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Biomedical subjects

D Moretti

Publications and source records attributed to D Moretti.

13 recordsLinked to original sources
PubMed2006

Cross-talk between calpain and caspase-3/-7 in cisplatin-induced apoptosis of melanoma cells: a major role of calpain inhibition in cell death protection and p53 status.

The contribution of different proteolytic systems, in particular calpains and effector caspases, in apoptotic cell death is still controversial. In this paper, we show that during cisplatin-induced apoptosis of human metastatic melanoma cells, calpain activation, as measured in intact cells by two different fluorescent substrates, is an early event, taking place well before caspase-3/-7 activation, and progressively increasing during 48 h of treatment. Such activation appears to be independent from any intracellular calcium imbalance; in fact, an increase of cytosolic calcium along with emptying of the reticular stores occur only at very late stages, uniquely in frankly apoptotic, detached cells. Calpain activation proves to be an early and crucial event in the apoptotic machinery, as demonstrated by the significant protection of cell death in samples co-treated with the calpain inhibitors, MDL 28170, calpeptin and PD 150606, where a variable but significant reduction of both caspase-3/-7 activity and cell detachment is observed. Consistently, such a protective effect can be at least partially due to the impairment of cisplatin-induced p53 activation, occurring early in committed, preapoptotic cells. Furthermore, in late apoptotic cells, calpain activity is also responsible for the formation of a novel p53 proteolytic fragment (approximately 26 kDa), whose function is so far to be elucidated.

Antineoplastic Agents↗
PubMed2005

[Organ donation in Switzerland].

Since 1985 Swisstransplant coordinates all allocations for organ transplantations in Switzerland. During these 20 years the number of deceased donors decreased, while the number of living donors increased. In the same period the number of patients on a waiting list for organ transplantation increased significantly, up to more than 1000 at the end of2004. During the year 2004 412 patients were transplanted, 43 (4%) died while waiting on the list. In comparison to other European countries the frequency of organ donation from deceased donors is relatively low in Switzerland, only 13 per million inhabitants. In order to treat the high number of patients needing organ transplantation, additional efforts have to be undertaken in future. The measures include the development of alternative therapies preventing or treating organ failure, the amelioration of legal conditions of organ transplantation with the new law, an increase of resources and knowledge to improve donor evaluation and donor pools in the donor hospitals, a further improvement of the allocation process, the enhancement of information and motivation of the population by the patient organisations, the medical staff, Swisstransplant and eventually public means.

Organ Transplantation↗
PubMed2004

EEG deblurring techniques in a clinical context.

OBJECTIVES: EEG scalp potential distributions recorded in humans are affected by low spatial resolution and by the dependence on the electrical reference used. High resolution EEG technologies are available to drastically increase the spatial resolution of the raw EEG. Such technologies include the computation of surface Laplacian (SL) of the recorded potentials, as well as the use of realistic head models to estimate the cortical sources via linear inverse procedure (low resolution brain electromagnetic tomography, LORETA). However, these deblurring procedures are generally used in conjunction with EEG recordings with 64-128 scalp electrodes and with realistic head models obtained via sequential magnetic resonance images (MRIs) of the subjects. Such recording setup it is not often available in the clinical context, due to both the unavailability of these technologies and the scarce compliance of the patients with them. In this study we addressed the use of SL and LORETA deblurring techniques to analyze data from a standard 10-20 system (19 electrodes) in a group of Alzheimer disease (AD) patients. METHODS: EEG data related to unilateral finger movements were gathered from 10 patients affected by AD. SL and LORETA techniques were applied for source estimation of EEG data. The use of MRIs for the construction of head models was avoided by using the quasi-realistic head model of the Brain Imaging Neurology Institute of Montreal. RESULTS: A similar cortical activity estimated by the SL and LORETA techniques was observed during an identical time period of the acquired EEG data in the examined population. CONCLUSIONS: The results of the present study suggest that both SL and LORETA approaches can be usefully applied in the clinical context, by using quasi-realistic head modeling and a standard 10-20 system as electrode montage (19 electrodes). These results represent a reciprocal cross-validation of the two mathematically independent techniques in a clinical environment.

Aged↗
PubMed2002

Papnet-assisted cytological diagnosis intensifies the already marked variability among cytological laboratories.

OBJECTIVE: The main objective was to assess the sensitivity, specificity and reliability of PAPNET-assisted diagnosis in comparison with conventional screening. SETTING: Seven Italian and one English University or Research Institutes, and a random sample of an other 20 Italian Laboratories of the Italian National Health Service (INHS) provided the cervical smears. METHODS: During the training phase every center examined in rotation four sets of slides for a total of 300 representative slides. Afterwards, 900 "positive" slides were added to the 3,100 slides which were collected consecutively without any selection or exclusion. The eight main centers were divided into four couples and each couple of centers examined 775 slides with the PAPNET system, "blindly" to the original diagnosis. An expert cytopathologist (M.A.) of the National Institute of Health (NIH) reassessed 40% of the slides with an original negative diagnosis to evaluate the false negative rate. Two expert NIH cytopathologists (M.A., G.M.) re-examined all slides where a disagreement had been observed between the original and one or both of the study diagnoses. The main analyses concerned the following three main categories: WNL and unsatisfactory for evaluation; ASCUS, AGUS and LSIL; HSIL and carcinoma. A special algorithm was devised to define the reference diagnosis for sensitivity and specificity assessment. RESULTS: Laboratories, even belonging to the same couple, classified as "no review" a very different proportion of slides ranging from 35% to 74%. The index of kappa agreement between the members of couples examining the same sets of slides was low or very low, ranging from 0.30 to 0.03. The sensitivity of the review classification was particularly low in some laboratories. Surprisingly, only a small correlation was observed between the sensitivity of the review classification and the proportion of slides classified as "review". The "tentative" diagnosis on PAPNET tiles of the "review" slides was almost as reliable as the microscopic diagnosis. In the overall performance, there were many significant differences among the eight laboratories. The best laboratory had a sensitivity of 95% and a specificity of 96%. At least three laboratories displayed unacceptably low sensitivity and one a very low specificity. CONCLUSION: Altogether these results seem to confirm that there are wide differences among cytological laboratories per se, and that these differences are intensified by the use of an instrument like PAPNET. The huge variation in performance may be explained by differences in basic skills and by different training, but it is difficult to understand exactly what could have been done to reduce it.

Autoanalysis↗
PubMed2001

Oral glycoprotein IIb/IIIa antagonism in patients with coronary artery disease.

Dose-finding studies and trials of interaction of oral glycoprotein IIb/IIIa antagonists with other antiplatelet agents have been limited. We hypothesized that these detailed assessments could be first performed in patients with stable coronary artery disease (CAD) and then extrapolated to the target population. To this end, we performed 2 sequential studies. The first study examined the dose-related effects on indexes of platelet and vascular function induced by the oral inhibitor RPR 109891, when given alone and in combination with aspirin, in patients (n = 100) with stable CAD. The second study (the Antagonism of the FIbrinogen Receptor after Myocardial Events trial) assessed the pharmacodynamics and safety of derived regimens in patients (n = 320) with unstable coronary syndromes. In patients with stable CAD, platelet aggregation was dose dependently inhibited by RPR 109891, and the dose-response relation was shifted to the right by the concomitant administration of aspirin (p = 0.0001). The degree of platelet inhibition induced by 3 doses of RPR 109891 (plus aspirin) was lower in patients with unstable than stable CAD. No drug-related major bleeding occurred in either study. RPR 109891 treatment was associated with acute and delayed thrombocytopenia. In conclusion, chronic treatment with an oral glycoprotein IIb/IIIa antagonist (1) induces antiplatelet effects that are potentiated by concomitant administration of aspirin, (2) may require dose adjustment in syndromes of platelet activation, (3) is associated with a low rate of clinically significant bleeding when doses inducing incomplete inhibition of platelet aggregation are used, and (4) requires frequent monitoring of platelet count unless reliable predictors of delayed thrombocytopenia become available.

Administration, Oral↗
PubMed2001

Chronic bilateral electrical stimulation of the subthalamic nucleus for the treatment of advanced Parkinson's disease.

Preliminary reports in patients with Parkinson's disease (PD) showed that subthalamic nucleus (STN) stimulation was able to reverse parkinsonian state. Since 1998 we evaluated the safety and the efficacy of STN stimulation in 7 patients affected by advanced PD. All patients were included using CAPIT protocol. Motor functions and quality of life were evaluated, before and after surgery, with UPDRS and PDQ38, respectively. At the 6-month follow-up, the off medication/on stimulation UPDRS motor score improved by 50.6% and the on medication/on stimulation by 20.3%. Motor fluctuations were reduced by 57.2% and dyskinesias by 73.5%. The total L-dopa equivalent daily dose was reduced by 40.7%. PDQ38 ameliorated by 49.9%. We did not observe any perioperatory complication and only mild and tolerable side effects after stimulation.

Aged↗
PubMed1998

Accuracy of cervical/vaginal cytology in the diagnosis of bacterial vaginosis.

BACKGROUND AND OBJECTIVES: The cytological pattern of bacterial vaginosis (BV) in the Papanicolaou smear has a controversial history (coccoid vs. Gardnerella type) that has not allowed an efficient use of cervical/vaginal cytology in the diagnosis of this condition. Our study is an attempt to clarify this topic. GOALS: To evaluate the accuracy of cervical/vaginal cytology in the diagnosis of BV. STUDY DESIGN: 1,896 separate examinations were performed on 1,471 women attending our sexually transmitted diseases center between 1990 and 1993. Amsel's composite clinical criteria were used as a gold standard. The Pap smear was prepared on two slides with the addition of a vaginal specimen. RESULTS: In the 166 cases of BV, sensitivity is 88.7%, and specificity is 98.8%. Positive predictive value is 89.8, and negative predictive value is 98.7. Kendall's correlation coefficient is 0.88 (p < 0.001). CONCLUSIONS: Our findings support the validity of the vaginal Pap smear in diagnosing BV and suggest the screening of such a disease.

Female↗
PubMed1993

Prolonged bronchodilating effect of formoterol versus procaterol in bronchial asthma.

The tolerability and the duration of effect of 12 micrograms of formoterol and 25 micrograms of procaterol administered via metered-dose aerosol to 12 stable asthmatic patients were evaluated in a double-blind, placebo controlled trial. FEV1, pulse rate, and blood pressure were measured at baseline and every two hours after dosing for 12 hours. The bronchodilation peak was observed after two hours for both drugs. Formoterol induced a significant bronchodilating effect for 12 hours compared with both baseline and placebo values. With procaterol, significant bronchodilation occurred for six hours compared with baseline values and four hours compared with placebo. No significant changes were observed in pulse rate and blood pressure with either drug. Four subjects complained of muscle tremor after procaterol administration. We conclude that in subjects with stable asthma, inhaled formoterol at a dose of 12 micrograms maintains significant bronchodilation for 12 hours after dosing and is very well tolerated. Further studies are required to evaluate effectiveness and tolerability of high dose formoterol treatment in acute severe asthma therapy.

Adolescent↗
PubMed1993

Bronchial responsiveness to inhaled propranolol in asthmatic children and adults.

Inhaled propranolol (P) was administered to a population which included asthmatic children (30 subjects) and adults (43 subjects): 1) to investigate the determinants of induced bronchial response; 2) to examine the relationship with treatment requirements; 3) to determine the relationship with responsiveness to methacholine (M) and ultrasonically nebulized distilled water (UNDW) (50 subjects); and 4) to establish the short-term repeatability of bronchial response to propranolol compared with methacholine (22 subjects). Bronchial response to propranolol and methacholine was expressed as the cumulative provocative dose (PD20 in mumol) and responsiveness to UNDW as the provocative output (PO20 in ml.min-1) producing a 20% fall in forced expiratory volume in one second (FEV1). Response to propranolol was significantly related to the degree of responsiveness to methacholine, but not to age, gender, presence of atopy, age at asthma onset, or baseline FEV1. PD20P was measurable in all but three subjects. A significant difference in mean PD20M but not in PD20P was found between subjects requiring more anti-asthmatic treatments compared to those without therapy. The difference between geometric mean PD20P and geometric mean PD20M was 14.1. PO20UNDW was measurable in only 21 out of 50 subjects. Both PD20P and PD20M were significantly lower in responders to UNDW than in nonresponders. Reproducibility of PD20P was comparable to that of PD20M (coefficients of repeatability: 1.17 and 1.09). We conclude that bronchial responsiveness to propranolol is safely measurable in most children and adults with asthma. Repeatability of bronchial response to propranolol is comparable to that of methacholine. Moreover, responsiveness to propranolol is not a predictor of treatment requirement.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMedDate not supplied

Detection of sexually transmitted diseases by urethral cytology, the ignored male counterpart of cervical cytology.

The detection of sexually transmitted diseases by urethral cytology was investigated in 270 men examined by urethral swabbing smears. Each sample was used to prepare a wet mount smear and smears for staining by the Papanicolaou, Gram and methylene blue techniques. A fifth smear was used for direct staining with fluorescein-conjugated monoclonal antibodies for the detection of Chlamydia trachomatis. The smears were examined for cytoplasmic and nuclear changes as well as for pathogenic organisms and inflammatory changes. Infections with Chlamydia trachomatis, Neisseria gonorrhoeae and human papillomavirus (HPV) produced distinctive cytologic patterns similar to those seen in cervicovaginal smears from women. The patterns in candidiasis, trichomoniasis and herpes simplex virus infection were not as diagnostic. Particularly noteworthy were the nuclear alterations, which appeared to be proplastic in HPV infection but retroplastic in Chlamydia infection. The results of this study indicate that urethral cytology would be an invaluable addition in diagnosing sexually transmitted diseases in men, particularly in the case of Chlamydia and HPV infections. The monomorphic structure of urethral columnar epithelium, as compared to the cervical epithelium, seems to result in a clearer and more constant response to pathogenic infections, as seen in the resulting smears.

Animals↗
PubMedDate not supplied

Fine needle aspiration cytopathology of phyllodes tumor. Differential diagnosis with fibroadenoma.

The differential diagnosis of benign or borderline phyllodes tumors of the breast in fine needle aspiration biopsy smears was studied. Smears from five histologically proven cases and 20 proven cases of fibroadenoma were evaluated with regard to their cytologic features. The findings indicate that the presence of a high cellularity of stromal fragments (including bipolar naked nuclei), clusters of hyperplastic ductal cells and giant cells and the absence of apocrine metaplasia may suggest a diagnosis of phyllodes tumor, as opposed to fibroadenoma. The borderline phyllodes tumor showed a sarcomatous atypia and/or small intranuclear cytoplasmic invaginations in some cells. The differential diagnosis of this tumor with malignant phyllodes tumor and plasma-cell mastitis is also discussed.

Adenofibroma↗