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Biomedical subjects

G Botti

Publications and source records attributed to G Botti.

At least 73 records · Page 4Linked to original sources
PubMed1995

Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PlGF) associated with malignancy in human thyroid tumors and cell lines.

Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells in vitro, promotes neoangiogenesis in vivo and increases the permeability of the vascular endothelium. VEGF overexpression occurs in several cultured tumor cell lines and in certain human malignancies. Placenta growth factor (PlGF) is a recently identified growth factor for endothelial cells (EC); PlGF strongly potentiates both the proliferative and the permeabilization effects exerted by VEGF on the vascular endothelium. To uncover the molecular mechanisms underlying neoangiogenesis in human thyroid tumors, we have analysed VEGF and PlGF expression in a panel of thyroid carcinoma cell lines with different tumorigenic potential as well as in human primary thyroid tumors. We show that a high tumorigenic potential is associated with an elevated VEGF expression in human thyroid tumor cell lines. Furthermore, VEGF overexpression occurs in 5/5 highly malignant anaplastic carcinomas. Papillary and follicular carcinomas express intermediate levels of VEGF mRNA. In contrast, PlGF expression is severely down regulated in the majority of thyroid tumor cell lines and in tumors. Furthermore, we show that both the VEGF receptors, FLT-1 and flk/KDR, are expressed in endothelial cells that line tumor-embedded microvascular vessels, suggesting that VEGF but not PlGF, contributes to thyroid tumor development.

Blotting, Western↗
PubMed1995

Dipyridamole echocardiography for diagnosis of coexistent coronary artery disease in hypertrophic cardiomyopathy. Echo-Persantine International Cooperative (EPIC) Study Group--Subproject Hypertrophic Cardiomyopathy.

The recognition of coexistent coronary artery disease (CAD) in patients with hypertrophic cardiomyopathy may be difficult by noninvasive testing based upon electrocardiographic changes or perfusion defects. Dipyridamole-stress echocardiography has proved a sensitive and highly specific test for noninvasive diagnosis of CAD in various patient subsets. To establish the feasibility, safety, and diagnostic accuracy of dipyridamole-stress echocardiography in patients with hypertrophic cardiomyopathy, we performed high-dose dipyridamole testing (up to 0.84 mg/kg over 10 minutes) in 88 patients with hypertrophic cardiomyopathy (63 men; mean age +/- SD, 46 +/- 17 years). A subset of 60 patients was referred for coronary angiography independently of test results; CAD was defined as > or = 50% diameter narrowing in at least 1 major coronary vessel. Dipyridamole echocardiography/electrocardiography testing was completed in all patients, with no limiting side effects or adverse reactions. In the subgroup of 60 patients with coronary angiography (14 with and 46 without CAD), chest pain occurred in 18 patients (8 with and 10 without CAD, p = NS); ST-segment depression > or = 2 mm from baseline in 28 (7 with and 21 without CAD, p = NS); and transient dyssynergy in 10 patients (10 with and none without CAD, p < 0.0001). Assuming the transient regional dyssynergy to be the only criterion of positivity, the dipyridamole echocardiography test showed 71% sensitivity, 100% specificity, 100% positive predictive value, and 93% diagnostic accuracy for diagnosis of angiographically assessed CAD. We conclude that high-dose dipyridamole echocardiography testing may be considered a feasible and accurate tool for the noninvasive diagnosis of CAD in patients with hypertrophic cardiomyopathy.

Adult↗
PubMed1995

Knowledge acquisition from the UMLS sources: application to the description of surgical procedures.

The re-usability of lexicons and knowledge in medicine is a crucial challenge. The Unified Medical Language System (UMLS) project has attempted to provide a repository of concepts, semantically categorized for biomedical domain. This paper describes some results about the relevance of UMLS structures for specific purposes. We have focused on the description of surgical procedures. Discussion concerns synonymy of terms, granularity of concepts, and ontology. A preliminary work on the exploitation of interconcept links by a computerized application reveals a heterogeneous implementation of those relationships. However, the UMLS provides a powerful knowledge base for developers.

General Surgery↗
PubMed1994

Tissue distribution of soluble and receptor-bound urokinase in human breast cancer using a panel of monoclonal antibodies.

Current evidence regarding the regulation of urokinase-dependent extracellular proteolysis indicates that plasminogen activation is a surface-associated process. We have compared the histological localization of urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) in breast cancer sections using a panel of monoclonal antibodies. First, the ability of six different anti-uPA monoclonal antibodies to recognize pro-uPA, uPA, and in vitro-formed complexes of uPA with either soluble uPAR or with plasminogen activator inhibitor type 1 was compared. Then the reactivity of the anti-uPAR antibodies was tested, and the occurrence of an uPA receptor of about M(r) 55,000 in samples from breast carcinoma was assessed by immunoprecipitating the uPA receptor from an in vitro 125I-labeled tumor extract. Immunocytochemical data from adjacent sections of 10 tumor specimens showed that antibodies recognizing free and bound uPA mostly stain the cytoplasm and the membrane of epithelial tumor cells in confined areas of the tumor and some fibroblast-like stromal cells. Acid pretreatment of tumor sections, which removes receptor-bound uPA, causes a strong reduction of the immunocytochemical reactivity of epithelial tumor cells, whereas staining of fibroblast-like cells is not considerably affected. Consistent with these results, epithelial tumor cells were mostly unreactive to anti-uPAR antibodies unless pretreated with acidic buffer, whereas fibroblast-like stromal cells showed a faint but acid-resistant staining with all anti-uPARs. In conclusion, these results show that occupied uPA receptors are definitely present on the membrane of epithelial tumor cells and suggest the occurrence of uPA-uPAR-dependent proteolytic activity on the surface of breast cancer cells.

Adult↗
PubMed1994

In vitro receptor imaging for characterization of human solid tumors.

Since many of the factors involved in tumor growth and progression act through a receptor-mediated mechanism, we applied in vitro receptor imaging techniques to study the intratumoral distribution and concentration of receptor-molecules having experimental biological relevance in such processes. Here we summarize the results of a study concerning the role of urokinase receptor (uPAR) in the acquisition of an invasive phenotype by tumor cells. Independently of the system studied, we demonstrated that in vitro receptor imaging techniques can be used to define the biological characteristics of human solid tumors and can contribute to clarify the complex network of ligand/receptor interactions leading to tumor spread.

Autoradiography↗
PubMed1994

[Anesthetists and continuing education].

Although the importance of continuing medical education (CME) is a recognized fact, its modalities are still a controversial matter. In order to obtain informations on the demands and the difficulties to which French anaesthetist (AN) are faced with, the Committee for Education of the French Society of Anaesthesia (SFAR) carried out an inquiry with a questionnaire circulated to 7000 AN. The rate of answers was about 10%. With regard to age, gender, mode of activity and length of service in the specialty, the group of responders was representative of the French population of AN. The inquiry seems to demonstrate a strong motivation for CME, as well as demands for training courses, courses extending over two days or more, and a self-assessment. The funding of the expenses as well as the difficulties to obtain a locum tenens were the two main obstacles which limited the access to CME.

Anesthesiology↗
PubMed1994

[A study of 82 cerebral infarctions in the area of posterior cerebral arteries].

Of 598 consecutive non-selected cases of cerebral infarction included in a stroke registry, 82 cases (54 men and 28 women, mean age 66 +/- 14 years) of spontaneous and isolated posterior cerebral artery (PCA) territory infarction (right PCA in 36, left PCA in 35 and both in 11) were identified on the basis of CT combined with MRI in 51 cases. Infarction was superficial in 25 (group A), combined deep-superficial in 23 (group B) and deep in 34 (group C). Of 48 superficial lesions, 29 were massive while 19 were restricted to the territory of one branch. Of 57 deep lesions, 21 were located in the inferolateral thalamic territory, 10 in the paramedian thalamic territory, 12 in other midbrain or thalamic territories, and 14 in a combination of various midbrain and/or thalamic territories. Of 41 patients with unilateral superficial involvement, 39 had homonymous visual field defect. Unawareness of the visual defect and visual release hallucinations were observed with the same frequency in right and left lesions. Of 7 patients with bilateral superficial involvement, only 5 had bilateral visual field defect including incomplete cortical blindness in 3. The frequency of confusional state (n = 24) did not differ significantly in left versus right sided lesions while it was significantly higher in superficial or combined versus deep lesions (p = 0.05). Of 18 clinically evaluable patients with left PCA territory infarct, 14 had speech disorders including pure alexia in only one case. Of 15 patients with right territory infarction, 10 had spatial judgement disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Designing a sub-set of the UMLS knowledge base applied to a clinical domain: methods and evaluation.

The UMLS is a complex collection of interconnected biomedical concepts derived from standard nomenclatures. Designing a specific subset of the UMLS knowledge base relevant to a medical domain is a prerequisite for the development of specialized applications based on UMLS. We have developed a method based on the selection of the appropriate terms in original nomenclatures and the capture of a set of UMLS terms that are linked to them in the network to a certain degree. We have experimented it as the foundation for a concept base applied to urology. Results depend on the exhaustiveness of the relationships between the Metal concepts. A preliminary analysis of the sub-base reveals that some adaptations of vocabulary and ontology are required for clinical applications.

Algorithms↗
PubMed1993

Human urokinase receptor concentration in malignant and benign breast tumors by in vitro quantitative autoradiography: comparison with urokinase levels.

We measured the tissue concentration of human urokinase receptor (uPAR) in 22 breast carcinomas and 9 benign breast lesions using in vitro quantitative autoradiography. Tissue sections were incubated with increasing concentrations of 125I-pro-urokinase in the presence or absence of unlabeled competitor. Breast carcinomas were found to contain 5 times more uPAR than benign breast lesions with respect to their protein content [523 +/- 72 versus 108 +/- 20 (SE) fmol/mg (P < 0.001)]. Simultaneous quantitation of urokinase (uPA) by immunoenzymatic assay on tissue extracts from the same specimens showed that breast carcinomas also contain 19 times more uPA than benign tumors (611 +/- 134 versus 32 +/- 8 fmol/mg) (P < 0.01). The reliability of quantitative autoradiography measurements was confirmed by uPAR cross-linking assay on membrane fraction from either U937 histiocytic lymphoma cells or breast carcinomas and immunoperoxidase staining with an anti-uPAR antibody on tumor sections. Also, immunoperoxidase staining with an anti-uPA monoclonal antibody showed that uPA is indeed localized on the plasma membrane of epithelial tumor cells in confined areas of breast carcinomas whereas cells from benign breast lesions were devoid of uPA under the same experimental conditions. In conclusion, our findings support the hypothesis that uPAR plays a central role in the acquisition of an invasive phenotye and favor its potential use as a prognostic factor in patients with breast carcinoma.

Adult↗
PubMed1993

PCNA/cyclin and P-glycoprotein as prognostic factors in locally advanced breast cancer. An immunohistochemical, retrospective study.

AIMS AND BACKGROUND: The aim of the present study was to determine, retrospectively, whether the immunohistochemical expression of two biologic markers of aggressively, P-glycoprotein (P-gp) and PCNA/cyclin (PCNA), could be related to response to chemotherapy and prognosis in locally advanced breast cancer. METHODS: PC 10 Mab was used to determine the proliferation index (PCNA) and C-219 Mab to determine P-gp in 25 locally advanced breast carcinomas subjected to preoperative chemotherapy with MDR-related drugs. RESULTS: P-gp and PCNA were expressed in 76% and 100% of the tumors, respectively. No case of high P-gp expression was associated with good chemosensitivity, and all P-gp-negative cases showed the best chemotherapeutic response. P-gp and PCNA were both highly expressed in patients who developed local-regional or distant metastases. No recurrence was associated with a negative or low P-gp score. CONCLUSIONS: Statistical analysis showed that high P-gp expression was related to a poor response to chemotherapy and a short disease-free survival. A high PCNA score was not found to be significant for predicting chemosensitivity or survival.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Tumour uptake of 57-cobalt-bleomycin in patients with breast cancer.

17 patients with breast carcinoma were studied with 57-cobalt-bleomycin scintigraphy. Scans showed increased tumour uptake in all patients. Results expressed as percentage of the injected dose (ID) normalised by the size of the tumour region (% ID/pixel) showed higher tumour uptake in patients with T3-T4 breast carcinomas (n = 5) than in patients with T1-T2 breast cancer (n = 12) (8.4 +/- 0.55 x 10(-3) vs. 5.25 +/- 1.71 x 10(-3)% ID/pixel, respectively, P < 0.05). An inverse correlation between tumour uptake of 57-cobalt-bleomycin and progesterone receptor concentration was also found in all tumours tested (r = -0.60, P < 0.05, n = 10) and was confirmed in the group of patients with T2 breast carcinomas (r = -0.89, P < 0.05, n = 6). We conclude that a quantitative analysis of 57-cobalt-bleomycin uptake can give additional information suitable for the presurgical characterisation of a tumour.

Adult↗
PubMed1993

[Analysis of parameters used for the evaluation of the Relative Complexity Index beta].

The Relative Complexity Index beta (RCI beta) has been devised as an indicator of the relative complexity and cost of anaesthesia. It takes into account the type of anaesthesia, the duration, the type of surgery and the patients' ASA status. This study analyses the relative weight of each component of RCI by a multiple regression analysis. The results show the pre-eminence of the surgical procedure in the formula. The weight of surgical procedure is responsible of 80 p. cent of the model's variance. In these conditions, the RCI beta cannot be accepted as an accurate complexity index of anaesthesia.

Anesthesia, General↗
PubMed1993

[Quantitative viremia and p24 antigenemia in short-term follow-up of the treatment with zidovudine in twenty HIV infected patients].

The authors emphasize the interest of detecting HIV p24 antigen after immune complexes dissociation as well as changes in cellular viremia titers in the therapeutic follow-up of HIV infected patients. A significant decline of cell virus titers was found in 4-8 weeks among 13 of 20 zidovudine treated patients. A significant decrease of immune complexes dissociated p24 antigenemia was noted in 11 out of 17 patients.

Acquired Immunodeficiency Syndrome↗
PubMed1992

[Survival after gastrectomy for cancer. 209 cases].

The long-term results of 209 gastrectomies performed for adenocarcinoma, including 117 which were prospectively collected, are presented. Resection was curative in 154 cases (73.6 percent). The TNM distribution of the tumours was: stage I (TxNOMO) 75 cases, stage II (TxN1MO) 46 cases, stage III (TxN2MO) 33 cases and stage IV (TxNxM1) 55 cases. Lymph node involvement was more frequent in the prospective than in the retrospective study. With a more than 5 years' follow-up of 80 percent of the patients operated upon, the actuarial survival rate at 5 years (operative mortality included) was 38 percent for all lesions, 52 percent for curative resection and 2 percent for palliative resection. Following curative resection, the survival rates for tumours of the upper, middle and lower thirds of the stomach were 40, 60 and 55 percent respectively. These rates were 60 percent for stage I tumours, 54 percent for stage II tumours and 25 percent for stage III tumours. The results obtained in this series, where most of the curative gastrectomies included excision of N1 and N2 lymph nodes, show that lymph node involvement has no significant importance for the prognosis when it is proximal (N1) and is not incompatible with prolonged survival when it is pedicular (N2).

Actuarial Analysis↗
PubMed1992

Clinical significance of coronary artery disease in hypertrophic cardiomyopathy.

The role of coronary artery disease (CAD) in hypertrophic cardiomyopathy (HC) has not been thoroughly clarified. To assess the clinical and prognostic significance of these 2 coexistent diseases, 96 patients with HC (62 men, mean age 45 years) who underwent coronary arteriography and 2-dimensional echocardiography were studied. Significant stenosis (greater than 70%) of 1 or more coronary arteries was detected in 11 patients, all aged greater than 45 years. This group, compared with the other group without significant CAD (n = 85), was characterized by an older age (59 +/- 7 vs 42 +/- 15 years; p less than 0.05), a greater prevalence of previous myocardial infarction (24 vs 0%; p less than 0.001), complex ventricular arrhythmias (100 vs 50%; p less than 0.05), non-obstructive forms (82 vs 46%; p less than 0.05), dilated (45 vs 7%; p less than 0.02) and hypocontractile left ventricle (36 vs 6%; p less than 0.01) and higher mortality (36 vs 8%; p less than 0.05) during a mean follow-up of 3.6 years. It is concluded that CAD associated with HC is a complex clinical syndrome, difficult to diagnose clinically, that can reliably be recognized by coronary angiography. CAD seems to play an important role in modifying the pathophysiology, the natural history and the prognosis of HC.

Adolescent↗
PubMed1992

Efficacy and tolerability of gallopamil in coronary heart disease: a double blind cross-over comparison with nifedipine.

Anti-ischaemic properties and tolerability of the calcium antagonist gallopamil were compared with those of nifedipine in a double-blind cross-over study performed in 20 patients affected by effort or mixed angina. The patients were of both sexes and aged 43-66 years; coronary angiography performed on 18 of them revealed at least one-vessel disease (stenosis greater than 70%). After a one week wash-out period the patients received placebo for 2 weeks; thereafter 10 patients were treated orally with gallopamil 150 mg daily and 10 patients with nifedipine 60 mg daily for 4 weeks. Before crossing-over to the alternate therapy a 2-week placebo period was allowed. The patients underwent cycloergometric exercise tests after each phase of treatment; workload was increased by 25 W every 3 min and the test was stopped in the presence of a typical angina or ST segment depression or age-predicted maximal heart rate. The results show that both exercise time and maximal workload were significantly increased by gallopamil and by nifedipine in comparison with placebo; also the maximal ST segment depression was significantly reduced by the two drugs. The number of patients developing angina and/or segment depression during exercise test was significantly reduced by both drugs compared to placebo. Time to onset of angina and time to ST depression greater than or equal to 1 mm were increased, though not significantly, by both calcium antagonists. No side effects were recorded with gallopamil while with nifedipine six patients reported side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗