Cardiac specific ATP-sensitive K(+) channel (K(ATP)) overexpression results in embryonic lethality

Transgenic mice overexpressing SUR1 and gain of function Kir6.2[?N30, K185Q] K_ATP channel subunits, under cardiac α-myosin heavy chain (αMHC) promoter control, demonstrate arrhythmia susceptibility and premature death. Pregnant mice, crossed to carry double transgenic progeny, which harbor high levels of both overexpressed subunits, exhibit the most extreme phenotype and do not deliver any double transgenic pups. To explore the fetal lethality and embryonic phenotype that result from K_ATP overexpression, wild type (WT) and K_ATP overexpressing embryonic cardiomyocytes were isolated, cultured and voltage-clamped using whole cell and excised patch clamp techniques. Whole mount embryonic imaging, Hematoxylin and Eosin (H&;E) and α smooth muscle actin (αSMA) immunostaining were used to assess anatomy, histology and cardiac development in K_ATP overexpressing and WT embryos. Double transgenic embryos developed in utero heart failure and 100% embryonic lethality by 11.5 days post conception (dpc). K_ATP currents were detectable in both WT and K_ATP-overexpressing embryonic cardiomyocytes, starting at early stages of cardiac development (9.5 dpc). In contrast to adult cardiomyocytes, WT and K_ATP-overexpressing embryonic cardiomyocytes exhibit basal and spontaneous K_ATP current, implying that these channels may be open and active under physiological conditions. At 9.5 dpc, live double transgenic embryos demonstrated normal looping pattern, although all cardiac structures were collapsed, probably representing failed, non-contractile chambers. In conclusion, K_ATP channels are present and active in embryonic myocytes, and overexpression causes in utero heart failure and results in embryonic lethality. These results suggest that the K_ATP channel may have an important physiological role during early cardiac development.     

Interchangeability of activated clotting time values across different point-of-care systems

Significant variability in activated clotting time (ACT) measurement exists based on the type of point-of-care system used. We sought to determine the degree of agreement in ACT measurements by the Hemochron Response and the Hemochron Signature Elite Whole Blood coagulation systems and whether these 2 systems can be used interchangeably. We prospectively compared 126-paired samples in 77 patients undergoing percutaneous coronary intervention. ACT was measured for each sample using the Hemochron Response system with glass test tubes and the Hemochron Signature Elite system with low-range ACT cuvettes simultaneously. We used correlation and Bland-Altman analyses. Mean age of the study cohort was 67 ± 11 years, 49% were women, and 65% of measurements were made after systemic anticoagulation. There was a significant correlation between the Hemochron Response and Hemochron Signature Elite systems (r = 0.84, p <0.01). However, the mean bias for the ACT measurement was 9 seconds (95% confidence interval -69 to 86). In the therapeutic range of ACT measurements, the mean bias was 15 seconds (95% confidence interval -60 to 91). Thirty-three percent of total samples had >10% disagreement and 8% of samples had >20% disagreement in the ACTs measured with the Hemochron Response compared to the Hemochron Signature Elite. In conclusion, the Hemochron Response and Hemochron Signature Elite ACT values cannot be used interchangeably. Institutions using these 2 devices should be cognizant of this difference for ensuring patient safety.     

Occupational transmission of hepatitis C in healthcare workers and factors associated with seroconversion: UK surveillance data

The study aims were to describe a case series of occupationally acquired hepatitis C (HCV) infections in UK healthcare workers and examine factors associated with transmission using exposure data reported to the Health Protection Agency between July 1997 and December 2007. Fifteen reported cases of documented HCV seroconversion occurred after percutaneous exposure, the majority from hollow-bore needles used in the source patient's vein or artery and contaminated with blood or blood-stained fluid. The seroconversion rate was 2.2% (14/626). In multivariable analysis of healthcare workers with percutaneous exposure to blood or blood-stained fluid, we demonstrate that blood sampling procedures (odds ratio [OR], 5.75; 95% CI, 1.33-24.91; P = 0.01) and depth of injury (OR for deep vs superficial injury, 21.99; 95% CI, 2.02-239.61; P = 0.02) are independently associated with a greater risk of HCV seroconversion. This is the first UK study of occupationally acquired HCV in healthcare workers. It has reinforced our knowledge of risk factors for HCV transmission. Most of these exposures and transmissions were preventable. Healthcare employers should provide regular education on the risks of occupational exposure and prevention through standard infection control procedures. They should ensure the availability of effective prevention measures and facilitate prompt reporting and adequate follow-up of exposures.     

Dental trauma: review of common dental injuries and their management in primary and permanent dentitions

Management of dental trauma in children can be a challenging problem in dental practices. Knowledge of current trauma guidelines is vital in effectively managing dental trauma so that favorable outcomes are achieved. The purpose of this paper is to review the current guidelines and management strategies of dental trauma in primary and permanent dentitions. When planning emergency treatment for a primary tooth, it is important to consider the lifespan of the tooth, the potential damage to the permanent dentition, and the behavior of the child. After injury to permanent teeth, the treatment strategy is dictated by the concern for vitality of the periodontal ligament and pulp of the injured tooth. The emergency nature of dental trauma requires that the dentist be knowledgeable and readily available during and after office hours to provide care.     

Metachronous T‐Lymphoblastic Lymphoma and Burkitt Lymphoma in a Child With Constitutional Mismatch Repair Deficiency Syndrome

Constitutional mismatch repair deficiency (CMMRD) is a cancer predisposition syndrome associated with a high risk of developing early‐onset malignancies of the blood, brain, and intestinal tract. We present the case of a patient with T‐lymphoblastic lymphoma at the age of 3 years, followed by Burkitt lymphoma 10 years later. This patient also exhibited numerous nonmalignant findings including café au lait spots, lipomas, bilateral renal nodules, a nonossifying fibroma, multiple colonic adenomas, and a rapidly enlarging pilomatrixoma. The spectrum of malignant and nonmalignant neoplasms in this patient highlights the remarkable diversity, and early onset, of lesions seen in children with CMMRD.     

Phantom experiments to improve parathyroid lesion detection

This investigation tested the hypothesis that visual analysis of iteratively reconstructed tomograms by ordered subset expectation maximization (OSEM) provides the highest accuracy for localizing parathyroid lesions using 99mTc-sestamibi SPECT data. From an Institutional Review Board approved retrospective review of 531 patients evaluated for parathyroid localization, image characteristics were determined for 85 99mTc-sestamibi SPECT studies originally read as equivocal (EQ). Seventy-two plexiglas phantoms using cylindrical simulated lesions were acquired for a clinically realistic range of counts (mean simulated lesion counts of 75 +/- 50 counts/pixel) and target-to-background (T:B) ratios (range = 2.0 to 8.0) to determine an optimal filter for OSEM. Two experienced nuclear physicians graded simulated lesions, blinded to whether chambers contained radioactivity or plain water, and two observers used the same scale to read all phantom and clinical SPECT studies, blinded to pathology findings and clinical information. For phantom data and all clinical data, T : B analyses were not statistically different for OSEM versus FB, but visual readings were significantly more accurate than T : B (88 +/- 6% versus 68 +/- 6%, p = 0.001) for OSEM processing, and OSEM was significantly more accurate than FB for visual readings (88 +/- 6% versus 58 +/- 6%, p < 0.0001). These data suggest that visual analysis of iteratively reconstructed MIBI tomograms should be incorporated into imaging protocols performed to localize parathyroid lesions.     

Differences of self-reported osteoarthritis disability and race

BACKGROUND: Differences in self-reported disability may be found for older black and white adults with knee osteoarthritis (OA). METHODS: This secondary analysis of data from a randomized single-blind clinical trial examined race differences in the relationship between self-reports and timed performance tests of walking. Study participants were 518 older adults (131 blacks, 387 whites), including 363 women and 155 men, with an average age of 68.6 years. RESULTS: Older black and white adults with radiographically documented knee OA reported equivalent functional ability and pain severity. However, both blacks' OA severity rating and tested performance were significantly worse than those of whites. Self-report and tested walking performance were significantly less correlated among black older adults than among white older adults. Analyses of potential confounding variables documented that the difference was not due to marital status, gender, education, income, body mass index, comorbidity, pain level, OA severity or general health. CONCLUSIONS: Self-reports of OA disability were less related to tested performance for walking among black older adults. Clinicians' knowledge of black patients' underestimation of their disability has compelling potential for improving clinical treatment and enhancing diagnostic approaches to care of older adults.