Systematic screening for diabetic retinopathy with a digital fundus camera following pupillary dilatation in a university diabetes department.

AIMS: Screening for diabetic retinopathy (DR) is highly inadequate in France because of insufficient infrastructure and increasing disease prevalence. We describe the results of the first systematic DR screening programme established in a university diabetes department. METHODS: In this cross-sectional study conducted over 1 year, consecutive adult patients underwent three-field retinal photography with the Topcon TRC NW6S digital fundus camera following pupillary dilatation with Tropicamide 1%. A questionnaire provided information on patients' systemic and ocular history. Glycated haemoglobin (HbA1c) was measured at the screening visit.Two ophthalmologists graded the retinal photographs in a masked fashion. RESULTS: Of 1157 patients attending the diabetes department, 1153 (99.7%)underwent photographic screening. Images were gradable in 96% patients.Diabetic retinopathy was detected in 522 (45%) patients and sight-threatening DR in 167 (14%). Of 704 (61%) patients previously believed to have no DR,254 (34%) screened positive. The presence of DR was associated with age,insulin use and non-Caucasian ethnicity in Type 2 patients, and with duration of diabetes and HbA1c in Type 1 and Type 2 patients. Associated ocular pathologies were diagnosed in 612 (53%) patients. CONCLUSIONS: Our photographic screening programme using pharmacological mydriasis provided a high screening coverage feasible in a hospital setting. We obtained information regarding prevalence and associated risk factors of DR inpatients attending a tertiary care centre. Screening was well accepted by patients and met with no protest from city ophthalmologists. It generated considerable interest among endocrinologists and feedback of results is expected to improve optimization of glycaemic control.     

CAR2 displays unique ligand binding and RXRalpha heterodimerization characteristics.

The constitutive androstane receptor (CAR; NR1I3) regulates the expression of genes involved in xenobiotic metabolism. Alternative splicing of the human CAR gene yields an array of mRNAs that encode structurally diverse proteins. One form of CAR, termed CAR2, contains an additional four amino acids (SPTV) that are predicted to reshape the ligand-binding pocket. The current studies show a marked, ligand-independent, CAR2-mediated transactivation of reporters containing optimal DR-3, DR-4, and DR-5 response elements, and reporters derived from the natural CYP2B6 and CYP3A4 gene promoters. Overexpression of the RXRalpha ligand binding domain was critical for achieving these effects. CAR2 interaction with SRC-1 was similarly dependent on the coexpression of RXRalpha. Mutagenesis of Ser233 (SPTV) to an alanine residue yielded a receptor possessing higher constitutive activity. Alternatively, mutating Ser233 to an aspartate residue drastically reduced the transactivation capacity of CAR2. The respective abilities of these mutagenized forms of CAR2 to transactivate a DR-4 x 3 reporter element correlated with their ability to interact with RxRalpha and to recruit SRC-1 in a ligand-regulated manner. Together, these results demonstrate a robust RXRalpha-dependent recruitment of coactivators and transactivation by CAR2. In addition, CAR2 displays novel dose responses to clotrimazole and androstanol compared with the reference form of the receptor while at the same time retaining the ability to bind CITCO. This result supports a hypothesis whereby the four-amino-acid insertion in CAR2 structurally modifies its ligand binding pocket, suggesting that CAR2 is regulated by a set of ligands distinct from those governing the activity of reference CAR.     

Risk stratification and dental management of the patient with cardiovascular diseases. Part II: Oral disease burden and principles of dental management.

Cardiovascular diseases are the leading cause of death in the United States and most other Western countries. In the United States alone, more than 1 million annual deaths and as many as three times that number of serious consequences can be attributed to these conditions. To provide care to patients with cardiovascular disease, oral health care providers must understand the disease, its treatment, and its impact on the patient's ability to undergo and respond to dental care.