Qiviut cortisol reflects hypothalamic-pituitary-adrenal axis activity in muskoxen (Ovibos moschatus).

Muskoxen (Ovibos moschatus) are increasingly exposed to a broad diversity of stressors in their rapidly changing Arctic environment. There is an urgent need to develop validated tools to monitor the impact of these stressors on the hypothalamic-pituitary-adrenal (HPA) axis activity of muskoxen to help inform conservation actions. Here, we evaluated whether muskox qiviut (dense wooly undercoat) cortisol accurately reflects changes in HPA axis activity. Two repeated pharmacological challenges, involving weekly administrations of saline (control group) or adrenocorticotropic hormone (ACTH) during five consecutive weeks, were done on captive muskoxen, in winter (no hair growth) and summer (maximum hair growth). Pre-challenge qiviut cortisol levels were significantly higher in the shoulder than in the neck, but neither differed from rump concentrations. Qiviut cortisol levels significantly increased (p < 0.001) in response to the administration of ACTH during the hair growth phase, but not in the absence of growth (p = 0.84). Cortisol levels in the qiviut segment grown during the summer challenge increased significantly over a six-month period in the ACTH-injected muskoxen with a similar trend occurring in the control animals. Finally, cortisol levels in shed qiviut were significantly higher and not correlated to those of fully grown qiviut shaved three months earlier. Our results show that cortisol is deposited in qiviut during its growth and that qiviut cortisol can thus be used as an integrated measure of HPA axis activity over the period of the hair's growth. Differences in qiviut cortisol across body regions, significant differences in qiviut segments over time, and differences between shed qiviut versus unshed qiviut, highlight the importance of consistent design and methodology for sample collection and analyses in order to account for sources of variation when using qiviut cortisol as a biomarker of HPA axis activity in muskoxen.

Baseline parameters for rotational thromboelastometry in healthy labouring women: a prospective observational study.

OBJECTIVE: The aim of this study was to establish rotational thromboelastometry (ROTEM® ) baseline parameters in labouring women at term gestation. The secondary aim was to compare these reference ranges with those from previous studies on labouring women and from the manufacturer. DESIGN: A prospective, observational study. SETTING: Tertiary referral hospital. PARTICIPANTS: Healthy women in labour. METHODS: Ethics approval was granted for an opt-out recruitment approach. ROTEM® testing was performed in labouring women at term gestation. Women with any condition affecting coagulation were excluded. ROTEM® Delta reference ranges were derived by calculating the 2.5% and 97.5% centiles for INTEM/EXTEM/FIBTEM parameters including amplitude at 5 minutes (A5), coagulation time (CT) and maximum clot firmness (MCF). MAIN OUTCOME MEASURES: ROTEM® parameters were measured in labouring women before delivery. The following tests were performed: FIBTEM, EXTEM and INTEM. RESULTS: One hundred and twenty-one women met the inclusion criteria, with a mean (± SD) age of 29.6 ± 5.4 years and median (interquartile range) gestation of 39.4 weeks (37.4-40.4 weeks). Seventy-five (62.0%) women were nulliparous and 71 (58.7%) delivered vaginally. The median and interquartile ranges for selected ROTEM® parameters were: FIBTEM A5, 21 mm (IQR 18-23 mm); EXTEM A5, 55 mm (52-58 mm); and EXTEM CT, 52 seconds (48-56 seconds). CONCLUSIONS: The FIBTEM/EXTEM/INTEM amplitudes were higher than the manufacturer's reference ranges for non-obstetric patients. The FIBTEM MCF upper and lower limits were higher and the EXTEM/INTEM CT was shorter and narrower in range. This study provides reference ranges for ROTEM® values in healthy labouring women at term gestation with uncomplicated pregnancies. TWEETABLE ABSTRACT: This is the first study to report on ROTEM® reference ranges with over 120 healthy labouring women of normal weight at term gestation.

Baseline parameters for rotational thromboelastometry (ROTEM®) in healthy pregnant Australian women: a comparison of labouring and non-labouring women at term.

BACKGROUND: Rotational thromboelastometry (ROTEM®) is a point-of-care coagulation test. Reference ranges in non-labouring women have recently been established from a cohort of women presenting for elective caesarean delivery using the recommended minimum sample size of 120. This study aimed to present baseline parameters for labouring and non-labouring women and to compare the mean values of these ROTEM® parameters. METHODS: Ethical approval was granted for an opt-out recruitment approach for labouring women and written consent was obtained from non-labouring women (data published previously). ROTEM® testing was performed in these two cohorts at term gestation. Women with any condition affecting coagulation were excluded. ROTEM® Delta reference ranges were derived by calculating the 2.5 and 97.5 percentiles for INTEM/EXTEM/FIBTEM amplitude at 5 min (A5), coagulation time (CT), maximum clot firmness (MCF) and clot formation time (CFT). RESULTS: One hundred and twenty-one labouring and 132 non-labouring women met inclusion criteria. The mean values for selected ROTEM® parameters for labouring and non-labouring women respectively were: FIBTEM A5, 21.05 and 19.7 mm (P=0.008); EXTEM A5, 54.8 and 53.2 mm (P=0.025); and EXTEM CT, 52.2 and 53.7 s (P=0.049). Significant differences between the groups were observed in measures of clotting onset and clot firmness. CONCLUSIONS: We demonstrated a significant decrease in the mean time-to-clotting onset in labouring women compared with non-labouring women. Mean values for measures of clot firmness were greater in labouring women. In comparison to previously established ROTEM® baseline parameters for non-labouring women, this study provides evidence that there is greater hyper-coagulability in labouring women.

Baseline parameters for rotational thromboelastometry (ROTEM®) in healthy women undergoing elective caesarean delivery: a prospective observational study in Australia.

BACKGROUND: Formal reference ranges for rotational thromboelastometry (ROTEM®) in pregnancy have not been obtained in the recommended minimum sample size of 120. This prospective observational study aimed to establish baseline parameters in an Australian population of women undergoing elective caesarean delivery. The secondary aim was to compare these reference ranges with those from prior studies and the manufacturer. METHODS: Women undergoing elective caesarean delivery at term were included if they were at term, of normal body mass index and had no conditions affecting coagulation. ROTEM® reference ranges were derived by calculating the 2.5 and 97.5 percentiles for INTEM/EXTEM/FIBTEM amplitude at 5 minutes (A5), amplitude at 15 minutes (A15), coagulation time (CT), maximum clot firmness (MCF), and clot formation time (CFT). RESULTS: Of 202 women screened, 132 met the inclusion criteria, having a mean age of 32.7 ±â€¯5.0 years and median body mass index of 23.8 kg/m2 (interquartile range 21.5-26.4). The reference ranges for selected ROTEM® parameters were as follows: FIBTEM A5 (13-28 mm), FIBTEM CT (40-74 s), FIBTEM MCF (16-34 mm), EXTEM A5 (39-66 mm), EXTEM CT (43-69 s), INTEM A5 (38-63 mm). CONCLUSIONS: ROTEM® reference ranges for women with uncomplicated term pregnancies were reported as per the International Federation of Clinical Chemistry. The FIBTEM MCF and FIBTEM/EXTEM/INTEM amplitudes were higher in comparison to the manufacturer's reference ranges for the non-obstetric population. The EXTEM CT was shorter than the non-obstetric reference ranges. These ranges show an increase in coagulability during normal pregnancy compared to the non-pregnant reference ranges.

Australian multicentre study of current real-world prophylaxis practice in severe and moderate haemophilia A and B.

INTRODUCTION: With the emergence of novel treatment products for haemophilia and an increasing focus on the benefits of pharmacokinetic driven individualized prophylaxis, robust national data with regard to current patterns of factor consumption and adherence are required. AIM: To characterize current Australian practice with regard to use of prophylactic clotting factor infusions in patients with moderate or severe haemophilia A (HA) and haemophilia B (HB). METHODS: This was a retrospective, non-interventional study utilizing Australian Bleeding Disorder Registry (ABDR) data collected over a 12 month period. Registered and consented patients with moderate or severe HA or HB without inhibitors were included. RESULTS: A total of 718 HA (551 severe, 167 moderate) and 166 HB (87 severe, 79 moderate) patients were included. Regular prophylaxis was prescribed in 453 patients (82%) with severe HA, 42 patients (25%) with moderate HA, 66 patients (75%) with severe HB and 11 patients (14%) with moderate HB. Near universal prophylaxis was achieved in the paediatric subgroup. The mean weekly dose of factor VIII in severe HA was 84 international units/kg/wk (IU/kg/wk) vs 71 IU/kg/wk of factor IX in severe HB. Most patients on prophylaxis were treated ≥3 times/wk (HA) or 2 times/wk (HB). Non-adherence peaked in the 20-29 year age group. Older individuals on regular prophylaxis used more factor than was expected for their prescribed regimen. CONCLUSION: Prophylaxis rates in severe haemophilia are comparable with other developed nations. The benefit of a national registry is demonstrable. Furthermore research into the underlying reasons for non-compliance in young adults with haemophilia is required.

Depo-Provera increases neural activity in the central amygdala of reindeer bulls.

Reindeer bulls are difficult to manage and dangerous to handlers during the rutting period. Progesterone agonists have been used anecdotally in the field to favorably influence behavior, but effects on reproductive signaling have not been determined. The objective of this study was to determine the effects of Depo-Provera (medroxyprogesterone acetate) on neural activity in the amygdala of reindeer bulls in the early (n = 4) and full (n = 4) rut. Treated bulls (n = 4) were injected with a single injection of Depo-Provera (400 mg i.m.) approximately 2 wk before rut was initiated. Control bulls were untreated. Bulls were exsanguinated and brains collected. Neural activity in the amygdala was determined using c-fos immunohistochemistry. Neural activity did not differ by treatment (P ≥ 0.5), collection period (P ≥ 0.5), or their interaction (P ≥ 0.3) in the medial and cortical amygdala nuclei. A treatment × time interaction (P = 0.009) was observed in the central amygdala. The amygdala nuclei are interconnected allowing for integration of sensory stimuli with a direct connection between the medial amygdala and the olfactory bulb. The central amygdala is responsible for alerting, fear, and initiating a state of arousal towards nonspecific stimuli in the surrounding environment. In wildlife, the central amygdala has a role in recognizing threats in the environment such as predators. During the rut, bulls normally have a decreased sense of fear and elevated aggressive behavior with Depo-Provera treatment seemly able to diminish that aggression. Although it is unlikely that this observed change in neural activity fully explains the decreased aggressive behavior noted in bulls treated with Depo-Provera, neural networks of aggression include the amygdala. It is possible that further changes in c-fos activity will be noted in other areas of the brain known to be necessary for processing social cues. Bulls treated with Depo-Provera maintain sexual interest and have offspring. Depo-Prevera increases the neural activity within the central amygdala and may partially account for their altered aggressive behavior during the rut.

Challenges in hemophilia care in Australia and New Zealand.

BACKGROUND: Health and life expectancy for people with hemophilia have improved significantly in recent years, but we face new challenges, especially in the context of resource-constrained health services. AIM: This paper aims to highlight such challenges and propose practical solutions. METHODS: Nine hemophilia specialists from Australia and New Zealand reached consensus on areas of greatest need for improvement in hemophilia care in these countries, based on clinical experience and published data, and agreed on how to address these. RESULTS: Demography, optimizing treatment and assessing treatment success were identified as broad areas of challenge which included: comorbidities in ageing patients; transitioning from pediatric to adult care; equity of care for remote populations; weight-based dosing in obese patients; tailoring prophylaxis; accurate diagnosis of acute joint pain; managing chronic arthropathy; providing psychosocial support; consistency in definitions and assessment; and quantifiable outcome measures. Practice points included increased cross-specialty coordination and including psychologists and rheumatologists as part of comprehensive care teams; close collaboration between pediatric and adult centers to facilitate transition of care; systems such as telehealth that ensure continuity of care for remote populations; using pharmacokinetic data to tailor therapy; rapid and accurate diagnosis of acute joint pain; using data from bleeding registries to assess treatment effects and help with service planning; and ensuring consistency through benchmarking and standardization of HTCs. SUMMARY: Achieving treatment equity, optimal outcomes and cost savings may be possible through investing in national governance structures, expanding the comprehensive model of care and implementing innovative solutions tailored to local needs.

Enhancing haemophilia care through registries.

Clinical registries or databases have an increasing role in the management of inherited bleeding disorders. Initially, research-based registries provided valuable data and now national databases are increasingly being developed with multiple stakeholders, including persons with haemophilia (PWH) and payers, to enable improvements and efficiencies in care. Registries are extending to international collaborations to collect adverse event data and comparisons of national approaches to the management of haemophilia to improve the availability of product to PWH.

How we use recombinant activated Factor VII in patients with haemophilia A or B complicated by inhibitors. Working group of hematology experts from Australia and New Zealand, Melbourne, April 2011.

The management of bleeds in patients with haemophilia A or B complicated by inhibitors is complex. Recombinant activated Factor VII (rFVIIa; NovoSeven RT) is an established therapy in these patients. To develop a consensus-based guide on the practical usage of rFVIIa in haemophilia complicated by inhibitors, nine expert haemophilia specialists from Australia and New Zealand developed practice points on the usage of rFVIIa, based on their experience and supported by published data. Practice points were developed for 13 key topics: control of acute bleeding; prophylaxis; surgical prophylaxis; control of breakthrough bleeding during surgery or treatment of acute bleeds; paediatric use; use in elderly; intracranial haemorrhage; immune tolerance induction; difficult bleeds; clinical monitoring of therapy; laboratory monitoring of therapy; concomitant antifibrinolytic medication; practical dosing. Access to home therapy with rFVIIa is important in allowing patients to administer treatment early in bleed management. In adults, 90-120 µg/kg is the favoured starting dose in most settings. Initial dosing using 90-180 µg/kg is recommended for children due to the effect of age on the pharmacokinetics of rFVIIa. In the management of acute bleeds, 2-hourly dosing is appropriate until bleeding is controlled, with concomitant antifibrinolytic medication unless contraindicated. The practice points provide guidance on the usage of rFVIIa for all clinicians involved in the management of haemophilia complicated by inhibitors.

Serum apolipoprotein C-III is independently associated with chronic hepatitis C infection and advanced fibrosis.

BACKGROUND: The hepatitis C virus (HCV) is known to disrupt lipid metabolism, making serum lipoprotein levels good candidates to explore as markers of HCV disease progression. Assessment of the major apolipoproteins (Apo) and their relationship to hepatic fibrosis remain largely unexplored. METHODS: We compared the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and Apo A-I, -B, -C-III, and -E between patients with cleared versus active infection (n = 83), and between those chronically infected patients (n = 216) with advanced versus mild-moderate hepatic fibrosis (METAVIR stage F3-4 vs. F0-2) using multiple logistic regression. RESULTS: Apo C-III levels were 25% higher in subjects with cleared infection versus those with active infection (p = 0.009). Low levels of Apo C-III (p = 1.3 × 10(-5)), Apo A-I (p = 2.9 × 10(-5)), total cholesterol (p = 5.0 × 10(-4)), LDL-C (p = 0.005), and HDL-C (p = 2.0 × 10(-4)) were associated with advanced fibrosis in univariate analyses. Multivariable analysis revealed Apo C-III as the most significant factor associated with advanced fibrosis (p = 0.0004), followed by age (p = 0.013) and Apo A-I (p = 0.022). Inclusion of both Apo C-III and Apo A-I in a model to predict advanced fibrosis improved the area under the receiver operator curve only modestly. CONCLUSIONS: Relative to other lipoproteins, low serum Apo C-III levels are the most strongly associated with chronic versus cleared infection and decline with increasing severity of hepatic fibrosis. Apo C-III deserves further attention as a possible marker of HCV disease progression.

Suppression of the critical temperature of superconducting NdFeAs(OF) single crystals by Kondo-like defect sites induced by alpha-particle irradiation.

We report the effect of alpha-particle irradiation on the reduction of the critical temperature T{c} of a NdFeAs(OF) single crystal. Our data indicate that irradiation defects cause both nonmagnetic and magnetic scattering, resulting in the Kondo-like excess resistance Delta rho(T) proportional to lnT over 2 decades in temperatures above T{c}. The critical density of magnetic irradiation defects which suppresses T{c} is found to be much higher than those for cuprates and multiband BCS superconductors. We suggest that such anomalously weak pair breaking by irradiation defects indicates that magnetic scattering in pnictides is coupled with pairing interactions mediated by spin fluctuations.

Gestation length in farmed reindeer.

Reindeer (Rangifer tarandus tarundus) are the only cervids indigenous to the arctic environment. In Alaska, reindeer are a recognized agricultural species and an economic mainstay for many native populations. Traditionally raised in extensive free-ranging systems, a recent trend toward intensive farming requires a more in-depth knowledge of reproductive management. Reported gestation length in reindeer varies, ranging from 198 to 229 d in studies performed at the University of Alaska Fairbanks. A switchback study that manipulated only breeding date demonstrated a mean increase in gestation length of 8.5 d among females bred early in the season. The negative correlation between conception date and gestation length is consistent with reindeer research at other locations and reports of variable gestation length in a growing number of domestic and non-domestic species. This paper reviews the phenomenon in reindeer and discusses some of the factors known to affect gestation length as well as possible areas for future research.

Variation in gestation length among captive reindeer (Rangifer tarandus tarandus).

An estimated 90% of reindeer females are mated in a 10- to 21-d interval and give birth in an equally synchronized manner. Reported gestation length in reindeer is highly variable (range, 203 to 240 d), almost twice the reindeer estrous cycle length. Previously, we identified a significant, negative relationship between gestation length and conception date in a small group of reindeer. In the current study, the negative relationship was investigated in a switchback design, where reindeer were divided into two groups synchronized for early and late mating over a 2-yr trial. Regression analysis of 11 paired observations produced a negative (P<0.001) association between gestation length and conception date (slope= -0.31). Dam weight at breeding and prior to parturition, calf birth weight, and calf sex were not significant variables in the regression. Regression analysis of a larger data set from two University of Alaska Fairbanks reindeer herds, where conception date (verified by systemic progesterone) and gestation length were recorded (historical data set), supported previous conclusions (n=70; slope= -0.37; P<0.001). Although the calf sex ratio did not differ with gestation length, there was a positive relationship (r(2)=0.19; P=0.014) between male birth weight and gestation length in the larger data set. The negative relationship between conception date and gestation length enhanced calving synchrony, though the limits of gestation plasticity and underlying mechanisms are not clear. The potential role of photoperiod on early embryonic development is discussed.

Steroid hormone secretion during the ovulatory cycle and pregnancy in farmed Alaskan reindeer.

Seasonal endocrine changes in 5 non-bred and 10 pregnant Alaskan reindeer have been documented. Blood samples were collected from early September until early May, spanning the breeding season, gestation, or the anovulatory period. Plasma was analyzed by RIA for progesterone (P4), estradiol-17beta, estrone, and estrone sulfate. Elevated P4 in 80% of the reindeer at the onset of the study indicated that ovarian activity had been initiated. The median date for the onset of the first recorded full-length ovulatory cycle was September 23. In nonbred reindeer, the mean ovulatory cycle length from September to May was 24 +/- 1 d (range 18 to 29 d). Nonbred females continued to cycle throughout the winter, displaying 6 to 8 ovulatory cycles after the beginning of blood sampling. Cycle length (mean 22 to 24 d) did not vary between individuals (P = 0.170) or over the course of the winter (P = 0.244). In early April, ovulatory cycles ceased with normal demise of the corpus luteum in 2 females, whereas the remaining 3 females formed apparently persistent corpora lutea. Natural service breeding occurred between September 10 and October 2, and P4 profiles indicated that all breeding females conceived to the first mating. Concentrations of P4 rose steadily after conception and remained elevated throughout gestation, with mean concentrations not varying significantly (P = 0.104) from 4 to 28 wk of gestation. Estrogens all followed patterns similar to each other, remaining at baseline concentrations until approximately 24 wk of gestation and rising coincidently as P4 declined just before parturition. There was a continual overlap throughout the winter in peak P4 concentrations observed in cycling and pregnant reindeer. Calving occurred between April 8 and May 2, resulting in a mean gestation length of 211 +/- 2.2 d (range 198 to 221 d). Information from this study can be used by Alaskan reindeer producers to improve management and profitability of reindeer production.

Dissolution of porcine incisor pulps in sodium hypochlorite solutions of varying compositions and concentrations.

BACKGROUND: The solubility of dental pulp tissue in sodium hypochlorite has been extensively investigated but results have been inconsistent; due most likely to variations in experimental design, the volume and/or rate of replenishment of the solutions used and the nature of the tissues assessed. Traditionally, the sodium hypochlorite solutions used for endodontic irrigation in Australia have been either Milton or commercial bleach, with Milton being the most common. Recently, a range of Therapeutic Goods Administration (TGA) approved proprietary sodium hypochlorite solutions, which contain surfactant, has become available. Some domestic chlorine bleaches now also contain surfactants. The purpose of this study was to perform new solubility assessments, comparing Milton with new TGA approved products, Hypochlor 1% and Hypochlor 4% forte, and with a domestic bleach containing surfactant (White King). METHODS: Ten randomly assigned pulp samples of porcine dental pulp of approximately equal dimensions were immersed in the above solutions, as well as representative concentrations of sodium hydroxide. Time to complete dissolution was measured and assessed statistically. RESULTS: White King 4% showed the shortest dissolution time, closely followed by Hypochlor 4% forte. White King 1% and Hypochlor 1% each took around three times as long to completely dissolve the samples of pulp as their respective 4% concentrations, while Milton took nearly 10 times as long. The sodium hydroxide solutions showed no noticeable dissolution of the pulp samples. CONCLUSIONS: The composition and content of sodium hypochlorite solutions had a profound effect on the ability of these solutions to dissolve pulp tissue in vitro. Greater concentrations provided more rapid dissolution of tissue. One per cent solutions with added surfactant and which contained higher concentrations of sodium hydroxide were significantly more effective in dissolution of pulp tissue than Milton.

Cooperative activation of transcription by autoimmune regulator AIRE and CBP.

Autoimmune regulator (AIRE) is a transcriptional regulator that is believed to control the expression of tissue-specific genes in the thymus. Mutated AIRE is responsible for onset of the hereditary autoimmune disease APECED. AIRE is able to form nuclear bodies (NBs) and interacts with the ubiquitous transcriptional coactivator CBP. In this paper, we show that CBP and AIRE synergistically activate transcription on different promoter reporters whereas AIRE gene mutation R257X, found in APECED patients, interferes with this coactivation effect. Furthermore, the overexpression of AIRE and CBP collaboratively enhance endogenous IFNbeta mRNA expression. The immunohistochemical studies suggest that CBP, depending on the balance of nuclear proteins, is a component of AIRE NBs. We also show that AIRE NBs are devoid of active chromatin and, therefore, not sites of transcription. In addition, we demonstrate by 3D analyses that AIRE and CBP, when colocalizing, are located spatially differently within AIRE NBs. In conclusion, our data suggest that AIRE activates transcription of the target genes, i.e., autoantigens in collaboration with CBP and that this activation occurs outside of AIRE NBs.

Dosing strategy for enoxaparin in patients with renal impairment presenting with acute coronary syndromes.

BACKGROUND: Phase III clinical studies have confirmed that enoxaparin is superior to standard heparin in reducing the rate of recurrent ischaemic events in patients with non-ST elevation acute coronary syndromes. Patients with moderate to severe renal impairment were, however, excluded from these studies. Due to the hydrophilic disposition of enoxaparin, accumulation is likely in patients with renal dysfunction, thereby increasing the risk of haemorrhagic complications if standard weight adjusted treatment doses are used. Arbitrary dose reduction has been reported to increase the risk of ischaemic events, presumably due to inadequate enoxaparin concentrations. AIM: The aims of this study were to investigate the influence of glomerular filtration rate (GFR) on the pharmacokinetics of subcutaneously administered enoxaparin, and to develop a practical dosing algorithm in renal impairment that can easily be used at the bedside. METHODS: Thirty-eight patients, median age 78 years (range 44-87), mean GFR 32 ml min(-1) (range 16-117) and mean weight 69 kg (range 32-95), presenting with acute coronary syndrome were recruited into the study. Approximately 10 anti-Xa concentrations were taken per patient over their period of therapy. A population pharmacokinetic model was developed using non linear mixed effects modelling techniques, utilizing the software NONMEM. Stochastic simulations were performed to identify the most suitable dosing regimen. RESULTS: Three hundred and thirteen anti-Xa concentrations were collected. A two compartment, first order input model was identified as the best baseline model. Covariates found to improve model fitting were GFR as a linear function on clearance (CL) and weight as a linear function on the central volume compartment (Vc). The fraction of drug excreted unchanged (Fu) was estimated at 71%. CL and Vc from the final covariate model were estimated as; CL (l h(-1)) = 0.681 per 4.8 l hr(-1) (GFR) + 0.229 Vc (l) = 5.22 per 80 kg (total body weight) CONCLUSIONS: Clearance of enoxaparin was predictably related to GFR estimated using the Cockroft and Gault equation, with ideal body weight used as the size descriptor. According to our model no dosage adjustment from the standard 1.0 mg kg(-1) 12 hourly is required for the first 48 h of treatment. Maintenance doses thereafter can be calculated using standard proportional adjustments based on Fu equal to 0.71.

Enzyme replacement therapy for Gaucher disease in Australia.

AIM: To study the effectiveness of a specific national programme of enzyme replacement therapy (ERT) for patients with severe forms of Gaucher disease, a disorder of sphingolipid metabolism resulting from an inherited deficiency of the lysosomal enzyme beta-Glucocerebrosidase. METHODS: Prospective analysis of data submitted at entry and every 6 months on therapy. The responses of haemoglobin (Hb) and platelet (plt) concentrations, liver and spleen volumes were assessed. PATIENTS: Forty-eight patients were treated with ERT for a minimum of 6 months. Forty patients had Type 1 disease and eight had Type 3B. The age range was 1-70 years (median 24 years). Duration of therapy at the time of analysis was 6-114 months. RESULTS: Thirty-six per cent of patients started with a normal Hb increasing to 76% after 6 months. The mean improvement in Hb from baseline to the end of study period was 20 g/L, when the Hb was normal in 85% (41 patients). Thirty per cent of patients had a normal plt count at the start of therapy, with a more gradual increase in the count at 6 monthly intervals of 50, 91, 108 and 142% of starting value. Seventy-five per cent of patients had a normal plt count at the end of study. Spleen volumes reduced by a mean of 56% in 33 evaluable patients, and the liver by 27% in 30 of 38 evaluable patients. Eight patients had an increase in liver volume of 28%. CONCLUSION: Enzyme replacement therapy produced a spectrum of beneficial responses in patients with Gaucher disease, but all had some evidence of reversal of haematological complications and/or reduction in visceromegaly. Future analyses will examine the effect of therapy on bone disease, prepubertal growth and quality of life.