 was continuously measured for 615 hours. Hypoperfusion in low density areas was detected by perfusional single photon emission computed tomography (SPECT). We recorded 22 episodes of induced or spontaneous increase of MAP. Initial PtiO2 regularly improved after the CPP increase (r2 0.74 in induced episodes). Low PtiO2 showed a greater percent increase for unitary changes of CPP than normal-high PtiO2. Baseline PtiO2 below 20 mm Hg was associated with normal CPPs; 5 readings of PtiO2 below 20 mm Hg normalized when a higher CPP was obtained. Our results show that in ischemic areas PtiO2 is dependent on CPP suggesting both a derangement of pressure autoregulation and high regional cerebrovascular resistences (CVRs). Low PtiO2 was associated with normal CPP, thus indicating that CPP could be an inadequate estimate of rCBF in focal ischemic areas. Arterial hypertension, capable of increasing CPP above normal values, appeared useful in normalizing tissue oxygenation in ischemic areas.

Adult↗

Plasma somatostatin-like immunoreactivity and somatostatin-28 levels in obese men.

Somatostatin (SS) impairs nutrient absorption. It has been suggested that hyposomatostatinaemia may be involved in the pathogenesis of obesity. However, data on postprandial SS-like immunoreactivity (SLI) levels in obese subjects are controversial and the levels of SS-28, the main molecular form of circulating SLI in healthy subjects, have not been determined. To characterise the fasting and postprandial plasma pattern of SLI and SS-28 in obese men, we studied eight obese men (age 24-32 yr, BMI 33-42 kg/m2), with normal glucose tolerance test and normal gastric emptying of solids, and eight healthy men (age 24-39 yr, BMI 21-24 kg/m2). Blood samples were taken at regular intervals in fasting conditions and for 2 h after a standard solid-liquid meal (2.3 MJ). Plasma SLI and SS-28 were measured by RIA. Our results showed that fasting and postprandial plasma SLI and SS-28 levels were not significantly different in healthy and obese subjects. In conclusion SS-28 is the predominant form of circulating SLI in obese subjects. The normal pattern of fasting and postprandial plasma SLI and SS-28 levels in such subjects suggests that somatostatin does not have a pathogenetic role in obesity.

Adult↗

Impaired left ventricular filling rate induced by treatment with recombinant interleukin 2 for advanced cancer.

BACKGROUND: Immunotherapy with recombinant interleukin 2 (rIL 2) has been extensively used to treat cancer but its use has been hampered by serious side effects including severe hypotension, arrhythmias, and myocardial infarction. OBJECTIVE: To assess the effects of rIL 2 on human left ventricular function. METHODS: Left ventricular (LV) function was monitored in 22 patients (9 women, 13 men) (mean (SD) age 53 (10) years) undergoing a 120 h continuous intravenous infusion of rIL 2 (18 x 10(6) IU/m2/day) for melanoma (4), renal cell (16), ovarian (1), and colon cancer (1). Radionuclide ventriculography was performed before and 1 h after the end of treatment. Ejection fraction (EF), peak emptying rate (PER), peak filling rate (PFR), and regional left ventricular wall motion were analysed. Heart rate (HR), central venous pressure (CVP), systolic (SBP) and diastolic blood pressures (DBP), the electrocardiogram, and myocardial enzyme concentrations were monitored throughout the study. RESULTS: All variables (mean (SD)) were normal before rIL 2 was given. After rIL 2 administration HR increased significantly from 84 (11) to 125 (18) beats/min (p < 0.0001), SBP fell from 128 (11) to 100 (9) mmHg (p < 0.001) and DBP from 76 (9) to 65 (7) mmHg (p < 0.0001). CVP decreased from 3.70 (3.2) to 1.30 (0.45) cm H2O (p < 0.001). EF (65 (7) to 64 (8%) and PER (3.56 (0.60) to 3.86 (0.83) EDV/s) did not change significantly. PFR decreased significantly at the end of the rIL 2 infusion from 2.68 (0.46) to 2.37 (0.43) EDV/s (p < 0.01). Left ventricular segmental hypokinesia developed in 6 patients. Myocardial enzyme concentrations remained normal throughout the study. CONCLUSIONS: The results of this study confirmed that rIL 2 produces important haemodynamic changes, predominantly related to decreased systemic resistance. However, the observed reduction in PFR in most patients suggested that rIL 2 might exert its action at the level of the heart muscle itself. The localised systolic dysfunction in some patients suggested that rIL 2 might also adversely affect myocardial perfusion.

Blood Pressure↗

Symptom-limited exercise testing causes sustained diastolic dysfunction in patients with coronary disease and low effort tolerance.

Exercise stress testing is routinely used for the noninvasive assessment of coronary artery disease and is considered a safe procedure. However, the provocation of severe ischemia might potentially cause delayed recovery of myocardial function. To investigate the possibility that maximal exercise testing could induce prolonged impairment of left ventricular function, 15 patients with angiographically proved coronary disease and 9 age-matched control subjects with atypical chest pain and normal coronary arteries were studied. Radionuclide ventriculography was performed at rest, at peak exercise, during recovery and 2 and 7 days after exercise. Ejection fraction, peak filling and peak emptying rates and left ventricular wall motion were analyzed. All control subjects had a normal exercise test at maximal work loads and improved left ventricular function on exercise. Patients developed 1 mm ST depression at 217 +/- 161 s at a work load of 70 +/- 30 W and a rate-pressure product of 18,530 +/- 4,465 mm Hg x beats/min. Although exercise was discontinued when angina or equivalent symptoms occurred, in all patients diagnostic ST depression (greater than or equal to 1 mm) developed much earlier than symptoms. Predictably, at peak exercise patients showed a decrease in ejection fraction and peak emptying and filling rates. Ejection fraction and peak emptying rate normalized within the recovery period, whereas peak filling rate remained depressed throughout recovery (p less than 0.002) and was still reduced 2 days after exercise (p less than 0.02). In conclusion, in patients with severe impairement of coronary flow reserve, maximal exercise may cause sustained impairement of diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗