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Abstract Background Population-based administrative data have been used to study osteoporosis-related fracture risk factors and outcomes, but there has been limited research about the validity of these data for ascertaining fracture cases. The objectives of this study were to: (a) compare fracture incidence estimates from administrative data with estimates from population-based clinically-validated data, and (b) test for differences in incidence estimates from multiple administrative data case definitions. Methods Thirty-five case definitions for incident fractures of the hip, wrist, humerus, and clinical vertebrae were constructed using diagnosis codes in hospital data and diagnosis and service codes in physician billing data from Manitoba, Canada. Clinically-validated fractures were identified from the Canadian Multicentre Osteoporosis Study (CaMos). Generalized linear models were used to test for differences in incidence estimates. Results For hip fracture, sex-specific differences were observed in the magnitude of under- and over-ascertainment of administrative data case definitions when compared with CaMos data. The length of the fracture-free period to ascertain incident cases had a variable effect on over-ascertainment across fracture sites, as did the use of imaging, fixation, or repair service codes. Case definitions based on hospital data resulted in under-ascertainment of incident clinical vertebral fractures. There were no significant differences in trend estimates for wrist, humerus, and clinical vertebral case definitions. Conclusions The validity of administrative data for estimating fracture incidence depends on the site and features of the case definition.

Abstract Background Previous research has shown that underlying dietary patterns are related to the risk of many different adverse health outcomes, but the relationship of these underlying patterns to skeletal fragility is not well understood. The objective of the study was to determine whether dietary patterns in men (ages 25-49, 50+) and women (pre-menopause, post-menopause) are related to femoral neck bone mineral density (BMD) independently of other lifestyle variables, and whether this relationship is mediated by body mass index. Methods We performed an analysis of 1928 men and 4611 women participants in the Canadian Multicentre Osteoporosis Study, a randomly selected population-based longitudinal cohort. We determined dietary patterns based on the self-administered food frequency questionnaires in year 2 of the study (1997-99). Our primary outcome was BMD as measured by dual x-ray absorptiometry in year 5 of the study (2000-02). Results We identified two underlying dietary patterns using factor analysis and then derived factor scores. The first factor (nutrient dense) was most strongly associated with intake of fruits, vegetables, and whole grains. The second factor (energy dense) was most strongly associated with intake of soft drinks, potato chips and French fries, certain meats (hamburger, hot dog, lunch meat, bacon, and sausage), and certain desserts (doughnuts, chocolate, ice cream). The energy dense factor was associated with higher body mass index independent of other demographic and lifestyle factors, and body mass index was a strong independent predictor of BMD. Surprisingly, we did not find a similar positive association between diet and BMD. In fact, when adjusted for body mass index, each standard deviation increase in the energy dense score was associated with a BMD decrease of 0.009 (95% CI: 0.002, 0.016) g/cm2 for men 50+ years old and 0.004 (95% CI: 0.000, 0.008) g/cm2 for postmenopausal women. In contrast, for men 25-49 years old, each standard deviation increase in the nutrient dense score, adjusted for body mass index, was associated with a BMD increase of 0.012 (95% CI: 0.002, 0.022) g/cm2. Conclusions In summary, we found no consistent relationship between diet and BMD despite finding a positive association between a diet high in energy dense foods and higher body mass index and a strong correlation between body mass index and BMD. Our data suggest that some factor related to the energy dense dietary pattern may partially offset the advantages of higher body mass index with regard to bone health.

Abstract Background The initiation of the Canadian Multicentre Osteoporosis Study in 1996, and subsequent follow-up of the cohort 5 years later, provided longitudinal body mass index (BMI) data for a random sample of Canadians. Methods Height and weight were measured at baseline and 5 years and used to calculate BMI and assign one of six weight categories. Multiple imputation was used to adjust for missing weight at year 5. Data were stratified by age and gender. The proportion of participants moving between categories was generated, and multivariable linear regression was used to identify factors associated with weight change. Results Baseline data were available for 8548 participants, year 5 data for 6721, and year 5 weight was imputed for 1827 (17.6%). Mean BMI for every age and gender group exceeded healthy weight guidelines. Most remained within their BMI classification over 5 years, but when change occurred, BMI category was more likely to increase than decrease. Several sociodemographic, lifestyle and clinical characteristics were associated with change. Conclusion Mean baseline BMI tended to be higher than recommended. Moreover, on average, men under age 45 and women under age 55 were gaining approximately 0.45 kilograms (one pound) per year, which leveled off with increased age and reversed in the oldest age groups. These findings underscore the need for public health efforts aimed at combating obesity.

Study Objective: Because alkalinization of the renal tubules can theoretically protect against the mechanisms of acute kidney injury, we sought to determine whether a sodium bicarbonate infusion can prevent acute kidney injury after cardiac surgery., Design: Prospective, randomized, double-blind, controlled trial., Setting: Cardiac surgery service in a community hospital., Patients: Ninety-two patients with stage 3 or higher chronic kidney disease who underwent cardiac surgery using cardiopulmonary bypass., Intervention: Forty-eight patients received a perioperative intravenous infusion of 0.9% sodium chloride 154 mEq/L, and 44 patients received an infusion of sodium bicarbonate infusion 150 mEq/L in 5% dextrose solution; the infusions were started 1 hour preoperatively and continued for 6 hours after cardiopulmonary bypass., Measurements and Main Results: The primary outcome was the development of any stage of acute kidney injury within 5 days after surgery as defined by the Acute Kidney Injury Network criteria. No statistically significant difference in the primary outcome was noted between the two groups: 32% in the bicarbonate group versus 42% in the sodium chloride group (p=0.12). Likewise, no significant differences in the 30-day hospital mortality rate or other adverse outcomes were noted between the two groups., Conclusion: A perioperative infusion of sodium bicarbonate did not reduce the rate of acute kidney injury or adverse outcomes in patients with chronic kidney disease who underwent cardiac surgery., (© 2013 Pharmacotherapy Publications, Inc.)

Expression of recombinant proteins across a range of different host organisms is often necessary in metabolic engineering applications. Doing so can be facilitated by the use of vectors having origins of replication with a broad-host-range, the option for antibiotic resistance cassettes that are compatible with a particular host, in addition to sequences allowing for the effective transcription and translation of target proteins. We have created a modular set of broad-host-range expression vectors for protein expression in Gram negative bacteria. These vectors use the broad-host-range pBBR1 replicon as well as the arabinose-inducible P(BAD) promoter and are available with six different antibiotic resistance cassettes. We have demonstrated the use of these vectors in Escherichia coli, Pseudomonas putida, and Burkholderia cepacia.

The bacterium Actinoplanes sp. ATCC 53771 is known to perform drug metabolism of several xenobiotics similarly to humans. We identified a cytochrome P450 enzyme from this strain, CYP107E4, and expressed it in Escherichia coli using the pET101 vector. The purified enzyme showed the characteristic reduced-CO difference spectra with a peak at 450 nm, indicating the protein is produced in the active form with proper heme incorporation. The CYP107E4 enzyme was found to bind the drug diclofenac. Using redox enzymes from spinach, the reconstituted system is able to produce hydroxylated metabolites of diclofenac. Production of the human 4'-hydroxydiclofenac metabolite by CYP107E4 was confirmed, and a second hydroxylated metabolite was also produced.

The results of 8 to 12 weeks of treatment of the anemia of uremia with rHuEPO in patients with chronic renal failure and uremia are: a sustained increased hematocrit; increased RBC mass, and subsequent increased MAP; and increased TPRI. The observed trends of decreased LVEF, and echo Doppler evidence of a trend toward LV systolic and diastolic dysfunction, although not individually statistically significant, represent 3 separate evaluation techniques coupled with hypertension and TPRI increase during administration of rHuEPO to increase the hematocrit and packed red blood cell volume in patients with chronic renal failure and anemia. Increased TPRI and hypertension associated with correction of uremic anemia vasodilation and the increased blood viscosity have been noted in earlier investigations with transfusions. The hypertension and elevated TPRI demonstrated during rHuEPO therapy in patients with progressive chronic renal failure associated with increased hematocrit, and the trends toward systolic and diastolic cardiac dysfunction are noted herein. These changes were associated with the combined increase of packed RBC mass and plasma volume in this study. The natural progressive course of worsening of renal function exhibited by these patients could have limited their ability to regulate plasma volume, making them vulnerable to volume-dependent hypertension and a significant preload adding to potential cardiac dysfunction in addition to the increased TPRI.

In severe appendicitis, the effect of a single intravenous dose of metronidazole (500 mg) was compared with cefoxitin (1 g). The antibiotics were given by random allocation once the diagnosis had been established at operation. In the metronidazole group, 5 out of 48 patients developed a wound infection whilst in hospital compared with 13 out of 48 in the cefoxitin group (P = 0.036). However, 57% of wound infections became apparent after the patient went home and the overall infection rates were similar. The mean length of postoperative hospital stay was 5.0 days in the metronidazole group and 6.8 days in the cefoxitin group (P = 0.052), but of those who did develop a wound infection, the length of stay was almost double in the cefoxitin group. Anaerobic organisms were cultured from the wound in 7 out of 15 patients who received cefoxitin but in none of 5 patients in the metronidazole group. Whilst metronidazole only delayed the discharge of pus from the wound, it did seem to reduce the severity of infection. Cefoxitin appeared to be less effective, given as a single intravenous injection at a dose of 1 g.