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Purpose/objectives: The purpose of this 2021 study was to explore experiences acquired from a school-based sealant program (SBSP), to improve understanding of the relationship between SBSP and dental hygiene (DH) student outcomes, and to inform institutions of the value of educational experiences aiming to reduce disparities in access to dental care., Methods: University of Missouri Kansas City School of Dentistry Senior DH students complete a community engaged course which includes participation in community projects and clinical activities targeting Kansas City's urban and surrounding rural environments. The SBSP is a component of this course. This investigation utilized a qualitative methodology to examine SBSP experiences through the experience of the primary investigator, on-site dentist, and DH students involved in the program., Results: Data analysis resulted in consensus of five synthesized conceptual models and twenty-three emergent themes. The conceptual models include: competence, roles and responsibilities, social justice, value added, and lessons learned., Conclusion: Based on triangulated results, SBSPs improve access to care for children, save dental costs, and provide essential experiences for DH students., (© 2023 American Dental Education Association.)

Background: Most skin and soft tissue infections (SSTIs) are managed in the outpatient setting, but data are lacking on treatment patterns outside the emergency department (ED). Available data suggest that there is poor adherence to SSTI treatment guidelines., Methods: We conducted a retrospective cohort study of Veterans diagnosed with SSTIs in the ED or outpatient clinics from 1 January 2005 through 30 June 2018. The incidence of SSTIs over time was modeled using Poisson regression using robust standard errors. Antibiotic selection and incision and drainage (I&D) were described and compared between ambulatory settings. Anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotic use was compared to SSTI treatment guidelines., Results: There were 1 740 992 incident SSTIs in 1 156 725 patients during the study period. The incidence of SSTIs significantly decreased from 4.58 per 1000 patient-years in 2005 to 3.27 per 1000 patient-years in 2018 (P < .001). There were lower rates of β-lactam prescribing (32.5% vs 51.7%) in the ED compared to primary care (PC), and higher rates of anti-MRSA therapy (51.4% vs 35.1%) in the ED compared to PC. The I&D rate in the ED was 8.1% compared to 2.6% in PC. Antibiotic regimens without MRSA activity were prescribed in 24.9% of purulent SSTIs. Anti-MRSA antibiotics were prescribed in 40.1% of nonpurulent SSTIs., Conclusions: We found a decrease in the incidence of SSTIs in the outpatient setting over time. Treatment of SSTIs varied depending on the presenting ambulatory location. There is poor adherence to guidelines in regard to use of anti-MRSA therapies. Further study is needed to understand the impact of guideline nonadherence on patient outcomes., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Importance: Oral β-lactam antibiotics are traditionally not recommended to treat Enterobacterales bacteremia because of concerns over subtherapeutic serum concentrations, but there is a lack of outcomes data, specifically after initial treatment with parenteral antibiotics. Given the limited data and increasing limitations of fluoroquinolones or trimethoprim-sulfamethoxazole (TMP-SMX), oral β-lactam antibiotics may be a valuable additional treatment option., Objective: To compare definitive therapy with oral β-lactam antibiotics vs fluoroquinolones or TMP-SMX for Enterobacterales bacteremia from a suspected urine source., Design, Setting, and Participants: A retrospective cohort study was conducted from January 1, 2007, to September 30, 2015, at 114 Veterans Affairs hospitals among 4089 adults with Escherichia coli, Klebsiella spp, or Proteus spp bacteremia and matching urine culture results. Additional inclusion criteria were receipt of active parenteral antibiotic(s) followed by conversion to an oral antibiotic. Exclusion criteria were previous Enterobacterales bacteremia, urologic abscess, or chronic prostatitis. Data were analyzed from April 15, 2019, to July 26, 2020., Exposures: Conversion of therapy to an oral β-lactam antibiotic vs fluoroquinolones or TMP-SMX after 1 to 5 days of parenteral antibiotics., Main Outcomes and Measures: The main outcome was a composite of either 30-day all-cause mortality or 30-day recurrent bacteremia. Propensity-based overlap weights were used to adjust for differences between groups. Log binomial regression models were used to estimate adjusted relative risks (aRRs) and adjusted risk differences (aRDs)., Results: Of the 4089 eligible patients (3731 men [91.2%]; median age, 71 years [interquartile range, 63-81 years]), 955 received an oral β-lactam antibiotic, and 3134 received fluoroquinolones or TMP-SMX. The primary outcome occurred for 42 patients (4.4%) who received β-lactam antibiotics and 94 patients (3.0%) who received fluoroquinolones or TMP-SMX (aRD, 0.99% [95% CI, -0.42% to 2.40%]; aRR, 1.31 [95% CI, 0.87-1.95]). Mortality rates were 3.0% (n = 29) for patients receiving β-lactam antibiotics vs 2.6% (n = 82) for those receiving fluoroquinolones or TMP-SMX (aRD, 0.06% [95% CI, -1.13% to 1.26%]; aRR, 1.02 [95% CI, 0.67-1.56]). Recurrent bacteremia rates were 1.5% (n = 14) among those receiving β-lactam antibiotics vs 0.4% (n = 12) among those receiving fluoroquinolones or TMP-SMX (aRD, 1.03% [95% CI, 0.24%-1.82%]; aRR, 3.43 [95% CI, 0.42-27.90])., Conclusions and Relevance: In this cohort study of adults with E coli, Klebsiella spp, or Proteus spp bacteremia from a suspected urine source, the relative risk of recurrent bacteremia was not significantly higher with β-lactam antibiotics compared with fluoroquinolones or TMP-SMX, and the absolute risk and risk difference were small (ie, <3%). No significant difference in mortality was observed. Oral β-lactam antibiotics may be a reasonable step-down treatment option, primarily when alternative options are limited by resistance or adverse effects. Further study is needed because statistical power was limited owing to a low number of recurrent bacteremia events.

Antistaphylococcal penicillins such as nafcillin and oxacillin are among the first choices of treatment for severe invasive methicillin-susceptible Staphylococcus aureus (MSSA) infections, although there has been limited safety evaluations between individual agents. Using the FDA Adverse Event Reports System (FAERS), oxacillin was observed to have a lower proportion of reports of acute renal failure (reporting odds ratio [ROR], 5.3 [95% confidence interval {CI}, 3.1 to 9.3] versus 21.3 [95% CI, 15.8 to 28.6], respectively) and hypokalemia (ROR, 0.7 [95% CI, 0.1 to 4.8] versus 11.4 [95% CI, 7.1 to 18.3], respectively) than nafcillin., (Copyright © 2020 American Society for Microbiology.)

Background: Skin and soft tissue infections (SSTIs) are a key antimicrobial stewardship target because they are a common infection in hospitalized patients, and non-guideline-concordant antibiotic use is frequent. To inform antimicrobial stewardship interventions, we evaluated the proportion of veterans hospitalized with SSTIs who received guideline-concordant empiric antibiotics or an appropriate total duration of antibiotics., Methods: A retrospective medication use evaluation was performed in 34 Veterans Affairs Medical Centers between 2016 and 2017. Hospitalized patients who received antibiotics for uncomplicated SSTI were included. Exclusion criteria were complicated SSTI, severe immunosuppression, and antibiotics for any non-SSTI indication. Data were collected by manual chart review. The primary outcome was the proportion of patients receiving both guideline-concordant empiric antibiotics and appropriate treatment duration, defined as 5-10 days of antibiotics. Data were analyzed and reported using descriptive statistics., Results: Of the 3890 patients manually evaluated for inclusion, 1828 patients met inclusion criteria. There were 1299 nonpurulent (71%) and 529 purulent SSTIs (29%). Overall, 250 patients (14%) received guideline-concordant empiric therapy and an appropriate duration. The most common reason for non-guideline-concordance was receipt of antibiotics targeting methicillin-resistant Staphylococcus aureus (MRSA) in 906 patients (70%) with a nonpurulent SSTI. Additionally, 819 patients (45%) received broad-spectrum Gram-negative coverage, and 860 patients (48%) received an antibiotic duration >10 days., Conclusions: We identified 3 common opportunities to improve antibiotic use for patients hospitalized with uncomplicated SSTIs: use of anti-MRSA antibiotics in patients with nonpurulent SSTIs, use of broad-spectrum Gram-negative antibiotics, and prolonged durations of therapy., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2020.)

Background: Although existing literature supports durations of 5-7 days for skin and soft tissue infections (SSTIs), longer durations are commonly used. Obesity and heart failure (HF) have been associated with increased risk for treatment failure of SSTIs; however, whether prolonged antibiotic durations reduce the risk of treatment failure is unknown. We evaluated practice patterns for SSTIs in patients with obesity and/or HF and whether short antibiotic durations (≤8 days) were associated with treatment failure., Methods: We performed a single-center, retrospective cohort study of inpatients between January 1, 2006, and December 30, 2016, with SSTIs based on International Classification of Diseases (ICD) coding, and obesity and/or HF. Charts were manually reviewed to collect demographic, clinical, treatment, and outcome data. Propensity score matching was used to estimate the risk of treatment failure between the 2 groups. Secondary outcomes included length of stay, 30-day readmission, and Clostridium difficile infection rates., Results: A total of 207 patients were included. Forty-nine (23.7%) received a short antibiotic duration and 158 (76.3%) a long duration. The median duration of therapy (interquartile range [IQR]) was 7 (7-8) days in the short group and 14 (10-15) days in the long group. In the propensity score-matched cohort, 28 (28.6%) treatment failures occurred in the long group, as compared with 5 (10.2%) in the short group ( P = .02), as well as a shorter length of stay (IQR) in the short- vs long-duration group (2 [2-3] vs 3 [2-5] days, respectively; P = .002). There was no difference in other secondary outcomes., Conclusions: The majority of patients with obesity or HF received a longer antibiotic course for SSTIs; however, a longer antibiotic course was not associated with lower treatment failure rates. Higher failure rates in the long-duration group may be reflective of clinical decisions made in the face of diagnostic uncertainty and warrant further evaluation.

Purpose: The purpose of this study was to compare three different types of blood pressure (BP) recording devices (an automated arm cuff, an automated wrist cuff, and a manual cuff / stethoscope combination) for accuracy, patient comfort, and ease of operation. Methods: Three types of sphygmomanometers were tested on 150 study participants (n=150) obtained from the patients presenting for dental hygiene services at an urban dental school in the Midwest. Descriptive statistics were calculated for all variables of interest by cuff type. Repeated measures ANOVA using the Greenhouse-Geisser adjustment were used to test for differences in means in BP and rating measure by cuff type. Post-hoc comparisons using Tukey's procedure were calculated to determine pair-wise differences. An association between the cuff type and convenience rating was evaluated using the Chi-square test, and between cuff type and convenience rating using the Fisher's exact test. Results: There was a significant difference in systolic BP recording by cuff type (p<0.001). The automatic wrist cuff recorded an average of 11.30mm and 8.76mm HG higher systolic BP than the standard cuff and the automatic arm cuff respectively (p<0.001 for both). There was no significant difference in the systolic BP readings between the standard and automatic arm cuff (p=0.226) nor was there a significant difference in diastolic BP by cuff type (p=0.137). Conclusion: Blood pressure cuff readings with traditional sphygmomanometer and stethoscope or an automated brachial cuff are comparable while wrist cuff BP readings deviated significantly. For consistency in blood pressure readings, the three different cuff types are not interchangeable., (Copyright © 2018 The American Dental Hygienists’ Association.)

The Infectious Diseases Society of America infection-specific guidelines provide limited guidance on the management of focal infections complicated by secondary bacteremias. We address the following 3 commonly encountered questions and management considerations regarding uncomplicated bacteremia not due to Staphylococcus aureus : the role and choice of oral antibiotics focusing on oral beta-lactams, the shortest effective duration of therapy, and the role of repeat blood cultures.

Background: Epidemiologic studies using half-mouth designs for assessment of periodontal disease prevalence have reported that environmental tobacco smoke (ETS) exposure of non-smokers is associated with a two- to three-fold increase in the odds of developing periodontitis. In response to the possibility of under-reporting of periodontitis, the Centers for Disease Control updated periodontal examination procedures in 2009 for the National Health and Nutritional Examination Survey (NHANES), including full-mouth, six-site periodontal probing, and attachment loss assessment. Aims of this study are to estimate prevalence of periodontitis among United States non-smoking adults exposed to ETS, report the values of the improved methods for estimating disease prevalence, and evaluate the predictive contribution of ETS exposure to periodontitis., Methods: A cross-sectional study was conducted using NHANES data from the 2009 to 2012 examination cycle. To address these aims, oral examination data were used to determine prevalence of periodontitis among United States non-smoking adults and to test the influence of ETS exposure on occurrence of periodontitis., Results: There was a 28% increase in the odds of periodontitis for those with any ETS exposure compared with those with no measurable exposure (Wald χ 2 test statistic [df] = 6.58 [1], P = 0.01; 95% confidence interval = 1.06 to 1.55)., Conclusion: ETS exposure increases the risk of an individual developing periodontitis.

To date, no comparative clinical studies have investigated the effects of different vancomycin products on nephrotoxicity. The objective of this single-center, retrospective, matched-cohort study was to investigate the impact of two different vancomycin products on the development of nephrotoxicity. The study population included adults receiving a single vancomycin product, from either Pfizer or Hospira, for their entire course of therapy. Patients were matched based on underlying nephrotoxicity risk factors. Secondary outcomes included the need for renal replacement therapy, length of hospital stay, and in-hospital mortality. One-hundred forty-six matched pairs (n = 292) were included, and they had no significant differences in demographics, comorbid conditions, severity of illness, or vancomycin-associated nephrotoxicity risk factors. The frequency of nephrotoxicity was 8.9% in the Pfizer group and 11.0% in the Hospira group as defined by the 2009 consensus vancomycin guidelines (P = 0.56), 17.1% in the Pfizer group and 13.0% in the Hospira group as defined by the Acute Kidney Injury Network (AKIN) (P = 0.33), and 10.3% in the Pfizer group and 11.6% in the Hospira group as defined by RIFLE (risk, injury, failure, loss, and end-stage renal disease) criteria (P = 0.71). There were no differences between groups in regard to nephrotoxicity by any definition or in secondary outcomes. In multivariate analysis of overall nephrotoxicity risk factors, the type of vancomycin product was not independently associated with increased odds of developing nephrotoxicity according to the RIFLE criteria. Based on our results, there are no discernible differences between Pfizer and Hospira vancomycin products in the frequency of nephrotoxicity. Confirmation of these results with other types of vancomycin and different patient populations is warranted., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Colistin has re-emerged as an essential antibiotic for the treatment of carbapenem-resistant Gram-negative infections. Unfortunately, its utility is limited by high rates of nephrotoxicity, even at potentially therapeutic concentrations, and an overall lack of understanding on how to optimally administer the agent. In this review, recent advancements in the understanding of the safety and efficacy of colistin are discussed and strategies and suggestions on how to balance the two are described.

Purpose: The association of second hand smoke or environmental tobacco smoke (ETS) and periodontitis in non-smokers has not been confirmed using a biomarker of ETS exposure. To estimate periodontitis prevalence in non-smokers with detectable serum cotinine, and to investigate racial/ethnic and socioeconomic variation in ETS exposure in a representative sample of the U. S. adult population. Determining periodontitis risk indicators occurring with ETS appears to be a salient purpose as this study is the first of its kind to provide a link (a salivary biomarker) between second hand smoke and risk for periodontitis., Methods: Data were collected from the 1999 to 2004 National Health and Nutrition Examination Survey (NHANES). Subjects were 3,137 adults who had smoked fewer than 100 cigarettes and had not used other forms of tobacco. ETS exposure was classified as negligible (cotinine concentrations below sex and race/ethnicity cut-points for smokers), moderate (cotinine 0.5-<1.5 μg/mL) or high (cotinine ≥ 1.5 ng/mL). Periodontitis was classified according to the Centers for Disease Control and Prevention (CDC) and the American Academy of Periodontology (AAP) case definition for moderate-severe disease. Survey estimation procedures were used to estimate prevalence and odds ratios (OR) were from multivariable logistic regression models., Results: ETS exposure was observed in 40.5% of subjects and 2.6% had periodontitis. ETS exposure was inversely associated with educational attainment and family income and was higher in non-Hispanic blacks than whites. After adjusting for age, sex and year of survey, adults with high ETS exposure (cotinine ≥ 1.5 ng/mL) had more than twice the odds of periodontitis as people with negligible exposure (OR=2.3, 95% confidence interval=1.3, 4.1)., Conclusion: High ETS exposure was a risk indicator for periodontitis in lifetime non-smokers.

A more complete understanding of amino acid (AA) metabolism by the various tissues of the body is required to improve upon current systems for predicting the use of absorbed AA. The objective of this work was to construct and parameterize a model of net removal of AA by the portal-drained viscera (PDV). Six cows were prepared with arterial, portal, and hepatic catheters and infused abomasally with 0, 200, 400, or 600 g of casein daily. Casein infusion increased milk yield quadratically and tended to increase milk protein yield quadratically. Arterial concentrations of a number of essential AA increased linearly with respect to infusion amount. When infused casein was assumed to have a true digestion coefficient of 0.95, the minimum likely true digestion coefficient for noninfused duodenal protein was found to be 0.80. Net PDV use of AA appeared to be linearly related to total supply (arterial plus absorption), and extraction percentages ranged from 0.5 to 7.25% for essential AA. Prediction errors for portal vein AA concentrations ranged from 4 to 9% of the observed mean concentrations. Removal of AA by PDV represented approximately 33% of total postabsorptive catabolic use, including use during absorption but excluding use for milk protein synthesis, and was apparently adequate to support endogenous N losses in feces of 18.4 g/d. As 69% of this use was from arterial blood, increased PDV catabolism of AA in part represents increased absorption of AA in excess of amounts required by other body tissues. Based on the present model, increased anabolic use of AA in the mammary and other tissues would reduce the catabolic use of AA by the PDV.

Five lactating dairy cows with a permanent cannula in the rumen were given (kg DM/d) a normal diet (7.8 concentrates, 5.1 hay) or a low-roughage (LR) diet (11.5 concentrates, 1.2 hay) in two meals daily in a two-period crossover design. Milk fat (g/kg) was severely reduced on diet LR. To measure rates of production of individual volatile fatty acids (VFA) in the rumen, 0.5 mCi 1-(14)C-acetic acid, 2-(14)C-propionic acid, or 1-(14)C-n-butyric acid were infused into the rumen for 22 h at intervals of 2 to 6 d; rumen samples were taken over the last 12 h. To measure rumen volume, we infused Cr-EDTA into the rumen continuously, and polyethylene glycol was injected 2 h before the morning feed. Results were very variable, so volumes measured by rumen emptying were used instead. Net production of propionic acid more than doubled on LR, but acetate and butyrate production was only numerically lower. Net production rates pooled across both diets were significantly related to concentrations for each VFA. Molar proportions of net production were only slightly higher than molar proportions of concentrations for acetate and propionate but were lower for butyrate. The net energy value (MJ/d) of production of the three VFA increased from 89.5 on normal to 109.1 on LR, equivalent to 55 and 64% of digestible energy, respectively. Fully interchanging, three-pool models of VFA C fluxes are presented. It is concluded that net production rates of VFA can be measured in non-steady states without the need to measure rumen volumes.

Four multiparous cows with cannulas in the rumen and proximal duodenum were used in early lactation in a 4 x 4 Latin square experiment to investigate the effect of method of application of a fibrolytic enzyme product on digestive processes and milk production. The cows were given ad libitum a total mixed ration (TMR) composed of 57% (dry matter basis) forage (3:1 corn silage:grass silage) and 43% concentrates. The TMR contained (g/kg dry matter): 274 neutral detergent fiber, 295 starch, 180 crude protein. Treatments were TMR alone or TMR with the enzyme product added (2 kg/1000 kg TMR dry matter) either sprayed on the TMR 1 h before the morning feed (TMR-E), sprayed only on the concentrate the day before feeding (Concs-E), or infused into the rumen for 14 h/d (Rumen-E). There was no significant effect on either feed intake or milk yield but both were highest on TMR-E. Rumen digestibility of dry matter, organic matter, and starch was unaffected by the enzyme. Digestibility of NDF was lowest on TMR-E in the rumen but highest postruminally. Total tract digestibility was highest on TMR-E for dry matter, organic matter, and starch but treatment differences were nonsignificant for neutral detergent fiber. Corn silage stover retention time in the rumen was reduced by all enzyme treatments but postruminal transit time was increased so the decline in total tract retention time with enzymes was not significant. It is suggested that the tendency for enzymes to reduce particle retention time in the rumen may, by reducing the time available for fibrolysis to occur, at least partly explain the variability in the reported responses to enzyme treatment.

Two experiments were conducted to determine effects of postrumen starch infusion on milk production and energy and nitrogen utilization in lactating dairy cows. In experiment 1, four cows in early lactation fed grass silage and concentrates were continuously infused into the duodenum with water or 700, 1400, or 2100 g of purified maize starch daily for 10 to 12 d in a 4 x 4 Latin square design with 2-wk periods. Starch infusion increased milk yield linearly and decreased milk fat concentration in a quadratic manner such that increases in fat-corrected milk and calculated milk energy yield were minimal except at the highest rate of infusion. Changes in milk energy output suggest that even at the highest infusion rate metabolizable energy supplied by infused starch was used for tissue energy or oxidized. In experiment 2 energy and nitrogen balance were measured in four cows in late lactation fed a mixture of dehydrated lucerne, grass silage, and concentrates during the last 6 d of 2-wk abomasal infusions of 1200 g of purified wheat starch daily or water in a balanced switchback design with 5-wk periods. Measurements of fecal starch concentration indicated nearly all the starch infused was digested, but decreased fecal pH and apparent nitrogen digestion suggested an increase in hindgut starch fermentation. Starch infusion decreased urine nitrogen output in part because of increased tissue nitrogen retention but had no effect on milk nitrogen output. In absolute terms, numerical decreases in feed energy intake and energy digestion reduced the recovery of starch energy infused as digestible and metabolizable energy, but in terms of changes in total energy supply with starch infusion, 79% was recovered as metabolizable energy. Starch infusion had no effects on heat or milk energy but increased net energy for lactation due to a numerical increase in tissue energy, implying that in late-lactation cows, starch digested postruminally was used with high efficiency for tissue energy retention as protein and fat.

The study set out to examine the effects of supplementing grass silage with various levels of protein concentration and degradability on dietary nitrogen (N) excretion in lactating dairy cows consuming at least 60% forage. Six Holstein/Friesian cows in early to midlactation were offered six diets comprising two levels of crude protein (210 and 290 g/kg DM) and three levels of protein degradability in the concentrate achieved using different amounts of untreated or formaldehyde-treated soybean meal. Despite a difference of almost 100 g/d in N intake, apparent fecal and milk N outputs were not significantly affected. Protein degradability also had no effect on N outputs in feces and milk. However, there was a major effect of both level and degradability of CP on urinary N output. Moreover, an interaction between level and degradability of CP was detected, such that the rate at which urinary N increases with increasing CP degradability was higher on the high-CP than on the low-CP diet. A low level of protein (150 g/kg DM in the diet) and medium to low rumen-degradable protein supplements provided a significant reduction in N excretion without compromising lactational performance (mean 24.8 kg/d), in terms of both milk yield and composition. This study also demonstrated that a high efficiency of N utilization could be achieved on low-CP diets (supplying less than 400 g N/d), with feces being the main route of N excretion, whereas an exponential excretion of urinary N was observed as N intake exceeded 400 g N/d.

An experiment was conducted to examine the effect that various isoenergetic diets, containing different quantities of soluble carbohydrate and fiber and different types of starch, have on nitrogen (N) balances. Six lactating dairy cows in early to midlactation consuming grass silage diets with not less than 600 g/kg total DMI as forage were used in the experiment. Four concentrates were prepared that had higher amounts of either fiber, soluble sugars, corn (low degradable starch source), or barley (high degradable starch source). Overall N utilization by the cows was poor, rarely exceeding 0.30 g milk N/g of dietary N intake. Fecal N outputs accounted for more than half of total N excreted in all treatments except for diets supplemented with high degradable starch, in which urinary N excretion was significantly higher compared with the other treatments. Milk yield was unaffected by concentrate type, averaging 19.9 kg/d, but milk protein content decreased from 32.9 for starch-based diets to 30.9 and 30.0 g/kg for the soluble sugar- and fiber-based diets, respectively. The efficiency of N utilization improved in the low degradable starch treatment, which had lower N excretion (65%) and higher protein concentration in milk. Furthermore, feeding cows corn-based concentrates reduced urinary N excretion by almost 30% compared with barley-based concentrates; therefore, feeding corn-based diets is recommended for the reduction of nitrogen pollution in lactating dairy cows.

Elements of the metabolizable protein system in the United Kingdom were examined for their suitability as potential predictors of milk protein concentration. Models were based on data from 163 cows offered five forage mixtures for ad libitum intake plus concentrates at 3, 6, or 9 kg/d of dry matter. The models were then tested on a separate data set of 100 cows offered seven forage mixtures for ad libitum intake plus concentrates at 6 kg/d of dry matter. To minimize problems with collinearity, variables were arranged hierarchically; successive elements were components of variables at higher element levels. Variables from different element levels were not used in the same models. Models were constructed using ridge regression to minimize problems with collinearity. The fit and precision of prediction were generally poor because these models did not take into account animal variables. Models using undergradable dietary protein performed slightly better than did those using digestible undegraded protein. The use of slowly degradable protein and quickly degradable protein rather than rumen-degradable protein generally resulted in improvements in prediction. Models using neutral detergent fiber and quickly fermented carbohydrate were better than those using total carbohydrate. We concluded that there was little to be gained from using the elements of the metabolizable protein system considered here for the prediction of milk protein concentration.

The hepatic responses of late gestation, dry dairy cows to acute (6 h) infusions of an amino acid (AA) mixture (Synthamin; 0.0, 1.1, 2.2, 4.4, 8.8 and 17.6 mumol/min) into the mesenteric vein were determined. Neither blood flow nor O2 consumption across the portal-drained viscera (PDV) and liver was significantly altered by infusion. Similarly, there were no effects on net absorption, or hepatic removal, of acetate, propionate, butyrate or NH3. Glucose PDV appearance was unchanged but hepatic glucose production increased (P = 0.032) by 0.2 mumol/min per mumol/min of AA infused. Additional extraction of alanine, glycine (both infused) and glutamine (not infused) by the liver was sufficient to account for most of the extra C required for glucose synthesis. The N that would be liberated from these glucogenic AA would also account for a large proportion of the increase in urea-N produced in response to the AA infusion. This supports the concept of a correlation between gluconeogenesis and ureagenesis. Furthermore, the amide-N liberated from the extracted glutamine would contribute up to 0.17 of hepatic NH3 flux and assist in balancing N inputs into the carbamoyl phosphate and arginosuccinate entry points of the ornithine cycle. Rates of fractional extraction of the various AA by the liver were best fitted by linear equations, indicating that even at the highest rates of administration (approximately twice maximal physiological absorption) the transport systems were not saturated. Hepatic fractional extractions of infused essential AA were highest for methionine (0.83) and phenylalanine (0.87) with the lowest proportion removed observed for valine (0.25), leucine (0.30), lysine (0.31) and isoleucine (0.49). For the non-essential AA, the highest apparent fractional extractions were for glycine (0.73), arginine (0.79) and tyrosine (0.63) followed by alanine (0.54), proline (0.47) and serine (0.37). Hepatic removal of AA-N exceeded the increase in urea-N formation such that, at the highest rate of infusion, approximately 10 mmol/min of the extracted AA was apparently available for hepatic anabolism, more than is required to account for assumed increases in liver mass and export protein synthesis. Similarly, the amount of AA available for peripheral tissue protein gain, when assessed against phenylalanine supply as the limitation, would be the equivalent of a maximum of 0.5 g protein retained/min (6 mmol AA-N/min). This would provide sufficient AA for replenishment of peripheral (muscle) protein stores plus support of the placenta and fetus.

Changes in the kinetics of leucine in the mammary gland were examined in four lactating goats (25, 38, 45, and 135 DIM) that were given an i.v. infusion of a mixture of 18 AA, not including leucine, to alter the availability of leucine to the gland relative to other AA. Arteriovenous monitoring of [1-13C]leucine kinetics across one-half of the mammary gland was conducted on the last day (d 6 or 7) of the saline (control) and the AA infusion periods. Although blood flow to the mammary gland and the arterial concentration of most AA other than leucine were increased by the AA infusion, milk and protein yields did not change. For goats in early lactation (n = 3), arterial leucine concentrations fell considerably during AA infusion; however, the arteriovenous difference of leucine was maintained, resulting in uncommonly low leucine concentrations in venous plasma (8 microM). Whole body leucine flux (protein synthesis plus oxidation) was unaffected by AA infusion, but, because whole body leucine oxidation was reduced, whole body utilization of leucine for protein synthesis increased. The AA infusion reduced mammary oxidation of leucine to approximately one-third of control values. These results suggest that leucine oxidation can be reduced considerably without affecting milk protein output; thus, leucine oxidation may not be an irrevocable consequence of mammary metabolism. If catabolism of other AA either by the gland or in the whole body can be reduced, then the efficiency of milk yield can be improved.

Four Holstein-Friesian cows were used to investigate the effects of intravascular infusions of AA mixtures on milk constituents. Cows were in wk 11 to 28 of lactation and were fed a basal concentrate (142 g of CP/kg of DM) and grass silage (149 g of CP/kg of DM) in a 60:40 ratio (percentage of DM). Cows were fed hourly, and feed intake was fixed at 95% of ad libitum intake for each experimental period. Each cow received a 4-d jugular saline infusion, followed by a 5-d jugular infusion of a mixture of AA. Two mixtures of AA were used in a crossover design. The first mixture contained both the essential AA and non-essential AA found in milk protein (total AA); this mixture was infused at 400 g of AA/d. The other mixture represented the essential AA fraction only and was infused at 208 g/d. Infusion of total AA increased milk protein concentration from 32.4 to 35.0 g/kg, and essential AA increased milk protein concentration from 32.5 to 36.9 g/kg; milk protein yield increased by 87 g/d (total AA) and 143 g/d (essential AA). Intravascular administration of AA specifically stimulated milk protein concentration, and the efficiency with which the AA were used was higher than had been previously reported when AA supply was increased either by dietary supplementation or by abomasal infusion.

Metabolism in the mammary gland was related to changes in milk output in response to changes in dietary protein intake. Three diets of grass silage and concentrate were fed to four lactating dairy cows equipped with intravascular catheters across the mammary gland. Concentrates differed in the inclusion of protected soybean meal and provided 11.3, 15.4, and 20.1% CP, respectively. Blood samples were taken to assess the effect of protein percentage on the nutrient fluxes across the gland and their relationship to milk production. Milk production, milk protein yield, and milk protein concentration were all increased as CP intake increased, although these responses were not linear. Concentrations of urea in milk reflected those in plasma and increased as dietary protein intake increased. Uptake of glucose and BHBA by the mammary gland tended to increase as milk production increased. Arterial supply of essential AA increased as the dietary protein increased. Supply and uptake of nonessential AA were unchanged by dietary treatment, and uptake was insufficient to account for output of nonessential AA residues in milk protein. The supply of essential AA was not limiting for milk protein synthesis, and some alternative mechanism must have existed for the control of milk protein yield.

The kinetics of blood free amino acids (AA) transfer into milk casein were compared in goats (n 4) at 61 (SE 5) d (Expt 1; post-peak, 4.51 (SE 0.26) kg milk/d) and at 180 (SE 6) d (Expt 2; late, 2.36 (SE 0.16) kg milk/d) of lactation during non-primed, continuous (Expt 1, 12 h; Expt 2, 16 h) intravenous infusions of mixtures of L-[1-13C]leucine and L-[1-13C]phenylalanine with either L-[1-13C]valine (Expt 1) or L-[5-13C]methionine (Expt 2). The 13C enrichments of blood free and casein-bound AA were fitted to a single exponential model to estimate isotopic plateaux and the fractional rate constant for milk casein labelling. Milk protein output and its contribution to whole-body flux was higher in Expt 1 (post-peak) than in Expt 2 (late lactation), but the kinetics of 13C labelling of the casein-bound AA were similar for all AA tracers in both experiments. At both stages of lactation the delay (6-8 h) between the attainment of isotopic plateau for the blood free AA and the corresponding attainment of plateau for the casein-bound AA indicated that the blood free pool was not the immediate precursor pool for milk casein biosynthesis. Plateau enrichments of casein-bound AA were generally higher than those for the corresponding blood free AA in both experiments. These results indicate that the relative contributions of different AA sources to the immediate precursor pool for milk casein biosynthesis are similar at different stages of lactation despite major changes in the partitioning of whole-body flux towards milk protein output. Non-milk protein fluxes were also similar in post-peak and late lactation.

Four lactating cows equipped with rumen and duodenal cannulas were fed a diet of grass silage and concentrates containing either 12.4 or 17.2% CP (DM basis) in a change-over design. Additional protein was supplied as white fish meal. Fish meal did not affect molar proportions of VFA in the rumen, but duodenal NAN supply was increased .69 g/g of N in supplementary feed. In Experiment 2, three lactating dairy cows that had been prepared with catheters across the mammary gland were fed the same diets using a switchback design. Blood samples were taken to determine changes in metabolite flux to the mammary gland. In both experiments, milk production and protein yield were nonsignificantly increased by addition of fish meal. Milk urea output was increased from 3.18 to 4.74 g/d by fish meal supplementation, reflecting increased arterial concentrations of urea. Concentrations of glucose, VFA, and BHBA in blood showed no substantial changes because of dietary supplementation of fish meal. Supply of essential AA increased 26% with fish meal supplementation, mammary uptake increased 34%, but milk protein output only increased 5%. The low efficiency of conversion of supplementary protein to milk protein appears to be related to the inability of the gland to utilize the additional AA.

The authors performed a study to document the impact of a clinical pharmacist on cost saving and cost avoidance in an intensive care unit, and to evaluate the cost saving and avoidance to justify additional clinical pharmacist positions. Over 13 consecutive 5-day weeks, a clinical pharmacist with 50% teaching responsibility documented time spent and all interventions that impacted the cost of drug therapy. Both cost avoidance and cost saving were documented on change in route, change in dosage, change to another drug, discontinuation of therapy, discontinuation of therapeutic duplication, discontinuation of inappropriate therapy, notification of pharmacy of discrepancy, and improper drug-level monitoring avoidance. Cost analysis was calculated based on acquisition costs. The final cost saving was derived from adding cost avoided and cost saved minus pharmacist salary for the time spent in conducting the study. A total of 310 interventions were documented during the 13 weeks (65 days) of the study. The final cost saving was $79,723, which would extrapolate to an annual savings of $318,891. Although 31.3% of interventions involved change of dosage, interventions involving change to another drug (13.9%) had the largest economic impact ($62,527). The majority (85.4%) of the savings involved costs of medications saved (actual dollars saved rather than avoided). The authors concluded that the clinical pharmacist had a significant impact on the cost of drug therapy in the intensive care unit and that the cost of additional clinical pharmacist positions should be justified.

Objective: To report a case of pancytopenia following colchicine overdose and to discuss the use of granulocyte colony-stimulating factor (G-CSF) for treating this severe complication., Case Summary: A 19-year-old man developed pancytopenia four days after ingestion of approximately 50-60 0.6-mg colchicine tablets in a suicide attempt. His pancytopenia resolved after subcutaneous administration of one 300-micrograms dose of G-CSF. The patient recovered from his other multiorgan disturbances during his hospitalization and was discharged from the hospital with elevated liver enzyme concentrations., Conclusions: Colchicine overdose is rare, but can be fatal. The use of G-CSF appears to be beneficial in alleviating bone marrow depression in colchicine overdose situations.

Blood flow across the lactating bovine mammary gland was measured by two techniques. The use of transit time flow probes appeared to give flows which correlated well with dye dilution in only one of five cows, although the relative changes in flow were similar between the techniques in four of the cows. Further studies were made on the effect of posture on mammary blood flow using both techniques. The crossover of venous blood from one side of the mammary gland was also studied using the dye dilution technique, and revealed large differences between animals and also with posture. These observations suggest that particular care should be taken when sampling blood from the milk vein of cows, if a representative sample is required. Changes in blood flow with posture may be indicative of a repartitioning of flow within the body, and the physiology of such a mechanism would be of interest in itself. The control of this mechanism may be useful in modifying blood flow to the mammary gland and thus milk yield, since blood flow is related to the level of milk production.

Four lactating Friesian cows with permanent cannulas in the rumen and proximal duodenum were given early (EC)- or late (LC)-cut grass silage ad lib., each with either 3 or 9 kg concentrate dry matter (DM)/d in a 4 x 4 Latin square design starting about 10 weeks after calving. Feed was offered twice daily at 08.30 hours and 15.30 hours. Periods lasted 5 weeks and measurements were made in the last 15 d. The higher amount of concentrates increased total DM intake but reduced silage DM intake and the fractional rate of degradation of silage-fibre DM. Later cutting date of silage had no effect on DM intake or the fractional rate of degradation of silage-fibre DM but reduced potential degradability of silage fibre. Dilution rate of CoEDTA in rumen fluid was greater during the day (eating period) than during the night (resting period). Dilution rates measured at the duodenum were lower than those measured in the rumen, but neither was affected by diet. Silage-particle passage rates were measured by use of ytterbium-labelled silage fibre (Yb-fibre) and chromium-mordanted faecal particles (Cr-faeces) and samples were taken at the duodenum and in the faeces. Values for slower rate constant (k1) and transit time were higher and for faster rate constant (k2) were lower for Yb-fibre than for Cr-faeces, but differences in total mean retention time were inconsistent. Values for k1 for both markers and k2 for Yb-fibre only were similar at both sampling sites, but values for k2 for Cr-faeces were lower in the faeces. No diet effects were established with Yb-fibre but, with Cr-faeces, k1 was reduced by more concentrates and EC-silage. Daily mean weights of wet digesta, liquid, neutral-detergent fibre (NDF) and indigestible NDF in the rumen were greater with LC-silage but were unaffected by the amount of concentrates whereas weight of rumen DM was increased by the amount of concentrates only. Maximum rumen fill occurred at 18.00 hours with all diets. Particle-size distribution of rumen contents did not vary markedly during the day. Mean particle size was generally greater with LC-silage than EC-silage. Very small particles, passing through the 0.3 mm screen, constituted about half the rumen DM. It is concluded that rumen fill could have limited intake of LC-silage but not EC-silage.(ABSTRACT TRUNCATED AT 400 WORDS)

Four lactating dairy cows received arterial infusions of insulin (1.41 U/h), an AA mixture (threonine, methionine, leucine, phenylalanine, and lysine at 5.87, 1.90, 3.55, 2.17, and 4.21 mmol/h, respectively), and a combination of the two in a 4 x 4 Latin square. The infusions were performed over a 3-d period directly into the extra pudic artery on both sides of the mammary gland, and samples were taken simultaneously of the downstream extra pudic arterial blood and also of subcutaneous abdominal venous blood. Blood flow was measured by dye dilution using p-amino-hippuric acid and was increased by 37% by infusion of insulin plus AA (P less than .05). Infusions of AA tended to increase the arteriovenous difference and uptake of the infused AA (P less than .05 for phenylalanine) and had varying effects on the uninfused AA. Inclusion of insulin in the AA infusion tended to increase uptake of infused AA, whereas infusions of insulin alone tended to decrease uptake. There were no significant effects of infusion on milk yield or composition.

Patients with systemic lupus erythematosus can often benefit from cooperative and collaborative interventions prescribed by both physicians and other arthritis health care professionals.

This prospective, double blind study was undertaken to test the efficacy of intravenous "minipulse" (100 mg) methylprednisolone (MP) therapy versus standard pulse (1000 mg) MP therapy in rheumatoid arthritis (RA). Thirty-six patients with RA synovitis flares were randomized to receive either 100 or 1000 mg MP IV QD x 3 doses. These 2 universally comparable groups exhibited no statistically significant differences in their striking prompt and sustained clinical improvement. These data suggest that minipulse MP is as efficacious as conventional pulse MP in the treatment of RA flares.

Sixty-six systemic lupus erythematosus (SLE) patients, 375 healthy female controls and 537 young Caucasian females were examined according to a recently suggested two-stage model for population screening for SLE. This model consisted in: a) administration of a 10-item questionnaire based on the ARA preliminary criteria for SLE; b) search of antinuclear antibodies (ANA) in the persons positive during the first stage. Among the SLE patients, the overall sensitivity of the two-stage screening was 90%, while its specificity in the healthy 375 normals reached 96%. 13% of 537 young Caucasian females answered affirmatively to 3 or more questions of the questionnaire. Out of these, 59 were tested for ANA. Two out of these 59 had a positive ANA test, but no one had SLE at a subsequent clinical survey. These data confirm the validity of this two-stage screening procedure for SLE. While the low prevalence of this disorder in the general population hardly justifies its massive application, the screening might be recommended for survey groups at high risk for SLE.

Cinnamyl anthranilate is a synthetic food flavouring and fragrance agent, formerly used at very low levels. There is currently some concern over the potential risk to man from its use, since it has been found to cause liver tumours in mice, following the administration of very large doses. This paper reports studies of its disposition and hepatic effects in B6C3F1 mice in relation to dose. Following a single oral dose of 500 mg cinnamyl anthranilate/kg body weight to B6C3F1 mice peak plasma levels of unchanged compound were reached in 30 min, and were higher in males than in females. Unchanged cinnamyl anthranilate in the urine accounted for 0.3-0.4% of the dose. Anthranilic acid (c. 17%) and hippuric acid (35%; the major metabolite of cinnamyl alcohol) were present in the urine, and recoveries of both were higher in females. Groups of male and female B6C3F1 mice were given 0, 10, 100, 1000, 5000, 15,000 and 30,000 ppm cinnamyl anthranilate in the diet. After 4 days, the diet was removed and urine collected for 24 hr. This contained cinnamyl anthranilate (more in males) hippuric and anthranilic acids (more in females) in concentrations that increased with dose. Other animals were given these diets for 19 days and then killed. Relative liver weight and hepatic microsomal cytochrome P-450 increased with increasing dose above 1000 ppm cinnamyl anthranilate, more markedly in males than in females although the maximum response (roughly twofold) was very similar in the two sexes. SDS-PAGE examination of the microsomes revealed the induction of a cytochrome P-450 isozyme of 53.1 kDa, but the aniline hydroxylase and p-nitroanisole O-demethylase activities of the 9000 g supernatant of liver were not induced. The data are discussed in terms of their significance for the human safety evaluation of cinnamyl anthranilate. It is important to note that liver hypertrophy, microsomal enzyme induction and the excretion of unchanged cinnamyl anthranilate all have the same dose-threshold for their appearance. This suggests that the hepatic effects of cinnamyl anthranilate may be mediated by unhydrolysed cinnamyl anthranilate, which is present only at very high doses due to the saturation of its hydrolysis.

The influence of dose size on the metabolic fate of the naturally occurring food flavouring trans-anethole has been investigated in human volunteers, using the [methoxy-14C]-labelled compound. The doses chosen were: 1 mg; close to the daily intake in the diet from foods, 50 mg; approximating to the amount present in a normal measure of an anise-flavoured beverage, and 250 mg. The order of administration was randomized. The major routes of elimination of 14C were in the urine (54-69% of the administered dose) and as exhaled 14CO2 (13-17%). Dose size had no systematic effect on either rate or route of excretion. Urinary metabolites were separated by high-pressure liquid chromatography, before and after treatment with beta-glucuronidase, and identified by comparison of their chromatographic mobilities with those of authentic standards. The principal metabolite (greater than 90% of urinary 14C) was 4-methoxyhippuric acid, accompanied by much smaller amounts of 4-methoxybenzoic acid and up to three other compounds, which were not examined further. The pattern of urinary metabolites was unaffected by dose size. These data are discussed with reference to the comparative metabolic disposition of trans-anethole in rats and mice, the species commonly used in toxicity testing and in which its fate exhibits a very marked dose dependence.

Patients hospitalized with arthritis require the expertise of nurses with a solid medical and surgical background, a base upon which approaches to rheumatic disease can be developed. The nurse should play a primary role in planning a realistic and integrated schedule for meeting the patient's pharmacotherapeutic and rehabilitation needs, in reinforcing physical medicine principles and programs, and in serving as a liaison between patient and physician, patient and other health care providers, patient and family, and patient and community. The nurse is pivotal in assuring that the comprehensive care and educational needs of the patient with arthritis are met, whether hospitalized or in an out-patient setting.

We present an in-depth study of rheumatoid arthritis (RA) in a Chippewa band. Of the 227 band members, 168 (74%) were evaluated. The unusually high prevalence of RA was confirmed in 7.1% of those studied or, minimally, 5.3% with a 100% completion rate without additional cases found. Seropositivity in those with clinically definite RA was 92% relative to rheumatoid factor and 75% for ANA. Despite the high prevalence (68%) of HLA-DR4 in this closed population, there was a significant correlation of DR4 with RA (100%). The implications of these observations in this population isolate are discussed.