Diagnostic efficacy of SonoVue, a second generation contrast agent, in the assessment of extracranial carotid or peripheral arteries using colour and spectral Doppler ultrasound: a multicentre study.

The purpose of this study was to demonstrate the improvement in diagnostic quality and diagnostic accuracy of SonoVue microbubble contrast-enhanced ultrasound (CE-US) versus unenhanced ultrasound imaging during the investigation of extracranial carotid or peripheral arteries. 82 patients with suspected extracranial carotid or peripheral arterial disease received four SonoVue doses (0.3 ml, 0.6 ml, 1.2 ml and 2.4 ml) with Doppler ultrasound performed before and following each dose. Diagnostic quality of the CE-US examinations was evaluated off-site for duration of clinically useful contrast enhancement, artefact effects and percentage of examinations converted from non-diagnostic to diagnostic. Accuracy, sensitivity and specificity were assessed as agreement of CE-US diagnosis evaluated by an independent panel of experts with reference standard modality. The median duration of clinically useful signal enhancement significantly increased with increasing SonoVue doses (p< or =0.002). At the dose of 2.4 ml of SonoVue, diagnostic quality evaluated as number of inconclusive examinations significantly improved, falling from 40.7% at baseline down to 5.1%. Furthermore, SonoVue significantly (p<0.01) increased the accuracy, sensitivity and specificity of assessment of disease compared with baseline ultrasound. SonoVue increases the diagnostic quality of Doppler images and improves the accuracy of both spectral and colour Doppler examinations of extracranial carotid or peripheral arterial disease.

Multi-centre clinical study evaluating the efficacy of SonoVue (BR1), a new ultrasound contrast agent in Doppler investigation of focal hepatic lesions.

OBJECTIVES: SonoVue is a new ultrasound contrast agent, which consists of stabilised microbubbles of a sulphur hexafluoride gas. The aim of the study was to assess its efficacy in the Doppler investigation of focal hepatic lesions. MATERIALS AND METHODS: Seventy patients with focal liver tumours were studied. Four doses (0.3, 0.6, 1.2 and 2.4 ml) of SonoVue were administered intravenously with at least 10 min delay between each injection. A complete colour/power and spectral Doppler imaging investigation of the lesions was performed at baseline pre-dosing and after each SonoVue injection. All examinations were recorded on SVHS videotapes. Baseline and post contrast videotapes were reviewed by the on-site (un-blinded) investigators and by two off-site blinded readers (a) to grade the global quality of the Doppler scans of the focal lesions vascularity and the normal parenchymal vessels (b) to measure the duration of clinically useful Doppler signal enhancement and (c) to determine the diagnostic accuracy and performance of the enhanced versus unenhanced scans using histopathology, tumour markers, CT and/or MR as the reference standard. RESULTS: A statistically significant improvement was observed at all four SonoVue doses in the off site assessment of global quality of the Doppler examination of tumoral and normal parenchymal vessels in comparison with the baseline (P < 0.05). The median duration of clinically useful enhancement was significantly increased with increasing doses (P < 0.001), ranging between 1.4-2.2 min for the lowest dose and 3.2-3.8 min for the highest dose for the off-site readers. On-site assessment of diagnostic accuracy showed a significant increase in the specificity of the Doppler diagnoses (P < 0.0016) with an increase in the positive and negative predictive values and in the likelihood ratio in differentiating between benign and malignant lesions. Off-site evaluation showed a significant increase in the accuracy of enhanced Doppler diagnosis in comparison with the baseline performance. CONCLUSION: The results suggest that SonoVue is effective in improving the display of tumoral vascularisation and may be useful in the characterisation of focal liver lesions.

Developmental effects of modifiers of the vg mutant in Drosophila melanogaster.

An analysis of the modifiers affecting the expression of the vg gene was performed. We selected for weak and strong expression of the vg mutant in F2 segregating populations obtained by crossing a vestigial stock with an Oregon laboratory stock (O) and with a wild strain (B) captured near Bologna, Italy. The selection for enlarged wings was more effective in the vg B population where wild wings appeared from the 10th generation. The assay of the three major chromosomes showed that the modifiers are located on chromosomes 2 and 3. The mutant imaginal disc cell death phenotype is evident in vg/vg strains that have a wild-type wing phenotype. It is suggested that the selected modifiers do not prevent cell death but induce regenerative growth.

Pathologic study of the cervix after cold coagulation.

In 20 patients Semm cold coagulation was performed on the exocervix to determine the depth of tissue necrosis and destruction of glandular crypts. Cold coagulation at 120 degrees C for 30 seconds achieves a depth of destruction of at least 4 mm.

Lack of mutagenic activity of ademetionine in vitro and in vivo.

Studies on the mutagenic activity of ademetionine (S-adenosylmethionine) tested in vitro at concentrations of 2 mg/sample and in vivo at doses up to 1500 mg/kg always gave negative responses. Moreover, a patent lack of abnormal methylated bases in the liver DNA of ademetionine-treated rats suggests that, if abnormal methylation occurs by exogenously administered ademetionine, the amount of formed methylated residues must be quite lower than that removable by the transmethylase enzymes responsible for the in vivo repair.

Temperature-Related Divergence in Experimental Populations of DROSOPHILA MELANOGASTER. I. Genetic and Developmental Basis of Wing Size and Shape Variation.

The effects of environmental temperature on wing size and shape of Drosophila melanogaster were analyzed in populations derived from an Oregon laboratory strain kept at three temperatures (18 degrees , 25 degrees , 28 degrees ) for 4 yr. Temperature-directed selection was identified for both wing size and shape. The length of the four longitudinal veins, used as a test for wing size variations in the different populations, appears to be affected by both genetic and maternal influences. Vein expression appears to be dependent upon developmental pattern of the wing: veins belonging to the same compartment are coordinated in their expression and relative position, whereas veins belonging to different compartments are not. Both wing and cell areas show genetic divergence, particularly in the posterior compartment. Cell number seems to compensate for cell size variations. Such compensation is carried out both at the level of single organisms and at the level of population as a whole. The two compartments behave as individual units of selection.

Age-related modification of dopaminergic and beta-Adrenergic receptor system: restoration to normal activity by modifying membrane fluidity with S-adenosylmethionine.

Microviscosity of membranes prepared from striata and cortex of 3 or 30-month-old rats was measured by fluorescence polarization and electron spin resonance. The viscosity of the hydrophobic core of the lipid bilayer was significantly increased in striatal but not in cortical membranes of old rats. In old rats the incorporation of methyl groups into phosphatidylcholine was significantly lower than in young rats. beta-Adrenergic specific binding sites were reduced in striata, cortex and pineal gland of old rats. In the striata of these animals, [3H] spiperone specific binding sites and dopamine-stimulated adenylate cyclase were also low. A chronic treatment of old rats with S-adenosyl-L-methionine, the cofactor in phospholipid methylation, lowered microviscosity to normal values in striata but not in the cortex. In the same old rats, the beta-receptor in striata and pineal gland returned towards juvenile values; in the cortex, the modification was in the same direction but did not reach significance. Neither putative dopaminergic receptors nor the adenylate cyclase age-dependent decrease was modified by treatment with S-adenosyl-L-methionine.

S-adenosylmethionine protects against erythrocyte membrane alterations induced in rabbits by cholesterol-rich diet.

In the erythrocyte membranes of rabbits fed a cholesterol rich diet for two months the cholesterol/phospholipid ratio was twice higher than in controls. The same diet induced a significant decrease in membrane fluidity and acetylcholinesterase activity. Two daily administrations of 25 mg X kg-1 b.w.-1 of S-adenosylmethionine (SAMe) have shown to protect against membrane alterations induced by hypercholesterolemic regimen. This observation would suggest the use of SAMe in those pathological conditions like hyperlipoproteinemias and liver diseases where membrane alterations are reported.

Endometrial pathological changes after Fallopian ring tubal ligation.

Endometrial biopsy was used to study the luteal phase in patients with Fallopian ring (Yoon ring) tubal ligation. Luteal phase insufficiency was found in 9.3% of patients in the study group and in 3.4% of patients in the control group. THe differences are statistically not significant (p = 0.5). The patients with histological evidence of poor luteal phase after tubal ligation presented with oligomenorrhea and dysfunctional uterine bleeding. These results exclude the possibility of some interference with the utero-ovarian circulatory system caused by Fallopian rings.

PIP: A study of the luteal phase of patients with tubal sterilizations in which the Fallopian rings 2 incision technique was used was conducted to determine the extent of luteal phase insufficiency caused by the procedure. Corpus luteum activity of 32 patients who had tubal sterilizations for a period of 12-15 months and of 29 patients awaiting the procedure was studied using endometrial biopsy. Increased frequency of luteal phase insufficiency after tubal sterilization was not statistically present. The condition was found in 3 patients in the study group (9.3%) and 1 patient in the control group (3.4%). The patients with luteal phase insufficiency after tubal ligation presented with oligomenorrhea of dysfunctional uterine bleeding. The results do not support the hypothesis that Fallopian ring tubal ligation interferes with the utero-ovarian circulatory system as suggested by other research. To avoid disturbance of the corpus luteum or enhance the success of future reanastomosis, the use of Hulka clips or Yoon rings is advised.

Distribution of S-adenosyl-L-(methyl-14C)methionine in animals.

The distribution of i.v. injected S-adenosyl-L-(methyl-14C) methionine was studied in the whole body of mice and in the cat brain using an autoradiographic technique. The drug was concentrated, at shorter survival times, mainly in the blood stream and in highly vascularized organs. Low concentration of radioactivity was found at longer times in the central nervous system (CNS). The quantitative analysis by means of organ radioassay was carried out in rats and confirmed the autoradiographic data.

[Anti-inflammatory and analgesic action of S-adenosyl-L-methionine (SAMe) in experimental tests on laboratory animals]. / Azione antiflogistica e analgesica della S-adenosil-L-metionina (SAMe) in prove sperimentali su animali da laboratorio

S-adenosyl-L-methionine (SAMe) always plays an important role in the metabolism of catecholamines. Since the importance of the latter in the inflammatory process has been reported by several Authors, we examined the effect of SAMe in various tests of acute inflammation (carrageenin and white egg oedema) and chronic inflammation (cotton pellet induced granuloma, adjuvant induced arthritis). Considering the positive results we have obtained and being aware that many drugs with antiinflammatory activity also have an antalgic activity, we examined the effects of a treatment with SAMe on animals subjected to analgesic tests: hot plate and streching by acetic acid in mice.