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Biomedical subjects

M Bolla

Publications and source records attributed to M Bolla.

At least 19 recordsLinked to original sources
PubMed2006

A topical nitric oxide-releasing dexamethasone derivative: effects on intraocular pressure and ocular haemodynamics in a rabbit glaucoma model.

BACKGROUND: Topical nitric oxide-releasing dexamethasone (NCX1021) may avoid the negative effects of dexamethasone phosphate. AIMS: To obtain more information on the role of nitric oxide in glaucoma and to compare a nitric oxide-releasing dexamethasone with dexamethasone phosphate with regard to intraocular pressure (IOP) and ocular haemodynamics in an experimental rabbit model. METHODS: Six rabbits were treated with dexamethasone phosphate 0.1% in the right eye and with NCX1021 in the left eye for 5 weeks. The parameters considered were IOP, nitric oxide marker levels in aqueous humour, ocular haemodynamics of ophthalmic artery (by means of colour Doppler imaging), expression of endothelial nitric oxide synthase (eNOS)in ciliary processes and histology of ciliary bodies. RESULTS: Dexamethasone increased IOP levels, NCX1021 did not. Nitrite and cyclic guanosine monophosphate levels in aqueous humour were lowered by dexamethasone and increased by NCX1021. Resistivity index of the ophthalmic artery was increased, eNOS expression was reduced and ciliary bodies showed histological lesions in dexamethasone-treated eyes, not in NCX1021-treated ones. CONCLUSIONS: NCX1021 may avoid the IOP increase, impairment of ocular blood flow and the morphological changes in the ciliary bodies possibly induced by corticosteroid treatment.

Animals↗
PubMed2006

[Retrospective analysis of 108 ductal carcinomas in situ of the breast treated by radiosurgery association].

PURPOSE: To evaluate survival and prognostic factors of 108 patients with clinically or mammographically detected ductal carcinoma in situ (DCIS), treated from 1980 to 1996 by complete local excision followed by external irradiation. PATIENTS AND METHODS: The median age was 51 (range 37-80). All the patients underwent surgery consisting of a wide resection of the mammary gland harbouring the tumour. The surgical specimens were sent to the pathologists to get information on histology and margin clearance; all the slides were reviewed by one of us to assess the tumoral diameter. External beam therapy was delivered within 8 weeks after surgery. The prescribed irradiation dose was 50 Gy in 25 fractions to be given in 5 weeks. The median duration of follow-up was 93 months (range 40-173). RESULTS: There were nine patients with local recurrence (8.3%); three patients had local recurrence of DCIS and six patients developed invasive breast cancer. The treatment of local recurrence consisted of mastectomy with or without axillary dissection (eight cases) and quadrantectomy (one case). The 5-year and 10-year ipsilateral recurrence-free rate was respectively 92 and 89%. The 10-year cause specific survival was 100%. In univariate analysis, size>or=10 mm, age<45 years old and margin status were significant P=0,02, P=0,03, P=0,005; margin status was significant in multivariate analysis (P<0,02). CONCLUSION: These results are in keeping with those of the literature. They could be improved by the mass screening campaign, which is going on since January 1990 among women aged 50-74 years.

Aged↗
PubMed2006

[Quantification of prostate movements during radiotherapy].

Decrease treatment uncertainties is one of the most important challenge in radiation oncology. Numerous techniques are available to quantify prostate motion and visualise prostate location day after day before each irradiation: CT-scan, cone-beam-CT-Scan, ultrason, prostatic markers... The knowledge of prostate motion is necessary to define the minimal margin around the target volume needed to avoid mispositioning during treatment session. Different kind of prostate movement have been studied and are reported in the present work: namely, those having a large amplitude extending through out the whole treatment period on one hand; and those with a shorter amplitude happening during treatment session one the other hand. The long lasting movement are mostly anterior-posterior (3 mm standard deviation), secondary in cranial-caudal (1-2 mm standard deviation) and lateral directions (0.5-1 mm standard deviation). They are mostly due to the rectal state of filling and mildly due to bladder filling or inferior limbs position. On the other hand, the shorter movement that occurs during the treatment session is mostly variation of position around a steady point represented by the apex. Ones again, the rectal filling state is the principle cause. This way, during the 20 minutes of a treatment session, including the positioning of the patient, a movement of less than 3 mm could be expected when the rectum is empty. Ideally, real time imaging tools should allow an accurate localisation of the prostate and the adaptation of the dosimetry before each treatment session in a time envelope not exceeding 20 minutes.

Environmental Monitoring↗
PubMed2005

[Conformal radiation therapy with or without intensity modulation in the treatment of localized prostate cancer].

Conformal radiation therapy has now to be considered as a standard treatment of localized prostatic adenocarcinomas. Using conformational methods and intensity modulated radiation therapy requires a rigorous approach for their implementation in routine, focused on the reproducibility of the treatment, target volume definitions, dosimetry, quality control, setup positioning. In order to offer to the largest number of patients high-dose treatment, the clinicians must integrate as prognostic factors accurate definition of microscopic extension as well as the tolerance threshold of critical organs. High-dose delivery is expected to be most efficient in intermediary risks and locally advanced diseases. Intensity modulated radiation therapy is specifically dedicated to dose escalation. Perfect knowledge of classical constraints of conformal radiation therapy is required. Using such an approach in routine needs a learning curve including the physicists and a specific quality assurance program.

Adenocarcinoma↗
PubMed2005

Pro-apoptotic effect of a nitric oxide-donating NSAID, NCX 4040, on bladder carcinoma cells.

Nitric oxide-releasing non steroidal anti-inflammatory drugs (NO-NSAIDs) are a promising class of compounds that cause cell cycle perturbations and induce apoptosis in cell lines from different tumors. We investigated the activity of a recently developed NO-NSAID (NCX 4040) in bladder cancer cell lines (HT1376 and MCR). Cells were treated with different drug concentrations for different exposure times. Cytostatic and cytocidal activity was tested by SRB assay and apoptosis was evaluated by TUNEL analysis, ANNEXIN V assay and fluorescence microscopy. To further investigate the cell death-inducing mechanisms of NCX 4040, we analyzed gp-170, caspase expression and mitochondrial membrane potential (Delta Psi) depolarization. NCX 4040 showed a striking cytocidal activity in both cell lines, reaching LC(50) at a 10-microM and 50-microM concentrations in HT1376 and in MCR cells, respectively, after an exposure of only 6 h followed by an 18-h washout. Apoptosis was triggered in up to 90% of cells and was associated with active caspase-3 expression and Delta Psi depolarization in both cell lines after a 6-h exposure. In conclusion, NCX 4040, which probably causes apoptosis via a mitochondrial-dependent mechanism, could prove to be a useful agent for improving bladder cancer treatment.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

EAU guidelines on prostate cancer.

OBJECTIVES: The first summary of the European Association of Urology (EAU) guidelines on prostate cancer was published in 2001. These guidelines have been continuously updated since many important changes affecting the clinical management of patients with prostate cancer have occurred over the past years. The aim of this paper is to present a summary of the 2005 update of the EAU guidelines on prostate cancer. METHODS: A literature review of the new data has been performed by the working panel. The guidelines have been updated and level of evidence/grade of recommendation added to the text. This enables readers to better understand the quality of the data forming the basis of the recommendations. RESULTS: A full version is available at the EAU Office or at . Systemic prostate biopsies under ultrasound guidance is the preferred diagnostic method and the use of periprostatic injection of a local anaesthetic can significantly reduce pain/discomfort associated with the procedure. Active treatment (surgery or radiation) is mostly recommended for patients with localized disease and a long life expectancy with radical prostatectomy being the only treatment evaluated in a randomized controlled trial. Follow-up is at large based on prostate specific antigen (PSA) and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy has become an option for selected patients with hormone refractory prostate cancer. CONCLUSION: The knowledge in the field of prostate cancer is rapidly changing. These EAU guidelines on prostate cancer summarize the most recent findings and put them into clinical practice.

Clinical Trials as Topic↗
PubMed2005

[Course and prognosis of basaloid squamous cell carcinoma: case-control study of 49 patients].

INTRODUCTION: The course and prognosis of basaloid squamous cell carcinoma (BSCC) are not well known. OBJECTIVES: To study the course and prognosis in a population of BSCC patients. MATERIALS AND METHODS: We analyzed a retrospective cohort of 49 patients with BSCC in comparison with a cross-matched population of 49 patients treated for well- to moderately differentiated squamous cell carcinoma (SCC). RESULTS: The statistical analysis showed that survival in BSCC group was lower than in the SCC group. Local recurrence in the BSCC group was not higher than in the SCC group, but mortality by distant metastasis was six times higher than in the SCC population. CONCLUSIONS: We consider BSCC patients as a high-risk population and we complete diagnosis explorations including a FDG-PET before curative treatment. We also recommend post-operative or exclusive radiotherapy which may be associated with concomitant chemotherapy.

Carcinoma, Basosquamous↗
PubMed2004

Effect of sono-abrasion in the microleakage of a pit and fissure sealant.

PURPOSE: To assess the microleakage of a pit and fissure sealant after preparing enamel with sono-abrasion, used alone or associated with acid etching. This technique was compared with classical enamel preparations i.e. acid etching and diamond bur associated with etching. MATERIALS AND METHODS: Ninety 3rd molars were used. In the mesial halves, the fissures were prepared with sono-abrasion and acid etching for 15 seconds. Then, the samples were randomly assigned to three groups of 30. They were either treated with acid etching alone (group 1), widened mechanically with a bur and etched for 15 seconds (group 2) or prepared with sono-abrasion alone (group 3). Then, the resin-based sealant was applied according to the manufacturer's recommendations. The teeth were thermocycled and placed in a 1% solution of methylene blue. The teeth showing microleakage and the means of infiltration were assessed with an image analysis system. RESULTS: The poorest results were obtained with sono-abrasion alone which showed a greater number of specimens with microleakage (73.3%) (p < 0.001). They also showed the highest mean of microleakage (0.85+/-0.79 mm vs 0.1+/-0.26 for acid; 0.35+/-0.85 for bur associated with etching p < 0.0001); and 0.19+/-0.45 for sono-abrasion associated with etching. CONCLUSION: No significant difference was noted between the three types of enamel preparation using etching. Sono-abrasion can be used for preparing dental enamel prior to sealing the tooth but it does not eliminate the need for etching.

Acid Etching, Dental↗
PubMed2003

In vitro action of Bordeaux red wine on the microhardness of human dental enamel.

Several studies have demonstrated that the regular and large consumption of wine is associated with increased risk of tooth erosion. Here, the effect of Bordeaux red wine on enamel was estimated by measuring changes in its Vickers microhardness. Thirty premolars were used; microhardness tests were performed on buccal areas before and after 10, 30, 90 and 120 s immersion in the wine (pH=3.9). Enamel surfaces were also observed by scanning electron microscopy. No statistically significant difference was found between the mean Vickers microhardness obtained at t=0 and 90 s, but slight signs of enamel demineralisation were observed with the scanning electron microscope. It appears that wine has no disastrous effect on the microhardness of dental enamel when the two are in contact for less than 90 s. When the exposure is for at least 120 s, it may become harmful, as the decrease in the microhardness of enamel was then significant (P<0.05).

Adolescent↗
PubMed2002

Estimating survival gain for economic evaluations with survival time as principal endpoint: a cost-effectiveness analysis of adding early hormonal therapy to radiotherapy in patients with locally advanced prostate cancer.

The problem of estimating expected outcomes for the economic evaluation of treatments for which the outcome of principal interest is (quality adjusted) survival time has so far not received sufficient attention in the literature. The best estimate of expected survival is mean survival time, but with censored survival data, the true survival time for all the subjects is not known, so the mean is not defined.A possible solution to this estimation problem is illustrated by a retrospective cost-effectiveness analysis of the addition of hormonal therapy to standard radiotherapy for patients with locally advanced prostate cancer. A recently proposed method is used to approach the problem caused by censored cost data, and the impact of uncertainty is assessed by bootstrap resampling techniques. Mean survival time is estimated by a restricted means analysis with the time point of restriction determined by statistical criteria. When average total costs and mean survival time is evaluated at this time point of restriction, the result is that the combined therapy (radiotherapy plus hormonal therapy) increases mean survival time by about 1 year, while reducing the costs per patient for the French health insurance system by 12 700 FF. The time point of restriction may also be determined by other criteria and mean survival time may be estimated by extrapolating the survival curves by means of various parametric survival distributions. We show that the exact results of the economic evaluation are decisively determined by the restriction time point chosen and the approach taken to estimate mean survival time.

Antineoplastic Agents, Hormonal↗
PubMed2002

Acute toxicity of conventional radiation therapy for high-risk prostate cancer in EORTC trial 22863.

OBJECTIVES: We analysed the acute toxicity observed in the European Organisation for Research and Treatment of Cancer (EORTC) randomised trial 22863 comparing conventional external irradiation with or without an agonist analogue of gonadotropin-releasing hormone in high-risk prostate cancer patients. METHODS: Four hundred five patients that received a dose of at least 30 Gy were considered evaluable for acute toxicity assessment. Toxicity was grouped in a few categories: general, genito-urinary, and lower gastro-intestinal. Univariate and multivariate analyses were performed using the World Health Organisation (WHO) toxicity score and grouping together toxicity scores in different bimodal and trimodal groups. RESULTS: Overall, our data show that age, previous surgery and irradiation dose are important predictive factors for acute toxicity, but not the use of combined hormone therapy. Fifteen percent of patients suffered of moderate to severe acute toxicity (WHO G3-G4). Life threatening toxicity was observed in six cases (1.5%). CONCLUSIONS: The assessment of toxicity combining in different groups the original five scores scale produced conflicting results similar to those commonly reported in literature. Interpretation of the role of pre-treatment factors with uneven distribution in the study requires careful evaluation. These data obtained with conventional curative irradiation of high-risk prostate cancer patients are proposed for comparison with results achieved using modern state-of-the-art irradiation techniques.

Adult↗
PubMed2002

[The French project ETOILE: review of clinical data for light ion hadrontherapy].

The Lawrence Berkeley Laboratory was the pioneer in light ions hadrontherapy with almost 2500 patients treated between 1957 and 1993 with Helium and Neon. The NIRS (National Institute For Radiological Science, Chiba, Japan) was the first dedicated medical centre for cancer with more than 1200 patients exclusively treated with carbon ion from 1994. A three-year 70 to 100% local control was reported for radio-resistant cancers, supporting the use of high LET particles. Hypo-fractionation was particularly explored for lung cancers and hepatocarcinoma (4 sessions only). Dose escalation studies demonstrated a tumour dose-effect and permitted to precise dose constraints for healthy tissues especially for the rectum. More than 140 patients were treated with carbon ion exclusively or associated with photons since 1997 in the GSI laboratory Gesellschaft Für Schwerionenforschung, Darmstadt, Germany). A very high local control was also obtained for radioresistant cancer of the base of the skull. Preliminary clinical data seem to confirm the expected therapeutic gain with light ions, due to their ballistic and radio-biological properties, and justify the European projects for the construction of dedicated medical facilities for cancers. The French "Etoile" project will be integrated in the European hadrontherapy network "Enlight", with the objectives to coordinate technologic, medical and economic features.

Carbon↗
PubMed2002

Periapical status, prevalence and quality of endodontic treatment in an adult French population.

AIM: The aim of this study was to determine the periapical status and the quality of root-canal treatment amongst an adult population attending the dental school in Nice, France during 1998. METHODOLOGY: Patients who attended the dental school for the first time during 1998 were included. Panoramic radiographs, taken by a trained radiology assistant, were used in this study. The periapical areas of all teeth with the exception of third molars, were examined and the technical quality of root fillings were evaluated for both apical extension and density. Statistical analyses were conducted using anova, Chi-square, Fisher's PLSD and Cohen's Kappa tests. RESULTS: The survey involved 344 patients: 180 females and 164 males. Males had significantly fewer natural remaining teeth than females (P<0.03). Similarly, the average number of root-filled teeth was lower for males (P<0.01). Nonroot-filled teeth (n=6126) had significantly fewer signs of periapical pathology than root-filled teeth (n=1429) (1.7% vs. 31.5%, P<0.0001). The majority of root fillings were poorly executed. There was a significant correlation between the presence of periapical pathology and inadequate root-canal fillings (P<0.001). CONCLUSIONS: The results of the present study indicate that many root-canal treatments were technically unsatisfactory in terms of quality and treatment outcome. There is a need for endodontic retreatment in the population examined.

Adult↗
PubMed2002

[Transmandibular buccopharyngectomy after radiotherapy for orpharyngeal cancer].

MATERIALS & METHODS: We present a retrospective study of 95 patients with recurrence of oropharyngeal carcinoma after exclusive radiotherapy. The treatment consisted in a salvage composite resection in all cases. RESULTS & DISCUSSION: Since the use of muscular flaps, the post-operative complications have been relatively minimised but the carcinologic results were disappointing: only 20% of patients were alive free of disease at 5 years. The main prognostic factors for overall survival were the stage rT of the relapse, the histologic invasion of the nodes and the quality of the resection. The anatomic site of relapse did not influence the survival. CONCLUSION: Our serie confirms the high frequency of second primary tumors in oropharyngeal cancers. Rigorous selection of patients for exclusive radiotherapy is mandatory to decrease the number of relapses and might avoid salvage surgery.

Adult↗
PubMed2001

Modulation of COX-2 expression by statins in human aortic smooth muscle cells. Involvement of geranylgeranylated proteins.

Cyclooxygenase (COX)-2 and COX-1 play an important role in prostacyclin production in vessels and participate in maintaining vascular homeostasis. Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, which is crucial in cholesterol biosynthesis. Recently, cholesterol-independent effects of statins have been described. In this study, we evaluated the effect of two inhibitors of HMG CoA reductase, mevastatin and lovastatin, on the production of prostacyclin and the expression of COX in human aortic smooth muscle cells. Treatment of cells with 25 microm mevastatin or lovastatin resulted in the induction of COX-2 and increase in prostacyclin production. Mevalonate, the direct metabolite of HMG CoA reductase, and geranylgeranyl-pyrophosphate reversed this effect. GGTI-286, a selective inhibitor of geranylgeranyltransferases, increased COX-2 expression and prostacyclin formation, thus indicating the involvement of geranylgeranylated proteins in the down-regulation of COX-2. Furthermore, Clostridium difficile toxin B, an inhibitor of the Rho GTP-binding protein family, the Rho selective inhibitor C3 transferase, and Y-27632, a selective inhibitor of the Rho-associated kinases, targets of Rho A, increased COX-2 expression whereas the activator of the Rho GTPase, the cytotoxic necrotizing factor 1, blocked interlukin-1alpha-dependent COX-2 induction. These results demonstrate that statins up-regulate COX-2 expression and subsequent prostacyclin formation in human aortic smooth muscle cells in part through inhibition of Rho.

Amides↗
PubMed2001

Odontometrical method useful in determining gender and dental alignment.

Rao et al.'s method of sex determination, which considers the mandibular canine index (MCI) is one giving satisfactory results. However, they did not take occlusion into consideration. The aim of this study, therefore, was to evaluate the effectiveness of this method with respect to tooth alignment. The study population involved the students enrolled in the University of Nice-Sophia Antipolis. Two hundred and ten girls and 214 boys were randomly sampled (1/20). Both tooth sizes and dental arches were measured using a vernier calliper to calculate MCI for both sexes. The results were compared to standard MCI, taking into account tooth alignment.Rao et al.'s method can only be used in the case of correct lower-anterior dental alignment and by using the standard MCI of the local population.

Adult↗
PubMed2001

Apolipoprotein E4 and coronary heart disease in middle-aged men who smoke: a prospective study.

BACKGROUND: The common isoforms of apolipoprotein E (apoE), E2, E3, and E4, are important determinants of plasma lipid concentrations, and the epsilon4 allele is associated with raised risk of coronary heart disease. We investigated whether the effect of smoking on coronary heart disease risk is affected by APOE genotype. METHODS: We enrolled 3052 middle-aged men who were free of coronary heart disease for prospective cardiovascular surveillance in the second Northwick Park Heart Study (NPHSII). Smoking habit was ascertained at baseline and yearly by questionnaire. APOE genotype was identified by PCR and restriction enzyme digestion. Endpoints were fatal coronary heart disease, non-fatal myocardial infarction, and coronary artery surgery and silent myocardial infarction at follow-up. FINDINGS: During 18836 person years of surveillance, 96 men had an acute myocardial infarction, 26 needed coronary artery surgery, and 14 had silent myocardial infarctions. Compared with never-smokers, risk of coronary heart disease in ex-smokers was 1.34 (95% CI 0.86-2.08) and in smokers it was 1.94 (1.25-3.01). This risk was independent of other classic risk factors. In never-smokers, risk was closely similar in men with different genotypes. Risk in men homozygous for the epsilon3 allele was 1.74 (1.10-2.77) in ex-smokers and 1.68 (1.01-2.83) in smokers, whereas in men carrying the epsilon4 allele risk was 0.84 (0.40-1.75) and 3.17 (1.82-5.50), respectively, with no significant differences in risk in the epsilon2 carriers. For the epsilon3 group, the genotype effect on risk was no longer significant after adjustment for classic risk factors (including plasma lipids). However, even after adjustment, smokers who were carriers of the epsilon4 allele, showed significantly raised risk of coronary heart disease compared with the non-smoking group (2.79, 1.59-4.91, epsilon4-smoking interaction p=0.007). INTERPRETATION: Smoking increases the risk of coronary heart disease in men of all genotypes but particularly in men carrying the epsilon4 allele.

Apolipoprotein E4↗