Composite resin fillings and inlays. An 11-year evaluation

The purpose of this randomized, clinical study was to evaluate the clinical performance of composite resin materials used for fillings and indirect inlays. Twenty-eight sets of five class II restorations (two fillings, three inlays) were placed in 88 premolars and 52 molars in 28 adults. Brilliant Dentin and Estilux Posterior were used for both fillings and inlays, and SR-Isosit for inlays only. After 11 years, 27 sets of restorations (96%) were evaluated clinically using modified United States Public Health Service criteria. Replaced or repaired restorations were observed in 16% of the fillings and 17% of the inlays, and a further 5% of the restorations were replaced for reasons not related to the restoration. The remaining 107 restorations exhibited optimal ratings in 30% of the fillings and 12% of the inlays (P<0.05) and acceptable ratings in 70% and 88%, respectively. The reasons for failure were fracture of restoration (four fillings, five inlays), secondary caries (two fillings, four inlays), fracture of tooth (two inlays), loss of proximal contact (two fillings), and loss of restoration (one inlay). Failures were seen more frequently in molar than premolar restorations (P<0.05), with no significant difference between fillings and inlays or between the five types of restoration (P>0.05).     

Hair loss,insulin resistance,and heredity in middle-aged women. A population-based study

CONTEXT: The association of androgenic alopecia (AGA) with insulin resistance, coronary artery disease and hypercholesterolemia has been previously reported in men, but no such association has been reported in women with female androgenic alopecia (AGA). Female AGA has usually been linked with hyper-androgenism and hirsutism and, most recently, also with polycystic ovarian syndrome (PCOS), even though epidemiological documentation of the latter association is scanty. Polycystic ovarian syndrome is quite common among Caucasian women, and its association with insulin resistance is well documented. OBJECTIVES AND DESIGN: The aim of this study was to obtain a more precise estimation of the prevalence on female AGA and to describe its possible connections with insulin resistance linked parameters and with paternal and maternal family history of alopecia. A cross-sectional population based cohort survey was carried out in the City of Oulu, Finland in 1998. SETTING AND PARTICIPANTS: As a part of a population based cohort study the hair status of 324 women aged 63 years was assessed by a modification of Ludwig's scale. The background data consisting of anthropometric measures (weight, height, body mass index, waist, hip and neck circumferences), smoking status, chronic diseases and their medication as well as the family history of AGA were collected by questionnaires and interviews made by study nurses and in clinical examination. Blood samples for laboratory tests were taken on the same occasion. RESULTS: The prevalence of extensive loss of hair (at least grade II or III on Ludwig's scale) was quite high (31.2%). The insulin resistance associated parameters, such as waist and neck circumferences, abdominal obesity measured by waist-to-hip ratio, mean insulin concentration (11.3 mU/l versus 9.95 mU/l, p=0.02) or urinary albumin-to-creatinine ratio (1.80 versus 1.58, p=0.01), were significantly higher in women with extensive hair loss compared to those with normal hair or only minimal hair loss (grade I on Ludwig's scale). The women belonging to the highest quintiles of neck or waist circumferences had significantly increased risk for extensive hair loss compared to those with normal hair or minimal hair loss, the unadjusted ORs being 2.25 (95% CI, 1.26-4.03) and 1.75 (95% CI, 1.00-3.07), respectively. Similarly in women with hyperinsulinemia (fs-insulin >10 mU/l), microalbuminuria (urinary albumin-to-creatinine ratio exceeding the highest microalbuminuria decile (>2.5 mg/mmol) and paternal history of AGA the ORs for alopecia were increased being 1.65 (95% CI, 1.02-2.67), 2.39 (95% CI, 1.21-4.73) and 2.08 (95% CI, 1.26-3.44). All of these ORs, except those for highest quintiles of waist and neck circumferences remained significant in multiple adjusted models. CONCLUSIONS: According to the results of this study, female AGA (grade II or III on Ludwig's scale) was quite common among Finnish women aged 63 years. Our results support the hypothesis that women with some markers of insulin resistance have significantly increased risk for female AGA. Paternal history of alopecia seemed to be more common in female AGA compared to women with normal or minimal loss of hair.     

Randomized trial of single agent paclitaxel given weekly versus every three weeks and with peroral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum

The aim of this study was to evaluate the efficacy and toxicity of paclitaxel given at the same dose intensity and administered weekly (arm A) or every 3 weeks (arm B), and to assess the safety of intravenous steroids versus standard peroral premedication. Two hundred and eight patients with advanced ovarian cancer previously treated with no more than one platinum-containing regimen were randomized to receive either a weekly infusion of paclitaxel or an infusion every 3 weeks. The median delivered dose intensity was 77.6 mg/m 2 /week in the weekly arm, and 72.7 mg/m 2 /week in the every 3 weeks arm. WHO grade 3-4 hematological and non-hematological toxicity occurred more frequently in arm B. No difference in number of severe events of hypersensitivity, response rate, time to progression or survival between arms was observed. Weekly paclitaxel at a dose of 67 mg/m 2 /week was found to have a better safety profile and seemed to be as effective as the equivalently dosed schedule every 3 weeks. Intravenous steroids are a safe alternative to oral steroids.     

SHP-2 is involved in heterodimer specific loss of phosphorylation of Tyr771 in the PDGF beta-receptor

We have previously shown that the binding site for GTPase activating protein of Ras (RasGAP) in the PDGF beta-receptor, Tyr771, is phosphorylated to a much lower extent in the heterodimeric configuration of PDGF alpha- and beta-receptors, compared to the PDGF beta-receptor homodimer. The decreased recruitment of the RasGAP to the receptor leads to prolonged activation of the Ras/MAP kinase pathway, which could explain the increase in mitogenicity seen upon induction of heterodimers. The molecular mechanism underlying these differences was investigated. We could show that the loss of phosphorylation of Tyr771 was dependent on presence of intact binding sites for the protein tyrosine phosphatase SHP-2 on the PDGF beta-receptor. Thus, in PDGF receptor mutants in which binding of SHP-2 was lost, a higher degree of phosphorylation of Tyr771 was seen, while other phosphorylation sites in the receptor remained virtually unaffected. Thus, SHP-2 appears to play an important role in modulating phosphorylation of Y771, thereby controlling RasGAP recruitment and Ras/MAP kinase signaling in the heterodimeric configuration of the PDGF receptors.     

Association of chromosome 19q13.2-3 haplotypes with basal cell carcinoma: tentative delineation of an involved region using data for single nucleotide polymorphisms in two cohorts

We have previously used single nucleotide polymorphisms to detect an association of basal cell carcinoma (BCC) in Caucasian Americans and Danes with the genome region 19q13.2-3, which contains several genes involved in the nucleotide excision repair of DNA. In this exploratory paper we have extended the data and used them in a chromosomal scan. The results indicate the presence of a gene variation modulating the risk of developing BSS in a submegabase region including and surrounding the gene RAI. Specifically, persons that are homozygous for the haplotype RAI intron 1(A) RAI exon 6(A) appear at increased risk for BCC. In addition, we have looked for possible synergisms between all pairs of markers. We find that a marker in GLTSCR1, presumably separated from RAI by several million bases, supplements the most significant marker in RAI in separating cases from controls, which may suggest the presence of an independent, risk-modulating variation in this second gene region.     

Inter-individual variation,seasonal variation and close correlation of OGG1 and ERCC1 mRNA levels in full blood from healthy volunteers

The mRNA levels of the nucleotide excision DNA repair gene ERCC1 and the base excision DNA repair gene OGG1 were quantified in 43 healthy volunteers in a dietary intervention trial as markers for the DNA repair capacity. Nine samples were collected from each subject over a period of 52 days. Sampling took place from January to May. The mRNA levels of OGG1 and ERCC1 correlated closely (r = 0.86, P < 0.0001) after normalization to either 18S ribosomal RNA or to beta-actin mRNA. The levels of OGG1 and ERCC1 mRNA were relatively constant within an individual with intra-individual correlation (R(2) = 0.45-0.46) in a General Linear Model. The amounts of ERCC1 and OGG1 relative to 18S RNA were doubled in May compared with January. This coincided with an increase in the monthly influx of sunlight from 18 MJ/m(2) in January to 242 MJ/m(2) in May. The mRNA levels of both ERCC1 and OGG1 were positively correlated to the average daily influx of sunlight in the previous 30 and 5 days (r = 0.49; r = 0.37, respectively, P < 0.001). There were no significant effects of the dietary interventions. The inter-individual variation was 5-10-fold, which is more than the observed 2-3-fold seasonal variation. Thus, despite seasonal variation of the individual mRNA levels, the inter-person variation is still far larger than the intra-person variation, supporting the use as biomarkers.     

Increased mRNA expression levels of ERCC1, OGG1 and RAI in colorectal adenomas and carcinomas

Background  

The majority of colorectal cancer (CRC) cases develop through the adenoma-carcinoma pathway. If an increase in DNA repair expression is detected in both early adenomas and carcinomas it may indicate that low repair capacity in the normal mucosa is a risk factor for adenoma formation.     

p53 mutations in leukemia and myelodysplastic syndrome after ovarian cancer.

PURPOSE: Although p53 mutations occur in alkylating agent-related leukemias, their frequency and spectrum in leukemias after ovarian cancer have not been addressed. The purpose of this study was to examine p53 mutations in leukemias after ovarian cancer, for which treatment with platinum analogues was widely used. EXPERIMENTAL DESIGN: Adequate leukemic or dysplastic cells were available in 17 of 82 cases of leukemia or myelodysplastic syndrome that occurred in a multicenter, population-based cohort of 23,170 women with ovarian cancer. Eleven of the 17 received platinum compounds and other alkylating agents with or without DNA topoisomerase II inhibitors and/or radiation. Six received other alkylating agents, in one case, with radiation. Genomic DNA was extracted and p53 exons 5, 6, 7, and 8 were amplified by PCR. Mutations and loss of heterozygosity were analyzed on the WAVE instrument (Transgenomic) followed by selected analysis by sequencing. RESULTS: Eleven p53 mutations involving all four exons studied and one polymorphism were identified. Genomic DNA analyses were consistent with loss of heterozygosity for four of the mutations. The 11 mutations occurred in 9 cases, such that 6 of 11 leukemias after platinum-based regimens (55%) and 3 of 6 leukemias after other treatments (50%) contained p53 mutations. Two leukemias that occurred after treatment with platinum analogues contained two mutations. Among eight mutations in leukemias after treatment with platinum analogues, there were four G-to-A transitions and one G-to-C transversion. CONCLUSIONS: p53 mutations are common in leukemia and myelodysplastic syndrome after multiagent therapy for ovarian cancer. The propensity for G-to-A transitions may reflect specific DNA damage in leukemias after treatment with platinum analogues.     

The effect of adding group-based counselling to individual lifestyle counselling on changes in dietary intake. The Inter99 study – a randomized controlled trial

Background  

Few studies have investigated the specific effect of single intervention components in randomized controlled trials. The purpose was to investigate the effect of adding group-based diet and exercise counselling to individual life-style counselling on long-term changes in dietary habits.