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Biomedical subjects

G Roncari

Publications and source records attributed to G Roncari.

At least 19 recordsLinked to original sources
PubMed1997

Relationship between left ventricular diastolic function and atrial natriuretic factor in never-treated mild hypertensives.

Using digitized M-mode echocardiograms, we evaluated the relationship between plasma atrial natriuretic factor (ANF) and morphofunctional characteristics of the left ventricle (LV) in 24 mild hypertensive men, never treated, with normal renal function. For each subject we collected a blood sample for plasma ANF evaluation and, immediately after, we recorded the LV echocardiogram. All the patients had normal LV diastolic diameter and systolic function; LV hypertrophy was present in 10 patients, 7 of whom had left atrial enlargement, and 13 patients had impaired LV diastolic function. ANF was similar between patients with and without LV hypertrophy, as well as between patients with and without left atrial enlargement, whereas ANF was significantly (P < .01) higher in patients with LV diastolic dysfunction than in patients with normal diastolic function. ANF was inversely correlated with both indices of diastolic function (peak lengthening rate and peak wall thinning rate), whereas it did not correlate with blood pressure, heart rate, end-systolic wall stress, and other LV parameters. In conclusion, from our results, ANF level in never-treated mild hypertensives is related neither to the degree of LV hypertrophy nor to the afterload, expressed as blood pressure or end-systolic wall stress, whereas it is mainly influenced by LV diastolic function: the diastolic impairment induces an increase in ANF level, probably through an increased atrial stretch.

Adult↗
PubMed1997

Integrated pharmacokinetics and pharmacodynamics of Ro 48-6791, a new benzodiazepine, in comparison with midazolam during first administration to healthy male subjects.

AIMS: This study was performed to investigate the pharmacokinetics and pharmacodynamics of ascending doses of Ro 48-6791, compared with midazolam, in healthy subjects during first administration to man studies. METHODS: The study was double-blind and five-way crossover with treatment on 5 consecutive days (three ascending doses, placebo, fixed midazolam dose) in two sequential groups of five healthy male subjects. Ro 48-6791 was administered as a slow i.v. infusion in doses of 0.1-0.3-1 mg in the first group, and 1-2-3 mg in the second. Midazolam was infused at 0.1 mg kg(-1). The infusions were stopped after 20 min or if sedation became too strong for proper performance of the tests. Consequently, infusion rates (mg min(-1)) differed considerably among doses. Blood samples were collected frequently for pharmacokinetic determinations (two-compartment model). Pharmacodynamics were assessed by recording of saccadic eye movements (saccadic peak velocity) and electroencephalography (beta-power). These parameters were used for pharmacokinetic/pharmacodynamic modelling. RESULTS: Ro 48-6791 and midazolam were both well tolerated. Most clinical events were dose-dependent central depressant effects. The volume of distribution (V(SS)) and plasma clearance of Ro 48-6791 were on average markedly larger than those of midazolam (171 +/- 65 vs 41 +/- 10 l and 2.2 +/- 0.9 vs 0.42 +/- 0.11 l min(-1), respectively). The doses of Ro 48-6791 leading to loss of saccadic eye movements were on average four times lower than that of midazolam. The corresponding predicted effect compartment concentrations differed by a factor of about six. Doses of Ro 48-6791 and midazolam eliciting similar maximum effects had a comparable onset and duration of action for saccadic peak velocity. Midazolam caused a significantly larger (33%, range 17, 55%) increase in beta-power than Ro 48-6791 at the highest administered dose. Ro 48-6792, a metabolite of Ro 48-6791, showed a considerably longer half-life than the parent compound. Although there were no indications of a discernable effect of Ro 48-6792 in the present study, the effects of possible accumulation during prolonged administration should be investigated further. CONCLUSIONS: This first study with Ro 48-6791 in humans has shown that this benzodiazepine is approximately four to six times as potent as midazolam, but has a comparable onset and duration of action.

Adjuvants, Anesthesia↗
PubMed1997

Integrated pharmacokinetics and pharmacodynamics of Ro 48-8684, a new benzodiazepine, in comparison with midazolam during first administration to healthy male subjects.

AIMS: This study aimed to investigate the pharmacodynamics and pharmacokinetics of ascending doses of Ro 48-8684, compared with midazolam, in healthy subjects during first administration to man. METHODS: The study was double-blind and five-way crossover (three ascending doses, placebo, fixed midazolam dose), performed in two groups of five males. Ro 48-8684 was infused in doses of 0.1-0.3-1 mg in the first group, and 1-3-10 mg in the second, with different infusion rates (expressed as mg min(-1)) among doses. Midazolam was infused at 0.1 mg(-1) kg. Infusions were stopped after 20 min or if sedation became too strong for proper performance of saccadic eye movements. Pharmacokinetics and pharmacodynamics and their relationships were evaluated as described in the companion article. RESULTS: Ro 48-8684 caused dose-dependent sedation. No serious adverse events occurred. The volume of distribution and clearance of Ro 48-8684 were larger than of midazolam (337+/-114 vs 50+/-121 and 2.4+/-0.5 vs 0.47+/-0.11 l min(-1), resp). The recovery of saccadic eye movements from equal levels of sedation was on average almost half an hour faster for Ro 48-8684 than for midazolam, with considerable interindividual differences (range 2, 55 min). The doses of Ro 48-8684 leading to the same clinical endpoint as midazolam were comparable, but the corresponding predicted effect compartment concentrations of Ro 48-8684 were on average 2.6 times lower (range 1.5, 4.9 times). The slope of the linear concentration-effect-relationship for saccadic peak velocity was on average 2.2 times steeper for 10 mg Ro 48-8684 than for midazolam (range 1.3, 3.3). The slope decreased on average 4.4-fold (range 1.6, 7.3 times), with doses of Ro 48-8684 increasing from 1 to 10 mg. The metabolite Ro 61-2466 had a longer half-life than the parent compound Ro 48-8684. The influence of this metabolite during prolonged administration should be further investigated. CONCLUSIONS: These results show that Ro 48-8684 has a considerably shorter duration of action than midazolam. There may be a reduction of sensitivity to Ro 48-8684 with repeated administration of rising doses due to as yet undetermined factors.

Adult↗
PubMed1997

Semi-quantitative assessment of 99Tcm-sestamibi uptake in lung cancer: relationship with clinical response to chemotherapy.

The objectives of this study were to measure semi-quantitatively uptake of 99Tcm-sestamibi (99Tcm-MIBI) by tumour tissue in patients with lung cancer and to investigate its relationship with clinical response to chemotherapy. 99Tcm-MIBI single photon emission tomography was performed at the time of diagnosis in 31 patients with biopsy-proven lung cancer (19 small cell carcinomas, 12 non-small cell carcinomas), all of whom were undergoing chemotherapy. Fifteen patients were also investigated 2 weeks after the first and third cycles of chemotherapy. To quantify 99Tcm-MIBI uptake, a tumour/lung (T/L) ratio was calculated for the tomographic slices. The response to chemotherapy was rated as complete remission, partial remission or no remission using dimensional criteria. The results were expressed as the median and inter-quartile range; non-parametric statistical analyses were used. Forty one neoplastic localizations (31 primary tumours and 10 hilar or mediastinal lymph node masses) were assessed. The median T/L ratio of the primary tumours was 1.85 (range 1.7-2.4). Patients with a different response to chemotherapy had a significantly different median T/L ratio before chemotherapy: complete remission (n = 8), T/L ratio = 2.95 (range 2.20-3.25); partial remission (n = 10), 2.15 (range 1.77-2.40); no remission (n = 13), 1.70 (range 1.47-1.75) (Kruskal-Wallis, P < 0.0001). A T/L ratio of 1.80 gave sensitivity of 83%, specificity of 85% and accuracy of 84% in the prediction of the response to chemotherapy. The patients with small cell carcinomas demonstrated greater 99Tcm-MIBI uptake than those with non-small cell carcinomas: T/L ratio, median 2.30 (range 1.76-3.00) vs 1.70 (range 1.50-1.78) (Mann-Whitney U-test, P = 0.001). No significant difference in 99Tcm-MIBI uptake was observed between the 10 lymph node metastases and the corresponding primary tumours: T/L ratio, median 2.30 (range 1.75-2.50) vs 2.15 (1.77-3.00) (Wilcoxon's paired samples rank test, N.S.). Of the 15 patients who were monitored with scintigraphy during chemotherapy, 10 showed complete or partial remission and a parallel reduction in their T/L ratio. The other five patients showed no response to chemotherapy and their T/L ratio was either unaffected or increased. We conclude that the semi-quantitative assessment of 99Tcm-MIBI uptake may have a significant role to play in the management of lung cancer, providing an effective means of predicting the efficacy of chemotherapy and of selecting subgroups of patients requiring radiotherapy or combined protocols before the start of treatment. 99Tcm-MIBI imaging may also be of use in monitoring clinical response to chemotherapy.

Aged↗
PubMed1997

Atrial natriuretic peptide and 24 h blood pressure.

BACKGROUND: Atrial natriuretic peptide (ANP) is a hormone involved in the cardiovascular modulation of blood pressure and volume homeostasis. OBJECTIVE: To compare ANP levels in normotensives and hypertensives and to correlate ANP levels with ambulatory blood pressure parameters. METHODS: Plasma samples for ANP determination (using a double-antibody radioimmunoassay Kit) were obtained from 33 consecutive subjects (24 hypertensives, nine normotensives) who had rested supine for 30 min. Afterwards, all of the subjects were subjected to 24 h non-invasive blood pressure monitoring. We found no significant difference between the two groups with regard to ANP levels (95.1+/-29 versus 96.9+/-33 pg/ml, in normotensives and hypertensives, respectively). Also, when hypertensive patients were divided according to their family history of hypertension, ANP levels were similar. There was no correlation between the ANP level and the pre-sampling blood pressure or between the ANP level and the following ambulatory blood pressure monitoring parameters: 24 h, diurnal and nocturnal systolic and diastolic blood pressures, systolic and diastolic loads, nocturnal blood pressure reduction and blood pressure variation coefficients. CONCLUSION: Both the pre-sampling blood pressure and ambulatory monitoring results (sustained blood pressures and pressure variations during the 24 h period) do not seem to influence basal ANP levels in patients with hypertension. These data do not account for a role of this peptide in cardiovascular control, in hypertension.

Journal Article↗
PubMed1996

Assessment of myocardial area at risk by technetium-99m sestamibi during coronary artery occlusion: comparison between three tomographic methods of quantification.

The aim of this study was to directly compare three currently used quantitative methods of analysis of technetium-99m sestamibi images in patients with selective balloon-induced transmural ischaemia. The area at risk (AR) was assessed in 19 patients undergoing single-vessel percutaneous transluminal coronary angioplasty by injecting the 99mTc-sestamibi at the time of coronary artery occlusion during balloon inflation. After imaging, the patients were classified according to localization of the perfusion defect as having anteroseptal (group I, 11 patients) or posterolateral defects (group II, eight patients). The planimetric technique based on polar maps, proposed by Verani et al. (J Am Coll Cardiol, 1988) (method A), the method described by Tamaki et al. (Circulation, 1982) (method B) and the technique validated by O Connor et al. (Eur J Nucl Med, 1990) (method C) were tested. Three threshold values of 45%, 50% and 60% of the maximum left ventricular count were used to define the limits of the perfusion defect. The mean values of the AR calculated by the three techniques with the original cut-off level (method A=16.5%+/-12.9; method B=10.4%+/-7.6%; method C=29.6%+/-15.7%) were statistically different (one-way analysis of variance: P<0.001; paired t test: method A vs B, P=0.003; method B vs C and method A vs C, P<0.0001). There was no significant difference between the mean values of the AR estimated by the three methods using the same cut-off levels. The use of 60% of the maximum left ventricular count provided the best correlation between the techniques (method A vs B, r=0.95; method B vs C, r=0.92; method A vs C, r=0.95). Nevertheless, a difference >10% between the values of AR assessed by the three methods was found in four subjects. There was no significant difference between the three methods in the evaluation of AR in the subjects of group I and group II. Reproducibility was good for all methods. It is concluded that the three methods of analysis of the AR by 99mTc-sestamibi SPET imaging showed comparable performance and good reproducibility using the same cut-off level. The location of perfusion defect does not affect the comparability of the three techniques. We suggest the use of a cut-off level of 60% for all three methods in the assessment of the AR by 99mTc-sestamibi SPET imaging.

Angioplasty, Balloon, Coronary↗
PubMed1996

Pharmacokinetic and pharmacodynamic interactions of bretazenil and diazepam with alcohol.

1. Interaction between alcohol and bretazenil (a benzodiazepine partial agonist in animals) was studied with diazepam as a comparator in a randomized, double-blind, placebo controlled six-way cross over experiment in 12 healthy volunteers, aged 19-26 years. 2. Bretazenil (0.5 mg), diazepam (10 mg) and matching placebos were given as single oral doses after intravenous infusion of alcohol to a steady target-blood concentration of 0.5 g l-1 or a control infusion of 5% w/v glucose at 1 week intervals. 3. CNS effects were evaluated between 0 and 3.5 h after drug administration by smooth pursuit and saccadic eye movements, adaptive tracking, body sway, digit symbol substitution test and visual analogue scales. 4. Compared with placebo all treatments caused significant decrements in performance. Overall, the following sequence was found for the magnitude of treatment effects: bretazenil+alcohol > diazepam+alcohol > or = bretazenil > diazepam > alcohol > placebo. 5. There were no consistent indications for synergistic, supra-additive pharmacodynamic interactions between alcohol and bretazenil or diazepam. 6. Bretazenil with or without alcohol, and diazepam+alcohol had marked effects. Because subjects were often too sedated to perform the adaptive tracking test and the eye movement tests adequately, ceiling effects may have affected the outcome of these tests. 7. No significant pharmacokinetic interactions were found. 8. Contrary to the results in animals, there were no indications for a dissociation of the sedative and anxiolytic effects of bretazenil in man.

Administration, Oral↗
PubMed1995

Pharmacokinetics and pharmacodynamics of Ro 41-3696, a novel nonbenzodiazepine hypnotic.

This report describes the first evaluation in humans of Ro 41-3696. Based on its preclinical profile, Ro 41-3696, a nonbenzodiazepine partial agonist at the benzodiazepine receptor, offers promising perspectives as an innovative hypnotic drug in that it does not exhibit most of the disadvantages associated with full agonists. Single oral doses of 0.1, 0.3, 1.0, 3.0, 10, and 30 mg were administered sequentially to six groups of six healthy male volunteers in a placebo-controlled, double-blind design. Tolerability was assessed and pharmacokinetic and pharmacodynamic measurements were conducted during a period of 28 hours after drug intake. Ro 41-3696 was well tolerated at all doses, causing no clinically relevant changes in vital signs or laboratory parameters. At doses of 10 and 30 mg there were signs of unsteady gait, indicating a central nervous system depressant effect. Pharmacokinetic analyses revealed that Ro 41-3696 was absorbed and eliminated rapidly (tmax = approximately 1 hour; t1/2 = approximately 4 hours). At all times plasma levels of Ro 41-3290, the desethylated derivative of Ro 41-3696, were higher than those of the parent drug (tmax and t1/2 values = approximately 2 and 8 hours, respectively). Area under the curve (AUC) data indicated dose-proportional pharmacokinetics for both Ro 41-3696 and Ro 41-3290. Performance in both a tracking and a memory search test was significantly affected by doses of 10 and 30 mg, and long-term memory, as assessed by a word learning and recall test, was slightly impaired at these doses. The results of this study support the initiation of therapeutic efficacy studies with Ro 41-3696 in doses up to approximately 5 mg and further exploration of the characteristics of Ro 41-3290.

Administration, Oral↗
PubMed1995

Myocardial uptake of indium-111 antimyosin after coronary angioplasty. Relationship with the total burden of ischaemia.

Indium-111 antimyosin scintigraphy was performed in 24 consecutive patients after percutaneous transluminal coronary angioplasty to assess whether repeated periods of ischaemia during balloon inflation results in myocardial cell damage even after a successful procedure. Patients with unstable angina, prior myocardial infarction and whose procedure was complicated were excluded. Indium-111 monoclonal antimyosin antibodies (80 MBq) were injected 24 h after coronary angioplasty and planar images were collected 24 h later. The relative antimyosin uptake was assessed subjectively and by a heart/lung count density ratio. In addition, the intracardiac gradient of activity was assessed by a count density profile analysis of the cardiac region of interest to distinguish better the focal as opposed to the diffuse antimyosin uptake. The antimyosin uptake index was calculated by multiplying the heart/lung ratio to the intracardiac gradient of activity. After coronary angioplasty, nine patients had minor ST-T wave changes on the surface ECG, but no patient demonstrated a new Q wave. Only three patients showed a mild rise in cardiac enzyme (CK-MB) serum levels. Indium-111 antimyosin uptake (heart/lung > 1.55) was present in eight patients (33%) and was intense (heart/lung > 1.9) in five (21%). Antimyosin uptake was always seen in myocardial segments corresponding to the treated coronary artery. Patients with a positive antimyosin scan had a longer duration of balloon-induced ischaemia compared with patients with no evidence of antimyosin uptake (541 +/- 211 vs 331 +/- 137 s, P < 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Nuclear medicine imaging in a case of hyperfunctioning parathyroid carcinoma associated with a parathyroid adenoma.

This report describes a rare case of parathyroid carcinoma associated with an adenoma. Nuclear imaging provided the most specific information about localization of the primary carcinoma and cervical metastasis, but failed to demonstrate evidence of a parathyroid adenoma. This could be explained by a partial inhibition of hormonal biosynthesis due to the high level of circulating parathormone produced by the carcinoma.

Adenoma↗
PubMed1995

Effective radiation dose to the patient and to the general population from nuclear medicine procedures: variations in the last twenty-year period.

We have evaluated how changes in nuclear medicine (NM) techniques over the last twenty-year period have modified radiation exposure to the patient and population. For this purpose, we estimated the variations in the mean effective dose to the patient, and both the collective and the per capita effective dose to the population of the province of Varese, derived from radioisotope examinations carried out in the four NM Centers of this province in the years 1972, 1981, and 1991. Dosimetric calculations were based on ICRP Publication 53 for most of the radiopharmaceuticals used, and tissue weighting factors were based on ICRP Publication 60. The total number of NM exams carried out was 19,744 in 1972, 31,973 in 1981, and 23,623 in 1991. Between 1972 and 1991 there has been a substantial decrease in the effective irradiation to the patient and to the general population (mean effective dose to the patient: from 21.2 to 6 mSv; per capita mean effective dose: from 0.58 to 0.18 mSv), and in the per capita equivalent dose to some target organs, such as the thyroid (9.6-->1.5 mSv) and liver (0.51-->0.07 mSv). At the same time, there has been a significant increase in the per capita equivalent dose to the bladder (0.05-->0.48 mSv), skeleton (0.08-->0.36 mSv), and testes (0.02-->0.15 mSv), and a less marked increase to the ovaries (0.03-->0.06 mSv). The per capita equivalent dose to red marrow (0.13-->0.1 mSv) and to the large intestine (0.1-->0.12 mSv) did not change significantly.

Adolescent↗
PubMed1995

Tissue polypeptide specific antigen (tps) and cytokeratin 19 fragment (CYFRA 21.1) immunoradiometric assay in non small cell lung cancer evaluation.

The aim of our work was the evaluation of the immunoradiometric assay (IRMA) of two cytokeratinic markers, TPS and CYFRA 21.1, in clinical setting on non small cell lung cancer (NSCLC). Serum samples were obtained from 148 untreated NSCLC patients, 60 patients with non malignant lung diseases and 100 healthy subjects: TPS and CYFRA 21.1 serum levels were assayed by IRMA methods. Diagnostic performance of the markers was evaluated and the TPS and CYFRA 21.1 distribution analysed according to some different clinical and biological variables as histological subtypes, stage and survival time by using the Mann-Whitney "U"-test. Sensitivity, specificity and accuracy were 0.54 (80/148), 0.47 (28/60), 0.52 (108/208) and 0.73 (108/148), 0.74 (44/60), and 0.73 (152/208) for TPS and CYFRA 21.1 respectively. CYFRA 21.1 demonstrate a higher sensitivity than TPS in all stages of the disease and in the spinocellular and adenocarcinoma histological subtypes while TPS sensibility is higher in large cell carcinoma. The CYFRA 21.1 specificity is better than TPS probably by reason of its preferential distribution in respiratory epithelium. Both markers serum levels differ significantly between Stage I-II and IV and between Stage I-II-IIIa and IIIb-IV but neither TPS nor CYFRA 21.1 can discriminate Stage IIIa from IIIb. No significant differences were found in the serum expression of the markers by the different histological subtypes. A value of both markers less than the selected cut-off is related to a longer survival of the patients apart from therapy (p < 0.05). Our conclusion supports similar behaviour of these markers in NSCLC and indicates CYFRA 21.1 as the more needed biochemical index to evaluate NSCLC patients.

Adult↗
PubMed1993

Flumazenil kinetics in the elderly.

In an open design, randomised, two-way cross-over study, a single 2 mg i.v. dose and a single 30 mg oral dose of flumazenil were each administered to a group of healthy young (n = 6) and elderly (n = 12) volunteers (male: female 2/1). Plasma samples were collected at intervals and intact drug was assayed. Both the i.v. and oral doses of flumazenil were very well tolerated by both age groups and no severe or unexpected adverse effects were observed. The main complaints were dizziness and headache, mainly after oral dosing, probably due to the higher Cmax and AUC following this route of administration. After 2 mg i.v. the disposition parameters in the two age groups (elderly/young) were very similar: volume of distribution (Vss): 0.88/0.90 l.kg-1; total body clearance (ClPL): 0.86/0.99 l.min-1; terminal elimination half-life (t1/2 beta): 1.02/0.91 h. After the 30 mg oral dose the mean Cmax of 87.6 ng.ml-1 (elderly) and 78.4 ng.ml-1 (young) were generally reached within 0.5 to 1 h. In 26% (elderly) and 23% (young), the absolute bioavailability of flumazenil was very similar. It is concluded that the absorption and disposition parameters of flumazenil were not significantly affected by aging.

Administration, Oral↗
PubMed1993

Performance evaluation of a hand-held gamma detector probe used for radioimmunoguided surgery.

The success of radioimmunoguided surgery (RIGS) is dependent on the performance parameters of the apparatus, its correct handling, and the employment of a suitable radioactive compound. In the present study the authors examined the performance of the Neoprobe 1000 device with respect to the radioisotope 99mTc. Detecting efficiency was evaluated experimentally using a phantom containing a radioactive point source which could be moved both vertically and horizontally with respect to the central axis of the probe. In this way curves representing the variations in efficiency as a function of the vertical and horizontal distances of the source from the probe were constructed. Furthermore, values of minimum detectable activity as a function of source depth, counting time and background radioactivity were calculated. These results were compared to those previously obtained using 125I, the radioisotope most frequently employed in RIGS. The graphs and tables included could serve as a practical aid to help the operator obtain the best possible measuring conditions, thereby maximizing his/her results.

Humans↗
PubMed1992

Percutaneous absorption of amorolfine following a single topical application of an amorolfine cream formulation.

In an open-label, parallel-group, randomized study percutaneous absorption of 14C-labelled amorolfine incorporated into a cream formulation was assessed in healthy male volunteers (n = 12). A single dose of 0.5 g of the 0.25% cream formulation was applied to 100 cm2 of intact (n = 6) and stripped (n = 6) skin for 24 h using occlusive dressing. The remaining drug was removed and the treated skin area of both groups was stripped with adhesive tape. Total urine and faeces were collected in portions up to 3 weeks after the experiment and blood samples were taken at intervals for 3 weeks. Radioactivity was measured in the skin strippings and in the urine, faeces and plasma samples. The intact drug was assessed in the plasma samples. Using mass balance techniques it could be shown that a mean of 92% (range: 84-101%) of the applied radioactivity could be recovered. Small differences in the absorption and elimination of the radioactivity were observed between the two groups but they were not statistically significant (alpha = 0.05). Therefore data from the two groups were pooled. Elimination of drug and drug-related material from the body was very slow. During the 3-week collection period, a mean of 7% (range: 3.8-10.2%) of the dose was excreted in urine and faeces. Another 0.9-3.3% of the dose was retained in the upper layers of the skin as shown by the skin strippings after treatment. Levels of radioactivity and of intact drug in plasma were below the detection limit of 0.5 ng-equiv./ml, respectively. Present data suggest that mean percutaneous absorption of amorolfine following topical application of the 0.25% cream formulation should not exceed 8-10% of the dose applied.

Administration, Cutaneous↗
PubMed1991

Vascular toxicity in dogs associated with overdoses of a novel benzodiazepine receptor partial agonist.

Necrotizing arteritis and periarteritis were found in Beagle and German Shepherd dogs treated for 13 or 52 weeks with the novel benzodiazepine receptor (BZR) partial agonist Ro 16-6028 (generic name bretazenil). Eight male and one female out of a total of 20 dogs treated with 40-60 mg/kg/day Ro 16-6028 developed the arteritis, predominantly in the heart or the epididymis. Two of these animals died prematurely following treatment at the initial dosing levels of 80 and 55 mg/kg/day; one of these two dogs was asymptomatic and in good general condition until death. Clinically, all but one of the dogs showed sedation, ataxia, stiff gait, body weight-loss and a deterioration of the general condition as well as changes of some laboratory parameters. No signs of arteritis and untoward clinical or laboratory findings were seen at lower doses. Possible aetiologies, as well as the mechanisms involved in arteritis in general and the genetic disposition of beagles in particular for this type of effect, are discussed. Reflections on the potential risk to man of this so far unknown finding after oral treatment with 1,4-benzodiazepines (BZs) are presented.

Animals↗
PubMed1990

[Comparison of the results obtained using 99mTc HM-PAO tomoscintigraphy and computer tomography in ischemic lesions of the brain].

Fifty patients suffering from cerebral ischemic attacks, transient or not, were studied with both 99mTc HM-PAO single photon emission computed tomography (SPECT) and computed tomography (CT). In 31 patients both SPECT and CT showed pathologic areas, the max diameters of which were measured on CT images and SPECT orbitomeatal reconstructed sections, and then compared. We observed that: only SPECT images are positive for pathologic conditions in transient ischemic attacks and in the very early phases of infarctions; in recent infarctions (less than 15 days earlier) both SPECT and CT scans are positive but SPECT lesion areas are greater than CT ones; pathologic areas, with clear-cut outlines, having the same dimensions on both CT and SPECT images, are supposed to result from old static infarctions. A persistent perilesional hypoactive area on SPECT images means, in our opinion, a hypoperfusional area liable to new vascular troubles; in which case, medical/surgical therapy seems necessary.

Adult↗