bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivorecovery of factor VIII and factor IX: intra‐ and interindividual variance in a clinical setting
Authors: BJÖRKMAN S. , FOLKESSON A. , BERNTORP E.
Published: December 2006

Summary. In vivorecovery (IVR) is traditionally used as a parameter to characterize the pharmacokinetic properties of coagulation factors. It has also been suggested that dosing of factor VIII (FVIII) and factor IX (FIX) can be adjusted according to the need of the individual patient, based on an individually determined IVR value. This approach, however, requires that the individual IVR value is more reliably representative for the patient than the mean value in the population, i.e. that there is less variance within than between the individuals. The aim of this investigation was to compare intra‐ and interindividual variance in IVR (as U dL−1per U kg−1) for FVIII and plasma‐derived FIX in a cohort of non‐bleeding patients with haemophilia. The data were collected retrospectively from six clinical studies, yielding 297 IVR determinations in 50 patients with haemophilia A and 93 determinations in 13 patients with haemophilia B. For FVIII, the mean variance within patients exceeded the between‐patient variance. Thus, an individually determined IVR value is apparently no more informative than an average, or population, value for the dosing of FVIII. There was no apparent relationship between IVR and age of the patient (1.5–67 years). For FIX, the mean variance within patients was lower than the between‐patient variance, and there was a significant positive relationship between IVR and age (13–69 years). From these data, it seems probable that using an individual IVR confers little advantage in comparison to using an age‐specific population mean value. Dose tailoring of coagulation factor treatment has been applied successfully after determination of the entire single‐dose curve of FVIII:C or FIX:C in the patient and calculation of the relevant pharmacokinetic parameters. However, the findings presented here do not support the assumption that dosing of FVIII or FIX can be individualized on the basis of a clinically determined IVR value.
Von Willebrand disease within the collective of haemophilic patients as reason for unexpected bleeding episodes
Authors: SIEGMUND B. , RICHTER H. , POLLMANN H.
Published: December 2006

Summary.  In the treatment of haemophilia A and B, recombinant coagulation factors are increasingly replacing plasma‐derived factor VIII and IX concentrates. Although provided with replacement therapy, individual patients may exhibit bleeding episodes, which are difficult to control. These bleeds may be caused by von Willebrand disease (VWD) as an additional underlying coagulation disorder. We report in the present study our experience that in the collective of haemophilic patients, VWD must be anticipated at least with the same order of magnitude as it appears in a normal healthy population. Among the patients at our treatment centre, two patients (1.5%) were identified as suffering from VWD in addition to haemophilia A. In the collective of haemophilia B patients at our centre, three patients (10%) with VWD were found. Two of these patients exhibited unexpected severe bleeding episodes, which could only satisfactorily be controlled by the administration of Haemate‐P or DDAVP supplementary to the recombinant coagulation factor concentrate.
Rituximab as an adjuvant therapy to immune tolerance in a haemophilia A boy with high inhibitor titre
Authors: CHUANSUMRIT A. , HUSAPADOL S. , WONGWERAWATTANAKOON P. , HONGENG S. , SIRACHAINAN N. , PAKAKASAMA S.
Published: December 2006

Summary.  We report a haemophilia A boy with high inhibitor titre (170 BU) who experienced five life‐threatening bleeding episodes during a one‐year period from 9 to 21 months. At the age of 22 months, he received rituximab (375 mg m−2 per dose) at one‐ and three‐week intervals, three courses each and alternative daily treatment with factor VIII concentrate at doses of 100 units kg−1 for 24 weeks and 50 units kg−1 for the following 28 weeks. Although the pretreatment inhibitor level of 4.5 BU showed an anamnestic response reaching the maximum level of 200 BU at the 9th week of treatment, it gradually declined to 30 BU at the 22nd week and was constantly maintained at 25–30 BU for the following 30 weeks. Only three bleeding episodes of two haematomas and one haemarthrosis were found during the one‐year treatment period. No opportunistic infection occured during this period.
Evaluation of pharmacokinetics, efficacy and safety of Immunate® solvent detergent in previously treated patients with severe haemophilia A
Authors: NEMES L. , LISSITCHKOV T. , KLUKOWSKA A. , DOBACZEWSKI G. , KOMRSKA V. , ZIMMERMANN R. , AUERSWALD G. , ENGL W. , PAVLOVA B. , ABBÜHL B. , EHRLICH H. J.
Published: December 2006

Summary.  Immunate® Solvent Detergent (S/D) is a plasma derived, purified, human factor VIII (FVIII) – von Willebrand factor (VWF) complex subjected to two virus inactivation/removal processes: S/D and vapor heat treatment. This prospective, multicentre, three‐part clinical study evaluated the pharmacokinetics (in comparison to the predecessor product Immunate®), efficacy and safety of Immunate® S/D in 56 previously treated patients with severe haemophilia A. Subjects received Immunate® S/D on‐demand, as a prophylactic regimen or both. The results of the pharmacokinetic population demonstrate that Immunate® and Immunate® S/D were equivalent with respect to the FVIII – and to the retrospectively VWF – parameters assessed. A total of 623 bleeding episodes were reported in 47/56 subjects. The duration of prophylaxis ranged from 0.1‐‐5.2 months with a total of 175.6 months. The median number of bleeds per month in subjects on prophylaxis was 0 (range 0‐‐10). Ninety‐six percent of bleeding episodes were rated as having an excellent or good response. For most bleeding episodes (89%), subjects required only one infusion with a mean dose of 29.6 IU kg−1. No FVIII inhibitory antibodies were observed in any subject. No related serious adverse events were reported. Thus, the introduction of S/D treatment did not alter the PK characteristics and function of VWF and FVIII molecules of Immunate® S/D which is effective and safe for treatment of bleeding episodes, management of surgical procedures, and prophylaxis.
Altered expression and endocytic function of CD205 in human dendritic cells, and detection of a CD205–DCL‐1 fusion protein upon dendritic cell maturation
Authors: Butler Matt , Morel Anne‐Sophie , Jordan William J. , Eren Efrem , Hue Susan , Shrimpton Rachel E. , Ritter Mary A.
Published: December 2006

CD205 (DEC‐205) is a member of the macrophage mannose receptor family of C‐type lectins. These molecules are known to mediate a wide variety of biological functions including the capture and internalization of ligands for subsequent processing and presentation by dendritic cells. Although its ligands await identification, the endocytic properties of CD205 make it an ideal target for those wishing to design vaccines and targeted immunotherapies. We present a detailed analysis of CD205 expression, distribution and endocytosis in human monocyte‐derived dendritic cells undergoing lipopolysaccharide‐induced maturation. Unlike other members of the macrophage mannose receptor family, CD205 was up‐regulated upon dendritic cell maturation. This increase was a result of de novo synthesis as well as a redistribution of molecules from endocytic compartments to the cell surface. Furthermore, the endocytic capacity of CD205 was abrogated and small amounts of the recently identified CD205–DCL‐1 fusion protein were detected in mature DC. Our results suggest that CD205 has two distinct functions – one as an endocytic receptor on immature dendritic cells and a second as a non‐endocytic molecule on mature dendritic cells – and further highlight its potential as an immuno‐modulatory target for vaccine and immunotherapy development.
Comparative transcriptional profiling of the lung reveals shared and distinct features of Streptococcus pneumoniae and influenza A virus infection
Authors: Rosseau Simone , Hocke Andreas , Mollenkopf Hans , Schmeck Bernd , Suttorp Norbert , Kaufmann Stefan H. E. , Zerrahn Jens
Published: December 2006

Pneumonia is the most common cause of death from infectious disease in the western hemisphere. Pathophysiological and protective processes are initiated by pattern recognition of microbial structures. To provide the molecular framework for a better understanding of processes relevant to host defence in pneumonia, we performed pulmonary transcriptome analysis in mice infected with the major bacterial and viral agents of community‐acquired pneumonia, Streptococcus pneumoniae and influenza A virus. We detected differential expression of 1300 genes after infection with either pathogen. Of these, approximately 36% or 30% were specific for pneumococcal or influenza infection, respectively, yielding pathogen‐specific as well as shared inflammatory transcriptional signatures. These results not only reveal a differential response on the cytokine and chemokine levels but also emphasize the important role of genes implicated in regulation and fine tuning of inflammation. As one, albeit unexpected, key feature of pneumococcal pneumonia we discovered down‐regulation of B‐cell responses, probably reflecting a pneumococcal virulence strategy. The pathophysiological consequences of influenza A virus infection were reflected by the emerging protective T‐cell response and differential induction of genes involved in tissue regeneration and proliferation. These data provide new insights into pathogenesis of the most common forms of pneumonia, highlighting the value of transcriptional profiling for the elucidation of underlying mechanisms.
Structural and functional comparison of native pentameric, denatured monomeric and biotinylated C‐reactive protein
Authors: Taylor Karolina E. , Van Den Berg Carmen W.
Published: December 2006

There are many controversies surrounding the biological activities of native C‐reactive protein (nCRP) and its various modified forms such as monomerized and biotinylated CRP (mCRP and bCRP). No simple methods have been described to distinguish among these forms. By adapting established electrophoresis methods, we have developed a useful quality control method with which we have investigated the structural and functional characteristics of these forms of CRP. Under all electrophoresis conditions, biotinylation altered the electrophoretic mobility of CRP. nCRP was sensitive to sodium dodecyl sulphate (SDS)‐induced monomerization, and only mCRP was susceptible to digestion by trypsin or neutrophil‐derived serine proteases. bCRP and mCRP but not nCRP bound to cells, suggesting that chemical modification by biotin and denaturation had altered the structural integrity of CRP. Neither nCRP nor mCRP had the ability to induce secretion of chemokines, nor did they increase intracellular adhesion molecule 1 (ICAM‐1) expression in endothelial cells.
Macrophages are essential for antitumour effects against weakly immunogenic murine tumours induced by class B CpG‐oligodeoxynucleotides
Authors: Buhtoiarov Ilia N. , Sondel Paul M. , Eickhoff Jens C. , Rakhmilevich Alexander L.
Published: December 2006

We explored the mechanisms of class B CpG‐oligodeoxynucleotide‐induced antitumour effects against weakly immunogenic tumours. Treatment with CpG‐oligodeoxynucleotide 1826 (CpG) induced similar antitumour effects in B16 melanoma‐bearing immunocompetent C57BL/6 mice and T‐cell‐deficient severe combined immunodeficient (SCID) mice, and NXS2 neuroblastoma‐bearing T‐cell‐depleted A/J mice. Both macrophages (Mφ) and natural killer (NK) cells from CpG‐treated C57BL/6 mice could mediate cytotoxicity in vitro, suggesting that these cell types might control tumour growth in vivo. However, CpG treatment of SCID/beige mice or T‐cell‐depleted and NK‐cell‐depleted A/J mice still induced antitumour effects in vivo, arguing against a major role of NK cells in the antitumour effects of CpG in the absence of T cells. In contrast, CpG treatment of interferon‐γ knockout (IFN‐γ–/–) C57BL/6 mice resulted in no antitumour effects in vivo and no Mφ‐mediated tumoristasis in vitro despite unaltered cytolytic function of NK cells in vitro. Moreover, Mφ inactivation by silica substantially reduced CpG‐induced suppression of tumour growth in vivo, revealing an important role of Mφ in CpG‐induced antitumour effects. The in vitro tumouritoxicity by CpG‐stimulated Mφ (CpG‐Mφ) correlated with tumour cell mitochondria dysfunction and involved nitric oxide (NO), tumour necrosis factor‐α (TNF‐α) and IFN‐γ, whereas interleukin‐1α (IL‐1α), IL‐1β, IFN‐α, TNF‐related apoptosis‐inducing ligand and Fas ligand played insignificant roles in CpG‐Mφ tumouritoxicity. Taken together, our results indicate that the growth control of weakly immunogenic tumours during CpG‐immunotherapy is mediated predominantly by Mφ, rather than T cells or NK cells.
Temporal and spatial dynamics of long‐distance Conyza canadensis seed dispersal
Authors: DAUER JOSEPH T. , MORTENSEN DAVID A. , VANGESSEL MARK J.
Published: December 2006

Glyphosate‐resistant Conyza canadensis populations now infest more than 44 000 ha of arable land in eastern USA, only 5 years after the first resistant population was reported. Seed dispersal, the expansive use of glyphosate and the lack of tillage are all factors contributing to this high invasion speed.

Seed collected from deliberately established C. canadensis source populations were found at the furthest seed traps in our empirical studies, providing one of the most complete dispersal kernels for studying long‐distance dispersal. The results indicate that seed regularly disperses at least 500 m from source populations. While a relatively small number of seeds moves long distances, 99% of the seed was found within 100 m of the source.

Empirical and mechanistic models were fitted to the data to predict the dispersal in the prevailing wind direction. Both models underestimated seed deposition beyond 200 m but the mechanistic model provided a better fit to the data (lower Akaike information criterion). A two‐dimensional analysis examined the correlation between angular directions of wind and seed movement. All trials were anisotropic but only the cumulative wind and seed direction were significantly correlated (P < 0·05).

The empirical model was used to explore the effect of increasing source strength, which would be expected as an infestation of glyphosate‐resistant C. canadensis expands on a producer's farm. At infestation levels consistent with a heavy infestation in a 5‐ha field, seed dispersed further than 1·5 km, easily affecting 10s to 100s of surrounding farms.

Synthesis and applications. Emigration of C. canadensis seed, from a source farm to adjacent farms, means that population dynamics and weed management are dependent on both intra‐ and interfield dispersal phenomena. Wind‐dispersed plants challenge the common practice of single field management as a viable management option for herbicide‐resistant weeds. Farms coupled by seed dispersal require proactive management practices by every producer to prevent and minimize the development of glyphosate‐resistant infestations of undesirable and alien plants.
The profile and incidence of cancer in Down syndrome
Authors: Sullivan S. G. , Hussain R. , Glasson E. J. , Bittles A. H.
Published: December 2006

Background  Down syndrome is one of the commonest causes of intellectual disability. As life expectancy improves with early and more intensive surgical and medical treatments, people with the disorder are more likely to exhibit classic morbidity and mortality patterns and be diagnosed with diseases such as cancer.

Methods  A profile of cancer cases among people with Down syndrome has been compiled, based on the analysis of a linked data set that included information from the Disability Services Commission of Western Australian and the State Cancer Registry.

Results and conclusions  Although the total age‐ and sex‐standardized incidence ratios (SIRs) for people with Down syndrome were similar to that for the general population, SIRs for leukaemia were significantly higher while the incidence of certain other types of cancers was reduced. Overall, there was a lower incidence of solid tumours in Down syndrome, possibly reflecting the age profile of the study cohort.
Chilika Lagoon: Restoring ecological balance and livelihoods through re‐salinization
Authors: Ghosh Asish K. , Pattnaik Ajit K. , Ballatore Thomas J.
Published: December 2006

This paper reviews the past and present conditions and management of Chilika Lagoon, the largest lagoon on India's eastern coast. Spatial and temporal salinity gradients, because of freshwater river inflow and seasonal seawater influx, have created unique characteristics of an estuarine ecosystem, and exercised a continuous, selective influence on the biota. Unfortunately, its biodiversity and the livelihoods that depend on it were being lost at a fast rate because of a blockage of the lagoon's mouth by silt coming from upstream catchments, as well as oceanic long‐shore transport. Projects to restore the dynamic characteristics of the lagoon included dredging a new mouth to the ocean, as well as prevention of soil erosion in upstream areas. Management efforts resulted in a dramatic revival of this ecosystem, and contributed to a sharp rise in the incomes of fisherfolk. The institutional aspects of implementing such large‐scale policy changes also are discussed, and the remaining issues and lessons learned are presented.
Kariba Reservoir: Experience and lessons learned
Authors: Magadza Christopher H. D.
Published: December 2006

The Kariba Reservoir is a large, tropical reservoir created nearly half a century ago on the Zambezi River in Zambia and Zimbabwe. It has a complex sociopolitical history, being designed during a period when human rights, social justice and equity in relation to colonial subjects were secondary concerns, as well as a period in which environmental management was an emerging discipline. Many of the management issues that have arisen over time were not foreseen when the dam was being planned. This paper examines several of these issues, including population increase in the basin, the need for ecological manipulations to optimize ecosystem functioning, and environmental problems such as eutrophication, microbial pollution, hyacinth invasion, and issues arising from pest control. The institutional arrangements also are critiqued, with a focus on how forced relocation of indigenous communities in the course of water resource development can lead to long‐lasting, trans‐generational social traumas. It is concluded that reservoir planning must explicitly address community needs, with equity issues in the sharing of water resource development benefits being clearly considered, and that post‐project integrated watershed management efforts must be part of reservoir planning.
Lake Baringo: Addressing threatened biodiversity and livelihoods
Authors: Odada Eric O. , Onyando Japheth O. , Obudho Peninah A.
Published: December 2006

Lake Baringo is a shallow, internal drainage, freshwater lake located in the Kenyan Rift Valley. The lake is an important source of water for humans and livestock, as well as a significant income source for local communities through activities such as tourism, biodiversity conservation, and fish sold in local markets. The lake has been subject to overfishing, as well as to greatly enhanced sedimentation as a result of land use changes in the drainage basin. This paper provides an analysis of the conditions prevailing at Lake Baringo, and examines in detail the management response to the problems facing the lake. The roles of the many and varied institutions in the lake basin's management are discussed, and an analysis of internationally funded projects designed to ameliorate the situation is provided.
Management of lakes in India
Authors: Reddy M. S. , Char N. V. V.
Published: December 2006

India is home to a wide range of water impoundments located in a diversity of climates, stretching from mountain conditions near the Himalayas in the north, to tropical conditions in the south. The impoundments include natural lakes, wetlands and coastal lagoons, as well as constructed reservoirs and tanks. This paper provides an overview of the lake management in India, focusing on wetlands, reservoirs and tanks. While there has never been a thorough survey of the lakes of India, it is possible to discuss the general conditions in which lake management is currently carried out in India. Overall, lakes all over the country are exhibiting varying degrees of environmental degradation caused by encroachments, eutrophication (from domestic and industrial effluents) and siltation. The high population density ensures that many water bodies are under severe and direct pressure from anthropogenic activities in their catchments. Actions to control and prevent these problems are addressed, with a focus on measures such as public interest litigation, the National Lake Conservation Plan, and the Special Purpose Vehicles. The role of national and international institutions is critiqued. Finally, the issues related to gaps in the knowledge base, delays in restoration, lack of coordination, ineffectiveness of legislation, and the general lack of an integrated approach to management are discussed, and possible solutions to these impediments are explored.
Aspergillosis of the scrotum: Non‐surgical management
Authors: Davido Helen T , Ryndin Igor , Köhler Tobias S , Hadegard Wade , Monga Manoj , Fung Leo
Published: December 2006

Abstract:  Disseminated aspergillar infection involving the genitourinary system is quite rare and often fatal. Only one previous case of aspergillosis of the scrotum has been reported. In the previous report, the patient died despite aggressive surgical debridement. We report a case of aspergillosis involving the scrotum in which the patient did well with conservative medical management.
A case of primary leiomyoma of the ureter
Authors: Naruse Katsuya , Yamada Yoshiaki , Aoki Shigeyuki , Taki Tomohiro , Honda Nobuaki , Iwafuchi Hideto
Published: December 2006

Abstract:  This report describes a case of primary leiomyoma of the ureter in which only partial ureterectomy was performed based on the diagnosis of benign tumor by rapid diagnosis using a frozen section during the operation. Surgical treatment was opted for upon diagnosis of a submucosal tumor of the right ureter, with no abnormal findings in the ureteral mucosa by ureteroscopy. To our knowledge, nine cases have been reported worldwide since 1955, suggesting this case to be the 10th.
Spurious prostate‐specific antigen (PSA) recurrence after radical prostatectomy: Interference by human antimouse heterophile antibodies
Authors: Park Sangtae , Wians Jr Frank H , Cadeddu Jeffrey A
Published: December 2006

Abstract:  Human antimouse heterophile antibodies (HAMA) are naturally occurring antibodies that can interfere with modern serum assays. We report a case of HAMA interference with a commonly used prostate‐specific antigen (PSA) assay, leading to false elevation (2.17–2.46 ng/mL) after radical prostatectomy. Pre‐operative PSA was 4.4 ng/mL, and final pathology was Gleason 3 + 3, pT2cNXMX. This markedly elevated postoperative PSA led to unnecessary imaging for metastasis and psychological distress to the patient. Direct measurement of HAMA in the patient’s serum yielded a value of 440 ng/mL (<74 ng/mL). An alternate PSA assay using goat detection antibody eliminated interference, with all values 0.05 ng/mL. When a patient’s PSA is inconsistent with the clinical scenario, one should consider immunological interference by HAMA in PSA assays.
Diagnostic and therapeutic use of radioisotopes for bony disease in prostate cancer: Current practice
Authors: Lawrentschuk Nathan , Davis Ian D , Bolton Damien M , Scott Andrew M
Published: December 2006

Abstract:  Nuclear medicine techniques continue to be important non‐invasive imaging tools assisting the diagnosis, monitoring and – in some cases – treatment of prostate cancer. Bone scintigraphy was the premier modality to have an extensive role in the staging of prostate cancer and has remained an integral tool for over three decades in the assessment of newly diagnosed disease or in follow‐up staging. Therapeutic treatment and palliation of disseminated disease, particularly in the skeleton, has also been successful with several radioisotopes including strontium‐89 chloride. Despite advances in nuclear medicine techniques and molecular imaging technology such as positron emission tomography and radioimmunoscintigraphy, bone scintigraphy still remains the gold standard in the assessment of osseous metastatic disease in prostate cancer. Thus, it is important to continually review the modalities that have remained important over time and not just to focus on newer technologies. This article summarizes the current diagnostic and therapeutic use of radioisotopes for bony disease in prostate cancer with particular reference to radionuclide bone scintigraphy and positron emission tomography.
Orbital cellulitis as a postoperative complication of sub‐Tenon anaesthesia in cataract surgery
Authors: Liang Steve Y‐W , Moloney Gregory , O’Donnell Brett A , Fernando Glen
Published: December 2006

Abstract

Orbital cellulitis is a rarely reported sight‐threatening complication of sub‐Tenon anaesthesia. We report a case of orbital cellulitis in a patient who had received sub‐Tenon anaesthesia for routine cataract surgery. We discuss the potential under‐reporting of complications of sub‐Tenon anaesthesia that had a delayed presentation, and the possible association between the use of hyaluronidase in the anaesthetic mixture and orbital cellulitis following sub‐Tenon anaesthesia.
Giant cell angiofibroma of the orbit with periosteal adherence
Authors: DeSousa Jean‐Louis , Meligonis George , Malhotra Raman
Published: December 2006

Abstract

We report a case of orbital giant cell angiofibroma, an unusual, recently reported benign spindle cell neoplasm. Preoperative clinical assessment and radiology suggested a benign mass and early operative findings were in concordance with this. Surgical excision was however, hampered by periosteal adhesion and lack of distinct encapsulation in the posterior part of the lesion. The histology of giant cell angiofibroma and its principle pathological differential diagnoses is discussed. As with some lymphangiomas, this is another benign orbital tumour which may present difficulties in complete surgical excision that are not anticipated based on the preoperative findings.
Bilateral macular cyst after lightning visualized with optical coherence tomography
Authors: Rivas‐Aguiño Pedro J , Garcia Reinaldo A , Arevalo J Fernando
Published: December 2006

Abstract

The authors report a 14‐year‐old girl who was struck by lightning with bilateral macular cyst that was diagnosed with optical coherence tomography (OCT). Her fundus examination revealed bilateral macular lesions that simulated macular holes. The Watzke–Allen sign was negative in the right eye and positive in the left eye. Fluorescein angiography showed a foveal window defect in both eyes. OCT demonstrated a small foveal cyst evident as a hyporeflective lucency, visible just anterior to the retinal pigment epithelium/choriocapillaris complex in both eyes. OCT seems to be useful in the evaluation of lighting maculopathy to rule‐out full‐thickness macular hole in these cases, and avoid unnecessary surgery.
Dynamic contour tonometry: principle and use
Authors: Punjabi Omar S , Kniestedt Christoph , Stamper Robert L , Lin Shan C
Published: December 2006

Abstract

Interindividual variability of central corneal thickness has been found to be a source of error for conventional Goldmann applanation tonometry. The dynamic contour tonometer represents a potentially new technology for non‐invasive and direct intraocular pressure (IOP) measurement, and has been proposed to accurately measure the true IOP irrespective of the corneal thickness. It is based on the principle that when the tip of the device exactly matches the contour of the cornea, the pressure measured by a transducer placed on its tip is an accurate indicator of the true IOP. This device is also capable of measuring the ocular pulse amplitude, a variable that has controversial significance in the diagnosis and management of glaucoma. Even though this technique seems to be very promising, further studies are required to conclusively determine the effectiveness of the dynamic contour tonometer in patients having an abnormal or irregular corneal contour.
Gillies Lecture: ocular motility in a time of paradigm shift
Authors: Demer Joseph L
Published: December 2006

Abstract

Recent progress in understanding of the structure and function of extraocular muscles, and our ability to image them clinically, allows prediction of revolutionary progress in diagnosis and treatment of strabismus in the coming decades. This perspective memorializes a lecture given in honour of Dr William Gillies, who has for decades been the paternal leader of strabismology in southern Australia.
Rapid evolution and ecological host–parasite dynamics
Authors: Duffy Meghan A. , Sivars‐Becker Lena
Published: December 2006

Traditionally, the termination of parasite epidemics has been attributed to ecological causes: namely, the depletion of susceptible hosts as a result of mortality or acquired immunity. Here, we suggest that epidemics can also end because of rapid host evolution. Focusing on a particular host–parasite system, Daphnia dentifera and its parasite Metschnikowia bicuspidata, we show that Daphnia from lakes with recent epidemics were more resistant to infection and had less variance in susceptibility than Daphnia from lakes without recent epidemics. However, our studies revealed little evidence for genetic variation in infectivity or virulence in Metschnikowia. Incorporating the observed genetic variation in host susceptibility into an epidemiological model parameterized for this system reveals that rapid evolution can explain the termination of epidemics on time scales matching what occurs in lake populations. Thus, not only does our study provide rare evidence for parasite‐mediated selection in natural populations, it also suggests that rapid evolution has important effects on short‐term host–parasite dynamics.
A niche for neutrality
Authors: Adler Peter B. , HilleRisLambers Janneke , Levine Jonathan M.
Published: December 2006

Ecologists now recognize that controversy over the relative importance of niches and neutrality cannot be resolved by analyzing species abundance patterns. Here, we use classical coexistence theory to reframe the debate in terms of stabilizing mechanisms (niches) and fitness equivalence (neutrality). The neutral model is a special case where stabilizing mechanisms are absent and species have equivalent fitness. Instead of asking whether niches or neutral processes structure communities, we advocate determining the degree to which observed diversity reflects strong stabilizing mechanisms overcoming large fitness differences or weak stabilization operating on species of similar fitness. To answer this question, we propose combining data on per capita growth rates with models to: (i) quantify the strength of stabilizing processes; (ii) quantify fitness inequality and compare it with stabilization; and (iii) manipulate frequency dependence in growth to test the consequences of stabilization and fitness equivalence for coexistence.
Ecosystem engineering in space and time
Authors: Hastings Alan , Byers James E. , Crooks Jeffrey A. , Cuddington Kim , Jones Clive G. , Lambrinos John G. , Talley Theresa S. , Wilson William G.
Published: December 2006

The ecosystem engineering concept focuses on how organisms physically change the abiotic environment and how this feeds back to the biota. While the concept was formally introduced a little more than 10 years ago, the underpinning of the concept can be traced back to more than a century to the early work of Darwin. The formal application of the idea is yielding new insights into the role of species in ecosystems and many other areas of basic and applied ecology. Here we focus on how temporal, spatial and organizational scales usefully inform the roles played by ecosystem engineers and their incorporation into broader ecological contexts. Two particular, distinguishing features of ecosystem engineers are that they affect the physical space in which other species live and their direct effects can last longer than the lifetime of the organism – engineering can in essence outlive the engineer. Together, these factors identify critical considerations that need to be included in models, experimental and observational work. The ecosystem engineering concept holds particular promise in the area of ecological applications, where influence over abiotic variables and their consequent effects on biotic communities may facilitate ecological restoration and counterbalance anthropogenic influences.
Patterns of thermal adaptation of Bacillus simplex to the microclimatically contrasting slopes of ‘Evolution Canyons’ I and II, Israel
Authors: Sikorski Johannes , Nevo Eviatar
Published: December 2006

Identification of selective forces that drive evolution and speciation of bacteria in natural habitats is a central issue in bacterial ecology and evolution. Exploring the adaptive evolution of Bacillus simplex at ‘Evolution Canyons’ I and II, Israel, we report here on the impact of high heat stress on the speciation progress of individual evolutionary lineages. These canyons represent similar ecological replicates, separated by 40 km, in which the orientation of the sun yields a strong sun‐exposed and hot ‘African’ south‐facing slope (SFS) versus a rather cooler and mesic‐lush ‘European’ north‐facing slope (NFS) within a distance of only 50–100 m at the bottom and 400 m at the top. Among 131 strains studied, in Luria–Bertani broth, ‘African’ strains grow better than ‘European’ strains at a stressful high temperature (43.25°C). The results suggest that adaptation to the hotter and more stressful SFS is continuously ongoing. The patterns of heat adaptation override the phylogenetic history of individual lineages. A positive correlation of growth rates at 43.25°C and 20°C, more markedly among ‘African’ strains, reflects probably the broader temperature range on the SFS. Summarizing, the hot temperature stress on the ‘African’ slope is a major environmental force driving the twin evolutionary processes of adaptation and speciation of B. simplex at ‘Evolution Canyon’. Finally, we discuss the data in light of current controversies on species concepts.
Molecular diversity of nitrite reductase genes (nirK) in nitrifying bacteria
Authors: Cantera J. Jason L. , Stein Lisa Y.
Published: December 2006

Sequences of copper‐containing nitrite reductase (nirK) genes obtained from completed nitrifier genome sequences were used to design polymerase chain reaction (PCR) primers to amplify partial nirK sequences from one Nitrosomonas and four Nitrosospira isolates. Deduced NirK protein sequences were highly similar to other copper‐containing nitrite reductases including conserved motifs. Phylogenetic comparisons of NirK protein sequences placed orthologues from Nitrosomonas, Nitrosospira and Nitrobacter species into multiple distinct clades. Products related to nirK genes were not amplified from seven additional Nitrosomonas and Nitrosospira isolates by PCR with nirK‐specific primers; however, DNA extracted from four of these isolates produced detectable signals in low‐stringency Southern hybridizations probed with nirK gene fragments from ammonia‐oxidizers with known nirK gene sequences. Analysis of promoter regions of nitrifier nirK genes revealed conserved binding motifs for the NsrR transcription factor in only one clade; other available nitrifier nirK gene promoters lacked characterized transcription factor binding motifs. Taken together, these results indicate that the sequences and regulation of nirK genes are diverse among nitrifiers. This study provides insight to the use of nirK genes for molecular diversity studies, establishes a framework to resolve the origins and diversification of nitrite reduction among the nitrifiers, and expands the database of nirK orthologues.
Nitrogen fixation by reductively dechlorinating bacteria
Authors: Ju Xiongfei , Zhao Liping , Sun Baolin
Published: December 2006

Significant advances in the ecology, physiology and genetics of reductively dechlorinating bacteria have revealed their important environmental roles in bioremediation and in the global chlorine cycle. N2 fixation has been widely observed in symbiotic, associative and free‐living bacteria. Here we show physiological and molecular evidence that reductively dechlorinating bacteria are capable of fixing atmospheric nitrogen. Furthermore, N2 fixation in some of these dechlorinating bacteria stimulated reductive dechlorination, which should help predict and regulate the environmental function of dechlorinating bacteria in in situ bioremediation of chlorinated pollutants. These results imply that N2 fixation in dechlorinating bacteria interacts with other biogeochemical cycles to control the nitrogen status of the anaerobic ecosystem.
Global update on defining and treating high‐risk localized prostate cancer with leuprorelin: a USA perspective – identifying men at diagnosis who are at high risk of prostate cancer death after surgery or radiation therapy
Authors: D’Amico Anthony
Published: December 2006

Prostate‐specific antigen doubling time (PSA‐DT) after surgery or radiotherapy (RT) is known to be a predictive factor for death from prostate cancer (prostate cancer‐specific mortality, PCSM). An analysis of two multi‐institutional databases, including 8669 men with prostate cancer treated with surgery or RT, found that a PSA‐DT of <3 months, and the specific value of the PSA‐DT when ≥ 3 months, appeared to be surrogate endpoints for PCSM after surgery or RT. While many PSA failures occur after local therapy for localized prostate cancer, few of these patients go on to die from their disease, so it is important to identify other factors associated with PCSM, so that the subgroup of high‐risk patients can be identified. An analysis was undertaken to determine whether patients at risk of PCSM could be identified using information available at diagnosis. The results showed that risk factors for PCSM were a PSA velocity of >2.0 ng/mL/year, a Gleason score of 8–10 and an increasing PSA level. However, the most important risk factor that had an impact on both PCSM and all‐cause mortality was a PSA velocity of >2.0 ng/mL/year. PSA kinetics are being increasingly used in the setting of rising PSA levels after radical prostatectomy or RT, and several studies showed that the rate of increase in PSA level at the time of recurrence is closely associated with time to cancer death. A PSA‐DT of <3 months is associated with a poor prognosis, and represents 15–20% of PSA failures in the general population and 6–7% of PSA failures in a screened population, such as those included in clinical trials. Better risk‐assessment models are needed to help to identify at an early stage men who are at high risk of prostate cancer death and those who are at low risk, so that each subgroup can receive the most appropriate therapy for their disease.
The current status of intermittent androgen deprivation (IAD) therapy for prostate cancer: putting IAD under the spotlight
Authors: Tunn Ulf
Published: December 2006

Intermittent androgen deprivation (IAD) is one approach to hormonal therapy for prostate cancer that has been developed with the aim of minimizing the negative effects of therapy while maximizing the clinical benefits and the patient’s quality of life (QoL). It can be used in any clinical situation where continuous AD (CAD) treatment could be applied. IAD is a cyclic therapy consisting of on‐treatment periods followed by observation periods, known as off‐treatment periods or intervals (OTIs), and the response to therapy, or occurrence of disease progression, is monitored by measuring the patient’s prostate‐specific antigen (PSA) levels. The on‐treatment period is generally fixed, normally lasting for 6–9 months or in some protocols until a PSA nadir of <4 ng/mL is reached. By contrast, the OTI is variable and treatment is re‐instituted depending on the patient’s PSA level; however, the exact trigger point is chosen empirically. The potential advantages of IAD over CAD therapy are an improved QoL, a prolonged period of androgen dependence, a reduced incidence of the side‐effects normally associated with AD therapy, and a decrease in the cost of care. Results from phase II clinical studies of IAD have shown that it has good acceptance and feasibility. QoL improves during the OTIs, there is reduced toxicity, and a positive affect on bone density compared with CAD therapy. In these studies IAD appeared to have no negative effects on time to progression or survival. Further investigations of IAD are ongoing in randomized, controlled, phase III trials in the USA, Canada and Europe. Most of these studies are not yet mature and final results are awaited; however, interim analyses from some studies suggest IAD and CAD therapy are equally effective in terms of progression‐free survival.
Contemporary use of hormonal therapy in prostate cancer: managing complications and addressing quality‐of‐life issues
Authors: Gomella Leonard G.
Published: December 2006

While both short‐ and long‐term androgen deprivation therapy (ADT) are effective for treating prostate cancer, with the clinical benefits patients can often have significant side‐effects. It is important that these complications are recognized and managed appropriately so that adverse effects on the patient's quality of life (QoL) are minimized. The incidence of deaths from prostate cancer has decreased over the last decade, probably as a result of various factors including improved screening and diagnosis, improved treatments, and better risk assessment to help guide therapy. A meta‐analysis of prostate cancer trials comparing the use of early vs late hormonal therapy found that 10‐year overall survival increased by up to 20% between 1990 and 2000, and this was attributed to the earlier use of hormone therapy (HT) in these patients. Data from the USA Cancer of the Prostate Strategic Urological Research Endeavor database also suggest a significant decrease in risk in the last two decades in the USA, with more patients being identified with low‐risk disease at diagnosis. In addition, there has been an increase in recent years in the use of HT at all stages of prostate cancer. The extensive use of ADT has raised concerns about potential adverse effects. ADT might be associated with a range of adverse effects that vary in their degree of morbidity and effect on the patient's QoL. They include hot flashes, osteoporosis, loss of libido or impotence, and psychological effects, e.g. depression, memory difficulties or emotional lability. Effective strategies are available for managing the major side‐effects of HT, but to many patients these unwanted effects are often less important than the benefits of treatment. An investigation of health‐related QoL found that men with prostate cancer receiving ADT had a poorer QoL than those not receiving ADT, but the difference was less pronounced after controlling for comorbidities. Many new therapies are currently under investigation which aim to maximize the clinical effects of ADT while reducing the adverse effects.
Monetary Policy and the Taylor Principle in Open Economies
Authors: Linnemann Ludger , Schabert Andreas
Published: December 2006

Nowadays, central banks mostly conduct monetary policy by setting nominal interest rates. A widely held view is that central banks can stabilize inflation if they follow the Taylor principle, which requires raising the nominal interest rate more than one‐for‐one in response to higher inflation. Is this also correct in an economy open to international trade? Exchange rate changes triggered by interest rate policy might interfere with inflation stabilization if they alter import prices. The paper shows that this destabilizing effect can prevail if (a) the central bank uses consumer (rather than producer) prices as its inflation indicator or directly reacts to currency depreciation, and (b) if it bases interest rate decisions on expected future inflation. Thus, if the central bank looks at current inflation rates and ignores exchange rate changes, Taylor‐style interest rate setting policies are advisable in open economies as well.
Acceptance of chronic illness in psoriasis vulgaris patients
Authors: Zalewska A , Miniszewska J , Chodkiewicz J , Narbutt J
Published: December 2006

Background  Acceptance of an illness is regarded as a considerable problem in patients with chronic diseases. Lack of acceptance can lead to lower adherence to medical treatment and delayed clinical improvement. Psoriasis, being a chronic skin disease, is known to cause considerable distress to patients.

Objectives  To examine whether selected demographic factors and personal resources have an impact on acceptance of illness in psoriasis vulgaris patients.

Methods  Self‐reported data on acceptance of illness, self‐efficacy, health locus of control, optimism and coping strategies were collected from 100 psoriasis vulgaris inpatients and PASI was calculated by a dermatologist. The following measures were employed: acceptance of illness scale, generalized self‐efficacy scale, multidimensional health locus of control scale, life orientation test and mental adjustment to disease scale.

Results  Physical factors such as sex, age, disease duration and severity, and family history of psoriasis had no effect on acceptance of illness. However, based on multiple regression analysis, higher levels of optimism, lower conviction of others’ influence on one's health and the less frequently employed coping strategy concentration on emotions, together with more severe disease expressed by PASI, were correlated with higher acceptance of disease in psoriasis patients.

Conclusions  The results obtained seem to confirm that personal resources play an important role in acceptance of chronic illness. Enhancement of optimism, and minimizing one's conviction that one's health depends on others could lead to higher acceptance of illness.
Relationship between sebostatic activity, tolerability and efficacy of three topical drugs to treat mild to moderate acne
Authors: Stinco G , Bragadin G , Trotter D , Pillon B , Patrone P
Published: December 2006

Background  Acne is a multifactorial disorder in which the sebum plays an important pathogenetic role.

Purpose of the study  To evaluate the sebostatic effect of three anti‐acneic ingredients (azelaic acid, adapalene and benzoyl peroxide) conveyed in cream and to determine whether there is a correlation with the therapeutic results.

Materials and methods  Sixty‐five patients with mild or moderate acne localized on the face were divided into three therapy groups at random: 25 applied azelaic acid once a day, 20, benzoyl peroxide and 20, adapalene. All the patients were observed at the time of enrolling and a further four times at fortnightly intervals. At each visit the sebum casual level on the forehead, chin and one cheek was measured using a sebumeter. Furthermore, side‐effects and clinical‐therapeutic effectiveness were noted.

Results  Four patients did not complete the study. Azelaic acid showed an average reduction of 13.9% in sebum production on the forehead, 14.2% on the chin and 15.2% on the cheek. Benzoyl peroxide caused an increase of 10.5% in sebum production on the forehead, 10.3% on the chin and 25.4% on the cheek. Adapalene reduced sebaceous secretion by 0.2% on the forehead and 6.7% on the cheek whereas sebum production increased by 6.2% on the chin. All three drugs showed a clinical improvement in the acneic lesions with moderate adverse effects.

Conclusion  The three topical drugs bring about good therapeutic results with scarce side‐effects that do not, however, seem to be correlated with the sebostatic activity.