Analysis of pelvic fracture pattern and overall orthopaedic injury burden in children sustaining pelvic fractures based on skeletal maturity.

PURPOSE: The purpose of this study was to review pelvic fractures and concomitant orthopaedic injuries in children who have a patent triradiate cartilage (TRO) compared with children whose triradiate cartilage has closed (TRC). We hypothesise that these injuries will differ, leading to correlated alterations in management. PATIENTS AND METHODS: Using a database, we retrospectively reviewed patients aged below 18 years with pelvic fractures presenting to our Level 1 trauma center. Radiographs and CT scans were reviewed to identify orthopaedic injuries and categorise pelvic injuries using the modified Torode classification between the two groups. RESULTS: A total of 178 patients met inclusion criteria (60 TRO and 118 TRC). Mean age ± SD for TRO and TRC groups were 8 ± 4 years and 16 ± 2 years, respectively. TRO patients were more likely to present as a pedestrian struck by a vehicle (odds ratio (OR) 6.0; p < 0.001) and less likely to present after a motor vehicle collision (OR 0.2; p < 0.001). TRO patients were more likely to sustain rami fractures (OR 2.1; p = 0.020) and Torode IIIA injuries (OR 3.6; p < 0.001). They were less likely to sustain acetabular fractures (OR 0.5; p = 0.042), sacral fractures (OR 0.4; p = 0.009), hip dislocations (p = 0.002) and Torode IV injuries (OR 0.4; p = 0.004). TRO patients were less likely to be treated operatively for their pelvic (OR 0.3; p = 0.013) and orthopaedic injuries (OR 0.4; p = 0.006). CONCLUSION: We suggest that patients with open triradiate cartilage are unique. Their pelvic injuries may be treated more conservatively as they have a greater potential for periosteal healing and bone remodelling. Patients with closed triradiate cartilage should be treated similarly to adults, as they share a similar mechanism of injury and need for operative fixation.

Introduction of an interdisciplinary heart team-based transcatheter aortic valve implantation programme: short and mid-term outcomes.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been developed to treat symptomatic aortic stenosis in patients deemed too high risk for open-heart surgery. To address this complex population, an interdisciplinary heart team approach was proposed. AIM: Present the short- and mid-term outcomes of the first 100 patients in the Royal Prince Alfred Hospital multidisciplinary TAVI programme. METHODS: Single-centre registry. Baseline and procedural data were prospectively recorded. Outcomes were recorded according to Valve Academic Research Consortium - version 2 guidelines. RESULTS: All patients underwent a comprehensive interdisciplinary pre-procedural evaluation. Sixty-eight transfemoral and 32 transapical implantations were performed. Mean age was 82 (±8.9) years old with an average logistic EuroSCORE of 33. Although 13 procedures had major complications, there was no intraprocedural mortality. During the first month, 9% of patients were re-admitted due to heart failure and 13% had a permanent pacemaker implanted. A 3% 30-day and 8% follow-up (mean 17 months) mortalities were recorded. While no significant differences in the rate of complications were found between the first and second half of the experience, all cases of mortality within 30 days (n = 3) occurred in the initial half. Sustained haemodynamic results were obtained with TAVI (immediate mean aortic valve gradient reduction from 47 to 9 mmHg; 1-year echocardiographic gradient 9.9 mmHg, with no moderate or severe aortic regurgitation). CONCLUSION: Excellent results can be achieved with TAVI in very high-risk patients at an Australian institution. A comprehensive evaluation based on a heart team can overcome most of the difficulties imposed by this challenging population.

Coronary artery revascularisation: selecting the appropriate strategy.

Advances in interventional cardiology, particularly in better efficacy and safety of drug-eluting stents, have made percutaneous coronary revascularisation practical for most patients requiring revascularisation. While this has reduced the perceived need for coronary bypass surgery, it has also focused attention on the appropriate use of coronary stents and the complexity of choosing the right revascularisation strategy. To achieve the best outcomes, it would seem that collaboration rather than competition between cardiac surgeons and interventional cardiologists is necessary.

Pharmacokinetics and in vivo potency of soluble epoxide hydrolase inhibitors in cynomolgus monkeys.

BACKGROUND AND PURPOSE: Soluble epoxide hydrolase inhibitors (sEHIs) possess anti-inflammatory, antiatherosclerotic, antihypertensive and analgesic properties. The pharmacokinetics (PK) and pharmacodynamics in terms of inhibitory potency of sEHIs were assessed in non-human primates (NHPs). Development of a sEHI for use in NHPs will facilitate investigations on the role of sEH in numerous chronic inflammatory conditions. EXPERIMENTAL APPROACH: PK parameters of 11 sEHIs in cynomolgus monkeys were determined after oral dosing with 0.3 mg·kg(-1). Their physical properties and inhibitory potency in hepatic cytosol of cynomolgus monkeys were examined. Dose-dependent effects of the two inhibitors 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) and the related acetyl piperidine derivative, 1-trifluoromethoxyphenyl-3-(1-acetylpiperidin-4-yl) urea (TPAU), on natural blood eicosanoids, were determined. KEY RESULTS: Among the inhibitors tested, TPPU and two 4-(cyclohexyloxy) benzoic acid urea sEHIs displayed high plasma concentrations (>10 × IC(50)), when dosed orally at 0.3 mg·kg(-1). Although the 4-(cyclohexyloxy) benzoic acid ureas were more potent against monkey sEH than piperidyl ureas (TPAU and TPPU), the latter compounds showed higher plasma concentrations and more drug-like properties. The C(max) increased with dose from 0.3 to 3 mg·kg(-1) for TPPU and from 0.1 to 3 mg·kg(-1) for TPAU, although it was not linear over this range of doses. As an indication of target engagement, ratios of linoleate epoxides to diols increased with TPPU administration. CONCLUSION AND IMPLICATIONS: Our data indicate that TPPU is suitable for investigating sEH biology and the role of epoxide-containing lipids in modulating inflammatory diseases in NHPs.

Prevention of cardiac disease: lifestyle modification or pharmacotherapy?

Cardiovascular disease is still the leading cause of death in Australia. There have recently been significant advances in the management of acute coronary syndromes, as well as secondary prevention strategies; however, much of our resources are still directed towards treatment rather than prevention. Prevention of cardiovascular disease involves first, identifying patients at greatest risk of cardiovascular events and second, managing modifiable risk factors. Both pharmacotherapy and lifestyle modification are useful in modifying risk factors; however, the relative importance of each is often dictated by the risk factor profile of the individual. Although there is growing evidence that those at all levels of risk may benefit from lifestyle modification, pharmacotherapy is likely to be most useful in those at higher risk.

Mechanisms of heat inactivation in Salmonella serotype Typhimurium as affected by low water activity at different temperatures.

AIMS: To determine the effect of reduced water activity (a(w)) on thermal inactivation of Salmonella serotype Typhimurium at different temperatures and its mechanism. METHODS AND RESULTS: D-value determinations at a range of different temperatures showed that heating at reduced a(w) (0.94, produced by addition of glucose or sodium chloride to nutrient broth) was protective at temperatures above 53-55 degrees C but sensitizing below this temperature. Using selective enumeration media to determine injury, it was shown that at lower heating temperatures cells survived at high a(w) with cytoplasmic injury whereas at low a(w) these cells were killed. At higher temperatures ribosome degradation was a more important cause of death and was inhibited by low a(w) heating media thereby providing greater heat resistance. CONCLUSIONS: The observed change in behaviour reflects the different reactions responsible for thermal death at different temperatures and their different response to reduced a(w). SIGNIFICANCE AND IMPACT OF THE STUDY: This work qualifies the previous assumption that reduced a(w) is protective and suggests that the efficacy of low temperature pasteurization regimes may be increased by reduced a(w).

Determination of survival, identity and stress resistance of probiotic bifidobacteria in bio-yoghurts.

AIMS: To determine the level of bifidobacteria in bio-yoghurts in the UK, identify the species, and compare the resistance of common Bifidobacterium spp. to acidity and oxidative stress. METHODS AND RESULTS: A storage trial of bio-yoghurts was carried out to determine the level and survival of bifidobacteria. The 16S rRNA gene targeted PCR was used to identify the species. Acid tolerance was determined by introducing the organisms to pH-adjusted skimmed milk and enumerating during storage at 4 degrees C. Oxidative stress resistance was determined using the H(2)O(2) disc diffusion assay technique. Nine of 10 bio-yoghurts contained bifidobacteria at levels >10(6) CFU g(-1) at the time of purchase. The viability of the organism decreased during storage and on expiry only five products retained viability >10(6) CFU g(-1) while two others were very close to the target population. Bifidobacterium animalis ssp. lactis showed superior survival abilities and stress tolerance compared with Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium bifidum, Bifidobacterium adolescentis and Bifidobacterium longum biotype infantis. CONCLUSIONS: Bifidobacterium animalis ssp. lactis, the only Bifidobacterium spp. found in bio-yoghurts, had the greatest resistance to acidity and oxidative stress. SIGNIFICANCE AND IMPACT OF THE STUDY: The technological properties of B. animalis ssp. lactis make it suitable for inclusion in bio-yoghurts although its putative health benefits need further investigation.

Disinfection of feline calicivirus (a surrogate for Norovirus) in wastewaters.

AIMS: To compare the inactivation of feline calicivirus (FCV) (a surrogate for Norovirus, NV) with the reduction of a bacterial water quality indicator (Escherichia coli), a human enteric virus (poliovirus) and a viral indicator (MS2, FRNA bacteriophage), following the disinfection of wastewaters. METHODS AND RESULTS: Bench-scale disinfection experiments used wastewater (sterilized by gamma-irradiation) seeded with laboratory-cultured organisms. Seeded primary effluent was treated with different doses of applied free chlorine (8, 16 and 30 mg l(-1)). FCV and E. coli were easily inactivated by >4 log10, within 5 min with a dose of 30 mg l(-1) of applied chlorine. Poliovirus was more resistant and a reduction of 2.85 log10 was seen after 30 min, MS2 was the most resistant organism (1 log10 inactivation). In further experiments seeded secondary effluent was treated with different doses of u.v. irradiation. To achieve a 4-log10 reduction of E. coli, FCV, poliovirus and MS2 doses of 5.32, 19.04, 27.51 and 62.50 mW s cm(-2), respectively, were required. CONCLUSIONS: Feline calicivirus and E. coli seeded in primary wastewater were very susceptible to chlorination compared with poliovirus and MS2. In contrast, FCV seeded in secondary wastewater was more resistant to u.v. irradiation than E. coli but more sensitive than poliovirus and MS2. SIGNIFICANCE AND IMPACT OF THE STUDY: FRNA phage was more resistant to inactivation than all the viruses tested. This suggests FRNA phage would be a useful and conservative indicator of virus inactivation following disinfection of wastewaters with chlorination or u.v. irradiation.

Premature Salmonella Typhimurium growth inhibition in competition with other Gram-negative organisms is redox potential regulated via RpoS induction.

AIMS: To identify the role of oxidation-reduction (redox) potential in the premature growth inhibition and RpoS induction in Salmonella serotype Typhimurium in competitive growth experiments. METHODS AND RESULTS: Oxidation-reduction potential was measured throughout the growth of a minority population of Salm. Typhimurium in mixed cultures with other Gram-negative and Gram-positive organisms. A lux-based reporter was also used to evaluate RpoS activity in Salm. Typhimurium in competitor studies. In a mixed culture, the multiplication of a minority population of Salm. Typhimurium was inhibited when competing Gram-negative organisms entered the stationary phase. This was not seen when the competing flora was Gram-positive. The change in redox potential during growth in mixed cultures was closely linked to the inhibition of Salm. Typhimurium growth by Gram-negative competitors. An artificially induced drop in redox potential earlier during growth in mixed cultures with Gram-negative organisms reduced the time to RpoS induction in Salm. Typhimurium and thus inhibited its multiplication prematurely. In contrast, RpoS induction and growth inhibition were prevented under high redox potential conditions. CONCLUSIONS: This work shows that the inhibitory activity of competitive organisms can be mediated through their effect on redox potential-regulated RpoS induction. SIGNIFICANCE AND IMPACT OF THE STUDY: Redox potential is shown to be an important determinant of Salm. Typhimurium growth, an observation with practical implications both for its control and detection.

Oxidation-reduction potential regulates RpoS levels in Salmonella Typhimurium.

AIMS: The aim of this work was to investigate the connection between oxidation-reduction (redox) potential and stationary phase induction of RpoS in Salmonella Typhimurium. METHODS AND RESULTS: A lux-based reporter was used to evaluate RpoS activity in S. Typhimurium pure cultures. During growth of S. Typhimurium, a drop in the redox potential of the growth medium occurred at the same time as RpoS induction and entry into stationary phase. An artificially induced decrease in redox potential earlier during growth reduced the time to RpoS induction and Salmonella entered the stationary phase prematurely. In contrast, under high redox conditions, Salmonella grew unaffected and entered the stationary growth phase as normal, although RpoS induction did not occur. As a consequence, stationary phase cells grown in the high redox environment were significantly more heat sensitive (P < 0.05) than those grown under normal conditions. CONCLUSIONS: This work suggests that redox potential can regulate RpoS levels in S. Typhimurium and can thus, control the expression of genes responsible for thermal resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: The ability to manipulate RpoS induction and control stationary phase gene expression can have important implications in food safety. Early RpoS induction under low redox potential conditions can lead to enhanced resistance in low cell concentrations to inimical processes such as heat stress. Inhibition of RpoS induction would abolish stationary phase protective properties making cells more sensitive to common food control measures.

Influence of estradiol on cortisol secretion in ovariectomized cynomolgus macaques (Macaca fascicularis).

In an investigation of cortisol secretion in fully mature, ovariectomized cynomolgus monkeys (Macaca fascicularis), we compared monkeys that were given either placebo (OVX, n = 26) or 17beta estradiol (E(2 )) (EST, n = 26) in a daily oral dose. Serum cortisol concentrations were measured prior to the experimental manipulation and 3, 6, 9, and 12 months following initiation of treatment. Pretreatment cortisol values did not differ between groups. Assessment of the treatment period values revealed that cortisol concentrations were significantly higher ( approximately 10%) in the EST than in the OVX monkeys. Cortisol also varied significantly across periods of sampling. This time-dependent variation was attributable to elevations in months 6 and 9 (when daylight was generally long), relative to months 3 and 12 (when daylight was relatively short). The modest stimulatory effect of estrogen on corticosteroid production observed in this study is consistent with what has been seen in women, and contrasts with the more robust effects observed in New World monkeys. The possible relationship between season and cortisol secretion observed here has not been previously described in monkeys.

Monitoring transfer of recombinant and nonrecombinant plasmids between Lactococcus lactis strains and members of the human gastrointestinal microbiota in vivo--impact of donor cell number and diet.

AIMS: The generation of data of real relevance to the purported risks of DNA transfer from food-borne genetically modified microorganisms (GMMOs) using the human biota associated (HBA) rat model. Plasmid transfer between Lactococcus lactis strains and between donor strains and human gut bacteria was monitored. METHODS AND RESULTS: Transfer of the recombinant plasmid pCK1 and/or the promiscuous nonrecombinant plasmid pAMbeta1 between L. lactis strains was monitored in vivo in HBA rats. No transfer of pCK1 was observed. Transfer of pAMbeta1 was observed to Enterococcus spp. present in the HBA rats. Transconjugants persisted for 30 d and were distributed throughout the gastrointestinal tract. Both HBA rat diet and donor cell numbers impacted on transconjugant numbers. Fewer transconjugants were observed in animals fed a high-fat human type diet, while high levels of plasmid transfer were only observed at doses of donor L. lactis greater than 109 cfu. CONCLUSIONS: The utility of models of the human gut in monitoring DNA transfer events within the gut microbiota was demonstrated. SIGNIFICANCE AND IMPACT OF THE STUDY: Such findings give some confidence for the use of GMMOs with recombinant DNA borne on nonconjugative elements in fermented foods. HBA rats are a suitable model for monitoring the fate of food-borne GMMOs.

Enhanced inactivation of Listeria monocytogenes by nisin in the presence of ethanol.

AIMS: The effect of combinations of nisin and ethanol on the survival of Listeria monocytogenes was investigated. METHODS AND RESULTS: Killing by nisin was enhanced during simultaneous exposure to ethanol (2-7% v/v). For example, while 10 IU ml(-1) nisin reduced viability by 1 log unit in 20 min, a combination of this antimicrobial peptide and 5% ethanol, reduced numbers of surviving cells by 3 log units. Increasing the concentrations of either ethanol (2-7%) or nisin (10-50 IU ml(-1)) led to increased cell death with synergy being demonstrated for all combinations tested and at a range of temperatures from 5 to 37 degrees C. CONCLUSIONS: Ethanol can act synergistically with nisin to reduce the survival of L. monocytogenes. SIGNIFICANCE AND IMPACT OF THE STUDY: Combinations of ethanol and nisin may be feasible as an effective way of controlling this pathogen in the food processing environment.

Prevention of myocardial infarction.

Despite the rapid advances that have been made in the treatment of coronary artery disease, myocardial infarction remains the major cause of death in the developed world and a growing problem for developing countries. To address this growing problem, a strategy aimed at prevention of events in high-risk individuals is required. This involves assessment of cardiovascular risk followed by risk reduction. At present there is no perfect technique available for risk prediction, although computed tomography and magnetic resonance imaging scanning, along with serum markers of inflammation, offer the greatest potential. The applicability of these techniques at present is also limited by cost and accessibility. Risk reduction is possible through lifestyle changes and drug therapy, and effective risk assessment is essential in selecting those most likely to benefit from these interventions.

Rescue percutaneous coronary intervention immediately following coronary artery bypass grafting.

Perioperative graft failure after coronary artery bypass graft (CABG) can result in acute myocardial infarction with dire clinical consequences. We report a case of rescue percutaneous coronary intervention immediately after unsuccessful CABG. This approach salvaged the patient from cardiogenic shock and should be recognized as a viable alternative to immediate reoperation for certain patients.

Temperature shock, injury and transient sensitivity to nisin in Gram negatives.

AIMS: The effect of thermal stresses on survival, injury and nisin sensitivity was investigated in Salmonella Enteritidis PT4, PT7 and Pseudomonas aeruginosa. METHODS AND RESULTS: Heating at 55 degrees C, rapid chilling to 0.5 degrees C or freezing at -20 degrees C produced transient sensitivity to nisin. Cells were only sensitive if nisin was present during stress. Resistance recovered rapidly afterwards, though some cells displayed residual injury. Injury was assessed by SDS sensitivity, hydrophobicity changes, lipopolysaccharide release and NPN uptake. LPS release and hydrophobicity were not always associated with transient nisin sensitivity. Uptake of NPN correlated better but persisted longer after treatment. CONCLUSIONS: Thermal shocks produce transient injury to the outer membrane, allowing nisin access. After treatment, the permeability barrier is rapidly restored by a process apparently involving reorganization rather than biosynthetic repair. SIGNIFICANCE AND IMPACT OF THE STUDY: Inclusion of nisin during food treatments that impose sub-lethal stress on Gram negatives could increase process lethality, enhancing microbiological safety and stability.

Cardiovascular structure and function in baboons with Type 1 diabetes -- a transvenous ultrasound study.

Diabetes mellitus is an important risk factor for both macrovascular and cardiac disease in humans. The availability of a novel intravenous ultrasound probe allows detailed interrogation of a large proportion of the vasculature, as well as the heart, during the same examination. Six male baboons (Papio hamadryas) with Type 1 diabetes and known microangiopathy, and six control animals were studied. Vascular structure in the major large arteries and cardiac function were studied using transvenous ultrasound introduced via the right femoral vein and positioned under fluoroscopy. All arteries were examined for atherosclerotic plaque and for presence of increased intima-media thickness (IMT). Left ventricular function was assessed at rest and following infusions of dobutamine (positive inotrope) and esmolol (negative inotrope). The procedure was performed safely and successfully in all cases. No atherosclerotic plaque was seen in either diabetic or normal baboons. There was no difference in the aortic IMT (0.38+/-0.04 vs. 0.37+/-0.05 mm, normal vs. diabetic, P=NS) or in doppler flow in the renal or iliac arteries between diabetic and normal baboons. Left ventricular wall thickness and systolic tissue velocity were similar in the two groups at rest (6.9+/-2.5 vs. 6.2+/-1.4 cm/s, normal vs. diabetic, P=NS), after dobutamine (15.5+/-2.2 vs. 12.7+/-3.9 cm/s, normal vs. diabetic, P=NS), and after esmolol (4.3+/-1.0 vs. 5.6+/-1.0 cm/s, normal vs. diabetic, P=NS). In a high primate model of diabetes with microangiopathy, the presence of hyperglycemia for 7 years per se does not produce abnormalities of macrovascular or cardiac structure.

Increased prostacyclin synthesis by atherosclerotic arteries from estrogen-treated monkeys.

We hypothesized that the atheroinhibitory and cardioprotective effects of estrogen may be mediated in part through increased prostacyclin formation by the artery wall. Atherosclerotic abdominal aorta was collected at necropsy from ovariectomized female monkeys fed an atherogenic diet alone or with added Premarin. Basal and arachidonate-stimulated prostacyclin and thromboxane synthesis by artery segments was measured by radioimmunoassay. In contrast to no observed differences in basal release of prostacyclin by the control and estrogen-treated arteries, there was a marked increase (approximately 165%) in arachidonate-stimulated formation of prostacyclin by estrogen-treated arteries, and prostacyclin synthesis was inversely correlated with plaque size. No differences were observed in basal or arachidonate-stimulated thromboxane synthesis by the control and estrogen-treated arteries. In light of known antiatherogenic and vasodilatory effects of estrogen, increased prostacyclin synthesis by estrogen-treated arteries may, in part, explain estrogen's beneficial effects on the artery wall.