Dental and craniofacial characteristics caused by the p.Ser40Leu mutation in IFITM5

Severe forms of osteogenesis imperfecta (OI) are usually caused by mutations in genes that code for collagen Type I and frequently are associated with craniofacial abnormalities. However, the dental and craniofacial characteristics of OI caused by the p.Ser40Leu mutation in the IFITM5 gene have not been reported. We investigated a 15‐year‐old girl with severe OI caused by this mutation. She had marked deformations of extremity long bones. There were no clinical or radiological signs of dentinogenesis imperfecta, but one tooth was missing and several teeth were impacted. Cone beam computed tomography revealed a generalized osteopenic appearance of the craniofacial skeleton, bilateral enlargement of mandibular bodies, and areas of cortical erosions. The cranial base and skull showed a generalized granular bone pattern with a mixture of osteosclerosis and osteolysis. Sphenoid and frontal sinuses were congenitally missing. Cephalometric analysis indicated a Class III growth pattern. In this case, the IFITM5 p.Ser40Leu mutation did not affect tooth structure but was associated with deformities in craniofacial bones that resemble those in the other parts of the skeleton.     

Assessing optimism and pessimism about genomic medicine: Development of a genomic orientation scale

Efforts to characterize stakeholder attitudes about the implementation of genomic medicine would benefit from a validated instrument for measuring public views of the potential benefits and harms of genomic technologies, which would facilitate comparison across populations and clinical settings. We sought to develop a scale to evaluate attitudes about the future of genomic medicine. We developed a 21-item scale that examined the likelihood of various outcomes of genomic medicine. The scale was administered to participants in a genomic sequencing study. Exploratory factor analysis was conducted and bivariate correlations were calculated. The genomic orientation (GO) scale was completed by 2895 participants. A two-factor structure was identified, corresponding to an optimism subscale (16 items, α = 0.89) and a pessimism subscale (5 items, α = 0.63). Genomic optimism was positively associated with a perceived value of genetic test results, higher health literacy, and decreased decisional conflict about participation in a genomic research study. Genomic pessimism was associated with concerns about genetic testing, lower health literacy, and increased decisional conflict about the decision to participate in the study. The GO scale is a promising tool for measuring both positive and negative views regarding the future of genomic medicine and deserves further validation.     

Cleanability of dental instruments--implications of residual protein and risks from Creutzfeldt-Jakob disease

Cleaning of dental instruments is the first line of control in reducing the adherent bioburden. The threat of vCJD and the difficulty in removing prion protein has provided a new challenge for cleaning surgical and dental instruments. Prion proteins are also more resistant to many disinfection and sterilisation techniques. A number of different methods are currently available in primary care for cleaning instruments including manual washing, ultrasonic cleaners and washer disinfectors. Manual cleaning of dental instruments is time-consuming, introduces operator error and the risk of puncture wounds, is not reproducible and does not completely remove debris from instruments. Ultrasonic baths are significantly more effective than hand cleaning alone and are currently used by the majority of dental surgeries (often as an adjunct to manual cleaning). Automated washer-disinfectors appear to provide a validated, reliable and reproducible procedure for disinfection and sterilisation of dental instruments to ensure both the safety of patients and dental staff. Dental instruments that are difficult to clean are frequently contaminated with tissue debris after routine reprocessing and cannot be excluded as a potential transmission risk for infectious agents, including prions. The transmission of vCJD via dentistry is considered to be low risk, however, the Department of Health (DoH) has recently advised dentists to ensure that endodontic reamers and files are treated as single-use as a precautionary basis in order to further reduce any risk of vCJD transmission.     

Hospitalization in the Program of All-Inclusive Care for the Elderly (PACE): rates, concomitants, and predictors.

BACKGROUND: The Program of All-Inclusive Care for the Elderly (PACE) replicates the model of comprehensive, community-based geriatric care pioneered by On Lok, that enrolls frail older adults who meet states' criteria for nursing home care, and that uses interdisciplinary teams to assess the participants and to deliver care in appropriate settings. As managed care, PACE receives capitated payment from Medicare and Medicaid. Thus, PACE's fiscal incentives are thought to be aligned with the goals of optimizing health, function, and quality of life through the delivery of effective primary, preventive, restorative, supportive, and palliative care and through the avoidance of inappropriate and expensive hospital and nursing home utilization. OBJECTIVES: To describe short-term hospital utilization, hospital discharge diagnoses, time from enrollment to first hospitalization and its clinical predictors, and hospitalization in relation to mortality among PACE participants. METHODS: Data on short-term hospitalization and participants were recovered from PACE's minimum data set. Bed use was evaluated in annual cross-sections of current participants. Primary hospital discharge diagnoses were available for discharges from September 1, 1993 through March 31, 1997. The time from enrollment to hospitalization was calculated for the participants (n = 5478) who were admitted between January 1, 1990 and March 31, 1997. The characteristics of this inception cohort were used to develop a Cox regression model of hospitalization. All PACE deaths were identified and the place of death was recovered, together with the medical records used in the hospital during PACE enrollment or 6 months before death. RESULTS: Bed-days per 1,000 PACE participants per year were comparable with the general Medicare (fee-for-service) population, at 2,046 (in 1998) versus 2014 (in 1997) despite the greater morbidity and disability for PACE participants, as reflected in their enrollment characteristics and primary hospital discharge diagnoses. The time to hospitalization was 773 days (median); 95% confidence interval, 725, 814, and was predicted by disease, treatment, social and demographic factors. Whereas 8% of PACE deaths occurred in acute hospitals, less than one-third of the decedents spent any time in the hospital in the 6-month interval before death. CONCLUSIONS: Overall, short-term hospital utilization among PACE participants is low in contrast with that for other older and disabled populations. Participant predictors of hospitalization in PACE are generally consistent with other studies in older clinical and community populations. Both utilization and risk vary considerably across PACE sites, independent of participant-level risk factors, hence suggesting that further investigation is required to study PACE's management of acute illness and hospitalization decisions. Critical to maintaining PACE's success is an understanding of the independent impact of the organization and the environment of health care on this management.     

Catheter ablation of accessory pathways, atrioventricular nodal reentrant tachycardia, and the atrioventricular junction: final results of a prospective, multicenter clinical trial. The Atakr Multicenter Investigators Group

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of a temperature-controlled radiofrequency catheter ablation system. METHODS AND RESULTS: The patient population included 1050 patients who had undergone ablation of atrioventricular nodal reentrant tachycardia (AVNRT), an accessory pathway (AP), or the atrioventricular junction (AVJ). Ablation was successful in 996 patients. The probability of success was highest among patients who had undergone ablation of the AVJ, lowest in patients who had undergone ablation of an AP, and in between for patients who had undergone ablation of AVNRT. A major complication occurred in 32 patients. Four variables predicted ablation success (AVJ, AVNRT, or left free wall AP ablation and an experienced center). Four factors predicted arrhythmia recurrence (right free wall, posteroseptal, septal, and multiple APs). Two variables predicted development of a complication (structural heart disease and the presence of multiple targets), and 3 variables predicted an increased risk of death (heart disease, lower ejection fraction, and AVJ ablation). CONCLUSIONS: These findings may serve as a guide to clinicians considering therapeutic options in patients who are candidates for ablation.     

The Escherichia coli SOS mutagenesis proteins UmuD and UmuD′ interact physically with the replicative DNA polymerase

The Escherichia coli umuDC operon is induced in response to replication-blocking DNA lesions as part of the SOS response. UmuD protein then undergoes an RecA-facilitated self-cleavage reaction that removes its N-terminal 24 residues to yield UmuD'. UmuD', UmuC, RecA, and some form of the E. coli replicative DNA polymerase, DNA polymerase III holoenzyme, function in translesion synthesis, the potentially mutagenic process of replication over otherwise blocking lesions. Furthermore, it has been proposed that, before cleavage, UmuD together with UmuC acts as a DNA damage checkpoint system that regulates the rate of DNA synthesis in response to DNA damage, thereby allowing time for accurate repair to take place. Here we provide direct evidence that both uncleaved UmuD and UmuD' interact physically with the catalytic, proofreading, and processivity subunits of the E. coli replicative polymerase. Consistent with our model proposing that uncleaved UmuD and UmuD' promote different events, UmuD and UmuD' interact differently with DNA polymerase III: whereas uncleaved UmuD interacts more strongly with beta than it does with alpha, UmuD' interacts more strongly with alpha than it does with beta. We propose that the protein-protein interactions we have characterized are part of a higher-order regulatory system of replication fork management that controls when the umuDC gene products can gain access to the replication fork.     

The use of atropine for facilitation of direct current cardioversion from atrial fibrillation--results of a pilot study.

BACKGROUND: The importance of the role of the autonomic nervous system (ANS) in the initiation and propagation of atrial fibrillation has been demonstrated in the condition of paroxysmal atrial fibrillation. However, the role of the ANS in patients with chronic atrial fibrillation is less clear. Some patients with chronic atrial fibrillation are resistant to the standard techniques of direct current (DC) cardioversion. HYPOTHESIS: We sought to investigate whether excessive vagal tone might prevent the restoration of sinus rhythm and to establish that the abolition of vagal tone using intravenous atropine will facilitate DC cardioversion in patients with atrial fibrillation who are resistant to the standard cardioversion techniques. METHODS: Beginning in August 1994, a change in the protocol for elective DC cardioversion of atrial fibrillation was made to include the use of intravenous atropine for patients resistant to the standard techniques of DC cardioversion. RESULTS: Over a 2-year period, 140 elective cardioversions were performed for atrial fibrillation. Sinus rhythm could not be restored on 31 occasions. Intravenous atropine prior to a further 360 J shock with paddles in the anteroposterior position allowed sinus rhythm to be restored on nine occasions. Patients with successful cardioversion after atropine had significantly better left ventricular function than those who remained in atrial fibrillation (p = 0.001) as well as a tendency toward a smaller left atrium. CONCLUSION: This study suggests that high vagal tone, which is dominant in patients with structurally normal hearts, may prevent the termination of atrial fibrillation by standard techniques of DC cardioversion, and that the abolition of high vagal tone by atropine facilitates the restoration of sinus rhythm.     

Renal assessment practices and the effect of nurse case management of health maintenance organization patients with diabetes.

OBJECTIVE: To examine baseline renal screening practices and the effect of nurse case management of patients with diabetes in a group model health maintenance organization (HMO). RESEARCH DESIGN AND METHODS: We performed both 1-year retrospective and 1-year prospective studies of renal assessment practices and ACE inhibitor usage in a cohort of 133 diabetic patients enrolled in a randomized controlled trial of a diabetes nurse case management program in a group model HMO. In accordance with American Diabetes Association recommendations, urine dipstick and quantitative protein and microalbuminuria testing rates were calculated. RESULTS: At baseline, 77% of patients were screened for proteinuria with dipsticks or had quantitative urine testing. Of patients with negative dipstick findings, 30% had appropriate quantitative protein or microalbumin follow-up at baseline. Baseline ACE inhibitor usage was associated with decreased follow-up testing (relative risk = 0.47). Nurse case management was associated with increased quantitative protein or or microalbumin testing and increased follow-up testing (relative risk = 1.65 and 1.60, respectively). CONCLUSIONS: We found a higher degree of adherence to recommendations for renal testing than has been reported previously. Nurse case management intervention further increased renal screening rates. The inverse association between ACE inhibitor usage and microalbumin testing highlights a potentially ambiguous area of current clinical pathways.