[Muir-Torre syndrome and Turcot syndrome]. / Syndrome de Muir-Torre et syndrome de Turcot.

INTRODUCTION: Lynch syndrome (LS) is a syndrome that carries a genetic predisposition to certain cancers associating, either in a single individual or in a family, a visceral tumour, mainly colorectal, with a high risk of other synchronous or metachronous cancers. LS is linked with mutations in the genes coding for proteins in the DNA repair system. Phenotypic variants of SL exist, including Muir-Torre syndrome (MTS) and Turcot syndrome (TS), both of which predispose to colorectal cancer. They may be distinguished by the presence of benign or malignant sebaceous tumours in MTS, and tumours of the central nervous system in TS. PATIENTS AND METHODS: A 59-year-old man, with a history of right colon cancer at the age of 36 years, consulted for a nose lesion shown by histopathological examination to be a sebaceous tumour. Immunohistochemistry revealed loss of expression of proteins MSH2 and MSH6, strongly suggesting a diagnosis of MTS. Eight years earlier, the man's son had developed a fatal glioblastoma; given the paternal phenotype of MTS, the hypothesis of TS in the son is probable. DISCUSSION: This case suggests that several variants of Lynch syndrome may be seen within the same family. It raises the issue of screening for cerebral tumours in patients with MTS and in their family members, even though such a recommendation does not exist; current recommendations in fact consist primarily of gastrointestinal and gynaecological monitoring.

Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) syndrome is a childhood cancer predisposition syndrome involving biallelic germline mutations of MMR genes, poorly recognised by clinicians so far. METHODS: Retrospective review of all 31 patients with CMMRD diagnosed in French genetics laboratories in order to describe the characteristics, treatment and outcome of the malignancies and biological diagnostic data. RESULTS: 67 tumours were diagnosed in 31 patients, 25 (37%) Lynch syndrome-associated malignancies, 22 (33%) brain tumours, 17 (25%) haematological malignancies and 3 (5%) sarcomas. The median age of onset of the first tumour was 6.9 years (1.2-33.5). Overall, 22 patients died, 9 (41%) due to the primary tumour. Median survival after the diagnosis of the primary tumour was 27 months (0.26-213.2). Failure rate seemed to be higher than expected especially for T-cell non-Hodgkin's lymphoma (progression/relapse in 6/12 patients). A familial history of Lynch syndrome was identified in 6/23 families, and consanguinity in 9/23 families. PMS2 mutations (n=18) were more frequent than other mutations (MSH6 (n=6), MLH1 (n=4) and MSH2 (n=3)). CONCLUSIONS: In conclusion, this unselected series of patients confirms the extreme severity of this syndrome with a high mortality rate mostly related to multiple childhood cancers, and highlights the need for its early detection in order to adapt treatment and surveillance.

Therapeutic properties of glass-ionomer cements: Their application to orthodontic treatment.

Fluoride has been shown to be an effective agent in the prevention of caries during orthodontic treatment. Resin-modified glass-ionomer cements possess therapeutic anticariogenic properties acting as a fluoride reservoir and releasing fluoride into the environment, particularly at low pH where there is a threat of enamel demineralisation and white spot lesions (WSL's). Patient compliance to instructions in standard oral hygiene measures limits the success of caries prevention and the routine use of glass-ionomer cements can mitigate the lack of compliance, although RMGIC's are not a panacea against WSL's. The adhesion of GIC's to the enamel surface is a physicochemical bond rather than a mechanical bond which reduces the risk of iatrogenic damage to the enamel when bonding and debonding attachments. RMGIC's can be recommended as a bonding adhesive for all attachments but one needs to be selective when bonding molar attachments to avoid occlusal interferences as masticatory forces can be high in these areas.

The contribution of germline rearrangements to the spectrum of BRCA2 mutations.

BACKGROUND: Few germline BRCA2 rearrangements have been described compared with the large number of germline rearrangements reported in the BRCA1 gene. However, some BRCA2 rearrangements have been reported in families that included at least one case of male breast cancer. OBJECTIVE: To estimate the contribution of large genomic rearrangements to the spectrum of BRCA2 defects. METHODS: Quantitative multiplex PCR of short fluorescent fragments (QMPSF) was used to screen the BRCA2 gene for germline rearrangements in highly selected families. QMPSF was previously used to detect heterozygous deletions/duplications in many genes including BRCA1 and BRCA2. RESULTS: We selected a subgroup of 194 high risk families with four or more breast cancers with an average age at diagnosis of < or = 50 years, who were recruited through 14 genetic counselling centres in France and one centre in Switzerland. BRCA2 mutations were detected in 18.6% (36 index cases) and BRCA1 mutations in 12.4% (24 index cases) of these families. Of the 134 BRCA1/2 negative index cases in this subgroup, 120 were screened for large rearrangements of BRCA2 using QMPSF. Novel and distinct BRCA2 deletions were detected in three families and their boundaries were determined. We found that genomic rearrangements represent 7.7% (95% confidence interval 0% to 16%) of the BRCA2 mutation spectrum. CONCLUSION: The molecular diagnosis of breast cancer predisposition should include screening for BRCA2 rearrangements, at least in families with a high probability of BRCA2 defects.

[Thromboembolic accidents in postmenopausal patients with adjuvant treatment by tamoxifen. Frequency, risk factors and prevention possibilities]. / Accidents thromboemboliques chez les patientes ménopausées sous traitement adjuvant par tamoxifène. Fréquence, facteurs de risque et possibilités de prévention.

Tamoxifen is the anti-estrogen the most widely used in breast cancer. The duration of its prescription, as adjuvant treatment, tends to increase (5 years, and even more) and now it is used in chemoprevention. A slight increase of thromboembolic complications was noted in some studies. This article evaluates the frequency of thromboembolic accidents (TEA) in 441 postmenopausal patients treated by an association of conservative radiosurgery, tamoxifen +/- chemotherapy, for a breast carcinoma T0, T1T2 < 4 cm. Nineteen patients (4.3%), all in remission, presented a TEA, between 1 and 44 months after the beginning of the tamoxifen treatment. We observed seven pulmonary embolisms (PE), 11 deep venous thromboses (DVT) and an acute arterial ischemia. Two patients aged 74 and 80 years died, the others had a favourable evolution under anticoagulant treatment. Among these 19 patients, six presented known risks factors (phlebitis, cardiovascular disorders) and ten had a "favouring circumstance" aggravating the risk of TEA (surgical operation, severe infection, fracture). Their median age was 65 years (61 for all the 441 patients). We noted eight cases of breast lobular cancer (42%) among these 19 patients (11% for all the patients). Among postmenopausal patients, the indication of tamoxifen must be evaluated according to the benefits expected in those with high risk factors of TEA (history of heart failure, obesity, spread varix, age > 65 years). In case of DVT and/or PE, this treatment seems contra-indicated. In case of "favouring circumstances", a hypocoagulant or systematic anticoagulant treatment must be proposed. In case of combined chemotherapy, it is better to start tamoxifen at the end of the treatment. These simple prophylactic measures should allow to reduce significantly the risk of TEA in postmenopausal patients with adjuvant anti-estrogenotherapy.

[Germ-line mutations of the BRCA1 gene in northeastern France]. / Mutations germinales du gène BRCA1 dans le Nord-Est de la France.

Thirty-seven breast/ovarian or breast-only cancer families selected on a regional basis have been analyzed for mutations at BRCA1. By combining direct sequence analysis and protein truncation test, mutations were detected in 14 families (38%). We found seven different mutations, two of which have not been described before. Mutations at BRCA1 were present in 60% of breast/ovarian and 32% of breast-only cancer families. Mutations were frequent in families with at least one breast cancer case before age 40 (44%) and/or one bilateral breast cancer case (54%). Two mutations, namely 3600del11 and G1710X, are frequent in the population native from northeastern France. Oriented BRCA1 analysis should facilitate carrier detection in breast and/or ovarian cancer families stemming from this French area.

[Li-Fraumeni syndrome: update, new data and guidelines for clinical management]. / Le syndrome de Li-Fraumeni: mise au point, données nouvelles et recommandations pour la prise en charge.

The Li-Fraumeni syndrome (LFS) is an inherited form of cancer, affecting children and young adults, and characterized by a wide spectrum of tumors, including soft-tissue and bone sarcomas, brain tumours, adenocortical tumours and premenopausal breast cancers. In most of the families, LFS results from germline mutations of the tumor suppressor TP53 gene encoding a transcriptional factor able to regulate cell cycle and apoptosis when DNA damage occurs. Recently, germline mutations of hCHK2 encoding a kinase, regulating cell cycle via Cdc25C and TP53, were identified in affected families. The LFS working group recommendations are the following: (i) positive testing (screening for a germline TP53 mutation in a patient with a tumor) can be offered both to children and adults in the context of genetic counseling associated to psychological support, to confirm the diagnosis of LFS on a molecular basis. This will allow to offer to the patient a regular clinical review in order to avoid a delay to the diagnosis of another tumor; (ii) the 3 indications for positive testing are: a proband with a tumor belonging to the narrow LFS spectrum and developed before age 36 and, at least, first- or second-degree relative with a LFS spectrum tumor, before age 46, or a patient with multiple primary tumors, 2 of which belonging to the narrow LFS spectrum, the first being developed before 36 or a child with an adenocortical tumour; (iii) presymptomatic testing must be restricted to adults; (iv) the young age of onset of the LFS tumors the prognosis of some tumors, the impossibility to ensure an efficient early detection and the risk for mutation carriers to develop multiple primary tumors justify that prenatal diagnosis might be considered in affected families.

[Preliminary results of a randomized trial comparing the efficacy of standard heparin with that of fragmine, a low molecular weight heparin, in the prevention of postoperative thrombosis in cancer surgery]. / Résultats préliminaires d'un essai randomisé comparant l'efficacité d'une héparine standard à celle de la fragmine, une héparine de bas poids moléculaire, dans la prophylaxie des thromboses post-opératoires en chirurgie oncologique.

Low molecular weight heparins have stimulated much interest because of their supposedly more selective action on Xa factor. A randomized study in 50 patients compared efficacy of low doses of a standard heparin, calciparin (5,000 IU/8 h) with that of a low molecular weight heparin, fragmine (Kabi 2165) (5,000 anti-Xa U/24 h), in the prophylaxis of postoperative thrombosis after oncologic surgery. Three of 25 patients receiving calciparin developed pulmonary embolism, as against one of 25 treated with fragmine who developed a periphlebitis. Hemorrhagic complications were comparable in the two groups. Anti-Xa activity was significantly higher in the fragmine group, whereas platelet counts, cephalin times with activator and anti-IIa activity were similar. These findings indicate equal efficacy of fragmine and calciparin in the prophylaxis of post-oncology surgery venous thrombosis.

[Congenital hypertrophy of retinal pigment epithelium: a marker in familial adenomatous polyposis]. / L'hypertrophie congénitale de l'épithélium pigmenté rétinien: un marqueur de la polypose adénomateuse familiale.

PURPOSE: Familial adenomatous polyposis (FAP) is an inherited autosomal dominant disorder with marked propensity for malignant transformation. The potential for congenital hypertrophy of retinal pigment epithelium (CHRPE) as a phenotypic marker for this disease is recognized. MATERIAL AND METHODS: We report our investigations in 11 families with familial adenomatous polyposis. CHRPE characteristics were described and the relations between genotype and phenotype and those between CHRPE and severity of FAP are discussed. DISCUSSION: All members of the family should undergo retinal examination at the earliest age possible. The results give an indication of the severity of the intestinal disease and allow an approximate localization of the mutation in the coding sequence, leading to a more rapid genetic analysis.

A new self-curing resin-modified glass-ionomer cement for the direct bonding of orthodontic brackets.

A new self-curing (chemically-cured), resin-modified glass-ionomer cement, Fuji Ortho (GC International Japan) is based on the technology of hybrid glass-ionomer restorative materials and features chemical adhesion to tooth structure and long-term fluoride release. These materials do not require acid etching of the tooth for adhesion, thereby preserving the integrity of the enamel prisms. This paper describes the clinical use of Fuji Ortho for the direct bonding of orthodontic (metal) brackets.

Bonding and debonding with a light-activated resin-modified glass-ionomer cement.

Light-activated resin-modified glass-ionomer cements have been shown to be satisfactory adhesives for the direct bonding of metal brackets in selected cases. They have the advantage over composite resins in that no etching of the enamel is required, thereby preserving the integrity of the enamel prisms. Debonding of brackets carries less risk of mechanical damage to tooth structure and the long-term fluoride leach reduces the incidence of demineralisation around bracket margins. This paper describes the clinical technique for bonding metal brackets with these materials and some recommendations when debonding.

A clinical comparison of different powder: liquid ratios of two glass ionomer cements on the retention of orthodontic molar bands.

The clinical significance of adding 50 percent more powder to a standard mix of two glass ionomer luting cements was assessed. Failure rates (loose bands) were recorded over a 12 month period and removal of cement was subjectively assessed at the time of band removal. There was no significant difference between Fuji I standard and heavy mix or between Ketac Cem standard and heavy mix. Cement deposits at band removal were always on enamel surfaces. The heavier mix of each cement was far more difficult to remove, and may have significance in restorative dentistry. There were no cases of enamel demineralisation around the margins of bands at the time of band removal.

A 12-month clinical study comparing four glass ionomer cements for the cementation of orthodontic molar bands.

Four different glass ionomer cements were evaluated in vivo as luting agents for orthodontic molar bands. A sample of 199 patients with full fixed appliances (Begg Light Wire) were monitored over a period of 12 months during active treatment for loose molar bands. Failures for each cement were: Fuji I, 2.5 percent, Fuji II, 4.5 percent, Ketac-Cem, 4.0 percent and Hy-Bond Luting, 3.0 percent. Chi squared tests showed no statistical difference in failure rates for each cement.

The bond strength of a glass polyalkenoate cement to enamel and stainless steel.

An in vitro evaluation of bond strength of a glass polyalkenoate cement to human dental enamel and stainless steel is reported. Shear testing of adhesive strength was measured over time at 23 degrees C following a one minute mixing time. It was found that there is a significant difference in bond strengths between enamel and stainless steel with strength to enamel the greater. Bond strength increases with time with very low strength measured within 30 minutes from commencement of mixing.

French women's breast self-examination practices with time after undergoing BRCA1/2 genetic testing.

To assess the impact of BRCA1/2 genetic test results on cancer-free women's breast-self-examination (BSE) practices and to prospectively determine their influence on psychological functioning. A prospective longitudinal study on French women's BSE practices and frequencies in BRCA1/2 carriers (N = 217) and non-carriers (N = 313) 1 and 2 years following disclosure of the test results, along with psychological factors predicting BSE practices. Before disclosure, BSE was practised by 47.2% of the women, and increased to 57.3% 1 year later. No change in the women's practices was noted between 12 and 24 months after the test. Carriers and non-carriers practicing regularly BSE at baseline were, respectively 8 to 6 times more likely to be practising BSE regularly at 12 months after being tested. Among the carriers, having fewer depressive symptoms at baseline and believing in the ability of BSE to detect breast cancer were found to be the most decisive factors associated with BSE practices 1 year after disclosure, following adjustment for BSE baseline practices. Among the non-carriers, believing in the ability of BSE to detect breast cancer, greater post-test anxiety, and a higher perceived risk of breast cancer were found to be predictors of post-test BSE practices after adjusting for BSE baseline practices. In France, where performing BSE is neither mandatory nor recommended, an increase in BSE practices was found to occur after disclosure of women's genetic test results, regardless of their carrier status.

Professionalism: what is it, why should we have it and how can we achieve it?

In this paper we argue that the terms 'profession', 'professional' and 'professionalism' provide us with important insights into the practice of dentistry and the priorities for the continuing development of dentistry as a profession. More significantly, we suggest that this understanding can assist us in designing continuing professional development (CPD) programmes aimed at maintaining the professionalism of dentists throughout their working lives. A CPD framework is required to support both the new graduate to develop from novice to expert as well as support experienced practitioners to maintain their expertise within a rapidly changing environment. Rather than an onerous task, CPD should be a positive and enjoyable experience, self-motivated to improve job satisfaction and self-confidence. Research is currently being undertaken to determine what is good CPD for the practising dentist with a view to recommending strategies based on sound educational theory.