Antibiotic Prophylaxis Regimens in Trauma and Orthopaedic Surgery: Are We Providing Adequate Cover Against Colonizing Organisms?

UNLABELLED: Trauma, elective orthopaedics, and an aging population will result in an increasing health burden and work load. The move to surgical podiatrists in the National Health Service within the United Kingdom will shift the surgical workload away from orthopaedic surgeons. A devastating complication of foot and ankle surgery is postoperative infection. While postoperative infection is multifactorial in etiology, concomitant diabetes mellitus increases the general risk of trauma and orthopaedic surgical site infections up to 8-fold. We therefore undertook a prospective study of our unit antibiotic prophylaxis regimes. Fifty patients participated. Swabs were obtained using aseptic technique from the plantar aspect of the feet, between the toes, and subsequently cultured on agar plates. Specimens were then incubated for 48 hours before being exposed to antibiotic plates. Cultured organisms were classified as susceptible to an antibiotic regimen if susceptibility to cefuroxime, or susceptibility to either drug of the flucloxacillin/gentamicin combination, was demonstrated. Statistical analysis e was performed. A P value <.05 was considered significant. Fifty patients were recruited, 26 (52%) were male. Mean age of 53 ± 19.4 years. The cohort included 15 diabetic, of which 11 (73.3%) insulin-dependent, and 35 nondiabetic patients. Comparing flucloxacillin/gentamicin against cefuroxime overall, susceptibility was noted in 84% and 70%, respectively (P = .096). Resistance to cefuroxime was significantly higher in diabetics than in nondiabetics (53% vs 25%, P = .046). The same pattern was observed for the flucloxacillin/gentamicin regimen (33% vs 9%, P = .049). While both regimens are active against colonizing organisms in this prospective observational study, flucloxacillin and gentamicin provide greater coverage overall. We have demonstrated that the use of flucloxacillin/gentamicin provides better coverage against commensal bacterial flora compared with cefuroxime alone. This is of even greater importance in the case of the specific high-risk subgroups, such as diabetic patients. LEVELS OF EVIDENCE: Level IV: Case Series.

Search for low-mass weakly interacting massive particles using voltage-assisted calorimetric ionization detection in the SuperCDMS experiment.

SuperCDMS is an experiment designed to directly detect weakly interacting massive particles (WIMPs), a favored candidate for dark matter ubiquitous in the Universe. In this Letter, we present WIMP-search results using a calorimetric technique we call CDMSlite, which relies on voltage-assisted Luke-Neganov amplification of the ionization energy deposited by particle interactions. The data were collected with a single 0.6 kg germanium detector running for ten live days at the Soudan Underground Laboratory. A low energy threshold of 170 eVee (electron equivalent) was obtained, which allows us to constrain new WIMP-nucleon spin-independent parameter space for WIMP masses below 6 GeV/c2.

Acute kidney injury as a presentation of primary renal diffuse large B-cell lymphoma in HIV.

We report a case of acute kidney injury due to primary renal diffuse large B-cell lymphoma, which developed after initiation of tenofovir-containing antiretroviral therapy in a 28-year-old HIV-positive man.

The slow component of VO(2) kinetics in very heavy and fatiguing square-wave exercise.

We hypothesized that oxygen consumption ( VO(2)) rises incrementally in very heavy and fatiguing exercise where the slow component gain increases with higher work rates. Eight trained males completed a graded exercise test and bouts of square-wave cycle ergometry at 40% and 60% of the difference between the estimated lactate threshold (LT) and VO(2peak) (designated 40%D and 60%D). Exhaled gases were collected and analyzed every breath using models that allowed for a linear slow component or a slow component with one or more exponential increments. All subjects were able to complete 30 min at 40%D but not at 60%D. The slow component was generally best fit with two increments at 40%D and two or three increments at 60%D. In further (, our results question the reliability of determining parameters of multiple slow component increments when repeated bouts are averaged together. This study demonstrates that VO(2) can continue to rise incrementally beyond the onset of the slow component in very heavy and fatiguing exercise. These results support the concept of a recurring mechanism underlying the slow component of VO(2) kinetics during square-wave exercise and suggest that the dynamics (time of onset, rate of development, magnitude) of this mechanism may vary from day to day.

Leg electromyography and the VO2-power relationship during bicycle ergometry.

PURPOSE: The relationship between oxygen consumption and power is not linear. The purpose of this investigation was to examine the nature of the relationship and the cause of the nonlinearity. METHODS: Eight male cyclists (60.5 +/- 3.8 mL O2.min-1.kg(-1) VO2 peak) completed an incremental exercise test (1 W.5 s(-1)) to exhaustion. VO2 was measured every breath, and rmsEMG was recorded continuously over the belly of vastus lateralis, biceps femoris, and lateral gastrocnemius. RESULTS: VO2 is a linear function of power in moderate exercise; the slope of the linear portion was approximately 9.7 mL O2.min(-1).W(-1), which is consistent with the steady state gain for moderate exercise. Beyond this initial break from linearity, the VO2.W(-1) plot demonstrates a second break that is not different from the point of respiratory compensation (break in VE.VCO2(-1)). These breaks were coincident with increased neuromuscular activity (1st break: 194 +/- 27 W for VO2, 191 +/- 25 W for vastus lateralis; 2nd break: 262 +/- 34 W for VO2, 258 +/- 27 W for vastus lateralis) and corresponded to approximately 58% VO2 peak for the first and 75% VO2 peak for the second break. CONCLUSIONS: VO2 is not a linear function of power. During an incremental test, neuromuscular activity and VO2 increase more rapidly in heavy exercise. Both VO2 and neuromuscular activity exhibit a second break at very high power output, which may mark an upper limit for sustainable exercise.

VO2 and heart rate kinetics in cycling: transitions from an elevated baseline.

The purpose of this study was to examine oxygen consumption (VO2) and heart rate kinetics during moderate and repeated bouts of heavy square-wave cycling from an exercising baseline. Eight healthy, male volunteers performed square-wave bouts of leg ergometry above and below the gas exchange threshold separated by recovery cycling at 35% VO2 peak. VO2 and heart rate kinetics were modeled, after removal of phase I data by use of a biphasic on-kinetics and monoexponential off-kinetics model. Fingertip capillary blood was sampled 45 s before each transition for base excess, HCO and lactate concentration, and pH. Base excess and HCO concentration were significantly lower, whereas lactate concentration and pH were not different before the second bout. The results confirm earlier reports of a smaller mean response time in the second heavy bout. This was the result of a significantly greater fast-component amplitude and smaller slow-component amplitude with invariant fast-component time constant. A role for local oxygen delivery limitation in heavy exercise transitions with unloaded but not moderate baselines is presented.

VO(2) slow component: to model or not to model?

PURPOSE: The purpose of this study was to compare several techniques often used in the literature for measuring the amplitude of the slow component of oxygen uptake kinetics. METHODS: Eight healthy male volunteer cyclists performed two identical bouts of square wave cycle ergometry, from a VO(2) of 60% of the lactic acid threshold (LAT) to 30% of the difference between LAT and VO(2) peak. Predetermined intervals (3--6 and 3--10 min) were chosen to reflect those often used in the literature, namely 3-6 min and 3 min to the end of exercise. Several procedures were used to estimate the 3, 6, and 10-min VO(2) values (20-s averaging, 60-s averaging, and mono-exponential modeling). These were compared with the modeled slow component amplitude using a two-phase model with independent time delays: VO(2)(t) = B VO(2) + A(1)(1 -- e(-(t-TD1)/tau(1)) + A(2)(1 -- e(-(t-TD2)/tau(2)). CONCLUSIONS: The results showed a significant underestimation for all methods of slow component amplitude estimation (P < 0.05) when compared with the actual (modeled) amplitude. In so far as research on oxygen uptake kinetics is used to understand the underlying physiology, it is imperative that the components of the kinetics be determined accurately. The use of a predetermined time frame for estimation of the amplitude of the slow component is not supported by this study. Future investigations should consider these results and make every effort to model the underlying response.

Effects of the transdermal nicotine patch on normalization of HDL-C and its subfractions.

BACKGROUND: Smoking reduces HDL-C and its subfractions, and smoking cessation leads to normalization of these lipoproteins. Nicotine replacement therapy is an important weapon employed by those attempting to quit smoking. This study examined the effects of the transdermal nicotine patch ("patch") on lipoproteins. METHODS: Ten male and 17 female smokers refrained from smoking for 77 days. The patch was utilized during the first 35 days and then removed for the remaining 42 days. Seven male and 9 female nonsmokers were controls. RESULTS: HDL-C, HDL(2)-C, and HDL(3)-C levels were significantly lower in smokers when compared with controls. These differences were sustained during the initial 35 days when using the patch. Over the following 42 days, however, these lipoproteins normalized to values similar to those of control subjects. Females who quit smoking gained 2.1 kg after the patch was removed. CONCLUSIONS: It was concluded that nicotine as administered by the transdermal nicotine patch inhibits normalization of HDL-C, HDL(2)-C, and HDL(3)-C in those who have quit smoking. Removal of the patch results in normalization of these lipoproteins. The patch appeared to prevent weight gain among female subjects.

VO(2) kinetics and the O(2) deficit in heavy exercise.

The purpose of this study was to examine a new method for calculating the O(2) deficit that considered the O(2) uptake (VO(2)) kinetics during exercise as two separate phases in light of previous research in which it was shown that the traditional O(2) deficit calculation overestimated the recovery O(2) consumption (ROC). Eight subjects completed exercise transitions between unloaded cycling and 25% (heavy, H) or 50% (very heavy, VH) of the difference between the lactic acid threshold (LAT) and peak VO(2) for 8 min. The O(2) deficit, calculated in the traditional manner, was significantly greater than the measured ROC for both above-LAT exercises: 4.03 +/- 1.01 vs. 2.63 +/- 0.80 (SD) liters for VH and 2.36 +/- 0.91 vs. 1.74 +/- 0.63 liters for H for the O(2) deficit vs. ROC (P < 0.05). When the kinetics were viewed as two separate components with independent onsets, the calculated O(2) deficit (2.89 +/- 0.79 and 1.71 +/- 0.70 liters for VH and H, respectively) was not different from the measured ROC (P < 0.05). Subjects also performed the same work rate for only 3 min. These data, from bouts terminated before the slow component could contribute appreciably to the overall VO(2) response, show that the O(2) requirement during the transition is less than the final steady state for the work rate, as evidenced by symmetry between the O(2) deficit and ROC. This new method of calculating the O(2) deficit more closely reflects the expected O(2) deficit-ROC relationship (i.e., ROC >/= O(2) deficit). Therefore, estimation of the O(2) deficit during heavy exercise transitions should consider the slow component of VO(2) as an additional deficit component with delayed onset.

Smoking-induced elevations in blood carboxyhaemoglobin levels. Effect on maximal oxygen uptake.

Many people engage in physical activity to reduce their cardiovascular risk associated with smoking. These people should be made aware of the metabolic and cardiorespiratory changes induced by chronic and acute smoking and, in particular, the exercise ramifications of increased levels of blood carbon monoxide (CO). Smoking-induced elevations in the CO content of the blood can reduce exercise tolerance and maximal aerobic capacity. Smoking also increases the reliance upon glycolytic metabolism during exercise. Together, these factors contribute to earlier fatigue in smokers compared with nonsmokers who exercise. Similar effects upon exercise tolerance are noted in those who inhale environmental tobacco smoke.

Effect of ENDUROX on metabolic responses to submaximal exercise.

Claims that ENDUROX enhances performance by altering metabolic responses to exercise were tested. In a double-blind crossover design, 10 male subjects were randomly assigned to consume 400 mg of placebo or 800 mg ENDUROX for 7 days. Cycle ergometry was performed for 30 minutes at 25%, followed by 10 min at 65% of peak oxygen consumption. After a 1-week washout period, subjects performed the identical exercise protocol following 7 days of reciprocal supplemental conditions. Expired gases were collected and analyzed continuously for oxygen consumption, minute ventilation, and respiratory exchange ratio. Heart rate, blood pressure, rating of perceived exertion, blood lactate, and serum glycerol data were also collected at regular intervals. A two-way ANOVA with repeated measures revealed no significant main or interaction effects involving group differences (p > 0.05) between trials for any variable during rest, 25% or 65% (VO2 peak), or recovery. Our findings do not support the ergogenic claims for ENDUROX.

The effect of smoking on energy expenditure and plasma catecholamine and nicotine levels during light physical activity.

A number of studies have found that cigarette smoking causes an acute increase in resting energy expenditure, but the effect on energy expenditure during light physical activity is less clear. Since both smoking and activity have been shown to increase plasma catecholamines, these could produce additive effects on energy expenditure when smoking during light physical activity. In this study, the impact of cigarette smoking on energy expenditure, cardiovascular function, plasma nicotine and plasma catecholamine levels was determined in adult male subjects at rest and while engaged in light physical activity. Smoking at rest resulted in a 3.6% increase in energy expenditure above the resting baseline; whereas the increase in energy expenditure caused by smoking during light physical activity (compared with the light physical activity baseline) was 6.3%. This increase during light physical activity was significantly greater than the increase observed at rest (p < 0.025). As expected, plasma nicotine increased with smoking during both rest and light physical activity. An increase in plasma nicotine was associated with smoking during light physical activity. When this increase was adjusted as a covariate, the difference in smoking-related energy expenditure between light physical activity and rest disappeared, suggesting nicotine accounts for the effect. Plasma epinephrine and norepinephrine levels increased with smoking and showed a significantly greater increase during light physical activity compared to rest. Cigarette smoking caused a significantly greater increase in heart rate during light physical activity than it did while at rest, but there was no significant effect of smoking on mean blood pressure. It was concluded that there is enhanced energy expenditure associated with cigarette smoking during light physical activity when compared with smoking at rest which could be due in part to smoking-induced increases in circulating plasma catecholamines and perhaps nicotine.

Encouragement during maximal exercise testing of type A and type B scorers.

The influence of verbal encouragement during assessment of maximal oxygen consumption of subjects scoring as Type A and Type B on the Jenkins Activity Survey, Form T was examined. Fourteen Type A and 12 Type B scorers performed two randomly assigned tests on a motor-driven treadmill with and without verbal encouragement during testing. Treadmill time, oxygen consumption (VO2), heart rate, and respiratory exchange ratio at exhaustion were examined. Verbal encouragement led to significantly greater treadmill time, VO2, and respiratory exchange ratio for Type B scorers when compared with the non-encouragement trial. Treadmill time, VO2, heart rate, and respiratory exchange ratio at exhaustion were not different between treatments for the Type A scorers. Type A scorers ran significantly longer without encouragement than Type B scorers; however, when encouragement was provided, treadmill time for Type A and Type B scorers did not differ significantly. The results suggest that attainment of maximal effort is not dependent on verbal encouragement for Type A scorers, whereas verbal encouragement is necessary to assure attainment of maximal physiologic effort for those individuals scoring as Type B.

In vitro fertilization in mice: Strain differences in response to superovulation protocols and effect of cumulus cell removal.

Strain differences have proven to be crucial components in mouse in vitro fertilization (IVF) and superovulatory protocols. To maximize the yield of IVF-derived mouse eggs, a series of experiments was conducted using different injection timing intervals for administration of pregnant mare serum gonadotropin (PMSG) and hCG to induce follicular development and ovulation. Strains were chosen that were representative of those commonly used in genetic engineering experimentation. These strains included ICR outbred, C57BL/6 inbred, and B6SJLF1 hybrid (C57BL/6J x SJL/J F1) mice. Females were superovulated using 4 PMSG/hCG/IVF timing regimens (group), with sperm obtained from males of the same strain. Group designations were based on the following PMSG/hCG and hCG/oocyte collection intervals, respectively: Group 1, 55 and 21.5 h; Group 2, 60 and 14.5 h; Group 3, 55 and 14.5 h; Group 4, 48 and 14.5 h. After overnight culture of ova, fertilization rates (development to the 2-cell stage) were assessed. A logistic regression was performed using indicator variables for both strain and group. There was a significant strain influence on ova fertilization rate, based on the coefficients of mouse strain (ICR, beta = -1.1067, P = 8E-17 and C57BL/6, beta = -0.5172, P = 8E-06). Additionally, group affected the proportion of fertilized ova obtained (coefficient of Group 1, beta = -1.3152, P = 0.00 and Group 3, beta = 0.9531, P = 3E-12). From the coefficients for the interaction terms, the effect of groups varies across mouse strain. Therefore, the treatment that produces the highest fertilization rate is related to and contingent upon the strain of mouse. In the second study, the Group 3 protocol was used to evaluate fertilization differences between cumulus-intact and cumulus-free oocytes. Again, there was a significant strain influence on ova fertilization rate based on the coefficients of mouse strain (ICR, beta = -2.6639, P = 0.00; C57BL/6, beta = -2.5114, P = 0.00). However, there was no difference between Cumulus and No Cumulus groups (cumulus coefficient, beta = 0.1640, P = 0.59872), indicating that there was no affect of cumulus presence on fertilization rate. In summary, responses to standardized mouse IVF protocols vary significantly. The efficiency of IVF procedures can be optimized between and within specific mouse strains by the timing of superovulatory regimens. However, absence of cumulus cells during the IVF procedure does not adversely affect fertilization rate.

Mitochondria transfer into mouse ova by microinjection.

A method for mitochondria isolation and interspecific transfer of mitochondria was developed in mice. Mitochondria were isolated from Mus spretus liver samples for microinjection into fertilized ova obtained from superovulated M. musculus domesticus females. Electron microscopic observations of mitochondria preparations used for microinjection demonstrated intact mitochondrial vesicles with little microsomal contamination. Species-specific nested PCR primers complementary to sequence differences in the mitochondrial DNA D-loop region revealed high rates of successful transfer of foreign mitochondria after isolation and injection into zygotes cultured through the blastocyst stage of embryonic development. Of 217 zygotes, 67 survived mitochondria injection and 23 out of 37 zygotes developed were at the blastocyst-stage of embryonic development after 4.5 days of in vitro culture. All 23 of these blastocysts contained detectable levels of foreign mitochondria. These results represent an initial step in developing a model system to study mitochondrial dynamics and development of therapeutic strategies for human metabolic diseases affected by aberrations in mitochondrial function or mutation.

Optimization of embryo transfer protocols for mice.

The efficiency of ova transfer and subsequent survivability were explored in this study. The goals of the experiment were to 1) determine the minimum number of ova necessary for pregnancy maintenance, 2) ascertain if the number of zygotes used in ova transfer approaches or exceeds uterine capacity, and 3) establish if location of deposition of ova influences embryo survival. A total of 1647 pronuclear zygotes were transferred in groups of 1, 2, 4, 6, 15 or 25 on Day 1 of gestation either via the oviducal ampulla or ostium to 156 nulliparous ICR pseudopregnant female mice. Pregnancy status was determined on Day 12 or Day 19 of gestation. Results indicated that pregnancy rates were not significantly increased by transferring larger numbers of zygotes (P < 0.1504) and that beyond transfer of 15 zygotes, the progressive increase in fetal numbers per litter declined. However, on Day 19 of gestation, no definitive evidence of limitation of uterine capacity was obtained with the numbers of zygotes transferred (P < 0.0531), and the estimates of numbers of viable and resorbed fetuses differed when determinations were made on Day 12 versus Day 19 of gestation. Mean numbers of developed fetuses per recipient declined (P < 0.0001), whereas the number of resorptions (partially resorbed fetuses or resorption sites) increased (P < 0.0001) over this period, reflecting fetal loss in mid- to late-gestation and possibly the transient nature of resorptions prior to Day 12. Additionally, there was no difference in pregnancy outcome when transferring ova into the oviducal ostium or isthmus (P < 0.5256). Finally, these results illustrated that when large numbers of zygotes were transferred into the oviducal ampulla, equivalent numbers of ova eventually implanted in the uterus; however, proportionally more of them began resorption.

Identification of transgenic mice by PCR analysis of saliva.

As an alternative to surgically obtaining samples (e.g., tail or tissue biopsy, toe dock, or blood sampling) from weanling mice to screen for transgene integration or other genetic monitoring procedures, we offer a simpler, nonsurgical method. A small amount of saliva, obtained from weanling mice by oral wash using a plastic pipet tip, contains enough oral epithelial cells and lymphocytes to yield sufficient DNA for nested primer polymerase chain reaction (PCR) analysis. The procedure can be repeated many times with minimal stress to the animal, in contrast to tissue biopsy procedures such as tail cutting. Sample analysis is rapid and straightforward; saliva is applied to sample collection paper and then purified using a solid phase DNA purification system. The paper, containing purified DNA, is added directly to PCR cocktail for the first round of amplification. For weanling mice, in the second round of amplification, a small amount of product from the first round is removed and added to PCR cocktail containing the second set of primers. With adult mice, an adequate volume of saliva may be obtained (dependent upon the sensitivity of the particular reaction) to eliminate the need for second-round amplification with nested primers. This technique is reliable, does not require organic solvents, and is more humane than protocols currently in use. Furthermore, this technique could replace hundreds of thousands of surgical biopsies on rodents annually, which are performed for both transgene determination and genetic monitoring procedures.

Influence of water run training on the maintenance of aerobic performance.

The purpose of this study was to examine the effect of a 6-wk deep water running program on the maintenance of cardiorespiratory performance (VO2max, ventilatory threshold, running economy); metabolic measurements of blood glucose, blood lactate, and plasma norepinephrine; and body composition. Sixteen trained male runners (VO2max = 58.6 +/- 3.6 ml.kg-1.min-1) were assigned to one of two groups matched by VO2max, treadmill run (R) or water run (WR). Subjects participated in their respective training programs, which consisted of workouts of a) 30 min at 90-100% VO2max and b) 60 min at 70-75% VO2max alternated daily for 5 d.wk-1. Following 6 wk of workouts, no significant intra- or intergroup differences were observed for treadmill VO2max for R (pre = 58.4 +/- 2.3, post = 60.1 +/- 3.6 ml.kg-1.min) and WR (pre = 58.7 +/- 4.7, post = 59.6 +/- 5.4 ml.kg-1.min-1). Similarly, ventilatory threshold was unaltered in R (pre = 47.5 +/- 1.8, post = 48.2 +/- 3.3 ml.kg-1.min-1) and WR (pre = 46.5 +/- 6.4, post = 47.4 +/- 6.7 ml.kg-1.min-1), nor were there any changes in running economy in R (pre = 48.4 +/- 2.3, post = 48.9 +/- 2.0 ml.kg-1.min-1 at 255 m.min-1) and WR (pre = 51.8 +/- 2.0, post = 48.9 +/- 2.2 ml.kg-1.min-1 at 255 m.min-1). No significant differences were observed within or between groups for maximal blood glucose, blood lactate, and plasma norepinephrine concentration as well as for body composition indices. It was concluded that deep water running may serve as an effective training alternative to landbased running for the maintenance of aerobic performance for up to 6 wk in trained endurance athletes.

Influence of worksite environmental tobacco smoke on serum lipoprotein profiles of female nonsmokers.

The purpose of this study was to examine the influence of environmental tobacco smoke (ETS) in the workplace on high-density lipoprotein cholesterol (HDL-C), HDL-C subfractions, and apolipoprotein (apo) A-I and apo B in female workers. Premenopausal women free from factors known to influence HDL-C (cigarette smoking, vigorous physical exercise, etc) who were not taking oral contraceptives, were moderate consumers of alcohol, caffeine, and dietary fat, and were between the ages of 21 and 50 years participated in one of two groups: (1) nonsmokers who had never smoked cigarettes and were generally free from ETS exposure (nonsmokers), and (2) nonsmokers who had never smoked but were subjected to concentrated doses of ETS at least 6 hours per day, 4 days per week, for at least 6 consecutive months (ETS-exposed). A third group consisting of current cigarette smokers who smoked a minimum of 20 cigarettes per day for at least the past 5 consecutive years served as smoking control (smokers). Subjects were matched by group as closely as possible with regard to criteria that can influence blood lipoprotein levels. Participants were solicited from taverns and restaurants where they were employed. It was hypothesized that individuals chronically exposed to ETS would demonstrate unfavorable lipoprotein profiles. Results showed that HDL-C, HDL2, and apo A-I were significantly (P < .05) depressed for ETS-exposed and smokers as compared with nonsmokers. Values for ETS-exposed were not different from those for smokers. Total cholesterol, triglycerides, HDL3, and apo B did not differ among the three groups. It was concluded that excessive exposure to ETS in female workers can have deleterious effects on HDL-C, HDL2, and apo A-I in nonsmokers that are similar to effects observed in cigarette smokers. It is possible that these effects increase coronary artery disease (CAD) risk.