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Biomedical subjects

G Pizzolato

Publications and source records attributed to G Pizzolato.

At least 37 records · Page 2Linked to original sources

Magnetic resonance and single-photon emission tomography findings in a pair of twins discordant for Alzheimer's disease.

The value of functional and morphological neuroimaging in the early diagnosis of Alzheimer's disease (AD) is still debated. Described here are cerebral perfusion and linear measures of medial temporal lobe atrophy in 2 monozygotic twins discordant for AD who were investigated with technetium 99m-hexamethylpropy-leneamineoxime single-photon emission tomography (SPET) and magnetic resonance (MR) imaging. Both showed pathological cortical perfusion findings on SPET, while medical temporal lobe atrophy was present only in the affected twin. MR measures of medial temporal lobe atrophy have greater agreement with clinical data than do SPET measures of cerebral perfusion. Evaluation of atrophy may be useful in the early diagnosis of AD.

Activities of Daily Living↗

Effects of fluoxetine and maprotiline on functional recovery in poststroke hemiplegic patients undergoing rehabilitation therapy.

BACKGROUND AND PURPOSE: In animals, drugs that increase brain amine concentrations influence the rate and degree of recovery from cortical lesions. It is therefore conceivable that antidepressants may influence outcome after ischemic brain injury in humans. We evaluated the effects of the norepinephrine reuptake blocker maprotiline and the serotonin reuptake blocker fluoxetine on the motor/functional capacities of poststroke patients undergoing physical therapy. METHODS: Fifty-two severely disabled hemiplegic subjects were randomly assigned to three treatment groups; during 3 months of physical therapy, patients were treated with placebo, maprotiline (150 mg/d), or fluoxetine (20 mg/d). Before and at the end of the observation period, we assessed activities of daily living by the Barthel Index, degree of neurological deficit by a neurological scale for hemiplegic subjects, and depressive symptomatology by the Hamilton Depression Rating Scale. RESULTS: The diverse treatments ameliorated walking and activities of daily living capacities to different extents. The greatest improvements were observed in the fluoxetine-treated group and the lowest in the maprotiline-treated group. Furthermore, fluoxetine yielded a significantly larger number of patients with good recovery compared with maprotiline or placebo. These effects of the drugs were not related to their efficacy in treating depressive symptoms. CONCLUSIONS: Fluoxetine may facilitate or, alternatively, maprotiline may hinder recovery in poststroke patients undergoing rehabilitation. The effects of fluoxetine as an adjunct to physical therapy warrant further investigation, since treatment with fluoxetine may result in a better functional outcome from stroke than physical therapy alone.

Activities of Daily Living↗

Reduced striatal dopamine receptors in Alzheimer's disease: single photon emission tomography study with the D2 tracer [123I]-IBZM.

Many patients with Alzheimer's disease (AD) develop parkinsonian symptoms, suggesting an overlapping between AD and Parkinson's disease (PD). However, pathologic and neurochemical studies indicate that the involvement of the dopamine system may be different in the two conditions. Using single photon emission tomography, we determined the relative specific striatal uptake (striatum to cerebellum ratio) of the D2 receptor ligand [123I]-IBZM in 15 AD patients without overt extrapyramidal symptoms (three subjects presented mild rigidity and bradykinesia) and nine age-matched controls. Mean specific activity in striatal regions of AD patients (1.35 +/- 0.09) was significantly reduced from control mean (1.59 +/- 0.03). Because such changes were evident even in the absence of overt parkinsonian symptomatology, our data indicate that alterations of striatal D2 receptors may be part of the pathologic abnormalities of AD. In addition, the mechanisms underlying extrapyramidal symptoms in AD (decline of postsynaptic striatal dopamine receptors) appear different from the prevalent presynaptic nigrostriatal alterations typical of PD.

Aged↗

The intercosto-brachial anastomosis in the treatment of cervical roots avulsions: clinical and neurophysiological considerations.

The Authors present their surgical and clinical experience about the intercosto-brachial anastomosis for treating traumatic avulsions of the cervical roots. The most interesting aspect in the postoperative course of these patients in their ability to regain a voluntary elbow flexion independently from the respiratory activity. A dinamic SPECT examination in a small series of cases suggests that some mechanisms of functional reorganization within the brain should be involved.

Brachial Plexus↗

Dose-dependent effects of buspirone on behavior and cerebral glucose metabolism in rats.

In this study we compared the effects of the anxiolytic buspirone on behavior and regional cerebral metabolic rates for glucose (rCMRglc) with those of the reference serotonin (5-HT)1A agonist 8-hydroxy-2(di-N-propylamino)tetralin (DPAT). Behavioral effects were assessed by scoring the 5-HT syndrome. rCMRglc was measured in 56 brain regions by using the quantitative autoradiographic [14C]2-deoxyglucose technique, at 10 min after i.p. injection of DPAT (1 mg/kg) or buspirone (0.4, 4 and 40 mg/kg) in awake male Fischer-344 rats. Whereas DPAT produced an intense 5-HT syndrome, buspirone had no behavioral effect. A low dose (0.4 mg/kg) of buspirone reduced rCMRglc in 18 brain areas (32%), more markedly in limbic areas and raphe nuclei. These were the only rCMRglc effects buspirone had in common with the potent 5-HT1A agonist DPAT and suggest that low dose buspirone activates preferentially 5-HT1A receptors. Hence, this receptor subtype may mediate buspirone functional effects on the limbic system and, given the role of these brain areas in mood control, possibly buspirone therapeutic actions. High doses (4 and 40 mg/kg) of buspirone produced widespread rCMRglc decreases in 46 (82%) and 44 (79%) of the areas studied and increased rCMRglc in one brain area, the lateral habenula, that was not affected by DPAT or a low dose of buspirone. The topographic distribution and direction of rCMRglc changes by high doses of buspirone differ from those produced by the 5-HT1A agonist DPAT. Instead these changes resemble the rCMRglc effects of dopaminergic D2 antagonists like haloperidol and are consistent with some pharmacological and binding properties of buspirone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cerebral metabolic responses to clomipramine are greatly reduced following pretreatment with the specific serotonin neurotoxin para-chloroamphetamine (PCA). A 2-deoxyglucose study in rats.

To determine if reported reductions of regional cerebral metabolic rates for glucose (rCMRglc) induced by the tryciclic antidepressant clomipramine (CMI) (10 mg/kg) are due to a presynaptic action on serotonin (5-HT) terminals, 3-month-old Fischer-344 rats were given parachloroamphetamine (PCA), a serotonin neurotoxin. rCMRglc was measured 3 weeks later in 55 brain regions after the administration of saline or CMI using the quantitative autoradiographic [14C]2-deoxyglucose procedure. PCA alone increased rCMRglc in the visual cortex. CMI alone reduced rCMRglc in 18 (33%) of the studied regions, including telencephalic, diencephalic, limbic, and brain stem areas. In PCA-lesioned rats, metabolic responses to CMI (10 mg/kg) were greatly reduced, and significant rCMRglc decreases were observed only in 4 (7%) of the brain areas, including the hippocampus and raphe nuclei. Abolition by PCA of the metabolic responses to CMI confirms that CMI, at the dose studied, reduces rCMRglc via a presynaptic mechanism, likely the 5-HT reuptake sites.

Animals↗

Corticobasal degeneration: neuropsychological assessment and dopamine D2 receptor SPECT analysis.

We report a case of clinically diagnosed corticobasal degeneration, in whom neuropsychological testing was performed along with functional imaging with IBZM SPECT. HM-PAO SPECT showed marked perfusion asymmetry in parietal cortical regions, lower to the right, contralateral to the most affected side. IBZM SPECT, which gives information about postsynaptic dopaminergic D2 receptors, showed severe reduction of tracer uptake in the right basal ganglia. Our findings suggest that a postsynaptic lesion in the basal ganglia might account for the lack of response of extrapyramidal motor symptoms to dopaminergic agonists in corticobasal degeneration.

Adult↗

Dementia of the frontal type: neuropsychological and [99Tc]-HM-PAO SPET features.

Dementia of the frontal type (DFT) is a degenerative disorder with early behavioral and language disturbances and with relative preservation of memory and visuospatial abilities. On neuropathology, DFT lacks the pathologic hallmarks of Alzheimer's disease (AD). We assessed the neuropsychological and SPET imaging features of 11 DFT and 16 AD patients. The two groups had similar performances on verbal learning, while the former had significantly higher nonverbal learning scores. Testing of verbal and nonverbal instrumental abilities showed that this different behavior could be due to poorer verbal fluency of DFT patients, and not necessarily to poorer learning. Neuropsychological data indicated that the often reported sparing of memory in daily functions of DFT patients can also be shown with formal neuropsychological testing of nonverbal learning. SPET showed a comparatively higher perfusion deficit of frontal regions in the left hemisphere of DFT patients, suggesting that this region might be affected more often in the disease.

Aged↗

Alterations of striatal dopamine D2 receptors contribute to deteriorated response to L-dopa in Parkinson's disease: a [123I]-IBZM SPET study.

Single photon emission tomography with the ligand [123I]-IBZM was used to image central dopamine D2 receptors in Parkinson's disease patients. The aim was to assess striatal receptor densities in relation to response to L-Dopa therapy. In the parkinsonian patients group who were untreated until SPET study and in the group of patients with a sustained response to chronic L-Dopa, striatal [123I]-IBZM uptake did not differ significantly from mean values of the control group. On the contrary, significantly diminished uptake of [123I]-IBZM was found in the basal ganglia regions of the group of patients who developed a complicated/fluctuating response to chronic L-Dopa treatment. Our results indicate that striatal D2 receptor alterations in Parkinson's disease may contribute to the altered response to L-Dopa.

Adult↗

Single photon emission computed tomography with [99Tc]-HM-PAO and [123I]-IBZM in Alzheimer's disease and dementia of frontal type: preliminary results.

Dementia of frontal type (DFT) is a fairly common degenerative disease distinct from Alzheimer's disease (AD), whose reportedly distinctive instrumental feature is frontal lobe hypoperfusion on SPECT. We evaluated the cortical dopaminergic system in 6 AD, 5 DFT, and 6 control subjects with SPECT and both [99Tc]-HM-PAO, a perfusion tracer, and [123I]-IBZM, a D2 postsynaptic ligand. Both in AD and DFT patients, [99Tc]-HM-PAO SPECT showed a relative frontal hypoperfusion. On the contrary, [123I]-IBZM SPECT showed significantly reduced ligand uptake in superior frontal regions of DFT (0.89 +/- 0.08 relative to control subjects) as compared to AD patients (0.97 +/- 0.02; difference of means: 0.08, 95% Confidence Interval 0.004 to 0.156; p = 0.041). Results suggest more marked involvement of the frontal cortical dopaminergic system in DFT than in AD patients.

Aged↗

Neuromuscular disorder in intensive care unit patients treated with pancuronium bromide. Occurrence in a cluster group of seven patients and two sporadic cases, with electrophysiologic and histologic examination.

During six consecutive months, seven patients admitted to our ICU (15 beds, general ICU, approximately 300 intubated patients per year) for acute respiratory failure requiring intubation and mechanical ventilation presented with a peculiar neuromuscular disorder. After the occurrence of this cluster group of patients, we detected two more similar but isolated cases in the following 18 months, ie, altogether 9 patients in 2 years of observation, or 1.55 percent of all intubated patients in our ICU. Sedation was achieved using midazolam, curarization was effected with the neuromuscular non-depolarizing agent pancuronium bromide (PB), and corticosteroids were administered to eight patients. Shortly after discontinuation of sedation and curarization, we observed a persistent tetraparetic syndrome and/or peroneal palsy with a concomitant increase of serum creatine kinase (CK). None of the patients was septic or had the multisystem organ failure. A strong association between CK increase and PB administration was found, whereas no patient suffered severe liver or kidney failure. The duration of the neurologic deficit ranged from 4 to 52 weeks, with only partial recovery for some patients; the duration of dysfunction was apparently related to the total dose of corticosteroids received. Two patients had difficulty being weaned from the respirator and required tracheostomy. Electrophysiologic studies showed signs of axonal neuropathy and myopathic changes, ie, motor units of brief duration, small amplitude, overly abundant for the voluntary effort being exerted. Muscle biopsies showed significant myopathic alterations, with foci of muscle necrosis in most patients and minimal lymphocytic inflammation in one patient. The neurologic complication described differs from the polyneuropathy in critically ill patients. Furthermore, PB or corticosteroids or both appear to be the causal agents. The duration of the neuromuscular dysfunction may be related to concomitant steroid therapy. The CK enzyme seems to be a marker of the disorder. This disorder is associated with myopathic alterations and axonal degeneration in some patients. Pancuronium bromide should be used with caution, particularly when associated with steroids therapy, and it may cause difficulty in weaning patients from the respirator.

Adult↗

The monosialoganglioside GM1 dose-dependently reduces regional cerebral metabolic rates for glucose in awake rats.

Using the quantitative autoradiographic [14C]2-deoxyglucose technique, regional cerebral metabolic rates for glucose (rCMRglc) were measured in awake male Fischer-344 rats at 1, 2, 3, 4 and 6 h after administration of GM1 30 mg/kg and at 3 h after GM1 150 or 300 mg/kg. GM1 is a natural compound that is able to prevent neuron degeneration induced by exposure to excitatory amino acids in vitro and by ischemia or neurotoxins in vivo. GM1 30 mg/kg, a dose very effective in preventing excitatory amino acid-induced neurotoxicity, produced minimal rCMRglc change over a 6 h period. GM1 150 and 300 mg/kg reduced rCMRglc, in 14 (31%) and in 29 (64%) brain regions, respectively. Maximal metabolic effects occurred in hippocampal areas which possess, in specific subfields, the highest brain concentrations of different excitatory amino acid receptor subtypes. This finding suggests an effect by GM1 on postreceptor mechanisms common to different excitatory amino acids.

Animals↗

The tricyclic antidepressant clomipramine dose-dependently reduces regional cerebral metabolic rates for glucose in awake rats.

The time course and the relation to dose of regional cerebral metabolic rates for glucose (rCMRglc) were measured in awake male Fischer-344 rats after administration of clomipramine (CMI), a serotonin (5-HT) uptake inhibitor and clinical antidepressant. rCMRglc was determined, using the quantitative autoradiographic [14C]2-deoxyglucose technique, in 64 brain regions at 20, 40, 60, 120, and 180 min after administration of CMI 50 mg/kg IP and 120 min after CMI 2 and 10 mg/kg IP. The peak metabolic effect was observed at 120 min after CMI. At that time, CMI 2 and 10 mg/kg IP significantly reduced rCMRglc from control values in 12 (19%) and 14 (22%) brain regions, which correspond to areas with high densities of 5-HT reuptake sites (e.g. visual and limbic areas and raphe nuclei). CMI 50 mg/kg produced widespread rCMRglc reductions in 34 (53%) brain regions, including cortical, hippocampal, raphe and cerebellar areas. The topographic distribution and the relation to time and dose of CMI effects on rCMRglc are different from those of 5-HT1A [8-hydroxy-2(di-N-propylamino) tetralin], 5-HT1B-C (m-chlorophenylpiperazine) and 5-HT3 (quipazine) agonists and resemble those produced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), an agonist of 5-HT2 receptors, suggesting that CMI may prefentially stimulate this 5-HT receptor subtype.

Animals↗

Dopamine receptor SPET imaging in Parkinson's disease: a [123I]-IBZM and [99mTc]-HM-PAO study.

Single photon emission tomography (SPET) with the novel ligand [123I]-IBZM was used to image central dopamine D2 receptors in Parkinson's disease (PD) patients. The aim was to assess basal ganglia (BG) receptor densities in relation to the response to L-dopa therapy. To better characterize the clinical potential of [123I]-IBZM SPET, each patient underwent a second study with the regional perfusion tracer [99mTc]-HM-PAO. Tracer activity ratios were calculated for caudate and putamen with mean activity over the cerebellar hemispheres as internal standard. In PD patients we found a significant decline of mean caudate [123I]-IBZM activity, as compared with age-matched control subjects. However, when patients were grouped according to their therapeutic behavior, the [123I]-IBZM uptake in BG ganglia regions of the PD patient group with a poor and fluctuating response to L-dopa was significantly reduced from mean values of patients with a sustained response to L-dopa therapy. [99mTc]-HM-PAO caudate and putamen uptake indexes in PD were similar to control values, even in patients with deteriorated therapeutic response. Our results indicate that BG D2 receptor alterations in PD may contribute to the altered response to L-dopa.

Adult↗