Predicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer before chemo-endocrine therapy.

BACKGROUND: We proposed that a test for sensitivity to the adjuvant endocrine therapy component of treatment for patients with stage II-III breast cancer (SET2,3) should measure transcription related to estrogen and progesterone receptors (SETER/PR index) adjusted for a baseline prognostic index (BPI) combining clinical tumor and nodal stage with molecular subtype by RNA4 (ESR1, PGR, ERBB2, and AURKA). PATIENTS AND METHODS: Patients with clinically high-risk, hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) breast cancer received neoadjuvant taxane-anthracycline chemotherapy, surgery with measurement of residual cancer burden (RCB), and then adjuvant endocrine therapy. SET2,3 was measured from pre-treatment tumor biopsies, evaluated first in an MD Anderson Cancer Center (MDACC) cohort (n = 307, 11 years' follow-up, U133A microarrays), cut point was determined, and then independent, blinded evaluation was carried out in the I-SPY2 trial (n = 268, high-risk MammaPrint result, 3.8 years' follow-up, Agilent-44K microarrays, NCI Clinical Trials ID: NCT01042379). Primary outcome measure was distant relapse-free survival. Multivariate Cox regression models tested prognostic independence of SET2,3 relative to RCB and other molecular prognostic signatures, and whether other prognostic signatures could substitute for SETER/PR or RNA4 components of SET2,3. RESULTS: SET2,3 added independent prognostic information to RCB in the MDACC cohort: SET2,3 [hazard ratio (HR) 0.23, P = 0.004] and RCB (HR 1.77, P < 0.001); and the I-SPY2 trial: SET2,3 (HR 0.27, P = 0.031) and RCB (HR 1.68, P = 0.008). SET2,3 provided similar prognostic information irrespective of whether RCB-II or RCB-III after chemotherapy, and in both luminal subtypes. Conversely, RCB was most strongly prognostic in cancers with low SET2,3 status (MDACC P < 0.001, I-SPY2 P < 0.001). Other molecular signatures were not independently prognostic; they could effectively substitute for RNA4 subtype within the BPI component of SET2,3, but they could not effectively substitute for SETER/PR index. CONCLUSIONS: SET2,3 added independent prognostic information to chemotherapy response (RCB) and baseline prognostic score or subtype. Approximately 40% of patients with clinically high-risk HR+/HER2- disease had high SET2,3 and could be considered for clinical trials of neoadjuvant endocrine-based treatment.

Role of sports psychology and sports nutrition in return to play from musculoskeletal injuries in professional soccer: an interdisciplinary approach.

Musculoskeletal injuries are prevalent in professional soccer and can result in lost training time or match play. It is intuitive that the "return to play" (RTP) pathway will depend, in large part, on the expertise of sports medicine practitioners (e.g. surgeons, physicians, physiotherapists) responsible for player's recovery. Consensus statements on returning athletes to sport following injury acknowledge the contributions of sport psychology and sports nutrition. However, specific consideration on how to integrate these two recognized - but often overlooked components of injury rehabilitation - into existing sport medicine approaches has yet to be examined. Using a framework of milestones directed by the medical physician and physical trainer, the evidence is summarized and suggestions provided on the integration of sports psychology and sports nutrition into an interdisciplinary RTP approach. We examine recovery from a phase approach (acute injury and functional recovery) to highlight interdisciplinary opportunities in the management of musculoskeletal soccer injuries. An interdisciplinary approach is understood to achieve outcomes that could not be achieved within the framework of a single discipline. The incorporation of sports psychology and nutrition theoretically compliment milestones used in current medically-based RTP models. Our hope is that this article serves as a catalyst for interdisciplinary practice and research - not only in sports nutrition and sports psychology - but across all sport and exercise disciplines.

Effect of four rounds of annual school-wide mass praziquantel treatment for schistosoma mansoni control on schistosome-specific immune responses.

This study evaluated potential changes in antischistosome immune responses in children from schools that received 4 rounds of annual mass drug administration (MDA) of praziquantel (PZQ). In a repeated cross-sectional study design, 210 schistosome egg-positive children were recruited at baseline from schools in western Kenya (baseline group). Another 251 children of the same age range were recruited from the same schools and diagnosed with schistosome infection by microscopy (post-MDA group). In-vitro schistosome-specific cytokines and plasma antibody levels were measured by ELISA and compared between the 2 groups of children. Schistosome soluble egg antigen (SEA) and soluble worm antigen preparation (SWAP) stimulated higher IL-5 production by egg-negative children in the post-MDA group compared to the baseline group. Similarly, anti-SEA IgE levels were higher in egg-negative children in the post-MDA group compared to the baseline group. Anti-SEA and anti-SWAP IgG4 levels were lower in egg-negative children in the post-MDA group compared to baseline. This resulted in higher anti-SEA IgE/IgG4 ratios for children in the post-MDA group compared to baseline. These post-MDA immunological changes are compatible with the current paradigm that treatment shifts immune responses to higher antischistosome IgE:IgG4 ratios in parallel with a potential increase in resistance to reinfection.

Determining Culex annulirostris larval densities and control efforts across a coastal wetland, Northern Territory, Australia.

The Darwin coastal wetlands provide suitable breeding conditions for Culex annulirostris, which is abundant between December and August each year. This species is the principal vector for arboviruses, including Ross River virus and Murray Valley encephalitis, and is an appreciable pest species. Aerial control is conducted when routine larval surveys for this species predict high numbers of emergent adults. We sought to determine the most productive vegetation categories and seasonal aspects associated with Cx. annulirostris breeding and control operations in these wetlands. By applying a generalized linear model to compare larval densities and aerial control efforts for each vegetation category, we found that Schoenoplectus reeds were the most productive vegetation type in May and June and were associated with the greatest amount of control required. Other vegetation categories associated with tidal mangroves and lower topographic elevation were also productive during these months for extended periods, while rain-affected reticulate areas and grassland floodplains were most productive in January and April. In addition, areas associated with nutrient rich organic matter appeared to initiate Cx. annulirostris breeding and were highly productive seasonally. This study has highlighted the vegetation categories most significantly associated with Cx. annulirostris breeding in a Darwin wetland. This knowledge can be applied to current control efforts to improve aerial control efficiency for this species and could be applicable in other areas of northern Australia.

Role of interleukin-10 (IL-10) in regulation of GABAergic transmission and acute response to ethanol.

Mounting evidence indicates that ethanol (EtOH) exposure activates neuroimmune signaling. Alterations in pro-inflammatory cytokines after acute and chronic EtOH exposure have been heavily investigated. In contrast, little is known about the regulation of neurotransmission and/or modulation by anti-inflammatory cytokines in the brain after an acute EtOH exposure. Recent evidence suggests that interleukin-10 (IL-10), an anti-inflammatory cytokine, is upregulated during withdrawal from chronic EtOH exposure. In the present study, we show that IL-10 is increased early (1 h) after a single intoxicating dose of EtOH (5 g/kg, intragastric) in Sprague Dawley rats. We also show that IL-10 rapidly regulates GABAergic transmission in dentate gyrus neurons. In brain slice recordings, IL-10 application dose-dependently decreases miniature inhibitory postsynaptic current (mIPSC) area and frequency, and decreases the magnitude of the picrotoxin sensitive tonic current (Itonic), indicating both pre- and postsynaptic mechanisms. A PI3K inhibitor LY294002 (but not the negative control LY303511) ablated the inhibitory effects of IL-10 on mIPSC area and Itonic, but not on mIPSC frequency, indicating the involvement of PI3K in postsynaptic effects of IL-10 on GABAergic transmission. Lastly, we also identify a novel neurobehavioral regulation of EtOH sensitivity by IL-10, whereby IL-10 attenuates acute EtOH-induced hypnosis. These results suggest that EtOH causes an early release of IL-10 in the brain, which may contribute to neuronal hyperexcitability as well as disturbed sleep seen after binge exposure to EtOH. These results also identify IL-10 signaling as a potential therapeutic target in alcohol-use disorders and other CNS disorders where GABAergic transmission is altered.

Physical employment standards for U.K. fire and rescue service personnel.

BACKGROUND: Evidence-based physical employment standards are vital for recruiting, training and maintaining the operational effectiveness of personnel in physically demanding occupations. AIMS: (i) Develop criterion tests for in-service physical assessment, which simulate the role-related physical demands of UK fire and rescue service (UK FRS) personnel. (ii) Develop practical physical selection tests for FRS applicants. (iii) Evaluate the validity of the selection tests to predict criterion test performance. METHODS: Stage 1: we conducted a physical demands analysis involving seven workshops and an expert panel to document the key physical tasks required of UK FRS personnel and to develop 'criterion' and 'selection' tests. Stage 2: we measured the performance of 137 trainee and 50 trained UK FRS personnel on selection, criterion and 'field' measures of aerobic power, strength and body size. Statistical models were developed to predict criterion test performance. Stage 3: matter experts derived minimum performance standards. RESULTS: We developed single person simulations of the key physical tasks required of UK FRS personnel as criterion and selection tests (rural fire, domestic fire, ladder lift, ladder extension, ladder climb, pump assembly, enclosed space search). Selection tests were marginally stronger predictors of criterion test performance (r = 0.88-0.94, 95% Limits of Agreement [LoA] 7.6-14.0%) than field test scores (r = 0.84-0.94, 95% LoA 8.0-19.8%) and offered greater face and content validity and more practical implementation. CONCLUSIONS: This study outlines the development of role-related, gender-free physical employment tests for the UK FRS, which conform to equal opportunities law.

The prevalence of ocular lesions associated with hypertension in a population of geriatric cats in Auckland, New Zealand.

AIMS: To provide an estimate of the prevalence of ocular lesions associated with hypertension in geriatric cats in Auckland, New Zealand and to evaluate the importance of examination of the ocular fundi of cats over eight years of age. METHODS: A total of 105 cats ≥8 years of age were examined and clinical signs recorded. Blood was collected for the laboratory measurement of the concentrations of blood urea nitrogen (BUN), glucose and creatinine in serum, urine was collected for determination of urine specific gravity (USG), and blood pressure (BP) was measured using high definition oscillometry equipment. A cat was determined to have systemic hypertension with a systolic BP ≥160 mm Hg and a diastolic BP ≥100 mm Hg. Each animal had an ocular fundic examination using a retinal camera to diagnose ocular lesions associated with hypertension, including retinopathies, choroidopathies and optic neuropathies. RESULTS: Blood pressure was successfully recorded in 73 cats. Of these, 37 (51%) had no hypertensive ocular lesions and no underlying disease diagnosed, 24 (33%) had no hypertensive ocular lesions detected, but underlying disease such as chronic kidney disease, hyperthyroidism or diabetes mellitus was diagnosed, and 12 (16%) cats had evidence of hypertensive ocular lesions. Ten of the cats with hypertensive ocular lesions were hypertensive at the time of the first visit and two were normotensive. One additional cat had hypertensive ocular lesions, but it was not possible to obtain consistent BP readings in this animal. Chronic kidney disease was the most commonly diagnosed concurrent disease in cats with hypertensive ocular lesions (n=6). Mean systolic BP for cats with hypertensive ocular lesions (168.0 (SE 6.29) mm Hg) was higher than for those with no ocular lesions (144.7 (SE 3.11) mm Hg) or those with no lesions but with underlying disease (146.0 (SE 4.97) mm Hg) (p=0.001). CONCLUSIONS: Ocular fundic examination of cats over eight years of age allows identification of cats with hypertensive ocular lesions, often before the owner or veterinarian is aware the cat has a problem with its vision. This may result in diagnosis of systemic hypertension allowing early treatment and resolution of lesions. CLINICAL RELEVANCE: The current study demonstrates that ocular lesions resulting from hypertension occur frequently enough in cats in Auckland to support the recommendation for fundic examination in cats over eight years of age as part of the routine physical examination.

An audit of platelet transfusion within the Wellington Cancer Centre.

AIM: An audit of platelet transfusion was performed to assess adherence to local prophylactic policy and to assess if therapeutic transfusions were administered in line with international recommendations. METHODS: A prospective audit of platelet transfusion therapy was conducted at the Wellington Cancer Centre in patients with hypoproliferative thrombocytopenia over a 3-month period from 26 January 2008 to 30 April 2008. There were 398 episodes of evaluable clinical decision activity generated through either platelet counts <50 × 10(9) /L or platelet transfusion events. Each episode was assessed and defined as either adhering to or breaching the local prophylactic platelet transfusion policy. RESULTS: Thrombocytopenia and/or platelet transfusion occurred in 63 patients aged 16-84 years with either a haematological or solid organ malignancy. Decisions to withhold prophylactic platelet transfusion in thrombocytopenic patients adhered to policy for 99% of platelet counts <50 × 10(9) /L. Where transfusions were administered, 77% were prophylactic and 23% were for therapeutic indications. Prophylactic transfusions adhered to policy for 72% of platelet counts <50 × 10(9) /L. Adherence to prophylactic transfusion policy for febrile patients with a threshold of ≤15 × 10(9) /L was 84%, compared to 63% for stable afebrile patients with a threshold of ≤10 × 10(9) /L. Where policy was breached, in 80% of cases the platelet count had not reached the prophylactic transfusion threshold. Of the clinical decisions leading to therapeutic transfusions, 67% were deemed appropriate and predominantly a single adult therapeutic dose of platelets was administered. Where multiple doses of platelets were transfused, 86% of these transfusion events either breached policy or were deemed suboptimal management. CONCLUSION: The audit demonstrated a high rate of adherence to local transfusion policy. Where policy was breached, predominantly a transfusion had occurred prior to a platelet count reaching the pre-defined trigger. The use of multiple dose platelet transfusions was almost never appropriate. Educating staff in the use of a stringent transfusion policy may lead to reductions in platelet product use.

Extremely high phenylalanine levels in a newborn on parenteral nutrition: phenylketonuria in the neonatal intensive care unit.

A 1890-g newborn on total parenteral nutrition (TPN) had phenylalanine levels reaching 4164 µM indicating phenylketonuria (PKU). Review of 64 PKU cases from the California Newborn Screening Program disclosed another newborn diagnosed while on TPN. Phenylalanine levels rose five times faster with TPN, as estimated from rates in these infants. Thus, TPN use is associated with very high phenylalanine levels in newborns with PKU. When starting TPN soon after birth (for example, on day 1), early detection of PKU-by newborn screening 12 to 24 h after infusions are begun-should be helpful in limiting exposures to toxic levels of phenylalanine.

Steer responses to feeding soybean hulls and steroid hormone implantation on toxic tall fescue pasture.

Crossbred steers were grazed in the spring and early summer on endophyte-infected (Neotyphodium coenophialum), Kentucky-31 tall fescue (Lolium arundinaceum) pastures to evaluate effects and interactions of feeding pelleted soybean hulls (PSBH) and steroid hormone implants (SHI) on steer performance, serum prolactin, and hair coat ratings (HCR). Steers were stratified by BW for assignment to six 3.0-ha toxic tall fescue pastures. With or without daily PSBH feeding, treatments were assigned randomly to pastures as the main plot treatment in a split-plot design. Pelleted soybean hulls were group-fed to provide 2.3 kg(steer·d(-1)) (as fed). With or without SHI (200 mg of progesterone and 20 mg of estradiol) treatments were randomly assigned as the subplot treatment to 2 steer subgroups within each pasture. Sixty-four steers were grazed for 77 d in 2007, and 60 steers were grazed for 86 d in 2008. Pasture forage mass declined linearly over time, but the rate of decline was greater (P = 0.001) in 2007 than in 2008. Pasture forage mass was never below 2,300 kg of DM/ha in either year. Average daily gain for steers on the combined PSBH and SHI treatments was greater (P < 0.01) than for those on the PSBH-only, SHI-only, and control (no SHI, no PSBH) treatments. Average daily gain for the PSBH-only steers was greater (P < 0.01) than for SHI-only and control steers and tended (P = 0.063) to be greater for SHI-only than for control steers. Steroid implants did not affect (P = 0.826) serum prolactin concentrations; however, prolactin concentrations in PSBH steers, with or without SHI, were increased (P = 0.01) 2-fold over SHI-only and control steers. Feeding PSBH and SHI treatments both reduced (P < 0.05) the percentage of steers with rough HCR, and a greater percentage of steers fed PSBH tended (P < 0.076) to have sleek hair coats. An economic analysis was conducted, which determined that costs of additional ADG with PSBH feeding were below breakeven costs over a wide range of PSBH costs and cattle prices. Breakeven costs for PSBH-only treatment for a range of cattle prices of $1.80 to $2.40/kg of BW were less than $120/t, whereas with PSBH feeding combined with SHI the breakeven cost was less than $240/t. Results indicate that steers grazing endophyte-infected tall fescue can be fed PSBH and implanted with steroid hormones to cost effectively increase ADG and that feeding PSBH can increase serum prolactin concentrations and induce some shedding of rough hair coats.

The effects of supplementation with creatine and protein on muscle strength following a traditional resistance training program in middle-aged and older men.

OBJECTIVES: Creatine and protein supplementation can enhance the training outcomes of young subjects, but it is not clear if there are benefits for older individuals. Therefore, the purpose of this study was to determine the effects of creatine and protein supplementation on strength gains following a traditional resistance training program for middle-aged and older men. DESIGN, SETTING, PARTICIPANTS: This study assessed changes in strength of men aged 48-72 years following 14 weeks of resistance training supplemented with creatine and/or protein. A double-blind, randomized, placebo-controlled design placed 42 males into one of four groups: Resistance Trained Placebo (RTP, n=10); Resistance Trained Creatine (RTCr, 5g Cr, n=10); Resistance Trained Protein (RTPr, 35g whey Pr, n=11); or Resistance Trained Creatine and Protein (RTCrPr, 5g Cr and 35g Pr, n=11). INTERVENTION: All groups trained 3 days per week for 14 weeks. The resistance training program was based on progressive overload. Training loads corresponded to 80% 1 RM (one repetition maximum strength), 3 sets of 8 repetitions for the following exercises: knee extension/knee flexion; bicep curl/tricep extension; military press; lat pull down; seated leg press; and bench press. MEASUREMENTS: 1 RM for each exercise and measures of lean body mass were assessed prior to and following the 14 week program. RESULTS: Each group significantly (p < 0.05) increased strength and lean body mass, however, there were no significant group effects or group X trial interactions. CONCLUSION: Resistance training in middle-aged and older men significantly increased muscular strength and added muscle mass with no additional benefits from creatine and/or protein supplementation.

Relative imbalance between T regulatory cells and activated T cells in mice with differential morbidity in chronic Schistosoma mansoni infections.

Chronic (20-week) Schistosoma mansoni infections of CBA/J male mice present as two distinct forms of morbidity. Most mice develop moderate splenomegaly syndrome (MSS) resembling the intestinal form of chronic human schistosomiasis mansoni, while approximately 20% of mice develop hypersplenomegaly syndrome (HSS), more consistent with the severe hepatosplenic form of chronic human schistosomiasis mansoni. Here, we report the relative proportions of natural T regulatory cells (Treg) and activated CD4(+) T cells (Tact) for both splenic and granulomatous cell populations of MSS and HSS mice. Proportions of both Treg and Tact are greater in HSS than MSS mice. However, the ratios of Treg to Tact in both splenic and granulomatous cell populations from MSS mice are significantly higher than those of HSS mice. For both HSS and MSS mice, in vitro proliferation of their CD3(+) splenic cells induced by soluble egg antigens is inversely correlated with the ratio of Treg to Tact. Also, spleen or granuloma cells from MSS mice produced higher mean levels of IFN-gamma than those from HSS mice. Differential IFN-gamma productive capacities dictated by Treg : Tact ratios may contribute to the development of differential morbidities in this model of chronic experimental schistosomiasis mansoni.

A comparison of Aedes vigilax larval population densities and associated vegetation categories in a coastal wetland, Northern Territory, Australia.

Darwin's northern suburbs border an extensive coastal reed and upper mangrove wetland recognized as an important larval habitat for Aedes vigilax (Skuse), the northern salt marsh mosquito, an established vector for Ross River and Barmah Forest viruses and an appreciable pest species. We sought to identify the most important vegetation categories associated with Ae. vigilax breeding to maximize the efficiency of mosquito control efforts. Using a generalized linear model with negative binominal distribution and log link, this study compares larval densities, determined by focused dipping, between 13 discernable vegetation categories. The incidence rate ratios (RR) generated can be used to compare the magnitude of larval densities for each vegetation category, compared with the reference category. Aedes vigilax larval densities were almost ten times greater in artificial drainage areas (RR=9.82), followed by tide-affected reticulate (Sporobolus/Xerochloa) areas (RR=8.15), then Schoenoplectus/mangroves (RR=2.29), compared with the reference vegetation category "lower mangroves." Furthermore, larval densities were highest in May, due to tidal inundation, for drainage areas and tide-affected reticulates (RR=12.2, 11.7, respectively) compared with March, the reference month. Thus, to maximize the efficiency of aerial salt marsh mosquito control operations in this wetland, larval control is best accomplished by concentrating on drains, Schoenoplectus/mangroves, and tide-affected reticulate areas, commencing early after the wet season. These results should apply to other areas of salt marsh mosquito breeding across northern Australia.

A geospatial evaluation of Aedes vigilax larval control efforts across a coastal wetland, Northern Territory, Australia.

Adjacent to the northern suburbs of Darwin is a coastal wetland that contains important larval habitats for Aedes vigilax (Skuse), the northern salt marsh mosquito. This species is a vector for Ross River virus and Barmah Forest virus, as well as an appreciable human pest. In order to improve aerial larval control efforts, we sought to identify the most important vegetation categories and climatic/seasonal aspects associated with control operations in these wetlands. By using a generalized linear model to compare aerial control for each vegetation category, we found that Schoenoplectus/mangrove areas require the greatest amount of control for tide-only events (30.1%), and also extensive control for tide and rain events coinciding (18.2%). Our results further indicate that tide-affected reticulate vegetation indicated by the marsh grasses Sporobolus virginicus and Xerochloa imberbis require extensive control for Ae. vigilax larvae after rain-only events (44.7%), and tide and rain events coinciding (38.0%). The analyses of vector control efforts by month indicated that September to January, with a peak in November and December, required the most control. A companion paper identifies the vegetation categories most associated with Aedes vigilax larvae population densities in the coastal wetland. To maximize the efficiency of aerial salt marsh mosquito control operations in northern Australia, aerial control efforts should concentrate on the vegetation categories with high larval densities between September and January.

Physical demands of firefighter search and rescue in ambient environmental conditions.

This study investigated the physiological responses and limitations to a simulated search and rescue scenario in a high-rise building under ambient conditions. Sixteen firefighters performed the scenario under four conditions: standard duration breathing apparatus (SDBA) and 45 mm hose; extended duration breathing apparatus (EDBA) and 45 mm hose; SDBA and 70 mm hose; EDBA and 70 mm hose. Core temperature, skin temperature and heart rate were monitored. In four of 32 trials the casualty was rescued; the remainder of the trials were terminated for safety, high core temperature or shortage of air. Final core temperature and heart rate were higher in the EDBA (39.1 degrees C; 72% heart rate reserve (HRR)) than SDBA conditions (38.6 degrees C; 67%HRR). No differences were observed between hose sizes. The scenario proved too onerous to complete successfully in the majority of cases. Replacing SDBA with EDBA eliminates air supply as a limiting factor, but brings with it challenges of managing thermal strain.

Sodium/hydrogen exchange inhibition with cariporide reduces leukocyte adhesion via P-selectin suppression during inflammation.

BACKGROUND AND PURPOSE: The Na(+)/H(+) exchange (NHE) inhibitor cariporide is known to ameliorate ischaemia/reperfusion (I/R) injury by reduction of cytosolic Ca(2+) overload. Leukocyte activation and infiltration also mediates I/R injury but whether cariporide reduces I/R injury by affecting leukocyte activation is unknown. We studied the effect of cariporide on thrombin and I/R induced leukocyte activation and infiltration models and examined P-selectin expression as a potential mechanism for any identified effects. EXPERIMENTAL APPROACH: An in vivo rat mesenteric microcirculation microscopy model was used with stimulation by thrombin (0.5 micro ml(-1)) superfusion or ischaemia (by haemorrhagic shock for 60 min) and reperfusion (90 min). KEY RESULTS: Treatment with cariporide (10 mg kg(-1) i.v.) significantly reduced leukocyte rolling, adhesion and extravasation after thrombin exposure. Similarly, cariporide reduced leukocyte rolling (54+/-6.2 to 2.4+/-1.0 cells min(-1), P<0.01), adherence (6.3+/-1.9 to 1.2+/-0.4 cells 100 microm(-1), P<0.01) and extravasation (9.1+/-2.1 to 2.4+/-1.1 cells per 20 x 100 microm perivascular space, P<0.05), following haemorrhagic shock induced systemic ischaemia and reperfusion. The cell adhesion molecule P-selectin showed a profound decrease in endothelial expression following cariporide administration in both thrombin and I/R stimulated groups (35.4+/-3.2 vs 14.2+/-4.1% P-selectin positive cells per tissue section, P<0.01). CONCLUSIONS AND IMPLICATIONS: The NHE inhibitor cariporide is known to limit reperfusion injury by controlling Ca(2+) overload but these data are novel evidence for a vasculoprotective effect of NHE inhibition at all levels of leukocyte activation, an effect which is likely to be mediated at least in part by a reduction of P-selectin expression.

Class II HLA allele polymorphism: DRB1, DQB1 and DPB1 alleles and haplotypes in the New Zealand Maori population.

Class II alleles of interest to transplantation comprise the DRB1, DQB1 and DPB1 loci. Sequence-based typing was used to determine the class II allelic variability present in New Zealand Maori, a population with close genetic ties to Polynesia and known anthropological and linguistic connections to mainland Asia. The most common DRB1 alleles identified were DRB1*1201, DRB1*110101, DRB1*0403 and DRB1*080302, with frequencies of 21.5%, 14%, 11.25% and 9.25%, respectively. Standard linkages between the DRB1 locus and the DRB3, 4 and 5 loci were maintained, with no novel patterns identified. The most common DQB1 alleles identified were DQB1*030101, DQB1*060101, DQB1*020101, DQB1*0602 and DQB1*050201, with frequencies of 29.5%, 8%, 7.8%, 6.4% and 6.2%, respectively. The most common DPB1 alleles identified were DPB1*0501, DPB1*040101 and DPB1*020102, with frequencies of 40.2%, 28.89% and 15.83%, respectively. A total of 80 estimated DRB1-DQB1 two-locus haplotypes were detected. DRB1*1201-DQB1*030101 was the most frequent (15.40%) haplotype, followed by DRB1*110101-DQB1*030101 (9.97%), DRB1*0403-DQB1*030201 (7.37%) and DRB1*080302-DQB1*060101 (5.96%). The allelic variation determined is being used in further analysis of the requirement for bone marrow transplantation in the New Zealand Maori population and has implications for optimal ethnic donor distribution on the New Zealand Bone Marrow Donor Registry, anthropological studies and disease association.

Cardiopulmonary bypass surgery in a patient with paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired haemolytic anaemia. Cardiac bypass surgery in patients with PNH may be complicated by aggravation of haemolysis in addition to increased risk of infection, renal failure, bleeding and thrombosis. We describe a case of uncomplicated cardiopulmonary bypass surgery for aortic valve replacement and aortoplasty in a patient with PNH and discuss some recommendations to reduce the risk of peri-operative complications.

Poly-3-hydroxybutyrate (P3HB) production by bacteria from xylose, glucose and sugarcane bagasse hydrolysate.

Fifty-five bacterial strains isolated from soil were screened for efficient poly-3-hydroxybutyrate (P3HB) biosynthesis from xylose. Three strains were also evaluated for the utilization of bagasse hydrolysate after different detoxification steps. The results showed that activated charcoal treatment is pivotal to the production of a hydrolysate easy to assimilate. Burkholderia cepacia IPT 048 and B. sacchari IPT 101 were selected for bioreactor studies, in which higher polymer contents and yields from the carbon source were observed with bagasse hydrolysate, compared with the use of analytical grade carbon sources. Polymer contents and yields, respectively, reached 62% and 0.39 g g(-1) with strain IPT 101 and 53% and 0.29 g g(-1) with strain IPT 048. A higher polymer content and yield from the carbon source was observed under P limitation, compared with N limitation, for strain IPT 101. IPT 048 showed similar performances in the presence of either growth-limiting nutrient. In high-cell-density cultures using xylose plus glucose under P limitation, both strains reached about 60 g l(-1) dry biomass, containing 60% P3HB. Polymer productivity and yield from this carbon source reached 0.47 g l(-1) h(-1) and 0.22 g g(-1), respectively.

HLA-DRB1 and HLA-DQB1 polymorphisms in Pacific Islands populations.

Allele frequency distributions of the HLA-DRB1 and HLA-DQB1 genes were investigated in four Pacific Islands populations from the Cook Islands, Samoa, Tokelau and Tonga. Limited diversity was observed for both the HLA-DRB1 and HLA-DQB1 loci. Five HLA-DRB1 alleles were observed to be the most frequent amongst all the studied Pacific Islands populations. They were: HLA-DRB1*0403, HLA-DRB1*08032, HLA-DRB1*09012, HLA-DRB1*11011 and HLA-DRB1*1201. Cook Islanders had the largest number of low frequency DRB1 alleles followed by Samoans, Tokelauans and Tongans, most of which may be attributed to reported non-Polynesian admixture. The most frequently observed DQB1 alleles in the four studied Pacific Islands populations were those of the DQ3 subgroup of alleles HLA-DQB1*03011, HLA-DQB1*0302 and HLA-DQB1*03032 as well as HLA-DQB1*05031 and HLA-DQB1*06011. Cook Islanders had the highest number of rare HLA-DQB1 alleles, the distibution being similar to that of the HLA-DRB1 allele. While, in general, the values of homozygosity for DRB1 and DQB1 were observed to be lower then expected under neutrality, a statistical significance was observed in Tongans, Samoans and Tokelauans for the DQB1 locus and in Tongans for the DRB1 locus. Differences were observed between allele frequency distributions for Tokelauans compared to the other three populations. This was also demonstrated by principal component analysis of DRB1 and DQB1 allele frequencies, which separated the Tokelauan population from Cook Islanders, Tongans and Samoans. Tongans and Samoans were separate from the other Polynesian populations in the phylogenetic trees. Observed allele and haplotype frequencies were found to be in agreement with previously published HLA-DRB and HLA-DQB Polynesian data.