bluuebunny/crossref_metadata_2025 huggingface dataset:
Native couch grasses for revegetating severely salinised sites on the inland slopes of NSW. Part 2
Authors: Semple W. S. , Cole I. A. , Koen T. B. , Costello D. , Stringer D.
Published: November 2006

Perennial ‘couch’ grasses that reproduce from rhizomes and or stolons have some advantages on scalded saline sites where they can reproduce in situations that are often hostile to germination and establishment of obligate seeders. Promising couch grass species from an earlier evaluation at Wagga Wagga and Manildra were Cynodon dactylon, Paspalum vaginatum, Sporobolus virginicus and, to a lesser extent, Sporobolus mitchellii. This paper reports results of a subsequent evaluation of these species as well as Eragrostis dielsii and Distichlis distichophylla at 3 other saline sites (Burrumbuttock, Cudal and Cundumbul). All accessions were established vegetatively and assessed for vigour and survival (all sites), groundcover production and its relationship with EC and pH (2 sites), biomass production, forage value and the effect of regular cutting on groundcover (1 site). S. virginicus appeared the most tolerant to saline conditions and produced high levels of groundcover and biomass but was sensitive to regular defoliation. At the 2 alkaline sites, C. dactylon and D. distichophylla generally outperformed the other accessions in terms of persistence and groundcover but appeared to be relatively low in forage value, and D. distichophylla appeared to have significant weed potential. Paspalum vaginatum produced high groundcover and relatively high biomass of moderate forage value at Burrumbuttock but performed poorly at the other sites. S. mitchellii and E. dielsii persisted on the more benign sites producing only low amounts of dry matter and groundcover and may be useful for environmental plantings where low weed potential is paramount. Despite spatially intensive testing of the topsoil chemistry, there were no obvious relationships between EC or pH and plant performance at the 2 main trial sites – a possible consequence of vegetative propagation.
Breaking seed coat dormancy in Macrotyloma daltonii
Authors: Chikumba N. , Mapiye C. , Poshiwa X.
Published: November 2006

Methods for breaking hard seed to allow germination of 2 seedlots of Macrotyloma daltonii (Webb) Verdc., were investigated. Treatments included soaking, application of dry heat, hot water, acid scarification, sand paper scarification, pre-chilling, alone and in combination with acid and dry heat. The treated seeds were tested for germination over 21 days in an incubator with 12 h of light and 12 h of darkness and temperatures of 25 and 18°C during the light and dark phases, respectively. A 20-min exposure to 98% concentrated sulphuric acid was most effective in increasing germination from 10 to 80% in seedlot 1. The 10-min acid treatment increased germination from 21 to 38% in seedlot 2, but 20 min reduced germination and increased the number of dead seeds. Seedlot 1 had greater levels of hard seed (88%) than seedlot 2 (61%). Soaking, hot water, dry heating, pre-chilling, or sandpaper scarification were not effective in breaking hard seed in either seedlot 1 or 2. Combining pre-chilling with 10 min of acid treatment damaged seed and impaired germination across the 2 seedlots. The range of pre-sowing seed treatments that indicated positive effects on germination, particularly acid treatments need to be further investigated in the field under different pedo-climatic conditions to allow appropriate rangeland management options to be developed.
An examination of the Stafford Smith - Morton ecological model: a case study in the Tanami Desert, Australia
Authors: Southgate R. , Allan G. , Ostendorf B.
Published: November 2006

The pattern of substrate, climatic, vegetation and fire features in the Tanami Desert were considered in relation to the ecological model for arid Australia proposed by Stafford Smith and Morton. The nature and accuracy of spatial data used to describe and quantify the pattern of the landscape features were also examined. Components of the ecological model were accurately reflected in the study area. For example, substrates identified as the most productive amounted to less than 8% of the region, and there was substantial spatial and interannual variation in rainfall. However, a strong climatic gradient was also evident in the study area, a feature not accommodated for in the model proposed by Stafford Smith and Morton. Vegetative ground and shrub cover decreased from north to south and was strongly associated with increasing aridity and lower maximum and minimum temperatures. Spinifex (Triodia spp.) cover showed a curvilinear response. The spatial data for both substrate and fire history were reasonably accurate (around 90%) when compared with ground-truthed data, and is considered suitable to reflect ecological pattern and process in the Tanami Desert. Both the adequacy of the ecological model and accuracy of spatial data are important issues to consider before the development of statistical modelling for prediction of species distribution.
The effects of temperature and salinity on Acacia harpophylla (brigalow) (Mimosaceae) germination
Authors: Reichman S. M. , Bellairs S. M. , Mulligan D. R.
Published: November 2006

Acacia harpophylla F. Muell. (brigalow) used to naturally occur over a range of about 50 000 km2 in Queensland and New South Wales, Australia. Large scale clearing for agriculture has reduced the area to less than 20 000 km2 and it is estimated that 20–25% of vertebrate fauna living in brigalow communities will become locally extinct as a result of the current clearing induced loss of habitat. Some coal mining companies in central Queensland have become interested in providing habitat for the endangered bridle nail-tailed wallaby that lives in brigalow vegetation. However, there is little known about establishment techniques for brigalow on mine sites and other disturbed ground; an understanding of brigalow biology and ecology is required to assist in the conservation of this threatened vegetation community and for re-creation of bridled nail-tail wallaby habitat in the post mining landscape. Brigalow is an unusual species of Acacia because it is not hard-seeded and germinates readily without the need to break seed-coat imposed dormancy. Germination trials were undertaken to test the ability of brigalow seed to germinate with a range of temperatures and salinity levels similar to those experienced in coal mine spoil. Optimum germination was found to occur at temperatures from 15 to 38°C and no germination was recorded at 45°C. Brigalow was very tolerant of high salt levels and germinated at percentages greater than 50% up to the highest salinity tested, 30 dS/m. Germination of greater than 90% occurred up to an electrical conductivity of 20 dS/m. The results indicate brigalow seed can be sown in summer when rains are most likely to occur, however, shading of the seed with extra soil or mulch may ensure the ground surface does not become too hot for germination. Because of its ability to germinate at high salinity levels, brigalow may be suitable for use in saline mine wastes which are common on sites to be rehabilitated after mining.
Construction of a mutated pro-nerve growth factor resistant to degradation and suitable for biophysical and cellular utilization
Authors: Pagadala Promila C. , Dvorak Laura A. , Neet Kenneth E.
Published: November 2006

Precursor of nerve growth factor (proNGF) has been found to be proapoptotic in several cell types and mediates its effects by binding to p75 neurotrophin receptor (p75
NTR
) and sortilin. The proNGF molecule is processed by proteases at three dibasic sites found in the pro domain to form mature NGF (termed herein as sites 1, 2, and 3 from the proNGF N terminus). Of these processing sites, site 3, adjacent to the N terminus of mature NGF, was thought to be the major site responsible for processing of proNGF to mature NGF. We found that mutating this major processing site (site 3) resulted in a form of proNGF that was only partially stable. On introducing additional mutations in the pro domain at the other two dibasic sites, we found the stability of proNGF to increase significantly. Here we describe the construction, expression, and purification of this more stable proNGF molecule. The two consecutive basic residues at each of the three sites were mutated to neutral alanine residues. Expression was performed in stably transfected Sf21 insect cells. Purification involved strong cation-exchange chromatography and N60 immunoaffinity column chromatography. The construct with all three sites mutated (termed proNGF123) gave all proNGF with no mature NGF and was not cleaved by three proconvertases (furin, PACE-4, and PC-2) known to proteolyze proneurotrophins
in vivo
. This stable proNGF molecule demonstrated proapoptotic activity on rat pheocytochroma PC12 cells, PC12nnr cells, C6 glioblastoma cells, and RN22 schwannoma cells.
Radiation dose-rate effects, endogenous DNA damage, and signaling resonance
Authors: Vilenchik Michael M. , Knudson Alfred G.
Published: November 2006

We previously concluded, from our analysis of the published data of other investigators, that the yield of germ-line and somatic mutations after exposure to ionizing radiation is parabolically related to the logarithm of the dose-rate at which a given dose is administered. Here we show that other data reveal a similarly parabolic relationship for other ionizing radiation-associated phenomena, namely, genetic recombination, chromosomal translocation, cell inactivation and lethality, and human leukemogenesis. Furthermore, the minima for all effects fall in a relatively narrow range of the dose-rate logarithms. Because the only mechanism common to all of these phenomena is the double-strand break (DSB) in DNA, we refer to our previous analysis of the endogenous production of DSBs, from which we concluded that ≈50 endogenous DSBs occur per cell cycle, although most are repaired without error. Comparison then reveals that their rate of production falls within the range of minima for the several end points pursuant to radiation-induced DSBs. We conclude that the results reflect a physiological principle whereby signals originating from induced DSBs elicit responses of maximal effectiveness when they are produced at a rate near that of the production of endogenous DSBs. We refer to this principle as “signaling resonance.”
FAK Potentiates Rac1 Activation and Localization to Matrix Adhesion Sites: A Role for βPIX
Authors: Chang Fumin , Lemmon Christopher A. , Park Dongeun , Romer Lewis H.
Published: November 2006

FAK, a cytoplasmic protein tyrosine kinase, is activated and localized to focal adhesions upon cell attachment to extracellular matrix. FAK null cells spread poorly and exhibit altered focal adhesion turnover. Rac1 is a member of the Rho-family GTPases that promotes membrane ruffling, leading edge extension, and cell spreading. We investigated the activation and subcellular location of Rac1 in FAK null and FAK reexpressing fibroblasts. FAK reexpressers had a more robust pattern of Rac1 activation after cell adhesion to fibronectin than the FAK null cells. Translocation of Rac1 to focal adhesions was observed in FAK reexpressers, but seldom in FAK null cells. Experiments with constitutively active L61Rac1 and dominant negative N17Rac1 indicated that the activation state of Rac1 regulated its localization to focal adhesions. We demonstrated that FAK tyrosine-phosphorylated βPIX and thereby increased its binding to Rac1. In addition, βPIX facilitated the targeting of activated Rac1 to focal adhesions and the efficiency of cell spreading. These data indicate that FAK has a role in the activation and focal adhesion translocation of Rac1 through the tyrosine phosphorylation of βPIX.
Modulation of Gene Expression and Cytoskeletal Dynamics by the Amyloid Precursor Protein Intracellular Domain (AICD)
Authors: Müller Thorsten , Concannon Caoimhin G. , Ward Manus W. , Walsh Ciara M. , Tirniceriu Anca L. , Tribl Florian , Kögel Donat , Prehn Jochen H.M. , Egensperger Rupert
Published: November 2006

Amyloidogenic processing of the amyloid precursor protein (APP) results in the generation of β-amyloid, the main constituent of Alzheimer plaques, and the APP intracellular domain (AICD). Recently, it has been demonstrated that AICD has transactivation potential; however, the targets of AICD-dependent gene regulation and hence the physiological role of AICD remain largely unknown. We analyzed transcriptome changes during AICD-dependent gene regulation by using a human neural cell culture system inducible for expression of AICD, its coactivator FE65, or the combination of both. Induction of AICD was associated with increased expression of genes with known function in the organization and dynamics of the actin cytoskeleton, including α2-Actin and Transgelin (SM22). AICD target genes were also found to be differentially regulated in the frontal cortex of Alzheimer's disease patients compared with controls as well as in AICD/FE65 transiently transfected murine cortical neurons. Confocal image analysis of neural cells and cortical neurons expressing both AICD and FE65 confirmed pronounced changes in the organization of the actin cytoskeleton, including the destabilization of actin fibers and clumping of actin at the sites of cellular outgrowth. Our data point to a role of AICD in developmental and injury-related cytoskeletal dynamics in the nervous system.
Odds ratio based multifactor-dimensionality reduction method for detecting gene–gene interactions
Authors: Chung Yujin , Lee Seung Yeoun , Elston Robert C. , Park Taesung
Published: November 2006

Motivation: The identification and characterization of genes that increase the susceptibility to common complex multifactorial diseases is a challenging task in genetic association studies. The multifactor dimensionality reduction (MDR) method has been proposed and implemented by Ritchie et al. (2001) to identify the combinations of multilocus genotypes and discrete environmental factors that are associated with a particular disease. However, the original MDR method classifies the combination of multilocus genotypes into high-risk and low-risk groups in an ad hoc manner based on a simple comparison of the ratios of the number of cases and controls. Hence, the MDR approach is prone to false positive and negative errors when the ratio of the number of cases and controls in a combination of genotypes is similar to that in the entire data, or when both the number of cases and controls is small. Hence, we propose the odds ratio based multifactor dimensionality reduction (OR MDR) method that uses the odds ratio as a new quantitative measure of disease risk.

Results: While the original MDR method provides a simple binary measure of risk, the OR MDR method provides not only the odds ratio as a quantitative measure of risk but also the ordering of the multilocus combinations from the highest risk to lowest risk groups. Furthermore, the OR MDR method provides a confidence interval for the odds ratio for each multilocus combination, which is extremely informative in judging its importance as a risk factor. The proposed OR MDR method is illustrated using the dataset obtained from the CDC Chronic Fatigue Syndrome Research Group.

Availability: The program written in R is available.

Contact:  tspark@snu.ac.kr
Modular organization of protein interaction networks
Authors: Luo Feng , Yang Yunfeng , Chen Chin-Fu , Chang Roger , Zhou Jizhong , Scheuermann Richard H.
Published: November 2006

Motivation: Accumulating evidence suggests that biological systems are composed of interacting, separable, functional modules. Identifying these modules is essential to understand the organization of biological systems.

Result: In this paper, we present a framework to identify modules within biological networks. In this approach, the concept of degree is extended from the single vertex to the sub-graph, and a formal definition of module in a network is used. A new agglomerative algorithm was developed to identify modules from the network by combining the new module definition with the relative edge order generated by the Girvan-Newman (G-N) algorithm. A JAVA program, MoNet, was developed to implement the algorithm. Applying MoNet to the yeast core protein interaction network from the database of interacting proteins (DIP) identified 86 simple modules with sizes larger than three proteins. The modules obtained are significantly enriched in proteins with related biological process Gene Ontology terms. A comparison between the MoNet modules and modules defined by Radicchi et al. (2004) indicates that MoNet modules show stronger co-clustering of related genes and are more robust to ties in betweenness values. Further, the MoNet output retains the adjacent relationships between modules and allows the construction of an interaction web of modules providing insight regarding the relationships between different functional modules. Thus, MoNet provides an objective approach to understand the organization and interactions of biological processes in cellular systems.

Availability: MoNet is available upon request from the authors.

Contact:  luofeng@cs.clemson.edu

Supplementary information: Supplementary Data are available at Bioinformatics online.
Biodiversity of an interface zone of a nutrient‐deficient lake (Nabugabo) in Uganda: macrophytes
Authors: Kateyo Eliezer M.
Published: November 2006

Lake Nabugabo was a big bay of Lake Victoria before being separated from the latter by a sand bar about 4000 years ago. Whereas conductivity of Lake Victoria is 100 μScm−1 that of Nabugabo has been less than 30 μ cm−2 since the Cambridge Scientific Expedition, 1962. Dissolved calcium carbonate is below detectable levels although nitrate and phosphate are not significantly different from those of Lake Victoria. However, the total cations and anions are five times more in Lake Victoria than Nabugabo. Along the eastern, southern and south‐western margins of the lake is an emergent swamp composed of different types of plants. In most places, Miscanthidium violaceum forms a floating platform of matted roots and rhizomes which border the open lake; it is associated with Sphagnum, a type of moss which normally grows in acidic and low‐temperature conditions at very high altitudes and latitudes. Because of the presence of this moss, the Nabugabo swamps are sometimes called ‘Sphagnum swamps’. Vossia cuspidata (hippo grass) is yet another emergent swamp plant in Lake Nabugabo, occurring in a number of isolated narrow mats stretching from a few metres to 0.5 km or longer along the edge of the emergent swamp. These floating mats are firmly anchored to the Micanthidium platform. Cyperus latifolia is another emergent‐floating plant in Lake Nabugabo firmly anchored on to the Miscanthidium platform. Cyperus latifolia and V. cuspidata tend to grow side by side but in completely sheltered bays the former plant grows alone. Cyperus papyrus L. occurs in very few patches within the emergent swamp. In the interface zone along the emergent swamp, there are a number of euhydrophyte plant species: Nymphaea caerulea is the most dominant and widespread euhydrophyte species except in the eastern tip of the lake where it is replaced by Nymphaea lotus; interspersed among these lilies is Ceratophyllum demersum in certain bays which could either be water inlets or out‐flows; Utricularia andNymphoides indica are associated with monospecific stand of N. caerulea in the south‐western end of the zone.
Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy in follicular and Hϋrthle cell thyroid lesions: results from a series of 505 consecutive patients
Authors: Rago T. , Di Coscio G. , Basolo F. , Scutari M. , Elisei R. , Berti P. , Miccoli P. , Romani R. , Faviana P. , Pinchera A. , Vitti P.
Published: November 2006

Objective  The cytological patterns of follicular and Hϋrthle cell nodules are included among the indeterminate results of fine‐needle aspiration cytology, because distinction between benign and malignant lesion can only be made on histological criteria. The diagnostic value of atypia at cytology, clinical parameters and echographic patterns were examined to establish the risk of malignancy in 505 patients with follicular and Hϋrthle cell thyroid nodules at cytology.

Design and patients  The study included 505 consecutive patients who had undergone thyroidectomy from the period 2002–2005.

Results  Histological diagnosis of malignancy was carried out in 125 of 505 (25%) patients, the follicular variant of papillary carcinoma being the most frequent histotype. Only atypia at cytology (P < 0·0001) and spot microcalcifications at ultrasound (P = 0·009) were predictive of malignancy. Male gender, normal thyroid volume, single nodularity, nodule hypoechogenicity, size and blurred margins were associated with malignancy, although not significantly. An arbitrary clinical score allowed the identification of patients with high (41%, 110 patients) and low (16%, 242 patients) risk of malignancy. Combining the clinical score with the presence of atypia at cytology we could identify 30 patients (6%) in whom the risk of malignancy was as high as 63%.

Conclusions  Twenty‐five per cent of patients with a cytological result of follicular and Hϋrthle cell thyroid lesion had a final diagnosis of malignancy. Only atypia at cytology and spot microcalcifications at thyroid ultrasound were significantly associated with malignancy. Other clinical parameters and thyroid ultrasound patterns can be used to set up a clinical score useful for predicting the individual risk of malignancy before surgery.
Serum thyroglobulin concentrations predict disease‐free remission and death in differentiated thyroid carcinoma
Authors: Heemstra Karen A. , Liu Ying Y. , Stokkel Marcel , Kievit Job , Corssmit Eleonora , Pereira Alberto M. , Romijn Johannes A. , Smit Johannes W. A.
Published: November 2006

Objective  Most studies on the diagnostic value of serum thyroglobulin (Tg) concentrations in differentiated thyroid carcinoma (DTC) use fixed cut‐off levels in heterogeneous groups of patients with respect to initial therapy and do not provide prognostic data. The objective was to investigate the prognostic values of serum Tg for disease‐free remission and death, measured at fixed time‐points after initial therapy using receiver operator characteristic (ROC) curve analyses.

Design  Single‐centre observational study with 366 consecutive patients with DTC, who had all been treated according to the same protocol for initial therapy and follow‐up.

Methods  Tg concentrations were measured at five fixed time‐points after initial surgery. Tg cut‐off values with the highest accuracy were calculated with ROC analyses.

Results  During the 8·3 ± 4·6 years of follow‐up, 84% of the patients were cured. Pre‐ablative Tg levels were an independent prognostic indicator for disease‐free remission (Tg cut‐off value 27·5 µg/l, positive predictive value 98%). The highest diagnostic accuracies of serum Tg for tumour presence were found during TSH‐stimulated Tg measurements, 6 months after initial therapy (Tg cut‐off value 10 µg/l; sensitivity 100%, specificity 93%). DTC‐related mortality was 14%. TSH‐stimulated Tg levels before ablation and 6 months after initial therapy were independent prognostic indicators for death.

Conclusion  Optimal institutional Tg cut‐off levels for diagnosis and prognosis should be defined using ROC analyses for each condition and time‐point. Tg measurements 6 months after initial therapy during TSH stimulation had an excellent diagnostic value. Tg levels are independent prognostic indicators for disease‐free remission and death. Using this strategy, high‐risk patient groups can be selected based on Tg levels, in addition to conventionally used prognostic indicators.
Anuran abundance and persistence in agricultural landscapes during a climatic extreme
Authors: PIHA HENNA , LUOTO MISKA , PIHA MARKUS , MERILÄ JUHA
Published: November 2006

Climate change in concert with habitat loss and degradation are major threats to global biodiversity. As part of climate change, the occurrence of extreme climatic events is expected to increase. Agricultural intensification has led to the increased homogeneity of agricultural habitats and declines in farmland species diversity. We investigated the abundance of common frogRana temporariapopulations in boreal farmlands in relation to multiple scales of landscape structure during years 2002–2003, and the effect of habitat structure onR. temporariapopulation persistence during a severe drought. On average, 113 and 24 egg clutches were observed per site in years 2002 and 2003, respectively. This dramatic decline was synchronized over the entire study area (ca. 320 km2), with some local variations. Population persistence was higher in sites where ground water levels decreased less but it was also positively correlated with the heterogeneity of the adjacent landscape. Under normal weather conditions, local habitat characteristics had a dominating role onR. temporariapopulation abundance, as it was positively correlated with the amount of ditches and ponds within the study sites. After the drought, however, population abundance was related to landscape and regional level factors. The results indicate that landscape homogenization can have negative effects on population persistence during climate change. They also show that the scale at which landscape characteristics affect populations can be strongly dependent of processes functioning at large scales, such as weather. In summary, heterogeneous landscapes may lower the risk of regional amphibian population declines under extreme weather perturbations and serve as sources of recovery in postdisturbance recovery phases. Thus, maintaining such areas should be promoted in long‐term biodiversity conservation.
Evaluation of immunodiagnostics for toxocarosis in experimental porcine cysticercosis
Authors: García Hector H. , Cancrini Gabriella , Bartalesi Filippo , Rodriguez Silvia , Jimenez Juan A. , Roldan William , Mantella Antonia , Nicoletti Alessandra , Bartoloni Alessandro
Published: November 2006

We assessed whether immunodiagnostic tests for cysticercosis can cross‐react with the currently available immunodiagnostic tests for Toxocara canis in an established animal model for cysticercosis infection in pigs, known host for Toxocara. We examined by TES‐enzyme‐linked immunosorbent test and immunoblot assay for toxocarosis and cysticercosis the baseline and final follow‐up sera of 10 pigs, before and after (3 months) infection with Taenia solium. After successful cysticercosis infection, the nine evaluable pigs became seropositive to T. solium (enzyme‐linked immunoelectrotransfer blot assay), but did remain seronegative for Toxocara in both assays, documenting the lack of cross‐reactivity with anti‐T. solium antibodies in both T. canis assays. These findings should help clinicians better interpret serology for toxocariosis and cysticercosis in endemic areas for both helminth infections.
A stepwise approach to the laboratory diagnosis of Buruli ulcer disease
Authors: Bretzel G. , Siegmund V. , Nitschke J. , Herbinger K. H. , Thompson W. , Klutse E. , Crofts K. , Massavon W. , Etuaful S. , Thompson R. , Asamoah‐Opare K. , Racz P. , Vloten F. , Van Berberich C. , Kruppa T. , Ampadu E. , Fleischer B. , Adjei O.
Published: November 2006

Objective  In view of technical and financial limitations in areas of endemicity, the current practice and recommendations for the laboratory diagnosis of Buruli ulcer disease (BUD) may have to be reconsidered. We reviewed diagnostic results in order to explore options for a modified, more practicable, cost‐effective and timely approach to the laboratory diagnosis of BUD.

Methods  Diagnostic specimens from 161 clinically diagnosed BUD patients from four different treatment centres in Ghana were subjected to laboratory analysis. The positivity rates of the laboratory assays were compared.

Results  The number of laboratory‐confirmed clinically diagnosed BUD cases with one positive confirmative test was 20% higher than that with two positive confirmative tests. The specificity of microscopy (MIC) and PCR was 96.6% and 100%, respectively. Subsequent analysis of specimens from surgically excised pre‐ulcerative tissue‐by‐tissue MIC and tissue PCR rendered 65% laboratory‐confirmed BUD cases. Subsequent analysis of diagnostic swabs from ulcerative lesions by swab smear MIC and swab PCR rendered 70% of laboratory‐confirmed BUD cases.

Conclusions  The specificity of the diagnostic tests used in this study suggests that one positive diagnostic test may be considered sufficient for the laboratory confirmation of BUD. Subsequent application of different diagnostic tests rendered a laboratory confirmation of 65% pre‐ulcerative and of 70% ulcerative lesions. Implementation of a stepwise, subsequent analysis of diagnostic specimens will result in considerable cost saving compared with simultaneous testing of specimens by several diagnostic assays.
Pharmacokinetics and variability of mycophenolic acid from enteric‐coated mycophenolate sodium compared with mycophenolate mofetil in de novo heart transplant recipients
Authors: Hummel Manfred , Yonan Nizar , Ross Heather , Miller Leslie W , Sechaud Romain , Balez Sebastien , Koelle Ernst Ulrich , Gerosa Gino ,   for the ERL 2401 Study Group
Published: November 2006

Abstract:  Sequential pharmacokinetic assessments were performed at five centers within the context of a multicenter, single‐blind, randomized clinical trial comparing the efficacy and safety of enteric‐coated mycophenolate sodium (EC‐MPS, myfortic®) and mycophenolate mofetil (MMF, CellCept®) in de novo heart transplant recipients. Patients were randomized to either EC‐MPS 1080 mg bid or MMF 1500 mg bid, as part of a triple immunosuppressive therapy including cyclosporine microemulsion. Steady‐state pharmacokinetic profiles of mycophenolic acid (MPA) and its inactive phenolic glucuronide (MPAG) were assessed at weeks 2, 12, and 52. Pharmacokinetic parameters were evaluated in 32 patients (17 on EC‐MPS and 15 on MMF). Dose‐normalized peak (Cmax,ss) and area under the curve (AUCτ,ss) of MPA and MPAG increased between week 2 and week 12 assessments for both treatments. Comparisons between EC‐MPS and MMF showed no statistically significant differences in MPA and MPAG AUCτ,ss, Cmax,ss, and trough (Cmin,ss) values (p‐values ranged from 0.225 to 0.990). Consistent with the delayed release characteristics of EC‐MPS, Cmax,ss occurred approximately one hour later compared with MMF. Inter‐subject coefficients of variation (%CV) for MPA pharmacokinetic parameters of both EC‐MPS and MMF were high (37–72% for AUCτ,ss at weeks 2 and 12). Also within patients, the pharmacokinetics of MPA varied considerably. Specifically, intra‐subject %CVs for MPA AUCτ,ss, Cmax,ss, and Cmin,ss were 28%, 63%, and 34% with EC‐MPS and 54%, 139%, and 41% with MMF respectively. These results indicate that a dose of EC‐MPS 1080 mg bid in combination with cyclosporine provides adequate systemic MPA exposure in de novo heart transplant patients, comparable with MMF 1500 mg bid. Overall, there is a large inter‐ and intra‐subject variability in MPA pharmacokinetic parameters with both treatments.
Early steroid withdrawal therapy in renal transplant recipients: a steroid‐free sirolimus and CellCept‐based calcineurin inhibitor‐minimization protocol
Authors: Jaber James J , Feustel Paul J , Elbahloul Ossama , Conti Alexander D , Gallichio Michael H , Conti David J
Published: November 2006

Abstract: Background: Maintenance steroid therapy is associated with significant morbidity and mortality in renal transplant recipients. Elimination of the many long‐term side effects of corticosteroids, including those that impinge on cardiovascular risk, remains a laudable goal in designing immunosuppressive protocols. However, concern persists that prednisone‐free maintenance immunotherapy in kidney transplant recipients will result in an increase incidence of acute rejections, renal dysfunction and ultimate graft loss.

Methods: From 24 March 2003 to 1 December 2004, 84 kidney transplant recipients (61 deceased donor, 23 living donors) discontinued prednisone on post‐operative day 6. Immunotherapy consisted of polyclonal antibody induction (thymoglobulin) for five d and prednisone intraoperatively with a rapid taper over the next six d. Maintenance therapy consisted of a sirolimus and CellCept‐based calcineurin inhibitor‐minimization protocol. Tacrolimus and mycophenolate mofetil (CellCept) were initiated on day 0. Sirolimus immunotherpay was started on post‐operative day 6 concomitant with the cessation of steroids. We compared outcomes with that of our historical controls, treated with sirolimus and tacrolimus, who did not discontinue steroids. In addition, we analyzed outcomes independently for recipients of living and deceased donors in the steroid‐free protocol.

Results: The recipients on prednisone‐free maintenance immunosuppression had excellent 2.5‐yr actuarial patient survival (97%), graft survival (93%), and acceptable acute rejection‐free graft survival (89%). The mean serum creatinine level (±SD) at one yr was 1.5 ± 0.6 mg/dL and at two yr was 1.5 ± 0.6 mg/dL. We noted that 5% of recipients developed cytomegalovirus (CMV) syndrome; 1%, polyoma nephropathy; 1%, post‐transplant lymphoproliferative disorder (PTLD), and 5% developed post‐transplant diabetes mellitus (PTDM). In all, 91% of kidney recipients with functioning grafts remain steroid‐free as of 31 December 2005. When compared with historical controls, the recipients on the early steroid‐withdrawal (ESW) protocol had comparable graft survival, acute rejection‐free survival, graft function, but significantly better patient actuarial survival (p = 0.048). In addition, recipients on the steroid‐free protocol had decreased prevalence of four risk factors for cardiovascular disease when compared with historical controls: hypertension (p = 0.008), hyperlipidemia (p = 0.003), weight gain (p = 0.024), and incidence of PTDM (p = 0.015).

Conclusion: Early steroid‐withdrawal in renal transplant recipients with a sirolimus and CellCept‐based calcineurin inhibitor‐minimimization protocol can effectively reduce many of the steroid‐related side effects, decrease risk factors for cardiovascular disease, and is associated with improved recipient survival without compromising graft function.
Safe restraint of the child passenger
Authors: Cameron Leanne , Segedin Elizabeth , Nuthall Gabrielle , Thompson John
Published: November 2006

Aim:  The aim of this study was to understand the need for, and use of, booster seats in the 4–12 years age group and to identify risk factors for booster seat‐non‐use.

Method:  A cross‐sectional sample of 1101 children aged 4–12 years travelling in 663 privately owned vehicles was taken from the Auckland region. Auckland is New Zealand’s largest population centre, with a population of over 1.5 million. Information was gathered using a short questionnaire followed by direct inspection to identify those children using booster seats. The SafetyBeltSafe USA ‘5‐step rule’ was used to look at those children not using a booster seat to determine whether one was still required.

Results:  While booster seat use has improved significantly in younger children since a similar study in 1992, only 40% of sampled children requiring a booster seat were using one. Booster seat use by children requiring them declined sharply as age increased. While 93% of 5‐ to 8‐year‐olds required a booster, only 30% were using one. The requirement for booster seats fell dramatically to 34% of 9‐ to 12‐year‐olds, but only 3% were using one.

Conclusion:  The high rate of need for booster seats and the lack of use of booster seats in children aged 5–8 years is a strong argument for legislation and education programmes targeting this age group. While the proportion of 9‐ to 12‐year‐olds needing a booster drops sharply, there would likely be benefits from educating parents on the ‘5‐step rule’ or similar method to help identify the 30% of these older children that would continue to benefit from a booster seat. Rear seating should be promoted alongside booster seat use in the age group 4–12 years.
Unrecognised hypoglycaemia in children and adolescents with type 1 diabetes using the continuous glucose monitoring system: Prevalence and contributors
Authors: Wiltshire Esko J , Newton Kirsty , McTavish Lindsay
Published: November 2006

Aim:  To determine prevalence of hypoglycaemia, and contributing factors, in children with type 1 diabetes, using the Medtronic MiniMed continuous glucose monitoring system (CGMS).

Methods:  Fifty‐one children and adolescents with diabetes were studied with the CGMS. The studies were analysed for frequency and duration of hypoglycaemia (below 3.5 and 2.5 mmol/L). Contributing clinical factors were determined. Occurrence of nocturnal hypoglycaemia was related to bedtime and fasting home glucose recording.

Results:  Hypoglycaemia was common, with 1 (0–4.2) (median (range)) episode per patient per 24 hours, and 0.33 (0–2) episodes per patient per night. Nocturnal episodes were longer than daytime episodes [97.5 (5–720) versus 35 (5–295) minutes for episodes below 3.5 mmol/L, P < 0.001; and 75 (10–640) versus 25 (5–200) minutes for episodes below 2.5 mmol/L, P < 0.001], and less likely to be recognised by the subject (P < 0.001 for episodes below both 3.5 and 2.5 mmol/L). Nocturnal hypoglycaemia was more common with a bedtime glucose recording <6 mmol/L, but also occurred frequently in subjects with glucose recordings >10 mmol/L. No bedtime glucose value reduced the risk of nocturnal hypoglycaemia to <10%.

Conclusion:  Hypoglycaemia, assessed using the CGMS, is common in children with type 1 diabetes and can be prolonged (although is predominantly mild). Bedtime home glucose recordings are poorly predictive of hypoglycaemia during the following night. Continuous glucose monitoring has proven very useful in management of individual patients, particularly adolescents experiencing difficulties with adherence to diabetes management.
Growth of infant communication between 8 and 12 months: A population study
Authors: Reilly Sheena , Eadie Patricia , Bavin Edith L , Wake Melissa , Prior Margot , Williams Joanne , Bretherton Lesley , Barrett Yin , Ukoumunne Obioha C
Published: November 2006

Aim:  To describe changes in infant prelinguistic communication skills between 8 and 12 months, and identify factors associated with those skills.

Methods:  Design: Parent questionnaire data for a prospective population‐based cohort of infants in metropolitan Melbourne, Australia. Participants: 1911 infants born November 2002‐August 2003. Outcome: Infant communication (Communication and Symbolic Behaviour Scales (CSBS)) at 8 and 12 months. Potential risk factors: sex; prematurity; multiple birth; sociodemographic indicators; maternal mental health, vocabulary and education; non‐English speaking background; and family history of speech‐language difficulties. Linear regression models were fitted to total standardised CSBS scores at 8 and 12 months.

Results:  Social communication, especially the use of gesture, developed rapidly from 8 to 12 months. Female sex, twin birth, and family history were strongly associated with CSBS scores. The combined model accounted for 5% and 6% of the total variation at 8 and 12 months, respectively. CSBS score at 8 months strongly predicted CSBS score at 12 months (coefficient = 0.56, partial R2 = 37.0).

Conclusions:  There is a dramatic increase in communication skills between 8 and 12 months, particularly the development of gesture, which (as in previous studies) predates and predicts future language development. Risk factors explained little variation in early communication trajectories and therefore, based on our findings, this developmental course is more likely to be biologically predetermined. Rather than focusing on risk factors, we suggest that language promotion activities in otherwise healthy young infants should either be universal or, if targeted, be based on the level of communication skills displayed.
Rotavirus outbreak in a remote Aboriginal community: The burden of disease
Authors: Gelbart Ben , Hansen‐Knarhoi Meredith , Binns Philippa , Krause Vicki
Published: November 2006

Aim:  To document the burden of disease caused by an outbreak of rotavirus (RV) gastroenteritis in a remote Aboriginal community.

Methods:  During an outbreak of RV gastroenteritis, data were collected from patients notes, hospital and laboratory data. Age, date of presentation, severity of illness, number of total presentations, presentations per patient, total clinic hours per presentation, stool analysis, treatment and outcomes were measured. These data were compared with a time period of equal duration in order to establish a baseline burden of gastroenteritis.

Results:  In a remote Aboriginal community 26 patients were managed for acute diarrhoea between 19 September 2005 and 5 October 2005. Gastroenteritis was the diagnosis in 24 cases for which there were 55 presentations. Stool specimens were analysed in 14 (58%) cases. RV was identified in eight (57%) of these specimens. The majority (80%) had mild disease. Moderate disease was noted in 15% and 5% were follow‐up reviews. There were no severe cases of gastroenteritis. Four patients required evacuation to hospital. From a total of 607 presentations to the clinic during this time period, 55 (9%) were managed for acute diarrhoea. In the comparative time period there were five (0.9%) cases of acute diarrhoea from a total of 571 presentations.

Conclusion:  Rotavirus gastroenteritis places a large burden on remote Aboriginal communities and health‐care centres in the form of morbidity, overworked clinic staff, economic cost and reduced capacity for primary health‐care duties.
Risk factors for preterm and small‐for‐gestational‐age babies: A cohort from the Pacific Islands Families Study
Authors: Gao Wanzhen , Paterson Janis , Carter Sarnia , Percival Teuila
Published: November 2006

Aim:  To explore risk factors that are associated with preterm birth and full‐term small‐for‐gestational‐age (SGA) birth for a Pacific population.

Methods:  Data were gathered from the Pacific Islands Families Study. Mothers of a cohort of 1398 Pacific infants born in South Auckland, New Zealand during 2000 were interviewed when their infants were 6 weeks old. Mothers were questioned regarding maternal health, antenatal care and life‐style behaviours. Data regarding birth outcomes were obtained from hospital records. Analyses focused on 1324 biological mothers who gave birth to a singleton and had valid data for birth outcomes.

Results:  Of 1324 singleton infants, the mean birthweight was 3.60 kg with standard deviation of 0.60 kg. Fifty‐two (3.9%) had birthweight less than 2500 g. Ninety‐four (7.1%) were born at less than 37 weeks of gestation. Most socio‐demographic factors were not associated with poor birth outcomes. Primiparous birth, less frequent attendance of antenatal care and mother’s history of high blood pressure were associated with preterm birth and SGA. Smoking during pregnancy increased the odds of having an SGA but not preterm birth. On the other hand, unplanned/unsure pregnancy and prior early pregnancy loss were associated with preterm birth but not SGA.

Conclusion:  Corroborating research conducted with other populations, most of the internationally and nationally recognised risk factors for preterm birth and SGA are also important for Pacific people. Smoking seems to explain more poor birth outcomes in Pacific Islands than in the New Zealand population as a whole.
Early manifestation of obesity and calcinosis cutis in infantile pseudohypoparathyroidism
Authors: Poomthavorn Preamrudee , Zacharin Margaret
Published: November 2006

Abstract:  Pseudohypoparathyroidism is a parathyroid hormone resistance condition, characterised by biochemical findings of hypocalcaemia or normocalcaemia with inappropriately elevated parathyroid hormone level and usually with a typical osteodystrophy feature. We report an infant with pseudohypoparathyroidism type Ia, who presented with obesity and calcinosis cutis as a clue to diagnosis. A 1‐year‐old female infant presented with suspected Cushing syndrome. She had round face, flushed cheeks, short nose and low nasal bridge. The infant was normotensive and not virilised. Investigations for Cushing syndrome were all negative. Calcinosis cutis was detected over both legs and the abdominal wall. Parathyroid hormone level was inappropriately elevated with a slightly high calcium level. Her mother was also noted to have Albright’s hereditary osteodystrophy features with normal calcium and parathyroid hormone levels. Therefore, the diagnoses of infantile pseudohypoparathyroidism type Ia and maternal pseudopseudohypoparathyroidism were made. This infant presented with an early manifestation of Albright’s hereditary osteodystrophy. Diagnosis of pseudohypoparathyroidism should be considered as an unusual cause of obesity in infants, particularly in the differential diagnosis of Cushing syndrome when tall stature rather than growth failure is present.
Abnormal glucose metabolism and features of the metabolic syndrome are common in patients presenting for elective cardiac catheterization
Authors: Harding S. A. , Anscombe R. , Weatherall M. , Prasad S. , Lever N. , Krebs J.
Published: November 2006

Background: Abnormalities of glucose metabolism and the metabolic syndrome, including excess bodyweight, are potentially modifiable risk factors for cardiac morbidity and mortality. This study aimed to determine the prevalence of these in a group of patients presenting for elective cardiac catheterization or percutaneous intervention.

Methods: Data were prospectively collected on 297 consecutive patients presenting for elective cardiac catheterization or percutaneous intervention at a single tertiary referral centre. Demographic data, risk factors, medications and coronary angiogram results were recorded. Fasting lipids, fasting glucose, HbA1c levels were measured and if necessary an oral glucose tolerance test was carried out. Logistic regression and contingency table analysis examined associations of these with ethnicity.

Results: Impaired glucose metabolism (diabetes, impaired glucose tolerance or impaired fasting glucose) was present in 46.1% with our screening programme detecting previously unknown impaired glucose metabolism in 22.9%. Impaired glucose metabolism was strongly associated with non‐European ethnicity (P < 0.0001). The metabolic syndrome was present in 49.2%. When defined by ethnic specific cut‐offs, overweight or obesity was present in >80% of patients in all ethnic groups.

Conclusion: There is a very high prevalence of impaired glucose metabolism and the metabolic syndrome in patients presenting for cardiac catheterization. Impaired glucose metabolism is particularly prevalent in the Polynesian and the Indian and the Sri Lankan ethnic groups. Screening of patients undergoing elective cardiac catheterization identifies a significant number of patients with undiagnosed impaired glucose metabolism and should be carried out routinely.
Current status of new drugs for the treatment of patients with multiple myeloma
Authors: Kenealy M. , Prince H. M.
Published: November 2006

Multiple myeloma, a malignant disorder of plasma cells, is the second most common haematological malignancy. Although treatable, multiple myeloma remains incurable in virtually all cases, with a median survival of 3–4 years. Fortunately for patients with this disease, traditional treatment paradigms have been challenged with the emergence of a number of new therapies entering clinical practice over the last 6 years. In this review, we focus on the use of thalidomide (Thalidomide Pharmion; Boulder, CO, USA), lenalidomide (Revlimid; Celgene Corporation, Summit, NJ, USA) and bortezomib (Velcade; Janssen Pharmaceutica N.V., Belgium) in the treatment of myeloma. We present the current clinical experience with respect to efficacy and toxicity of these promising new agents and how the incorporation of these drugs with traditional therapies may improve the outcome for patients with multiple myeloma.