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Biomedical subjects

M Bolla

Publications and source records attributed to M Bolla.

At least 37 records · Page 2Linked to original sources
PubMed2001

The role of apolipoprotein E in cognitive decline after cardiac operation.

BACKGROUND: Recently, Tardiff and colleagues have suggested that the presence of the apolipoprotein E, epsilon4 allele was associated with increased likelihood of cognitive decline after coronary artery bypass grafting. The objective of the current study was to replicate this earlier work using an increased sample size. The increased sample also enabled an analysis by individual genotype in cognitive decline after coronary artery bypass grafting. METHODS: Apolipoprotein E genotyping was performed on 111 individuals undergoing coronary artery bypass grafting. Each participant underwent a battery of nine neuropsychological tests before operation and 4 to 7 weeks after operation. RESULTS: Cognitive decline, assessed by both continuous Z change scores and two categoric measures of cognitive deficit, was not significantly associated with either individual apolipoprotein E genotypes or categorization by the presence or absence of the epsilon4 allele. The examination of potential moderating factors did not alter this finding. CONCLUSIONS: This study suggests that the epsilon4 allele is not associated with cognitive decline in the weeks after coronary artery bypass grafting.

Apolipoproteins E↗
PubMed2001

Cost-effectiveness of the addition of early hormonal therapy in locally advanced prostate cancer: results decisively determined by the cut-off time-point chosen for the analysis.

We present a retrospective cost-effectiveness analysis using data from a randomised controlled trial (EORTC 22863) of the addition of early hormonal therapy with a luteinising hormone-releasing hormone (LHRH) analogue to radiotherapy in the treatment of patients with locally advanced prostate cancer. Data on the use of medical resources were extracted from the hospital charts of 90 patients recruited into the trial by one French hospital. Costs are assessed from the viewpoint of the French healthcare financing system and adjusted for censoring. Expected costs per patient of each treatment is related to the expected outcome, mean survival time, estimated by a restricted means analysis. The time point of restriction is determined by statistical criteria. In the base case analysis with a cut-off time point at 8.58 years, the combined therapy group (COMB) had a gain in mean survival time of 1.06 years (7.05 versus 5.99 years) and a reduction of average total costs of 12700 French francs (FF) (58300 FF versus 71000 FF). The analysis of uncertainty uses bootstrap techniques with 5000 replicates to examine the joint distribution of cost and survival outcomes. In 76% of the cases, COMB results in longer mean survival time and lower costs than the radiotherapy group (RT). In cases where COMB therapy raises costs (13% of the cases), it is rarely by more than 20000 FF per patient, no matter the size of the associated survival gain. It is thus highly likely that COMB should be considered a cost-effective option compared with RT for these patients. The exact result of the economic evaluation is decisively determined by the restriction time point selected for the determination of mean survival time, partly also because the average total costs of the two treatments develop entirely differently as a function of the survival time.

Antineoplastic Agents, Hormonal↗
PubMed2001

Curved molar root canal preparations using Hero 642 rotary nickel-titanium instruments.

AIM: The Bramante method was used to study how the natural curvature of root canals was modified when using the Hero 642 nickel-titanium rotary system. METHODOLOGY: Twenty-four canals were selected in freshly extracted human mandibular molars. Every root canal had an angle of curvature greater than 20 degrees. Roots were embedded in clear casting resin using a plaster mould. Cross-sectional cuts were made in the apical, middle and coronal thirds of each root. A first group (control) of 12 curved root canals was prepared using stainless steel hand instruments and the step-back technique. A second group of 12 curved root canals was instrumented using the Hero sequence according to the manufacturer's instructions. For each sectioning level, the amount of dentine removed, the change of shape factor and the canal centre displacement were calculated with the aid of a digital image analysis system. The results were subjected to the Mann-Whitney U-test. RESULTS: No significant difference occurred in the amount of dentine removed, change of shape factor or canal centre displacement in the coronal and middle thirds of the curved canals. In the apical third, transportation was significantly higher (P=0.0171) with stainless steel hand instruments than with the Hero system. CONCLUSIONS: The original canal shape was maintained better in the apical third of curved canals when using the Hero system in a crown-down technique when compared to a hand preparation technique with stainless steel instruments.

Adult↗
PubMed2001

Leukotriene D4-induced activation of smooth-muscle cells from human bronchi is partly Ca2+-independent.

Cysteine-containing leukotrienes (cysteinyl-LTs) are potent bronchoconstrictors and play a key role in asthma. We found that histamine and LTD4 markedly constrict strips of human bronchi (HB) with similar efficacy. However, in human airway smooth-muscle (HASM) cells, LTD4, at variance with histamine, elicited only a small, transient change in intracellular calcium ion concentration. HASM cells express both Ca2+-dependent and -independent isoforms of protein kinase C (PKC) (i.e., PKC-alpha and PKC-alpha ). Western blot analysis showed that PKC-alpha is activated by histamine and, to a lesser extent, by LTD4, whereas only LTD4 translocates PKC-alpha. This translocation was specifically inhibited by the LTD4 antagonist pobilukast. Phorbol-dibutyrate ester (PDBu) (a PKC activator) contracted HB strips to the same extent in the presence as in the absence of extra- and intracellular Ca2+. In the absence of Ca2+, LTD4 contracted HB strips to the same extent as did PDBu, suggesting the involvement of a Ca2+-independent PKC in LTD4-mediated signal transduction. PDBu-induced desensitization and the PKC inhibitor H7 abolished the slow and sustained LTD4-triggered contraction of HB strips in the absence of Ca2+, although H7 did not greatly affect the response in the presence of the ion. Thus, in human airways, we identified a novel LTD4 transduction mechanism linked to bronchial smooth-muscle contraction, which is partly independent of Ca2+ and involves the activation of PKC-alpha.

Bronchi↗
PubMed2001

[Absorbed dose during helical acquisition CT. Effect of acquisition parameters].

PURPOSE: European directive 97/43 specifies that the dose delivered to the patient during a radiological procedure should be estimated. In order to prepare for implementation of this new regulation, we have studied the dose delivered during spiral CT acquisition. MATERIALS AND METHODS: We have studied the influence of slice thickness, pitch, tube voltage and intensity, and acquisition volume length. We present measurements for single and dual detector CT scanners. We used a pencil ionization chamber to measure air kerma. We measured absorbed dose in water with a waterproof ionization chamber set in a semi-customized phantom filled with water. Chambers were set on the rotation axis of the CT scanners. We studied the dose outside the acquisition volume. RESULTS: We quantified the influence of each parameter on the absorbed dose. We used our measurements to calculate the dose for different acquisition protocols. Also we evaluated the dose to organs distant from the acquisition area. CONCLUSION: This study is one step toward a systematic estimation of the dose delivered to patient during helical CT exams. To use these results in daily practice, we have to develop software using our measurements.

Equipment Design↗
PubMed2001

S-phase fraction and DNA ploidy in 633 T1T2 breast cancers: a standardized flow cytometric study.

The lack of a standardized methodology for quantifying DNA ploidy and S-phase fraction (SPF) by flow cytometry is hindering routine use of these markers in breast cancer management. In a retrospective clinical multicenter study, we validated a standardized flow cytometry protocol. We tested 633 frozen T(1)T(2), N(0)N(1), M(0) breast tumors obtained in four institutions. Cell preparation was standardized, and precise rules for data interpretation were followed. Three SPF classes were defined on the basis of tertiles after adjustment for ploidy. DNA aneuploidy was observed in 61.0% of cases. No significant difference was observed among centers. Aneuploidy and high SPF were associated with large tumor size, node involvement, high histological grade, and hormone receptor negativity. In the overall population (median follow-up, 69 months), patients with medium and high SPF values had shorter disease-free survival (DFS) than those with low SPF values (P < 0.0001). Ploidy had no significant influence. By Cox analysis, SPF, pN, and estrogen receptor status were independent predictors of DFS (P = 0.0002, P = 0.001, and P = 0.05). In node-negative patients, SPF was the only predictor of DFS (P = 0.01), whereas in node-positive patients, the risk of relapse increased with both high SPF (P = 0.003) and estrogen receptor negativity (P = 0.004). Low SPF values distinguished grade II tumors with a particularly good outcome. Our results strongly support the use of SPF in multicenter studies and clinical trials and suggest that node-negative patients with slowly proliferating tumors do not require systemic adjuvant therapy.

Adult↗
PubMed2000

Prognostic of DNA-synthesizing enzyme activities (thymidine kinase and thymidylate synthase) in 908 T1-T2, N0-N1, M0 breast cancers: a retrospective multicenter study.

Among the methodological approaches of tumor proliferation, thymidine kinase (TK) and thymidylate synthase (TS) assays take into account the specific pathways of pyrimidine synthesis. Studies pointing to a prognostic value of TK and TS in breast cancer involved small numbers of patients. We investigated the prognostic value of these enzymes and their combination in a large retrospective multicenter study. Nine hundred eight T1T2, N0N1, M0 primary breast cancer samples (median follow-up 68 months) were tested. TK and TS were measured in cytosols by using standardized radioenzymatic methods. Although a positive correlation was obtained between TK and TS (p<10(-5)), major discrepancies were observed in some tumors. High levels of both enzymes were associated with large tumor size, histological grade III and steroid receptor-negative tumors. Univariate analysis showed that TK, TS and their combination were predictive of poor metastasis-free (MFS) (p < 10(-4); p=0.004; p < 10(-4)) and disease-free survival (DFS) (p < 10(-4); p=0.007; p=0.0001). TK was selected as an independent factor for MFS in Cox analysis. It was the only variable selected in node-negative patients. Subgroups with specific outcomes, with possible therapeutic implications, were identified: a) in node-negative patients not receiving adjuvant treatment, TK values in the 4th quartile were associated with poor MFS (p=0.0002) and DFS (p=0.0005) as compared to the other quartiles; b) in node-positive patients receiving adjuvant chemotherapy, low levels of both TK and TS were associated with the highest survival rates (MFS: p=0.04; DFS: p=0. 03).

Adult↗
PubMed2000

Patient set-up using portal images: 2D/2D image registration using mutual information.

OBJECTIVE: Conformal radiation therapy requires accurate patient set-up for each fraction delivery. Electronic portal imaging devices allow the acquisition of portal images just before and even during dose delivery. However, the quantitative interpretation of these images in determining and correcting the patient's position remains uncertain, and automated methods are therefore being developed. Such methods must be usable for the different radiation therapy techniques. They must be robust and as automated as possible for use in clinical routines. This work was undertaken to establish the feasibility of 2D/2D registration for portal/portal and portal/simulator images in radiotherapy. MATERIALS AND METHODS: This paper describes an automated method based on the combination of calibration algorithms and pixel-based registration algorithms. We present experiments with the different imaging techniques, some of which use a phantom with and without a gold standard. Preliminary results obtained using patient data are also presented and discussed. RESULTS: The results obtained with a phantom demonstrated that this automated method for 2D/2D registration is fast, accurate, and robust, even in the case of blurred images for small treatment fields. CONCLUSIONS: Mutual information is a feasible method for 2D/2D portal/portal and portal/simulator image registration in radiotherapy.

Algorithms↗
PubMed2000

Effect of surface penetrating sealant on surface texture and microhardness of composite resins.

The application of Fortify (Bisco, Lombard, IL), an unfilled resin, to the surface of composite resin restorations is intended to fill in defects in the surface that persist despite polishing, improve marginal integrity, and increase these materials' resistance to abrasion. The aim of this study was to observe the surface texture by scanning electron microscopy and measure the microhardness of the surface. For each sample of composite resin covered with glaze, 40 measurements were made of the thickness of the resin. Measurements of the Vickers microhardness included three samples of composite resin, three samples of glaze, and six samples of composite resin covered with glaze. A relationship was established between microhardness and thickness. Scanning electron microscopy showed a noticeable improvement in the surface texture. Nevertheless, areas were seen in which glaze seemed very thin or even completely absent. Measurements of the thickness ranged from 0-70 microm. The mean microhardness of composite resin was 65.8 +/- 0.7, while the mean hardness of glaze was 7.3 +/- 0.7. The microhardness of the double layer was reduced, depending on the thickness of the glazing resin. The capacity of glaze to mask surface defects of composite resin was shown, but it was difficult to obtain a regular surface with liquid resin. The application of this product caused a decrease of the microhardness of the composite resin's surface.

Composite Resins↗
PubMed2000

Post-radiation severe xerostomia relieved by pilocarpine: a prospective French cooperative study.

BACKGROUND AND PURPOSE: The aim of the study was: (1) to confirm the action of pilocarpine hydrochloride (Salagen) against xerostomia: (2) to correlate the response to dose/volume radiotherapy parameters. MATERIALS AND METHODS: From June 1995 to February 1996, 156 patients with severe radiation induced xerostomia received pilocarpine hydrochloride orally. IS mg per day with a 5 mg optional increase at S weeks up to a daily dose of 25 mg beyond 9 weeks. RESULTS: One hundred and forty five patients are fully evaluable. Treatment compliance was 75%. Thirty eight patients (26%) stopped treatment before week 12 for acute intolerance (sweating, nausea, vomiting) or no response. No severe complication occurred. Ninety ses en patients (67%) reported a significant relief of symptoms of xerostomia at 12 weeks. Within 12 weeks, the size of the subgroup ith normal food intake almost doubled (13-24 patients) while the size of the subgroup with (nearly) impossible solid food ingestion decreased by 38% (47 vs. 29 patients). The impact on quality of life was considered important or very important by 77% of the responders. CONCLUSIONS: No difference was found according to dose/volume radiotherapy parameters suggesting that oral pilocarpine hydrochloride: (1) acts primarily by stimulating minor salivary glands: (2) can be of benefit to patients suffering of severe xerostomia regardless of radiotherapy dose/volume parameters: (3) all responders are identified at 12 weeks.

Administration, Oral↗
PubMed2000

Fast growing cervical carcinomas. A retrospective analysis of 20 IB-IIB FIGO.

INTRODUCTION: Fast growing cervix carcinomas have a pejorative outcome: they may occur quickly after cervical smears qualified as normal - within an interval from 12 to 18 months in women less than 50 years old, and involveing the endocervix. This retrospective analysis is aimed at assessing 5-year outcomes. MATERIALS AND METHODS: Twenty cases of fast-growing cancer of the uterine cervix classified according to the FIGO clinical staging system as IB (n=14), IIA (3), and IIB (3), have been reviewed and compared to a cohort of 160 cases not having this feature. As regard to fast-growing carcinoma, the median age was 41 years (range 25-50), and the median follow-up 22 months (8-213) as compared to 54 years (27-79) and 80 months (5-199) for the reference cohort. The comparison of the two cohorts shows only a difference of breakdown which concerns the histological pelvic lymph nodes status (P<0.05), more often positive in fast-growing forms. The treatment policy was equally distributed between a radio-surgical approach, cesium 137 intracavitary irradiation followed by radical hysterectomy and lymphadenectomy, or a definitive irradiation with pelvic external irradiation followed by cesium 137 intracavitary irradiation. RESULTS: Thirteen deaths are reported in the fast-growing series instead of 54 in the other series. The 5-year overall survival is, respectively, 34 (13-55) vs. 74% (68-82) (P<0.001), the loco-regional-free survival 58 (33-84) vs. 85% (79-81) (P<0.001), the 5-year metastasis-free survival 61 (38-84) vs. 84% (78-90) (P=0. 004). CONCLUSION: These poor results emphasize the need to intensify loco-regional therapy with a concurrent cisplatin-based chemotherapy within the framework of a multidisciplinary approach.

Adult↗
PubMed2000

Clinical impact of dosimetry quality assurance programmes assessed by radiobiological modelling of data from the thermoluminescent dosimetry study of the European Organization for Research and Treatment of Cancer.

The European Organization for Research and Treatment of Cancer (EORTC) Radiotherapy Group initiated its mailed thermoluminescence dosimetry (TLD) programme in 1986. The aim of the present study was to evaluate the clinical relevance of variations in beam output detected in the period 1993 to 1996. A total of 140 beam outputs were checked (26 for cobalt-60 units and 114 for linear accelerators) in 35 centres. Clinical dose-response data for tumour control and normal tissue morbidity were used to assess the variation in clinical outcome resulting from variability in beam output. For 75 checked beams with nominal accelerating potentials (n. a.p.) of 6 MV or less the mean ratio, +/- standard deviation (S.D.) of measured to stated output was 1.004+/-0.020. For 65 beams with n. a.p. of 8 MV or more, the ratio was 1.009+/-0.021. Even with this relatively high level of precision, broad distributions of estimated tumour control or normal tissue morbidity were found. In the 10% of the beams with the most pronounced underdosage, the loss in tumour control probability was estimated at 7-8 percentage points. Likewise, in the 10% of the beams with the most pronounced overdosage, the increase in mild/moderate morbidity was 19-22 percentage points. For severe morbidity the same beams raised the estimated incidence of severe complications from 5% to 9-10%. An estimation of the loss of uncomplicated cure probability was about 1% for both high and low energy beams. Sequential mailings considerably improved the uniformity of clinical outcome. We conclude that small deviations in beam output may lead to clinically important variations in outcome. Substantial reductions in the variation between measured and stated output can be achieved by sequential mailings. Mailed TLD checks should be an integral part of a continuously ongoing quality assurance activity in radiotherapy.

Dose-Response Relationship, Radiation↗
PubMed2000

Effect of endogenous and exogenous prostaglandin E(2) on interleukin-1 beta-induced cyclooxygenase-2 expression in human airway smooth-muscle cells.

We studied the effect of endogenous and exogenous prostaglandin E(2) (PGE(2)), a metabolite of arachidonic acid through the cyclooxygenase (COX) pathway, on interleukin (IL)-1 beta-induced COX-2 expression, using primary cultures of human bronchial smooth-muscle cells (HBSMC). Treatment with exogenous PGE(2) resulted in enhanced expression of IL-1 beta-induced COX-2 protein and messenger RNA (mRNA) as compared with the effect of the cytokine per se. Inhibition of PGE(2) production with a nonselective COX inhibitor (flurbiprofen, 10 microM) resulted in a significant reduction in IL-1 beta- induced COX-2 expression, supporting a role of endogenous COX metabolites in the modulation of COX-2 expression. None of the experimental conditions used in the study affected the expression of constitutive cyclooxygenase (COX-1). Treatment with cycloheximide to inhibit translation, and with dexamethasone or actinomycin D to inhibit transcription, linked the effect of PGE(2) to the transcriptional level of COX-2 mRNA rather than to a potential effect on protein and/or mRNA stabilization. PGE(2) increased adenylate cyclase activity in a concentration dependent manner, and forskolin, a direct activator of adenylate cyclase, caused a marked increase in IL-1 beta-dependent COX-2, suggesting the existence of a causal relationship between the two events. The same results were observed with salbutamol, a bronchodilator that acts by increasing cyclic adenosine monophosphate. The effect of PGE(2) on COX-2 expression may contribute to the hypothesized antiinflammatory role of PGE(2) in human airways, providing a self-amplifying loop leading to increased biosynthesis of PGE(2) during an inflammatory event.

Adenylyl Cyclases↗
PubMed2000

Phase II trial of up-front accelerated thoracic radiotherapy combined with chemotherapy and optional up-front prophylactic cranial irradiation in limited small-cell lung cancer. Groupe d'Oncologie Thoracique des Régions Alpines.

PURPOSE: To investigate the feasibility and outcome of bifractionated, up-front thoracic radiotherapy (TR) (45 Gy in 30 fractions of 1.5 Gy twice daily over 3 weeks) combined with chemotherapy (CT) (six cycles of cisplatin and etoposide) and optional low-dose, up-front prophylactic cranial irradiation (18 Gy in 10 fractions of 1.8 Gy twice daily over 5 days) in limited small-cell lung cancer. PATIENTS AND METHODS: CT (etoposide 100 mg/m(2) for 3 days and cisplatin 25 mg/m(2) for 3 days) was started on day 8 or 15 after the first TR treatment. In the five subsequent cycles, cisplatin was given as a single 100-mg/m(2) dose on day 1 every 4 weeks. A total of 52 patients were entered (41 men and 11 women); the median age was 55 years (range, 33 to 67 years). World Health Organization performance status was 0 in 34 patients, 1 in 16 patients, and 2 in two patients. Thirty-six patients (69%) received the full planned six cycles of CT. RESULTS: All treated patients were assessable for response. Thirty-one patients (60%) achieved a complete response, and 16 (30%) had a partial response. One-, 3-, and 4-year survival rates were 74% (95% confidence interval [CI], 60% to 84%), 34% (95% CI, 21% to 49%), and 32% (95 CI, 16% to 46%), respectively. The median survival time was 18 months. Event-free survival at 1 year was 45% (95% CI, 32% to 58%) and at 3 years, 30% (95% CI, 18% to 44%). The main radiation-related acute toxicity was esophageal: 38% of the patients experienced grade 3 or 4 acute toxicity. CT was well tolerated. Although grade 3/4 neutropenia was observed in 86% of the patients, only 4% presented with associated fever. Grade 3/4 nausea and vomiting was seen in 35% of patients. CONCLUSION: This trial demonstrates that up-front accelerated TR associated with CT is feasible, has acceptable toxicity, and shows considerable long-term survival potential.

Adult↗
PubMed2000

[Breast, cervical and colo-rectal simultaneous mass screening program for women 50 to 69 years old in Isere].

A cervical screening campaign is implemented in the Isere department since 1990 for women aged 50 to 69, together with breast cancer and colo-rectal cancer screening. The attendance rate is about 30% but a survey performed among this population shows that 68.6% of these women did presented for screening during the year following their invitation. One and a half per cent of all smears were abnormal or ASCUS smears. Cancer detection rate for invasive cancer and CIN III was 1.3/1000. General practitioners and gynaecologists took the same part in the programme. During a postal survey conducted among them, they declared that they felt concerned with cancer screening, even if they met some difficulties. This results suggest that nominative invitations and a good cooperation of GPs may improve the coverage of eligible women. For the future success of the National Programme, which is to be implemented in France, organisational arrangements have to be set up. The review of positive points and difficulties met by Isere's local programme may help to discuss it.

Aged↗
PubMed2000

[Multidisciplinary approach in the treatment of localized forms of cancer of the prostate].

Localized prostate cancer can be treated by surgery, 3D conformal radiotherapy, brachytherapy: age, clinical stage, Gleason grade, baseline PSA, multidisciplinary approach enable physicians to tailor the therapeutic strategy. Patients are more informed of therapeutic morbidity and health related quality of life and want to give their feeling. Clinical research remains mandatory to set up the treatment policy with more objectivity.

Brachytherapy↗
PubMed2000

[Image fusion methods for the repositioning of the patient in radiotherapy].

Conformal radiotherapy requires the accurate and reproducible setup of the patient for each fraction delivery. Megavoltage imaging could enable this. This requires the development of image processing and data fusion algorithms. We describe an automated method based on the use of mutual information for registration. Such a method does not require any preliminary segmentation of the images. This method has been extensively tested on phantom as well as on some patient data. The obtained results demonstrated that this automated method for 2D/2D registration is rapid, accurate and robust even in the case of blurred images for small treatment fields.

Humans↗