Preclinical dilated cardiomyopathy in the dobermann.
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Animals↗
Biomedical subjects
Sarah Smith
Publications and source records attributed to Sarah Smith.
ATM and ATR promote Mre11 dependent restart of collapsed replication forks and prevent accumulation of DNA breaks.
Ataxia-telangiectasia mutated (ATM), ataxia-telangiectasia Rad3-related (ATR) and the Mre11/Rad50/Nbs1 complex ensure genome stability in response to DNA damage. However, their essential role in DNA metabolism remains unknown. Here we show that ATM and ATR prevent accumulation of DNA double-strand breaks (DSBs) during chromosomal replication. Replicating chromosomes accumulate DSBs in Xenopus laevis egg extracts depleted of ATM and ATR. Addition of ATM and ATR proteins to depleted extracts prevents DSB accumulation by promoting restart of collapsed replication forks that arise during DNA replication. We show that collapsed forks maintain MCM complex but lose Pol epsilon, and that Pol epsilon reloading requires ATM and ATR. Replication fork restart is abolished in Mre11 depleted extracts and is restored by supplementation with recombinant human Mre11/Rad50/Nbs1 complex. Using a novel fluorescence resonance energy transfer-based technique, we demonstrate that ATM and ATR induce Mre11/Rad50/Nbs1 complex redistribution to restarting forks. This study provides direct biochemical evidence that ATM and ATR prevent accumulation of chromosomal abnormalities by promoting Mre11/Rad50/Nbs1 dependent recovery of collapsed replication forks.
Animals↗
Pfeiffer-type cardiocranial syndrome: a patient with features of this condition and with an unbalanced subtelomeric rearrangement involving chromosomes 1p and 17q.
Pfeiffer-type cardiocranial syndrome (MIM 218450) was first delineated in 1987; several further patients have been reported confirming this as a distinct nosological entity. The aetiology of this condition remains unknown although an autosomal recessive pattern of inheritance has been suggested following the description of sib pairs. A patient is described with features of this condition including sagittal suture synostosis, growth retardation, learning difficulties, hypertelorism, low-set ears, micrognathia, congenital heart defects and genital anomalies. Telomere studies on blood and skin samples identified a de novo unbalanced rearrangement resulting in partial monosomy for 1p36.1 to pter and partial trisomy for 17q25.1 to qter. This case provides the first insight into the possible aetiology of this condition.
Acrocephalosyndactylia↗
Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation: three-year results.
BACKGROUND: Historically, antibody induction has been used because of the higher immunologic risk of graft loss or rejection observed in simultaneous pancreas and kidney (SPK) transplantation compared with kidney transplantation alone. This trial was designed to assess the effect of antibody induction in SPK transplant recipients receiving tacrolimus, mycophenolate mofetil, and corticosteroids. Induction agents included T-cell-depleting and interleukin-2 receptor antibodies. METHODS: A total of 174 SPK transplant recipients were enrolled in a prospective, open-label, multi-center study. They were randomized to induction (n=87) or non-induction (n=87) groups and followed for 3 years. RESULTS: At 3 years, actual patient (94.3% and 89.7%) and pancreas (75.9% and 75.9%) survivals were similar between the induction and non-induction groups, respectively. Actual kidney survival was similar at 1 and 2 years, but at 3 years, it was significantly better in the induction group compared with the non-induction group (92% vs. 81.6%; P =0.04). At 3 years, median serum creatinine and hemoglobin A1C were similar between the induction and non-induction groups (1.35 mg/dL and 1.20 mg/dL, 5.4% and 5.5%, respectively). Three-year cumulative incidence of biopsy-confirmed, treated acute kidney rejection in the induction and non-induction groups was 19.5% and 27.5% (P =0.14), respectively, with odds 4.6 times greater in African Americans regardless of treatment (P =0.004). Significantly higher rates of cytomegalovirus (CMV) viremia and CMV syndrome occurred in those receiving T-cell-depleting antibody induction (36.1%) when compared with those receiving anti-interleukin-2 receptor antibodies (2%) and non-induction (8.1%) (P <0.0001). CONCLUSIONS: Tacrolimus, mycophenolate mofetil, and corticosteroids resulted in excellent safety and efficacy in SPK transplant recipients. Actual 3-year kidney survival was significantly better in the induction group; however, CMV viremia and CMV syndrome rates were significantly higher in the T-cell-depleting antibody group. African Americans demonstrated a significantly greater risk of acute rejection despite antibody induction. Decisions regarding the use of induction therapy must weigh the risk of kidney graft loss or rejection against the risk of infection.
Antibodies, Monoclonal↗
Characteristics of triple and quadruple toe-loops performed during the Salt Lake City 2002 Winter Olympics.
The purpose of this study was to compare triple (T) and quadruple (Q) toe-loop figure skating jumps and quantify basic characteristics of these jumps to provide information to coaches that will assist them in teaching quadruple toe-loops to elite figure skaters. High-speed video was taken during men's practice and competition sessions at the 2002 Salt Lake City Winter Olympics; three-dimensional analyses of selected triple and quadruple jumps were completed. The most significant difference between triple and quadruple toe-loops was an increase in rotational velocity in the air. Additionally, increased vertical velocity at take-off and subsequent time in the air were also observed. Three main conclusions were developed: 1) The timing of rotation of the hips and shoulders was different for quadruple toe-loops compared to triples with the differences being observed before toe-pick; 2) Increases in rotational velocity occurred primarily as a result of the skaters assuming different body positions from take-off through landing which resulted in tighter rotating positions for longer durations of the jump; 3) Greater vertical velocity was gained during the propulsive phase due to the extension of the legs during the press off the ice.
Adult↗
Levobupivacaine spinal anesthesia in neonates: a dose range finding study.
BACKGROUND: Our aim was to determine the clinical efficacy of levobupivacaine for awake spinal anesthesia in ex-premature infants having lower abdominal surgery. The secondary aim was to determine the minimum local analgesic dose (MLAD) defined as the median effective local anesthetic dose for spinal anesthesia in neonates. METHODS: Fifty neonates < 55 weeks postconceptional age having lower abdominal surgery were enrolled. The dose of levobupivacaine was determined by up-down sequential allocation. The first infant received 1.25 mg x kg(-1) 0.5% levobupivacaine with subsequent doses determined by the response of the previous patient. Dose interval was 0.25 mg x kg(-1). RESULTS: There were no significant adverse effects attributable to levobupivacaine. Success rates for 1.25, 1, 0.75 and 0.5 mg x kg(-1) were 100, 83, 81 and 46%, respectively. Mean duration (95% confidence interval) of lower limb motor blockade was 81.7 min (75.8-87.6 min). Duration of anesthesia far exceeded surgical duration in all but one case. The up-down sequences were analyzed with the Dixon and Massey method. The motor block MLAD (95% confidence interval) was 0.48 mg x kg(-1) (0.42-0.54). Probit analysis was used to compare calculated ED50 and to calculate an ED95 by extrapolation of data into the clinical range. The ED(50) (95% C.I.) was 0.52 mg x kg(-1) (0.30-0.73). The calculated ED95 was 1.14 mg x kg(-1) (0.78-1.50). These values were confirmed by logit analysis. CONCLUSIONS: Levobupivacaine is an effective agent for spinal anesthesia in neonates at a recommended dose of 1 mg x kg(-1). It appears to be of equivalent potency to racemic bupivacaine for motor blockade in ex-premature infants requiring lower abdominal surgery.
Anesthesia, Spinal↗
Evaluation of a Clostridium perfringens predictive model, developed under isothermal conditions in broth, to predict growth in ground beef during cooling.
Proper temperature control is essential in minimizing Clostridium perfringens germination, growth, and toxin production. The U.S. Department of Agriculture (USDA) Food Safety and Inspection Service (FSIS) offers two options for the cooling of meat products: follow a standard time-temperature schedule or validate that alternative cooling regimens result in no more than a 1-log(10) CFU/g increase of C. perfringens and no growth of Clostridium botulinum. A mathematical model developed by Juneja et al. (Food Microbiol. 16:335-349, 1999) may be helpful in determining if the C. perfringens performance standard has been achieved, but this model has not been extensively validated. The objective of this study was to validate the Juneja 1999 model in ground beef under a variety of changing temperature and temperature abuse situations. The Juneja 1999 model consistently underpredicted growth of C. perfringens during exponential cooling of ground beef. The model also underpredicted growth of C. perfringens in ground beef cooled at two different rates. The results presented here show generally good agreement with published data on the growth of C. perfringens in similar products. The model error may be due to faster-than-expected exponential growth rates in ground beef during cooling or an error in the mathematical formulation of the model.
Animals↗
Influence of several methodological factors on the growth of Clostridium perfringens in cooling rate challenge studies.
Proper temperature control is essential in preventing Clostridium perfringens food poisoning. The U.S. Department of Agriculture Food Safety and Inspection Service cooling guidelines offer two options for the cooling of meat products: follow a standard time-temperature schedule or validate that alternative cooling regimens result in no more than a 1-log CFU/g increase of C. perfringens and no growth of Clostridium botulinum. The latter option requires laboratory challenge studies to validate the efficacy of a given cooling process. Accordingly, the objective of this study was to investigate the role of several methodological variables that might be encountered during typical C. perfringens challenge studies. Variables studied included plastic bag type (Whirlpak or Spiral Biotech), sealing method (Multivac or FoodSaver), initial spore inoculum size (1 to approximately 3 log CFU/g), and growth environment (ground beef or Trypticase-peptone-glucose-yeast extract [TPGY] broth). The major factors that affected growth were sample bag type and growth environment. Samples incubated in Whirlpak bags showed significantly less growth than those incubated in Spiral Biotech bags, which was likely due to the former bag's greater oxygen permeability. C. perfringens spores showed shorter germination, outgrowth, and lag times and C. perfringens cells showed faster growth rates in ground beef compared with TPGY broth. No significant difference was observed between two different sealing methods. Initial spore inoculum levels in the range studied had no significant effect on final C. perfringens cell concentration.
Animals↗
Evaluation of a predictive model for Clostridium perfringens growth during cooling.
Proper temperature control is essential in minimizing Clostridium perfringens germination, growth, and toxin production. The U.S. Department of Agriculture Food Safety and Inspection Service offers two options for the cooling of meat products: follow a standard time-temperature schedule or validate that alternative cooling regimes result in no more than a 1-log CFU/g increase of C. perfringens and no growth of Clostridium botulinum. The Juneja 1999 model for C. perfringens growth during cooling may be helpful in determining whether the C. perfringens performance standard has been achieved, but this model has not been extensively validated. The objective of this study was to validate the Juneja 1999 model under a variety of temperature situations. The Juneja 1999 model for C. perfringens growth during cooling is fail safe when low (<1 log CFU/ml) or high (>3 log CFU/ml) observed increases occur during exponential cooling. The Juneja 1999 model consistently underpredicted growth at intermediate observed increases (1 to 3 log CFU/ml). The Juneja 1999 model also underpredicted growth whenever exponential cooling took place at two different rates in the first and second portions of the cooling process. This error may be due to faster than predicted growth of C. perfringens cells during cooling or to an inaccuracy in the Juneja 1999 model.
Clostridium perfringens↗
Lessons for the NHS from Kaiser Permanente.
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Delivery of Health Care↗
Investigation of pimobendan versus benazepril in canine myxomatous valvular disease.
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Angiotensin-Converting Enzyme Inhibitors↗
Efficacy of a commercial produce wash on bacterial contamination of lettuce in a food service setting.
Many microorganisms (including a number of important foodborne pathogens) can be present on raw fruits and vegetables. Since these products are frequently eaten raw, any pathogens present represent a potential risk to the consumer. The objective of this study was to compare the efficacy of a commercial produce wash with that of water for reducing the total bacterial population on lettuce when used by food service employees in university dining halls. Because this study was carried out in actual food service facilities during their daily operation, we used indigenous produce microflora instead of actual pathogens. Over the course of the study, more than 40 heads of lettuce were divided into thirds, and each section was analyzed for total plate count either before washing, after washing in water, or after washing in Victory produce wash. When initial contamination levels were > or = 100 CFU/g (n = 36 samples), reductions obtained with Victory produce wash (1.8 log CFU/g) were significantly larger (P = 0.0006) than those obtained with water (0.8 log CFU/g). Our results indicate that Victory produce wash is effective in reducing indigenous flora on lettuce during food service preparation. Our results also show that care must be taken in the analysis of microbial reduction data: only a slight reduction in total plate count (ca. 0.1 log CFU/g) and no significant difference in reductions (P = 0.84) were observed when all samples (irrespective of initial contamination level) were compared.
Bacteria↗
Refractive surgery: an overview.
The status of refractive surgery is a dynamic and exciting field in ophthalmology. Current procedures are effective, safe and well tolerated. The future of refractive surgery continues to evolve, developing new and exhilarating forms of refractive correction. It remains to be seen which procedure will prove the most successful overall; or perhaps a variety of procedures will ultimately be the solution to the many facets of individual patient needs and desires.
Cornea↗