Search PubMed⌕ Search

Biomedical subjects

A Ferrari

Publications and source records attributed to A Ferrari.

At least 19 recordsLinked to original sources

Immature human NT2 cells grafted into mouse brain differentiate into neuronal and glial cell types.

NT2 cells are a transfectable human embryonal carcinoma cell line, that can be differentiated into postmitotic neuron-like cells (NT2N cells), and transplanted into rodent brains. Differentiation requires a 5-week-long treatment with retinoic acid prior to transplantation. Here, we show that this step can be omitted, and that undifferentiated NT2 cells migrate over long distances and differentiate into both neuron- and oligodendrocyte-like cell types upon grafting into brains of immunocompetent newborn mice. Grafted cells can be traced by fluorogold, with no evidence for tumor formation. Our approach provides an experimental model system which allows the immunohistological and biochemical study of neuronal and glial differentiation of human cells in vivo, and which may be suitable as an in vivo model for pharmacological studies.

Animals↗

Novel 7-substituted camptothecins with potent antitumor activity.

The natural alkaloid camptothecin is the lead compound of a new class of antitumor agents with a unique mechanism of action (i.e. inhibition of DNA topoisomerase I). The pharmacological interest of these agents has generated a large number of derivatives and analogues endowed with potent cytotoxic activity, two of them being in clinical use as antitumor drugs. We have synthesized a new series of camptothecins substituted in position 7 with an alkyl or alkenyl chain bearing cyano and/or carbethoxy groups. These compounds showed potent cytotoxic activity in vitro against the human non-small-cell lung carcinoma H460 cell line, most of them exhibiting IC(50) values in the 0.05-1 microM range, more active than topotecan used as a reference compound. In particular 7-cyano-20S-camptothecin (5a) showed high in vitro cytotoxicity against a topotecan-resistant H460 cell subline (H460/TPT) and a cisplatin-resistant ovarian carcinoma subline (IGROV-1/Pt 1). In an in vivo evaluation of the antitumor activity, 5a appeared significantly more effective than topotecan in the H460 tumor model and comparable with topotecan in a small-cell lung carcinoma model and a colon carcinoma model. The efficacy and good tolerability of this compound increase interest for further preclinical development.

Animals↗

Result of liver resection as treatment for metastases from noncolorectal cancer.

BACKGROUND AND OBJECTIVES: While liver resection for metastatic disease from colorectal cancer extends survival in selected patients, the efficacy of hepatectomy for metastases from other malignancies has not been defined. METHODS: Between 1988 and 1998, 20 hepatic resections were performed in 18 patients (2 underwent a double resection due to recurrence) as treatment of noncolorectal metastases. One-, 2-, and 5-year overall and disease-related actuarial survival rates were calculated. RESULTS: No intraoperative or early postoperative deaths were reported. Seven minor (30%) and 1 major (5%) postoperative complications occurred; mean blood loss was 401 +/- 324 ml. In 25% of patients, intra- or postoperative blood transfusion was needed. The mean postoperative hospital stay was 13. 2 days (range 9-23). The overall actuarial survival rate was 54% at 1 year, 42% at 2 years, and 21% at 5 years (mean 38 +/- 11 months). Survival is related to the primary tumor nature. CONCLUSIONS: Hepatic resection for metastases from noncolorectal carcinoma is safe and feasible, with a relatively low incidence of intra- or postoperative complications and a short hospital stay. Although it achieves good results in terms of survival in patients suffering from neuroendocrine metastases, it could also have a cytoreductive effect for other tumors.

Breast Neoplasms↗

Prevention of early postmenopausal bone loss with cyclical etidronate.

Cyclical etidronate has been shown to be effective in the treatment of established postmenopausal osteoporosis but less is known about its effects on early menopausal bone loss. The aim of the study was to establish the effects of cyclic etidronate therapy on spinal and proximal femoral bone mineral loss in early postmenopausal women. One hundred and seven women who were within 6 months to 3 years of the menopause were recruited into a 2-year, randomised, placebo-controlled, double-blind trial. Spinal bone mineral density was within 2 SD of the age-matched mean reference value at baseline. Bone mineral density in the lumbar spine and proximal femur was assessed by dual energy X-ray absorptiometry at baseline and thereafter at 6 monthly intervals for 2 years. Urinary collagen cross-links (deoxypyridinoline and pyridinoline) were measured at the same time points. Seventy-seven women completed the study. At the end of the treatment period, the mean bone mineral density change from baseline in the treated group was +0.14% and -0.06% in the lumbar spine and femoral neck, respectively, compared to -1.49 and -2.22 in the control group. Overall, there was a significant difference between the two groups at both these sites (p=0.01 and 0.001, respectively). No significant differences between the groups were demonstrated at the greater trochanter or Ward's triangle. The conclusion was that cyclical etidronate therapy prevents bone loss in the spine and femoral neck in early postmenopausal women. It provides a safe and effective therapeutic option for the prevention of postmenopausal osteoporosis in women who are unwilling or unable to tolerate hormone replacement therapy.

Absorptiometry, Photon↗

Dermoscopic features of cutaneous local recurrent melanoma.

We describe for the first time the dermoscopic features of cutaneous recurrent melanoma including a globular pattern and a diffuse nonhomogeneous pigmentation. These findings greatly differ from those observed in primary cutaneous melanoma and should be considered in the dermoscopic differential diagnosis of pigmented skin lesions.

Adult↗

Central white scarlike patch: a dermatoscopic clue for the diagnosis of dermatofibroma.

In this study, dermatoscopic examination of 24 dermatofibromas was performed to evaluate specific dermoscopic criteria. A central white scarlike patch was appreciable in 22 of 24 lesions, whereas 20 of 24 dermatofibromas exhibited a delicate pigment network at the periphery. This stereotypical dermatoscopic finding allowed the diagnosis of dermatofibroma in most instances. (J Am Acad Dermatol 2000;43:1123-5.).

Adult↗

Teledermoscopy--results of a multicentre study on 43 pigmented skin lesions.

We performed a multicentre study to evaluate the agreement between the direct clinical diagnosis and the telediagnosis of 43 cutaneous pigmented lesions. Digital clinical and dermoscopic images of the 43 pigmented skin lesions (11 melanomas, 23 melanocytic naevi, three basal cell carcinomas, three lentigines, two seborrhoeic keratoses and one angiokeratoma) were sent by email to 11 colleagues (six dermatologists, two residents in dermatology, one oncologist, one specialist in internal medicine and one general practitioner) in 10 centres. These 11 colleagues had different degrees of experience in dermoscopy. With histopathology as the gold standard, an average of 85% of the telediagnoses were correct, with results varying from 77% to 95%, whereas face-to-face diagnosis by an expert dermatologist was correct in 91% of cases. The kappa value for all participants ranged from 0.35 to 0.87. The results confirm that teledermoscopy can be a reliable technique for the diagnosis of pigmented skin lesions but one that will depend on the expertise of the observer.

Adolescent↗

The enhanced green fluorescent protein as a tool for the analysis of protein dynamics and localization: local fluorescence study at the single-molecule level.

The green fluorescent protein (GFP) has emerged, in recent years, as a powerful reporter molecule for monitoring gene expression, protein localization and protein-protein interaction. Several mutant variants are now available differing in absorption, emission spectra and quantum yield. Here we present a detailed study of the fluorescence properties of the Phe-64-->Leu, Ser-65-->Thr mutant down to the single molecule level in order to assess its use in quantitative fluorescence microscopy and single-protein trafficking. This enhanced GFP (EGFP) is being used extensively as it offers higher-intensity emission after blue-light excitation with respect to wild-type GFP. By means of fluorescence spectroscopy we demonstrate the absence of the neutral form of the chromophore and the lack of photobleaching recovery after ultraviolet light irradiation. Furthermore, we show that the EGFP spectral properties from isolated to densely packed molecules are highly conserved. From these experiments EGFP emerges as an ideal molecule for quantitative studies of intra and intercellular tagged-protein dynamics and fluorescence-activated cell sorting, but not for monitoring single-protein trafficking over extended periods of time.

Base Sequence↗

Polycystic ovary syndrome: evidence for reduced 3 beta-hydroxysteroid dehydrogenase gene expression in human luteinizing granulosa cells.

In a preview study we found that luteinizing granulosa cells from follicles of patients with polycystic ovary syndrome (PCOS) have a reduced capacity to synthesize progesterone in vitro. Because the 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta-HSD) is an important enzyme for the biosynthesis of progesterone, the reduced capacity of PCO luteinizing granulosa cells to synthesize progesterone in vitro may be due to reduced 3 beta-HSD gene expression. A reverse transcriptase polymerase chain reaction for 3 beta-HSD was performed and the relative intensity of signals for 3 beta-HSD was evaluated using computer-assisted densitometry. Cells from polycystic ovaries expressed less 3 beta-HSD in follicles < or 10 mm (p < 0.05) and in follicles > or 16 mm (p < 0.05) than cells from normal ovaries. Furthermore, after human chorionic gonadotropin stimulus (50 ng/ml), cells from polycystic ovaries expressed less 3 beta-HSD in follicles > or = 16 mm (p < 0.01) than cells from normal ovaries. The data show that there is a specific change in the gene expression of 3 beta-HSD in PCO granulosa cells resulting in a suppressed capacity to secrete progesterone.

3-Hydroxysteroid Dehydrogenases↗

[The usefulness of the association of clinical probability, rapid plasma measurement of D-dimer, compression echography of the lower limbs and echocardiography in the diagnosis of acute pulmonary embolism].

BACKGROUND: The aim of this study was to investigate the diagnostic utility of clinical probability, rapid plasma D-dimer assay, compression ultrasonography (CUS) and transthoracic echocardiography (TTE) in patients with suspected pulmonary embolism. METHODS: One hundred forty consecutive outpatients with suspected pulmonary embolism were enrolled in a prospective trial. We evaluated sensitivity, specificity, positive and negative predictive value of a combination of clinical probability, D-dimer, CUS and TTE using perfusion lung scan and pulmonary angiography as a combined gold standard for determining the presence or absence of pulmonary embolism. Clinical probability was assessed in accordance with the PIOPED criteria. The D-dimer (Nycocard) level was considered as abnormal > 0.3 mg/l, the CUS if incompressibility of the leg veins was showed, and the TTE if right ventricular dilation was present, in the absence of chronic pulmonary disease. The combination of these tests was considered consistent with the presence of pulmonary embolism if D-dimer plus CUS and/or TTE showed abnormal results. A pulmonary embolism was excluded if D-dimer and CUS showed normal findings or a low clinical probability was associated with normal findings of CUS and TTE. RESULTS: One hundred eleven patients were evaluated. Pulmonary embolism was present in 45/111 (40%) patients. The combination of tests showed positive findings in 39/39 patients with pulmonary embolism, negative findings in 47/50 without pulmonary embolism and non-diagnostic results in 22/111 (20%) patients (95% confidence interval--CI 12-28%). There were three false positive and no false negative results. Sensitivity and specificity were 100 and 94% respectively (95% CI 92-100% and 87-100%); positive and negative predictive values were 93 and 100% (95% CI 85-100% and 93-100%). None of these tests, separately, showed enough sensitivity and specificity. CONCLUSIONS: The combination of clinical probability, D-dimer, CUS and TTE was highly accurate to confirm or rule out pulmonary embolism.

Acute Disease↗

[A cardiac embolic stroke due to malposition of the pacemaker lead in the left ventricle. A case report].

Misplacement of a permanent pacemaker lead has been described in several locations but rarely in the left ventricle. Less commonly, as described in our report, malposition may occur when the lead perforates the interatrial septum and extends across the left atrium and through the mitral valve into the left ventricle. The actual incidence of this pacemaker complication is unknown. Consequences may include perforation and systemic or cerebral thromboembolic events. We report the case of a patient with unintentionally misplaced left heart pacemaker lead admitted for neurological symptoms consistent with embolic stroke. The patient was on aspirin when symptoms occurred. The lead misplacement was not recognized at the time of implantation. Pacing threshold was normal. A 12-lead electrocardiogram showed right bundle branch block configuration paced complexes. By two-dimensional and transesophageal echocardiography, the pacemaker lead was carefully evaluated. The pacemaker lead crossed the interatrial septum, the left atrium, the mitral valve to be implanted in the left ventricular endocardium. To avoid the risk of future embolization, it was felt that the lead should be removed and right ventricular pacing established, once anticoagulation treatment was initiated. Successful percutaneous lead replacement was accomplished without sequelae. Measures to avoid lead misplacement are suggested.

Electrodes↗

Synovial sarcoma: report of a series of 25 consecutive children from a single institution.

BACKGROUND: The role of postoperative radiotherapy and adjuvant chemotherapy in the treatment of synovial sarcoma remains to be determined. PROCEDURE: Twenty-five children were treated during a 23-year period with a multimodality approach. All of them had resection of the primary tumor (three amputations), followed by surgical retreatment in eight. Postoperative radiotherapy was delivered to 16 patients and adjuvant chemotherapy was given to 22. RESULTS: At the time of the report, 19 patients were alive and without evidence of disease. Six developed distant metastases (one associated with local recurrence); five of them died of their disease and one was alive in complete remission at 4 years from relapse. With a median follow-up of 9 years (range 2-23), the survival and the event-free survival at 5 years were 80% (SE 8.2) and 74% (SE 9.2), respectively. All relapsing patients had been classified as T2B. CONCLUSIONS: Multimodality treatment yielded satisfying survival results using limb-preserving surgery in most cases. Tumor size > 5 cm and invasiveness, which defined stage T2B, were the most important predictors of poor outcome. Evaluation of the role of adjuvant chemotherapy and radiotherapy awaits prospective studies, even if T2B patients, as well as children having nonradical surgery, seem worth managing by adjuvant treatments.

Adolescent↗

An analysis of urban collisions using an artificial intelligence model.

Traditional studies on road accidents estimate the effect of variables (such as vehicular flows, road geometry, vehicular characteristics), and the calculation of the number of accidents. A descriptive statistical analysis of the accidents (those used in the model) over the period 1992-1995 is proposed. The paper describes an alternative method based on the use of artificial neural networks (ANN) in order to work out a model that relates to the analysis of vehicular accidents in Milan. The degree of danger of urban intersections using different scenarios is quantified by the ANN model. Methodology is the first result, which allows us to tackle the modelling of urban vehicular accidents by the innovative use of ANN. Other results deal with model outputs: intersection complexity may determine a higher accident index depending on the regulation of intersection. The highest index for running over of pedestrian occurs at non-signalised intersections at night-time.

Accidents, Traffic↗

The use of Matrigel at low concentration enhances in vitro blastocyst formation and hatching in a mouse embryo model.

OBJECTIVE: To determine the effect of Matrigel at a low concentration on the growth of mouse embryos in culture. DESIGN: Randomized case-control study of mouse embryos. SETTING: An academic research environment. ANIMALS: Mouse embryos. INTERVENTION(S): Embryos were cultured in Quinn's or Celbio's human tubal fluid (HTF) enriched with 1.5% bovine serum albumin and 0.8% liquid Matrigel. Each HTF was compared with the same medium devoid of Matrigel. Afterward, Quinn's and Celbio's HTF, both containing Matrigel, were compared directly. Embryos were cultured in four-well dishes, and their morphology and viability were assessed at 96 hours. MAIN OUTCOME MEASURE(S): Level of interleukin-1alpha in media collected at the end of culture. RESULT(S): In both types of HTF, the presence of Matrigel allowed a larger number of embryos to reach the blastocyst stage and to hatch; blastocyst morphology also was improved. These positive effects were enhanced in Quinn's HTF: embryos cultured in its Matrigel-enriched version secreted a higher level of interleukin-1alpha than those in Celbio's HTF plus Matrigel and also showed a better morphology. CONCLUSION(S): In the mouse embryo model, Matrigel improves culture conditions in terms of both embryo viability and morphology, and these effects are enhanced in Quinn's HTF.

Animals↗

Effect of consumption of a ready-to-eat breakfast cereal containing inulin on the intestinal milieu and blood lipids in healthy male volunteers.

OBJECTIVE: To investigate the effect of a breakfast cereal containing inulin on blood lipids and colonic ecosystem in normolipidemic young men. SETTING: Department of Food Science and Microbiology,University of Milan, Italy. SUBJECTS: Twelve healthy male volunteers, age 23.3 +/- 0.5 y, body mass index (BMI) 25.7 +/- 1.2 kg/m2 (mean +/- s.e.m.). INTERVENTIONS: Subjects consumed daily, for three periods of four weeks, 50 g of a rice-based ready-to-eat cereal (placebo) and the same cereal containing 18% inulin (test) in substitution of their habitual breakfast, then returned to the habitual diet (wash-out). They followed no other dietary restrictions. RESULTS: No changes in body weight, dietary habits, faecal and bile acid output, faecal short-chain fatty acid (SCFA) and faecal pH, were observed at the end of each period, whereas plasma total cholesterol and triacylglycerols significantly decreased at the end of test period by 7.9 +/- 5.4 (P < 0.05) and 21.2 +/- 7.8% (P < 0.005) respectively. Meal glucose tolerance test (MTT) resulted in the same incremental area under the curve for both cereals (IAUC test 124 +/- 35; placebo 118 +/- 33 mmol x min/l, ns). Inulin markedly enhanced breath H2 excretion (IAUC test 280 +/- 40; placebo 78 +/- 26 ppm x h, P < 0.005), as well as faecal concentration of L-lactate. Total facultative anaerobes significantly decreased after test, and bifidobacteria increased after correction for total anaerobes (P < 0.05). Changes in blood lipids were negatively correlated with bifidobacteria counts and positively with secondary bile acid excretion (P < 0.05). CONCLUSIONS: Inulin seems to have a lipid lowering potential in normolipidemic men possibly mediated by mechanisms related to colonic fermentation.

Adult↗