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Biomedical subjects

G Cannizzaro

Publications and source records attributed to G Cannizzaro.

At least 19 recordsLinked to original sources

Reversal of prenatal diazepam-induced deficit in a spatial-object learning task by brief, periodic maternal separation in adult rats.

In the rat, prenatal exposure to diazepam (DZ) induces a permanent reduction in GABA/BZ receptor (R) function and behavioural abnormalities. Environmental modifications during early stages of life can influence brain development and induce neurobiological and behavioural changes throughout adulthood. Indeed, a subtle, periodic, postnatal manipulation increases GABA/BZ R activity and produces facilitatory effects on neuroendocrine and behavioural responses. We here investigated the impact of prenatal treatment with DZ on learning performance in adult 3- and 8-month-old male rats and the influence of a brief, periodic maternal separation on the effects exerted by prenatal DZ exposure. Learning performance was examined employing a non-aversive spatial, visual and/or tactile task, the "Can test". Behavioural reactivity, emotional state and fear/anxiety-driven behaviour were also examined using open field (OF), acoustic startle reflex (ASR) and elevated plus-maze (EPM) tests. A single daily injection of DZ (1.5mg/kg, s.c.), over gestational days (GD) 14-20, induced, in an age-independent manner, a severe deficit in learning performance, a decrease in locomotor and explorative activity and an increase in peak amplitude in the ASR. Furthermore, anxiety-driven behaviour in EPM was disrupted. Daily maternal separation for 15 min over postnatal days 2-21 exerted opposite effects in all the paradigms examined. Prenatally DZ-exposed maternal separated rats, in contrast to respective non-separated rats, showed an improvement in learning performance, a decrease in emotionality and a normalization of the exploratory behaviour in EPM. These results suggest that a greater maternal care, induced by separation, can serve as a source for the developing brain to enhance neuronal plasticity and to prevent the behavioural abnormalities induced by prenatal DZ exposure.

Acoustic Stimulation↗

Comparison of the safety of drug delivery via HFA- and CFC-metered dose inhalers in CAO.

The objective of this study was to compare the long-term safety of a fixed combination of fenoterol hydrobromide (50 microg) and ipratropium bromide (20 microg) delivered using a metered dose inhaler (MDI) formulated with a non-chlorinated propellant, hydrofluoroalkanel34a (HFA-MDI), with delivery using the conventional chlorofluorocarbon propellant (CFC-MDI, Berodual/Bronchodual). The study was designed according to Safety Assessment of Marketed Medicines (SAMM) guidelines, to reflect as far as possible the use of MDls under normal prescribing conditions. Two thousand and twenty-seven patients with chronic airways obstruction (CAO) were enrolled from 99 centres in France, 95 centres in Germany and 24 centres in Italy. Following a 2-week run-in period, patients were randomized on a 2:1 basis (1,348 patients to HFA-MDI, 679 patients to CFC-MDI) to receive a flexible dose regimen of the combination (2 puffs, 2-4 times a day, as prescribed by the investigator) during a 12-week open label phase. The overall incidence of adverse events was comparable between both groups. In addition, the incidence of respiratory side effects was also similar, with CAO exacerbations or bronchitis the most frequently recorded events. The safety profile of the HFA formulation was comparable to those of the marketed CFC-MDIs used in Germany and France/Italy. No clinically significant differences were detected between HFA134a or CFC driven inhalers on the switch from CFC- to HFA-MDI (2 weeks before randomisation versus 2 weeks after randomization). There was a trend for taste complaints to be reported more frequently by patients in the HFA-MDI group (0.7% before randomization versus 3.4% after randomization). This, however, was an expected finding as the HFA134a formulation does have a different taste to the CFC formulation. No difference between formulations was observed in the incidences of coughing or paradoxical bronchospasm. The incidence of falls in FEV1 >15% within 15 min following inhalation at each of the clinic visits was 1.2% for both CFC- and HFA-MDIs. In conclusion, administration of a fenoterol/ipratropium bromide combination via hydrofluoroalkane-metered dose inhaler is as safe as delivery by the currently available chlorofluorocarbon-metered dose inhaler, in an extended population of patients with CAO under normal prescribing conditions.

Administration, Inhalation↗

Dobutamine stress echocardiography and thallium-201 SPECT for detecting ischaemic dilated cardiomyopathy in patients with heart failure.

AIMS: A diagnosis of ischaemic aetiology of a dilated cardiomyopathy has important therapeutic and prognostic implications. In such patients, abnormal ECG and atypical symptoms limit the usefulness of standard ECG-ergometry in detecting myocardial ischaemia. To assess the values of high-dose dobutamine stress echocardiography and of Thallium-201 SPECT (exercise-reinjection-rest protocol) in differentiating between ischaemic and non-ischaemic dilated cardiomyopathy, 37 patients with suspected myocardial ischemia, low ventricular ejection fraction (23 +/- 5%) and heart failure were studied. METHODS AND RESULTS: Coronary artery disease was defined as >50% coronary stenosis in at least one coronary artery. By dobutamine stress echocardiography, ischaemic dilated cardiomyopathy was considered present when either an ischaemic response (biphasic response or direct deterioration) or a scar (fixed dyssynergy) was documented in at least two segments. By Thallium-201 SPECT, severe perfusion defects, either reversible (ischaemia) or fixed (scar), in at least two segments were considered markers of ischaemic dilated cardiomyopathy. Twenty-three patients had ischaemic dilated cardiomyopathy, while 14 had normal coronary arteries. The presence of myocardial ischaemia and/or scar by dobutamine stress echocardiography identified patients with ischaemic dilated cardiomyopathy with a sensitivity of 100% and a specificity of 86%. The sensitivity of Thallium-201 SPECT was 92%, its specificity was 69%. Three of the four false positive results occurred in patients with left bundle branch block. Thirty-two patients were concordantly classified by the two techniques (agreement=86%, k=0.73). CONCLUSION: Both dobutamine stress echocardiography and Thallium-201 SPECT are sensitive techniques for detecting the ischaemic aetiology of dilated cardiomyopathy. The specificity is lower, particularly by SPECT, when left ventricular branch block is present.

Cardiomyopathy, Dilated↗

Comparison of dobutamine stress echocardiography and exercise stress Thallium-201 SPECT for detection of myocardial ischemia after acute myocardial infarction treated with thrombolysis.

In order to compare the ability of dobutamine stress echocardiography (DSE) and exercise Thallium-201 SPECT to detect myocardial ischemia in patients with myocardial infarction (MI) treated with thrombolysis, 43 prospectively selected patients with MI treated with thrombolysis underwent within 1 month from MI DSE, stress-redistribution-reinjection Thallium-201 SPECT and coronary angiography. The echocardiographic and scintigraphic images were analyzed for the presence of myocardial ischemia using a 11-segment left ventricular model. DSE and exercise Thallium-201 SPECT detected myocardial ischemia in the infarct zone in 72% and 72% (31/43) of patients and ischemia at a distance in 12% (5/43) and 19% (8/43) of patients with a concordance of 67% and 88%, respectively. A significant agreement between DSE and exercise Thallium SPECT was found in the evaluation of the extent of both myocardial necrosis and stress-induced myocardial ischemia. DSE and exercise Thallium SPECT showed similar sensitivity (79 vs 76%), specificity (60 vs 60%) and accuracy (77 vs 74%) for detection of a critical stenosis of the infarct-related artery; there was also no significant difference between the tests in sensitivity, specificity and accuracy for detection of the multivessel disease. In conclusion, initially after thrombolyzed MI, DSE and exercise Thallium-201 SPECT detect myocardial ischemia in the infarct zone in a high proportion of patients and show a similar accuracy for the diagnosis of a critical stenosis of the infarct-related coronary artery and of the multivessel disease.

Aged↗

Correction of hypoxia and hypercapnia in COPD patients: effects on cerebrovascular flow.

To assess the responsiveness of cerebral blood flow to arterial carbon dioxide tension (Pa,CO2), arterial oxygen tension (Pa,O2), and pH modifications, in chronic hypercapnia, we measured middle cerebral blood flow velocity (CBFV) by transcranial Doppler ultrasound in 13 chronically hypercapnic, long-term ventilated patients with chronic obstructive pulmonary disease (COPD), in the following conditions: 1) breathing room air; 2) with oxygen supplementation; 3) during mechanical noninvasive intermittent positive pressure ventilation (nIPPV) with O2 enrichment. Under baseline conditions (room air), the CBFV was within the normal range. During oxygen administration, a statistically significant increase was obtained in Pa,O2 (6.5 +/- 0.6 vs 11.2 +/- 1.9 kPa (49.1 +/- 4.3 vs 84.3 +/- 14.6 mmHg)), without relevant variations in: CBFV (54.2 +/- 9.1 cm.s-1), Pa,CO2 (8.6 +/- 1.0 kPa (64.7 +/- 7.7 mmHg)) and hydrogen ion concentration [H+] (42.9 +/- 2.9 nM), compared to baseline values (CBFV = 52.8 +/- 10.7 cm.s-1; Pa,CO2 = (8.4 +/- 0.9 kPa (63.1 +/- 7.1 mmHg; [H+] = 41.8 +/- 2.8 nM). After nIPPV, Pa,O2 did not increase any further (10.6 +/- 1.7 kPa (79.2 +/- 12.7 mmHg)), while CBFV (40.9 +/- 12.6 cm.s-1), Pa,CO2 (7.5 +/- 1.3 kPa (56.2 +/- 9.4 mmHg)) and [H+] (39.1 +/- 4.6 nM) showed a significant reduction compared to oxygen therapy (p < 0.01). We therefore conclude that in chronically hypercapnic long-term ventilated patients cerebral blood flow depends mainly on changes in Pa,CO2 and [H+], whilst oxygen does not seem to interfere with cerebral flow velocity. The reduction of Pa,CO2, due to mechanical ventilation, may determine cerebral blood vessel constriction, with possible impairment of cerebral functions.

Blood Flow Velocity↗

Assessment of right ventricular function in patients with congestive heart failure by echocardiographic automated boundary detection.

In patients with chronic heart failure, echocardiographic automated boundary detection (ABD) can reliably assess right ventricular function. The measurements obtained by ABD were highly reproducible, strongly correlated with radionuclide right ventricular ejection fraction, and superior to those obtained by conventional manual echocardiographic methods.

Electrocardiography↗

Effects of desipramine and alprazolam on forced swimming behaviour of adult rats exposed to prenatal diazepam.

Pregnant rats were treated with a single daily s.c. injection of diazepam (2 mg/kg) over gestation days 14-20. This treatment led to a reduction in GABA receptor complex function since adult male offspring showed a strong decrease in electrographic hippocampal responses to alprazolam and a strongly increased response to picrotoxin after intra-locus coeruleus injection of the two compounds. No difference in immobility time in the forced swimming test and in spontaneous motor activity was observed between prenatally vehicle- and diazepam-exposed offspring. Conversely, prenatal exposure to diazepam potentiated the anti-immobility effect of subchronic desipramine (10 mg/kg i.p.) and made active a dose of desipramine (5 mg/kg i.p.) that was ineffective in prenatally vehicle-exposed rats. This effect was observed only in pretested rats. Prenatal exposure to diazepam blocked the anti-immobility effect of subchronic alprazolam (15 mg/kg i.p.) in both non-pretested and pretested rats. Spontaneous motor activity was strongly reduced in all groups. These findings suggest that a persistent reduction in GABA receptor complex function, induced by prenatal exposure to diazepam, does not alter the mobility of adult progeny in the forced swimming test, but it may have consequences when drugs acting on the GABA receptor complex are used.

Alprazolam↗

Assessment of myocardial viability after thallium-201 reinjection or rest-redistribution imaging: a multicenter study. The Italian Group of Nuclear Cardiology.

UNLABELLED: To establish the real nature of 201Tl defects in the assessment of myocardial viability (e.g., fixed versus reversible), 201Tl reinjection was evaluated in a multicenter trial involving 402 consecutive patients with ischemic heart disease and exercise 201Tl defects. METHODS: Twelve hospitals, using the same type of gamma camera and computer software, adopted one of the two most widely used reinjection protocols. In 230 patients (Group A), reinjection was performed immediately after stress-redistribution planar imaging; in 172 patients (Group B), reinjection was performed on a separate day and followed by rest-redistribution imaging. The images were interpreted by three blinded observers in a core laboratory on a five-point qualitative scale; the reproducibility in visual scoring was excellent. RESULTS: Groups A and B had a similar prevalence of myocardial segments with abnormal uptake at stress (39%, 40%), as well as with reversible (16%, 17%), partially reversible (21%, 19%) and irreversible (63%, 64%) defects at redistribution. After reinjection, 201Tl uptake improved in 27% and 36% of both partially reversible and irreversible defects in Groups A and B. No differences were found when comparing early and delayed reinjection imaging in Group B. CONCLUSION: This study confirms the validity of 201Tl reinjection in a large, unselected population, but the discordance with stress/redistribution is less than has been previously reported for both 201Tl reinjection protocols, the prevalence of improved segments after reinjection was higher with the separate day approach.

Exercise Test↗

[Use of ultrasonography methods in the diagnosis of neurogenic paraosteoarthropathy in spinal cord injury].

To assess the role of the ultrasonic imaging evaluation of articular lesions suspected to be the initial presentation of heterotopic ossifications (HO), 59 consecutive injured patients were studied. 32 out of 59 patients showed clinical signs of local inflammation in one of the articular sites of the upper or lower limbs, sonographic scans proved to be diagnostic of HO in 7 out of those 32 patients before their radiographic findings. Serial sonographic examinations were performed utilizing a 7.5 MegaHertz transducer probe for 2 months. The imaging abnormalities were correlated with biochemical levels of serum alkaline phosphatase, modifications of radiographic features and bone 99nTC scintigraphy. Scintigraphy revealed to have a high sensitivity but a low specificity for the diagnosis of HO. Also the serum levels of alkaline phosphatase were not a sensitive indicator of early HO in our group of patients. Moreover serial sonographic scans confidently excluded the HO in the 25 patients with no initial signs of the disease without any false negative results. Thus, early sonographic assessment of patients, with spinal cord injury in which local signs of inflammation suggest initial HO formation, revealed to be superior to the other utilized technique for the diagnosis of HO and may be considered a valuable alternative in particular to evaluate the evolutive pattern of this disease.

Adolescent↗

NMDA-GABA interactions in an animal model of behaviour: a gating mechanism from motivation toward psychotic-like symptoms.

We studied the effects of desipramine, alprazolam, muscimol and dizocilpine (MK-801) (alone or associated with desipramine) in the forced swimming test in rats after long-lasting termination of chronic exposure to vehicle and pentylenetetrazol. Sensitisation with pentylenetetrazol was ineffective in changing immobility time in the forced swimming test compared to vehicle treatment; pentylenetetrazol enhanced the anti-immobility effect of desipramine, abolished the anti-immobility effect of alprazolam and did not affect the anti-immobility effect of muscimol. MK-801 at the dose that did not modify immobility time in vehicle-treated rats and in pentylenetetrazol-treated animals strongly potentiated the anti-immobility effect of desipramine in pentylenetetrazol-treated rats. MK-801 in association with desipramine induced a marked hyperlocomotion and hyperexcitability, with swaying movements and oral stereotypies in pentylenetetrazol-sensitised rats. Results are considered the experimental representation of a 'gating mechanism' toward psychotic-like symptoms.

Alprazolam↗

Cortical kidney scan evaluation in the follow-up of children with vesico-ureteric reflux.

We present the results obtained in the follow-up of 66 children with vesico-ureteric reflux (VUR) of different grades (111 refluxing renal units, RU; the VUR being bilateral in 47 children), employing the renal cortical agent 99mTc-aprotinin (TcA). Together with the visual inspection of the scan, we adopted a quantitative approach, expressing the results as the split percent uptake of the injected dose. The detection of morphological anomalies was more frequent in the cases of more severe reflux. Scars were noted in 38 RU, with a higher prevalence in more severe grades, except for grade V where severe impairment was more frequent. With regard to the amount of functioning parenchyma, the probability of a significant loss of nephrons (expressed by a low uptake of TcA), rose with the grades, although the higher grades were not invariably associated with parenchymal failure. The abnormality detection rate is higher by about 2:1 with the TcA scan than with other diagnostic modalities such as i.v. pyelography or echography. No differences were found between RU with or without scars as regards evolution over time; only when the TcA uptake at presentation was lower than 10% was the normal development of the RU likely to be hindered. From these data it can be concluded that early diagnosis is the key factor in the management of these children with VUR; the morpho-functional assessment with TcA uptake is probably the most effective technique for the detection of parenchymal abnormalities. In addition, the test has a high prognostic value, an uptake lower than 10% indicating an unfavourable prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗

A multicenter trial on interobserver and intraobserver reproducibility of segmental scoring of thallium-201 planar myocardial imaging before and after reinjection. Italian Group of Nuclear Cardiology.

UNLABELLED: Inter- and intraobserver reproducibility (R) of segmental 201Tl scores after stress (ST), redistribution (RD) and reinjection (RI) planar imaging were evaluated. METHODS: Images were examined from 396 patients with suspected coronary artery disease, demonstrated by means of post-ST imaging of at least one perfusion defect. To eliminate external sources of variability, the same gamma camera, acquisition protocol and computer software were used in this multicenter study. Thallium-201 images of the anterior, left anterior oblique and left lateral projections were obtained immediately, 4 hr after exercise and 30 min after the injection of additional 201Tl either on the same day or on a different day. The left ventricle was divided into 15 segments and evaluated by three independent observers, blinded to clinical data, according to a five-point scale. RESULTS: The R score for ST, RD and RI images, expressed as an intraclass correlation coefficient, was 0.76, 0.74 and 0.72, respectively. After averaging multiple observer scores, R increased to 0.91, 0.90 and 0.89, respectively. Individual observer measurement of the R score was 0.48, 0.51 and 0.32 for ST-RD, ST-RI and RD-RI image pairs, respectively, and multiple observer scores showed R increases to 0.74, 0.76 and 0.58. CONCLUSION: This qualitative scale reliably assesses the severity of 201Tl perfusion defects, particularly when multiple-observer scores are averaged. Individual observer change scores should be taken with great caution, especially in studies involving the visual evaluation of RD-RI image changes.

Coronary Disease↗

Exercise thallium scintigraphy versus high-dose dipyridamole echocardiography testing for detection of asymptomatic restenosis in patients with positive exercise tests after coronary angioplasty.

The usefulness of high-dose (< or = 0.84 mg/kg over 10 minutes) dipyridamole echocardiography testing was compared with that of exercise thallium-201 scintigraphy in detecting restenosis (> 70% lumen reduction) in 50 asymptomatic patients with ST-segment depression during maximal exercise testing 3 months after successful coronary angioplasty. Dipyridamole echocardiography testing and exercise thallium scintigraphy showed a similar sensitivity (75 vs 83%; p = NS) and specificity (90 vs 84%; p = NS) for the detection of restenoses, which occurred in 12 patients. It is concluded that dipyridamole echocardiography testing is as accurate as exercise thallium testing for the noninvasive detection of severe restenosis in patients with exercise-induced asymptomatic ST-segment depression after successful angioplasty. Furthermore, the site, extent and severity of the thallium perfusion defects during exercise are correlated to those of the dyssynergy during dipyridamole echocardiography.

Angioplasty, Balloon, Coronary↗

Effects of desipramine and alprazolam in the forced swim test in rats after long-lasting termination of chronic exposure to picrotoxin and pentylenetetrazol.

Rats were treated for 5 weeks with three subconvulsant doses of picrotoxin (PTX) and pentylenetetrazol (PTZ) per week to induce a persistent reduction of the GABAA receptor function which results in chemical kindling. Fifteen days after termination of this treatment schedule, the effect of desipramine (DMI) and alprazolam (ALP) on immobility time in the forced swim test (FST) was evaluated. Chronic PTX and PTZ did not alter the immobility time. Acute PTX and PTZ reduced the immobility of rats chronically treated with vehicle but not of those exposed chronically to PTX and PTZ. Chronic PTX did not influence the anti-immobility effect of DMI, but blocked that of ALP. Chronic PTZ markedly potentiated the anti-immobility effect of DMI but blocked that of ALP. Concomitant administration of chlordiazepoxide prevented the effects of chronic PTX and PTZ. These findings suggest that a long-lasting reduction in GABAA receptor function, unlike acute reduction, does not play an important role in the mobility of rats in the FST and in the anti-immobility effect of DMI while it blocks that of ALP.

Alprazolam↗

Antidepressant and anxiolytic effects of alprazolam versus the conventional antidepressant desipramine and the anxiolytic diazepam in the forced swim test in rats.

The antidepressant and anxiolytic effects of alprazolam were compared to those of desipramine, diazepam and buspirone in the forced swim test. Subchronic alprazolam induced a reduction in immobility similar to that of desipramine in 'non-pretested' and 'pretested' rats. In 'non-pretested' rats, the anti-immobility effect of desipramine was potentiated by diazepam and alprazolam, given before subchronic desipramine, while the anti-immobility effect of subchronic alprazolam was counteracted by diazepam. Diazepam, administered before the pretest session, counteracted, 24 h later, the anti-immobility effect of subchronic desipramine and alprazolam; alprazolam counteracted the anti-immobility effect of alprazolam but not of desipramine, buspirone at the highest doses tested potentiated the anti-immobility effect of subchronic desipramine but not of alprazolam. These data provide further support for the hypothesis that the GABA/benzodiazepine/Cl complex is directly implicated in the action of antidepressants and that systems other than the GABA system are involved in the antidepressant and anxiolytic effects of alprazolam.

Alprazolam↗

Interaction between naloxone, chlordiazepoxide and valproic acid evaluated by emotional operant behaviour in the rat.

The effects of chlordiazepoxide (CDP, 5 mg/kg i.p.), the sodium salt of valproic acid (VPA, 200 mg/kg i.p.) and naloxone (Nx, 1 mg/kg s.c.) alone and CDP-Nx, VPA-Nx association on schedule controlled behaviour with signalled unpunished and punished periods, were investigated. Our results show that CDP and VPA under both the unemotional (variable ratio reinforcement schedule 20%) and the emotional (continuous reinforced schedule associated with electric shock) components significantly increase responding in the Skinner box. Nx, on the multiple schedule, non-significantly reduces responding under both components. With CDP-Nx association the increase in responding under the unemotional component is less than in the case of the benzodiazepine alone, while under the emotional component the increase in responding is not appreciably affected. With the VPA-Nx association the responding rate is lower than that of the control under the unemotional component while under the emotional component the increase in responding is reduced compared to the VPA alone. The higher rates of unemotional and emotional responding with both CDP and VPA depend on the dipsogenic and disinhibiting effects by both drugs. The different rate of emotional and unemotional responding with CDP-Nx and VPA-Nx associations indicates a specific influence on GABAergic and other systems by CDP and VPA.

Animals↗