bluuebunny/crossref_metadata_2025 huggingface dataset:
Symmetry of nerve conduction studies in different stages of diabetic polyneuropathy
Authors: Perkins Bruce A. , Ngo Mylan , Bril Vera
Published: October 2004

Nerve conduction studies (NCS) in diabetic sensorimotor polyneuropathy (DSP) are sensitive, noninvasive, and associated with small coefficients of variation, and correlate well with underlying peripheral nerve morphological change. For these reasons, the current reference standard for DSP involves multivariate instruments that emphasize NCS results. However, the interside symmetry of NCS findings in different stages of DSP are unknown, although requirement for symmetry has been suggested in clinical trials of DSP. We therefore aimed to determine the degree of symmetry of NCS findings in DSP of differing severity stages. A cohort of diabetic patients, including patients without neuropathy and those with mild to severe DSP, was studied. We also studied a series of nondiabetic, healthy subjects. A variation of stratified sampling by means of a clinical neuropathy score ensured that a broad spectrum of neuropathy was studied. A total of 478 subjects was ascertained; patient accrual was discontinued when the smallest clinical group consisted of 50 subjects. Nerve conduction studies were conducted prospectively and in a blinded fashion using surface recordings, averaging for sensory action potentials, control of limb temperature, and standardized techniques. Median and ulnar motor and sensory, peroneal and tibial motor, and sural NCS were performed. Interside symmetry, independent of neuropathy severity, was observed for all investigated nerves, except for the median sensory nerve action potential amplitude, which was lower on the right side. These results confirm that abnormal NCS findings consistent with DSP are reliably symmetrical with the exception of the amplitude of the median sensory nerve action potential. Thus, unilateral evaluation of NCS in DSP is sufficient as a reference standard in clinical trials. We also conclude that great degrees of asymmetry in NCS results are reason to question inclusion of DSP patients in clinical trials. © 2002 John Wiley & Sons, Inc. Muscle Nerve 25: 212–217, 2002 DOI 10.1002/mus.10044
Altered mandibular development precedes the time of palate closure in mice homozygous for disproportionate micromelia: An oral clefting model supporting the Pierre‐Robin sequence
Authors: Ricks James E. , Ryder Victoria M. , Bridgewater Laura C. , Schaalje Bruce , Seegmiller Robert E.
Published: October 2004

Background

Development of the human craniofacial anatomy involves a number of interrelated, genetically controlled components. The complexity of the interactions between these components suggests that interference with the spaciotemporal interaction of the expanding tongue and elongating Meckel's cartilage correlates with the appearance of cleft palate. Mice homozygous for the semi‐dominant Col2a1 mutation Disproportionate micromelia (Dmm), presenting at birth with both cleft palate and micrognathia, provide the opportunity to test the hypothesis that mandibular growth retardation coincides with formation of the secondary palate as predicted from our understanding of the Pierre Robin sequence. The present study was conducted in embryonic day 14 (E14) mice, 1 day before palate closure, to describe the relationship between growth of the lower jaw/tongue complex versus genotype of the embryo.

Methods

Whole heads, isolated from E14.25, E14.5 and E14.75 wild‐type and homozygous mutant embryos, were fixed in Bouin's solution, embedded in paraffin, and serially sectioned. Mid‐sagittal sections, stained with toluidine blue, were used to estimate growth of both tongue and lower jaw (Meckel's cartilage length) during a 12‐hr period preceding palate closure.

Results

In control embryos, the largest increase in Meckel's cartilage length occurred between E14.5 and E14.75. Compared to control, the mean Meckel's cartilage length in the mutant was similar at E14.25, but was significantly less at E14.5 and E14.75. Absolute tongue size in control embryos increased linearly during this period of E14.25 to E14.75. Relative to the rapidly growing Meckel's cartilage, however, relative tongue size in control embryos actually decreased over time. Absolute tongue size in the mutant was not significantly different from that of control at any of the embryonic stages examined, however, relative tongue size in the mutant was significantly greater at E14.75 compared to control.

Conclusion

Mandibular growth retardation, coupled with relative macroglossia in E14 Dmm/Dmm mice, suggests that the concerted development of the palate and lower jaw complex in the mutant is aberrant. Detection of micrognathia and pseudomacroglossia in homozygotes, before the time of palate closure, supports the hypothesis that a relationship exists between growth retardation of Meckel's cartilage and malformation of the secondary palate, as predicted by the Pierre‐Robin sequence. Teratology 65:116–120, 2002. © 2002 Wiley‐Liss, Inc.
360‐Degree Canalith Repositioning Procedure for the Horizontal Canal
Authors: Tirelli Giancarlo , Russolo M.
Published: October 2004

OBJECTIVES

To evaluate the efficacy of modifications to the standard canalith repositioning procedure (CRP) in the treatment of benign positional vertigo (BPV) of the horizontal semicircular canal (HSC).

STUDY DESIGN AND SETTING

Prospective trial of 72 patients with BPV of the HSC treated with a modified 360‐degree CRP.

RESULTS

51 of the 62 patients treated for canalolithiasis made a complete recovery (82.2%) after a single 360‐degree CRP.

CONCLUSIONS AND SIGNIFICANCE

It is proposed a full 360‐degree rotation of the HSC involved. It is essential to begin rotation of the patient departing from the affected side towards the healthy side, especially for canal side cupulolithiasis and for canalithiasis of the ampullar branch of the HSC. The head resting on the chest at angle of 30‐degree during rotating encourages free‐floating debris in the HSC to move into the utricle. Instead of using an oscillator for oscillation of the mastoid bone the head is shaken manually.
Correlation of Histopathological Variants, Cellular DNA Content, and Clinical Outcome in Adenoid Cystic Carcinoma of the Salivary Glands
Authors: Enamorado Ileana , Lakhani Raam , Korkmaz Hakan , Yoo George H. , Del Mar Alonso Maria , Pietraszkiewicz Haline , Maciorowski Zosia , Kim Harold , Kucuk Omer , Jacobs John R. , Ensley John F.
Published: October 2004

OBJECTIVE

To study the correlation between flow cytometrically measured DNA ploidy with prognostically important histopathologic groups and clinical outcome in patients with adenoid cystic carcinoma of the salivary glands.

STUDY DESIGN

46 tumor specimens were analyzed flow cytometrically for DNA content and assessed for histological grade. Correlations were made between tumor DNA ploidy and histopathological grade, and disease‐free and overall survival of these patients.

RESULTS

Of the 46 patients, 31 had a cribiform/tubular histologic pattern, and 15 had a solid pattern. 84% of the tumors with cribriform/tubular pattern were DNA diploid, compared with 33% of tumors that were graded solid. This difference proved to be statistically significant (χ211.75, P = 0.0006). Overall and disease‐free survival periods were longer for patients with DNA diploid tumors in both groups, 63% vs. 36% and 62% vs 38%, respectively.

CONCLUSIONS

Tumor DNA ploidy correlates with prognostically important tumor histopathology as well as overall and disease‐free survival in patients with adenoid cystic carcinoma of the salivary gland. EBM rating: B‐3.
Molecular Diagnosis of Nasopharyngeal Carcinoma: Detecting LMP‐1 and EBNA by Nasopharyngeal Swab
Authors: Hao Sheng‐Po , Tsang Ngan‐Ming , Chang Kai‐Ping , Ueng Shir‐Hwa
Published: October 2004

OBJECTIVES

The aim of this study was to investigate the feasibility of molecular diagnosis of nasopharyngeal carcinoma (NPC) by combining nasopharyngeal swab and polymerase chain reaction (PCR) to detect Epstein‐Barr virus (EBV) derived latent membrane protein‐1 gene (LMP‐1) and Epstein‐Barr nuclear antigen gene (EBNA).

METHODS

437 adults underwent nasopharyngoscopy, possible biopsy, and nasopharyngeal swab to obtain nasopharyngeal cells for the detection of LMP‐1 and EBNA by PCR.

RESULTS

By detecting LMP‐1 and EBNA in the nasopharyngeal swabs, NPC could be diagnosed with a false‐positive rate of 1.7% (6/354), a false‐negative rate of 8.6% (6/70), a sensitivity of 91.4% (64/70), a specificity of 98.3% (348/354), positive predictive value of 91.4% (64/70), and negative predictive value of 98.3% (348/354).

CONCLUSION

Detecting EBV genomic LMP‐1 and EBNA by nasopharyngeal swab verifies NPC with a sensitivity of 91.4% and specificity of 98.3%. The nasopharyngeal swab coupled with PCR based EBV LMP‐1 and EBNA detection could serve as a good supplement to pathological diagnosis of NPC.
Safety and Efficacy of Radioallergosorbent Test‐Based Allergen Imunotherapy in Treatment of Perennial Allergic Rhinitis and Asthma
Authors: Yeoh Kian Hian , Wang De Yun , Gordon Bruce R.
Published: October 2004

OBJECTIVE

This study was undertaken to demonstrate the safety and efficacy of in vitro, radioallergosorbent test (RAST)‐based inhalant allergen immunotherapy.

STUDY DESIGN AND SETTING

Prospective 22 year single site clinical study, with outcome evaluations of 480 perennial allergic rhinitis patients, including 96 with concomitant asthma.

RESULTS

Rhinitis symptom control after 2 years of immunotherapy was excellent in 32.5% of patients, good in 45.6%, and fair in 14.2%. There was no improvement in 7.7%. For patients with asthma, 81% had good or excellent pulmonary symptom improvement, and no patient failed to improve. No severe reactions occurred, but there were 5 limited systemic reactions, or 0.008% of injections, during a 2.5‐year mean immunotherapy treatment course.

CONCLUSION

RAST‐based immunotherapy is safe and effective for patients with perennial allergic rhinitis, with or without concomitant asthma.

SIGNIFICANCE

This is the first large, multiyear study of safety and efficacy of RAST‐based immunotherapy for treatment of perennial allergic rhinitis and asthma. EBM rating: C.
Contact Diode Laser Tonsillectomy in Children
Authors: D'eredità Riccardo , Marsh Roger R.
Published: October 2004

OBJECTIVE

To compare contact diode laser (CDL) tonsillectomy to monopolar cautery (MPC) with regard to pain and other morbidity during recovery.

STUDY DESIGN AND SETTING

Single‐blind, randomized trial in a tertiary‐care pediatric hospital. Tonsillectomy was performed by CDL in 30 children and by MPC in 28. Parents completed a daily questionnaire for 10 days after surgery.

RESULTS

There was significantly less pain in the CDL group than in the MPC group. The CDL group also required much less medication, and was much less likely to experience multiple awakenings (P < 0.001 for all comparisons).

CONCLUSION

Recovery after CDL tonsillectomy was associated with much less pain and discomfort than after MPC surgery.

SIGNIFICANCE

Postoperative pain is a major concern for surgeons, patients, and their parents. The long recovery period also has costs in school days missed for the child and work missed for the parents. CDL tonsillectomy may greatly mitigate these burdens.
Protein Nitration in Chronic Sinusitis and Nasal Polyposis: Role of Eosinophils
Authors: Bernardes Julio Freire , Shan Jichuan , Tewfik Marc , Hamid Qutayba , Frenkiel Saul , Eidelman David H.
Published: October 2004

OBJECTIVES

To investigate the possible role of eosinophil peroxidase (EPO) in 3‐nitrotyrosine (3NT) formation.

STUDY DESIGN AND SETTING

Observational study employing immunocytochemistry to assess the presence of 3NT, inducible nitric oxide synthase (iNOS), eosinophils, mast cells, neutrophils, and lymphocytes in ethmoid sinus mucosal biopsies from normal controls and subjects with allergic and nonallergic chronic sinusitis and nasal polyposis.

RESULTS

3NT was more evident in biopsies from sinusitis patients (2.67 ± 0.14, n = 21) than in healthy mucosa (0.43 ± 0.2, n = 7, P < 0.01), but scores in atopic and nonatopic subjects were similar. Colocalization studies confirmed that 3NT was largely confined to eosinophils. No relationship was found between 3NT and other immune cells. 3NT detection was not correlated with the amount of immunostaining for iNOS.

SIGNIFICANCE

Chronic sinusitis is accompanied by 3NT formation, which is largely restricted to the eosinophils, and likely driven by the action of eosinophil peroxidase, rather than by nitric oxide levels. EBM rating: B‐2.
Effects of Buffered Saline Solution on Nasal Mucociliary Clearance and Nasal Airway Patency
Authors: Keojampa Bounmany K. , Nguyen Mai Hoang , Ryan Matthew W.
Published: October 2004

OBJECTIVE

To compare the effects of buffered hypertonic and buffered normal saline nasal spray on mucociliary clearance and nasal airway patency. STUDY DESIGN AND SETTING: Double‐blind trial with subjects acting as their own controls. Tertiary care academic medical center.

RESULTS

Buffered hypertonic saline and buffered normal saline both improved saccharine clearance times (P < 0.0001 for buffered hypertonic and P = 0.002 for buffered normal saline). Buffered hypertonic saline improved saccharine clearance times more than buffered normal saline (39.6% vs 24.1%, P = 0.007). Neither buffered hypertonic nor buffered normal saline significantly affected nasal airway patency.

CONCLUSIONS

Both buffered hypertonic and buffered normal saline nasal spray significantly improved saccharine clearance times without affecting nasal airway patency. Buffered hypertonic saline affected saccharine clearance times to a greater degree than buffered normal saline.

CLINICAL SIGNIFICANCE

Buffered hypertonic and buffered normal saline sprays both improve mucociliary clearance and should therefore be beneficial in conditions such as rhinitis and sinusitis, which are associated with disruption of mucociliary clearance. However, these sprays do not appear to affect the nasal airway. Patients may therefore benefit from other treatments for “nasal congestion.” EBM rating: B‐2.
Selective Acquisition of Individual Cell Types in the Vestibular Periphery for Molecular Biology Studies
Authors: Cristobal Ricardo , Wackymy P. Ashley , Cioffi Joseph A. , Erbe Christy B. , Popper Paul
Published: October 2004

OBJECTIVES

To develop a method for characterizing the transcriptome of individual cell types in the inner ear sensory epithelia.

STUDY DESIGN

We employed the technique of laser capture microdissection to obtain enriched populations of hair cells and supporting cells. The respective mRNAs were extracted, reverse transcribed, and amplified using PCR.

RESULTS

We were able to isolate RNAs with good integrity from enriched cell populations obtained with laser capture microscopy and amplify specific mRNA targets.

CONCLUSIONS

We can now investigate the molecular differences between the different cell types in the inner ear sensory epithelia as identified by morphological criteria.

SIGNIFICANCE

Analysis of gene expression profiles in the inner ear cell types has been hampered by the small size of this tissue and by the compact histoarchitecture of the sensory epithelia; however, the present technique offers new possibilities for the analysis of transcriptomes in the vestibular periphery using available high‐throughput gene expression analysis methods.
Motivation in Real-Life, Dynamic, and Interactive Learning Environments: Stretching Constructs and Methodologies
Authors: Järvelä Sanna , Volet Simone
Published: October 2004

Recent research on motivation has taken a leading role in the study of learning and instruction. Theory-based studies carried out in real-life, dynamic, and interactive learning environments have attempted to bridge the gap between basic and applied psychological and educational research. Constructs and methodologies have been stretched to include new, innovative features, with motivation commonly conceptualized as a dual psychological and social phenomenon and researched using multiple methodological approaches in combination. This paper discusses the major challenges faced by researchers who are grappling with those issues.
The Bay of Naples (southern Italy): Constraints on the volcanic structures inferred from a dense seismic survey
Authors: Judenherc S. , Zollo A.
Published: October 2004

The bays of Naples and Pozzuoli host volcanic areas that have been active within recent history. In addition, the vicinities areas around the Vesuvius volcano and the Campi Flegrei caldera are extremely densely inhabited. Over the past decade, this situation has prompted several active seismic experiments focused on the Vesuvius volcano. More recently, the Serapis active seismic survey covered the entire Bay of Naples, with particular attention to Pozzuoli Bay. The processed Serapis P wave travel time collection, extended with a previously acquired data set, has allowed the computation of the most comprehensive three‐dimensional P wave velocity distribution for the Bay of Naples, which includes a small‐scale high‐resolution model of the Campi Flegrei caldera. The joint interpretation of the velocity distribution together with both the available gravity measurements and models and the geothermal drilling information has allowed us to locate and map lithological units at depths. We propose a model of the Campi Flegrei caldera in relation to the underlying Mesozoic limestone unit. In this model, no magma chamber exists in the upper 6 km beneath the Bay of Naples. The feeding system of the Campi Flegrei caldera is directly controlled by the tectonic structures affecting the limestone unit beneath the Bay of Naples. Two NE‐SW normal faults run beneath the Vesuvius volcano and Campi Flegrei, which are related to the pre‐Pleistocene Apenninic tectonics.
Boreal forest fires burn less intensely in Russia than in North America
Authors: Wooster M. J. , Zhang Y. H.
Published: October 2004

Around 5–20 million hectares of boreal forest burns annually, mainly in Russia and North America. However, there are reports of significant differences in predominant fire type between these regions, which may have major implications for overall emissions of carbon, gases and aerosols. We examine boreal forest fire intensities via MODIS observations of fire radiative energy release rate. Results support the contention of a consistent difference in fire intensity and mean fuel consumption in Russia and North America, due to differences in dominant fire type. North American fires have higher mean intensities, increasing in proportion to percentage tree cover, characteristics indicating likely crown fire dominance. Russian fires have lower mean intensities, independent of percentage tree cover, characteristics more indicative of surface fire activity. Per unit area burnt, the results suggest Russian fires may burn less fuel and emit fewer products to the atmosphere than do those in North America.
Regeneration of sweet potato transgenic plants withoryzacystatin-I(OCI) gene
Authors: Sheng-Jun Jiang , Qing-Chang Liu , Hong Zhai , Li-Sha Wu , Yu-Ping Wang
Published: October 2004

Regeneration of sweet potato (Ipomoea batatascv. Lizixiang) transgenic plants withoryzacystatin-I(OCI) gene was achieved using anAgrobacterium tumefaciens-mediated method.A. tumefaciensstrain LBA4404, harbouring a binary vector pBinh withneomycin phosphotransferase IIandOCIgenes, was used. After 3 days of subculture, Lizixiang embryogenic suspension cultures were co-cultivated with LBA4404 (OD600nm=0.5) for 4 days. Next, the infected suspension cultures were first cultured for 5 days in MS medium with 2 mg/l 2,4-dichlorophenoxyacetic acid (2,4-D) and 300 mg/l carbencillin (Carb) but without kanamycin (Kan) and then transferred to MS medium supplemented with 2 mg/l 2,4-D, 50 mg/l Kan and 300 mg/l Carb for the selection culture. Four weeks after selection, 200 Kan-resistant cell aggregates (∼1 mm in size) from the embryogenic suspension cultures were transferred to MS solid medium supplemented with 2 mg/l 2,4-D, 50 mg/l Kan and 300 mg/l Carb, and eight embryogenic calluses were obtained. After transferring to MS medium supplemented with 1 mg/l ABA, 50 mg/l Kan and 100 mg/l Carb, these embryogenic calluses formed 13 plantlets via somatic embryogenesis. PCR and PCR–Southern blot analysis indicated that seven of the 13 plantlets were transgenic.
Heterogeneity in the response of pigs and mice to specific CpG oligodeoxynucleotides
Authors: Guang-Fu Li , Hong-Fei Zhu , Guo-Qing Shao , Jian-Zhong Zhu , Yan-Qing Ma , Zhao-Song Zhang
Published: October 2004

Differences in immunostimulation activity of CpG oligodeoxynucleotides (ODNs) between pigs and mice were studied. In accordance with current research data, three kinds of CpG ODN – 2006, D19 and 1826, which were identified as optimally active in humans, pigs and mice, respectively – and control ODN D48, a non CpG-containing ODN, were selected and synthesized. Results indicated that CpG ODN D19 strongly stimulated the proliferation of porcine peripheral blood mononuclear cells (PBMCs), and the amount of γ-interferon in the supernatant of activated cells increased, exceeding that of all other ODNs tested, while mouse splenocytes did not respond. CpG ODN 1826 strongly stimulated the proliferation of mouse splenocytes, but porcine PBMCs remained unresponsive. CpG ODN 2006 effectively stimulated proliferation of both porcine PBMCs and mouse splenocytes. Therefore some specific CpG ODNs, D19 and 1826, selectively stimulated animal species, while CpG ODN 2006 possessed a common stimulation effect. In addition, CpG ODN D19 predominantly induced the response of type 1 T-helper cellsin vivo.
Identification of spatial specifically expressed genes in rice (Oryza sativa) seedlings using cDNA microarray
Authors: Liang-Xian Sun , Hai-Tao Dong , Xiao-Feng Zhuang , Feng Zhang , De-Bao Li
Published: October 2004

Membranous cDNA microarrays containing 2200 unique rice transcripts were designed for screening the characteristics of spatially expressed genes in post-germination rice seedlings. By comparing the profiles obtained, 31 genes were identified as expressed specifically in the plumule, 36 in the mesocotyl and 73 in the radicle. Several genes, such aspolyubiquitin,UDP-glucose pyrophosphorylase,sucrose synthaseandphosphoglycerate kinase, which encode components of the carbohydrate or protein metabolic reaction cascades, were expressed specifically in the mesocotyl, indicating that degradation reactions of the endospermous reserve starch and proteins occur mainly in the mesocotyl during the post-germination stage. A number of genes involved in defence mechanisms or in the processes of replication, transcription and translation were identified as expressed specifically in the plumule or radicle. Among plumule specifically expressed genes,translation initiation factor 5a,40s ribosomal protein s28andribosomal protein 136are considered to have a critical role in protein biosynthesis; whileallergenic protein, β-D-glucan exohydrolaseandactin 11are genes with defending functions. Among the catalogue of radicle specifically expressed genes,EF-1a,Tat binding protein,replication protein A2,histone h3.2,ribosomal protein s29aand40s ribosomal protein s19are genes that function in the process of replication, transcription or translation; whereasglycine-rich protein,wound-induced basic protein,Bowman-Birk proteinase inhibitorandlipid transfer protein-2are genes involved in defence responses. Results of this experiment have provided insight into post-germination molecular physiology at the genomic level of gene expression.
History of the American College of Toxicology (ACT)
Authors: Christian Mildred S.
Published: October 2004

This manuscript is one of two written to celebrate the 25th Anniversary of the American College of Toxicology (ACT). This history of ACT describes its evolution from an entrepreneurial, risk taking model to a conservative business model, fully accepted in the scientific community. ACT started with a small group of scientists who were dissatisfied with the relatively narrow approach to full membership then taken by the Society of Toxicology (SOT). They were excited by new research and collaborative opportunities resulting from an enhanced public awareness of the impact of chemicals on the environment and emerging new methodologies to evaluate human risks of exposure to be chemicals and pharmaceuticals. These toxicologists, many of whom were from industry and government, rather than academia, were tired of being considered socond class citizens and envisioned more open and cross-disciplined approaches. They favored balanced input by academia, industry and government in the overall toxicologic evaluation and risk assessment process. The history of the founding and early development of ACT, as well as the College’s growth and eventual acceptance into the scientific community, including its impact on the status quo during the Society’s first 25 years, are told by its successive presidents.
Responses to Low Doses of Ionizing Radiation in Biological Systems
Authors: Feinendegen Ludwig E. , Pollycove Myron , Sondhaus Charles A.
Published: October 2004

Biological tissues operate through cells that act together within signaling networks. These assure coordinated cell function in the face of constant exposure to an array of potentially toxic agents, externally from the environment and endogenously from metabolism. Living tissues are indeed complex adaptive systems.

To examine tissue effects specific for low-dose radiation, (1) absorbed dose in tissue is replaced by the sum of the energies deposited by each track event, or hit, in a cell-equivalent tissue micromass (1 ng) in all micromasses exposed, that is, by the mean energy delivered by all microdose hits in the exposed micromasses, with cell dose expressing the total energy per micromass from multiple microdoses; and (2) tissue effects are related to cell damage and protective cellular responses per average microdose hit from a given radiation quality for all such hits in the exposed micromasses.

The probability of immediate DNA damage per low-linear-energy-transfer (LET) average microdose hit is extremely small, increasing over a certain dose range in proportion to the number of hits. Delayed temporary adaptive protection (AP) involves (a) induced detoxification of reactive oxygen species, (b) enhanced rate of DNA repair, (c) induced removal of damaged cells by apoptosis followed by normal cell replacement and by cell differentiation, and (d) stimulated immune response, all with corresponding changes in gene expression. These AP categories may last from less than a day to weeks and be tested by cell responses against renewed irradiation. They operate physiologically against nonradiogenic, largely endogenous DNA damage, which occurs abundantly and continually. Background radiation damage caused by rare microdose hits per micromass is many orders of magnitude less frequent. Except for apoptosis, AP increasingly fails above about 200 mGy of low-LET radiation, corresponding to about 200 microdose hits per exposed micromass. This ratio appears to exceed approximately 1 per day for protracted exposure. The balance between damage and protection favors protection at low cell doses and damage at high cell doses. Bystander effects from high-dosed cells to nonirradiated neighboring cells appear to include both damage and protection.

Regarding oncogenesis, a model based on the aforementioned dual response pattern at low doses and dose rates is consistant with the nonlinear reponse data and contradicts the linear no-threshold dose-risk hypothesis for radiation-induced cancer. Indeed, a dose-cancer risk function should include both linear and nonlinear terms.
The Bystander Effect: Recent Developments and Implications for Understanding the Dose Response
Authors: Mitchel R. E. J.
Published: October 2004

The bystander effect refers to the biological response of a cell resulting from an event in an adjacent or nearby cell. Such effects depend on intercellular communication and amplify the consequences of the original event. These responses are of particular interest in the assessment of ionizing radiation risk because at public or occupational exposure levels not every cell receives a radiation track. Current radiation protection regulations and practices are based on the assumption of a linear increase in risk with dose, including low doses where not all cells are hit. Mechanisms that amplify biological effects are inconsistent with these assumptions. Evidence suggests that there are two different bystander effects in mammalian cells. In one type, a radiation track in one cell leads to damaging, mutagenic, and sometimes lethal events in adjacent, unhit cells. In the other type, a radiation track in one cell leads to an adaptive response in bystander cells, increasing resistance to spontaneous or radiation-induced events. This paper describes some of the data for radiation-induced bystander effects in vitro and correlates that data with in vitro and in vivo observations of risk at low doses. The data suggest that protective effects, including beneficial bystander effects, outweigh detrimental effects at doses below about 100 mGy, but that the reverse is true above this threshold.
The 4q subtelomere harboring the FSHD locus is specifically anchored with peripheral heterochromatin unlike most human telomeres
Authors: Tam Rose , Smith Kelly P. , Lawrence Jeanne B.
Published: October 2004

This paper investigates the nuclear localization of human telomeres and, specifically, the 4q35 subtelomere mutated in facioscapulohumeral dystrophy (FSHD). FSHD is a common muscular dystrophy that has been linked to contraction of D4Z4 tandem repeats, widely postulated to affect distant gene expression. Most human telomeres, such as 17q and 17p, avoid the nuclear periphery to reside within the internal, euchromatic compartment. In contrast, 4q35 localizes at the peripheral heterochromatin with 4p more internal, generating a reproducible chromosome orientation that we relate to gene expression profiles. Studies of hybrid and translocation cell lines indicate this localization is inherent to the distal tip of 4q. Investigation of heterozygous FSHD myoblasts demonstrated no significant displacement of the mutant allele from the nuclear periphery. However, consistent association of the pathogenic D4Z4 locus with the heterochromatic compartment supports a potential role in regulating the heterochromatic state and makes a telomere positioning effect more likely. Furthermore, D4Z4 repeats on other chromosomes also frequently organize with the heterochromatic compartment at the nuclear or nucleolar periphery, demonstrating a commonality among chromosomes harboring this subtelomere repeat family.
Developmental regulation of calcium-dependent feedback inXenopusrods
Authors: Solessio Eduardo , Mani Shobana S. , Cuenca Nicolas , Engbretson Gustav A. , Barlow Robert B. , Knox Barry E.
Published: October 2004

The kinetics of activation and inactivation in the phototransduction pathway of developing Xenopus rods were studied. The gain of the activation steps in transduction (amplification) increased and photoresponses became more rapid as the rods matured from the larval to the adult stage. The time to peak was significantly shorter in adults (1.3 s) than tadpoles (2 s). Moreover, adult rods recovered twice as fast from saturating flashes than did larval rods without changes of the dominant time constant (2.5 s). Guanylate cyclase (GC) activity, determined using IBMX steps, increased in adult rods from ∼1.1 s−1 to 3.7 s−1 5 s after a saturating flash delivering 6,000 photoisomerizations. In larval rods, it increased from 1.8 s−1 to 4.0 s−1 9 s after an equivalent flash. However, the ratio of amplification to the measured dark phosphodiesterase activity was constant. Guanylate cyclase–activating protein (GCAP1) levels and normalized Na+/Ca2+, K+ exchanger currents were increased in adults compared with tadpoles. Together, these results are consistent with the acceleration of the recovery phase in adult rods via developmental regulation of calcium homeostasis. Despite these large changes, the single photon response amplitude was ∼0.6 pA throughout development. Reduction of calcium feedback with BAPTA increased adult single photon response amplitudes threefold and reduced its cutoff frequency to that observed with tadpole rods. Linear mathematical modeling suggests that calcium-dependent feedback can account for the observed differences in the power spectra of larval and adult rods. We conclude that larval Xenopus maximize sensitivity at the expense of slower response kinetics while adults maximize response kinetics at the expense of sensitivity.
Modelling the advection and diffusion of eggs and larvae of Greenland halibut (Reinhardtius hippoglossoides) in the north‐east Arctic
Authors: Ådlandsvik Bjørn , Gundersen Agnes C. , Nedreaas Kjell H. , Stene Anne , Albert Ole T.
Published: October 2004

Since the late 1980s there has been considerable uncertainty in recruitment levels of the north‐east Arctic stock of Greenland halibut (Reinhardtius hippoglossoides). The abundance of several year classes, originally considered very low at 0–3 yr age, appeared higher than expected at the age of 6+. This may be due to poor targeting of recruitment surveys of the younger year classes. The present work considers the transport and dispersion of eggs and larvae of Greenland halibut by numerical modelling in order to predict the locations of the initial recruitment grounds. Current fields from a 3D baroclinic hydrodynamic model are fed into a Lagrangian particle‐tracking model developed for the Barents Sea area. The particles are released into the current at the spawning field along the shelf slope from Lofoten to Bear Island (69–75°N). Vertically, the particles can follow a predefined depth‐by‐age curve or be kept at a fixed depth. This model system is used for different years to examine changes in the drift pattern. The results indicate that spawning location, transport depth and inflowing activity to the Barents Sea are important factors influencing the distribution of juveniles.
Methylprednisolone intravenously 1 day after surgery has sustained analgesic and opioid‐sparing effects
Authors: Romundstad L. , Breivik H. , Niemi G. , Helle A. , Stubhaug A.
Published: October 2004

Background:  In previous studies on glucocorticoids for postoperative pain, the test drug has been given perioperatively, usually before measurement of baseline pain. In order to evaluate the time course and magnitude of the analgesic effect of a glucocorticoid in well‐established postoperative pain, we compared methylprednisolone with ketorolac and placebo, after assessment of baseline pain on the first postoperative day.

Methods:  This was a double‐blind, single dose, randomized, parallel comparison of intravenous (i.v.) methylprednisolone 125 mg, ketorolac 30 mg as an active control, and placebo in 75 patients with moderate to severe pain 1 day after orthopaedic surgery. Outcome variables were pain intensity (0–100 VAS), pain relief (0–4 PAR) and rescue opioid consumption.

Results:  Methylprednisolone was not significantly different from ketorolac and gave significantly lower pain intensity from 1 h (0–6 h, P < 0.02), and more pain relief 2–6 h after test drugs (P < 0.05) compared with placebo. After 24 h, pain intensity was lower in both active drug groups compared with placebo (methylprednisolone, P < 0.0001; ketorolac, P < 0.007). Number needed to treat (NNT) calculated from patients having more than at least 50% of maximum obtainable total pain relief during the first 6 h (>50%maxTOTPAR6 h ) was 3.6 for methylprednisolone and 3.1 for ketorolac. Number needed to treat calculated from the percentage reporting at least 50% pain relief for at least 4 h (>50%PAR4 h) was 2.8 for both groups. Opioid consumption was significantly reduced for 72 h after methylprednisolone compared with ketorolac (P < 0.02) and placebo (P < 0.003).

Conclusion:  Methylprednisolone 125 mg i.v. 1 day after surgery gave similar early reduction of pain as i.v. ketorolac 30 mg. Less pain than placebo 24 h after methylprednisolone, and lower opioid consumption for 72 h compared with ketorolac and placebo indicate sustained analgesic effects of methylprednisolone.
Treatment of a transdiaphragmatic fistula with an endobronchial‐blocking catheter
Authors: Glümer Jensen M. , Knudsen L. , Schønemann N. K.
Published: October 2004

We report a case of a bronchosubphrenic fistula in a 59‐year‐old female following hemicolectomy complicated by fecal peritonitis. The patient needed intubation and positive‐pressure ventilation, which caused a massive air leak. The fistula was treated using an endobronchial blocking catheter in combination with antibiotic treatment and drainage.
The impact of global climate change on tropical forest biodiversity in Amazonia
Authors: Miles Lera , Grainger Alan , Phillips Oliver
Published: October 2004

Aim  To model long‐term trends in plant species distributions in response to predicted changes in global climate.

Location  Amazonia.

Methods  The impacts of expected global climate change on the potential and realized distributions of a representative sample of 69 individual Angiosperm species in Amazonia were simulated from 1990 to 2095. The climate trend followed the HADCM2GSa1 scenario, which assumes an annual 1% increase of atmospheric CO2 content with effects mitigated by sulphate forcing. Potential distributions of species in one‐degree grid cells were modelled using a suitability index and rectilinear envelope based on bioclimate variables. Realized distributions were additionally limited by spatial contiguity with, and proximity to, known record sites. A size‐structured population model was simulated for each cell in the realized distributions to allow for lags in response to climate change, but dispersal was not included.

Results  In the resulting simulations, 43% of all species became non‐viable by 2095 because their potential distributions had changed drastically, but there was little change in the realized distributions of most species, owing to delays in population responses. Widely distributed species with high tolerance to environmental variation exhibited the least response to climate change, and species with narrow ranges and short generation times the greatest. Climate changed most in north‐east Amazonia while the best remaining conditions for lowland moist forest species were in western Amazonia.

Main conclusions  To maintain the greatest resilience of Amazonian biodiversity to climate change as modelled by HADCM2GSa1, highest priority should be given to strengthening and extending protected areas in western Amazonia that encompass lowland and montane forests.
Patterns of diversity, altitudinal range and body size among freshwater fishes in the Yangtze River basin, China
Authors: Fu Cuizhang , Wu Jihua , Wang Xinyi , Lei Guangchun , Chen Jiakuan
Published: October 2004

Aim To document patterns in diversity, altitudinal range and body size of freshwater fishes along an elevational gradient in the Yangtze River basin.

Location The Yangtze River basin, China.

Methods We used published data to compile the distribution, altitudinal range and body size of freshwater fishes. Correlation, regression, clustering and graphical analyses were used to explore patterns in diversity, altitudinal range and body size of freshwater fishes in 100‐m elevation zones from 0 to 5200 m.

Results Species richness patterns across the elevational gradient for total, non‐endemic and endemic fishes were different. The ratio of endemics to total richness peaked at mid elevation. Land area on a 500‐m interval scale explained a significant amount of the variation in species richness. Species density displayed two peaks at mid‐elevation zones. The cluster analysis revealed five distinct assemblages across the elevation gradient. The relationship between elevational range size and the midpoint of the elevational range revealed a triangular distribution. The frequency distribution of log maximum standard length data displayed an atypical right‐skewed pattern. Intermediate body sizes occurred across the greatest range of elevation while small and large body sizes possessed only small elevational amplitudes. The size‐elevation relationship between the two major families revealed a very strong pattern of body size constraint among the Cobitidae with no corresponding elevational constraint and a lot of body size and elevational diversification among the Cyprinidae.

Main conclusion The data failed to support either Rapoport's rule or Bergmann's rule.
A mélange of curves – further dialogue about species–area relationships
Authors: Scheiner Samuel M.
Published: October 2004

Scheiner (2003) presented a classification of species–area curves into six types based on the pattern of sampling and how the data are combined to form the curves. Gray et al. (2004) contended that five of those types should be termed ‘species‐accumulation curves’, reserving ‘species–area curve’ for those based on island‐type data. Their proposition contradicts 70 years of usage and confounds curves that are area‐explicit with those that are area‐undefined. In exploring these issues, I highlight additional aspects of species–area and species‐accumulation curves, including the assumption of nesting in Type IV (island) curves, how to convert area‐unspecified curves into area curves, and the effects of the grain of the analysis on the properties of the curve. Further exploration, theoretical development, and dialogue are needed before we will understand all the biology that species–area curves summarize.
Extinction and endemism in the New Zealand avifauna
Authors: Duncan Richard P. , Blackburn Tim M.
Published: October 2004

Aim Species belonging to higher taxa endemic to islands are more likely to go extinct following human arrival. This selectivity may occur because more highly endemic island species possess features that make them uniquely vulnerable to impacts associated with human arrival, specifically: (1) restricted distribution (2) reduced predator escape response, including loss of flight, and (3) life history traits, such as large body mass, associated with greater susceptibility to hunting or habitat loss. This study aims to identify which of these features can explain the selective extinction of more highly endemic bird species in New Zealand.

Location North and South Island, New Zealand.

Methods Bird species breeding in New Zealand prior to human arrival were classified according to whether they became extinct or not during two periods of human settlement, prehistoric (post‐Maori but pre‐European arrival) and historic (post‐European arrival). We modelled the relationships between extinction probability, level of endemism and life history traits in both periods.

Results The prehistoric extinction–endemism relationship can be explained entirely by the selective extinction of large‐bodied species, whereas the historic extinction–endemism relationship appears due to increased susceptibility to introduced predators resulting from the loss of predator escape responses, including loss of flight.

Conclusions These features may explain extinction–endemism relationships more generally, given that human hunting and predator introductions are major impacts associated with human arrival on islands.
In Vitro Testing of Antimicrobial Activity of Bone Cement
Authors: Alt Volker , Bechert Thorsten , Steinrücke Peter , Wagener Michael , Seidel Peter , Dingeldein Elvira , Domann Eugen , Schnettler Reinhard
Published: October 2004

The purpose of this study was to establish a reliable and cost-effective microplate proliferation assay for in vitro antimicrobial testing of bone cement samples. Cement samples devoid of antimicrobial agents, loaded with 2% gentamicin or with different concentrations of high-porosity silver, were incubated in a 96-well microplate with several staphylococcal,Pseudomonas aeruginosa, andEnterococcus faeciumisolates exhibiting different susceptibilities to gentamicin. After being rinsed, the samples were brought into a soy medium in which adherent cells on the cement surface either were killed by the antimicrobial surface or started to release clonal counterparts. The medium was monitored in real time by recording a time proliferation curve for each well. Microplate testing revealed no antibacterial effect of plain bone cement. The antibacterial activity of gentamicin-loaded bone cement was shown by the microplate test to depend on the gentamicin susceptibilities of the strains. The effect of high-porosity silver was dose dependent. Bactericidal activity against all tested strains was found for bone cement loaded with 1% high-porosity silver. The accuracy of this new proliferation assay was shown by the high correlation between the types of proliferation curves and antibiotic susceptibility. In contrast to routine agar diffusion testing, it assesses the dynamic response of microorganisms to antimicrobial agents in biomaterials and allows high-throughput screening and detection of antimicrobial properties of poorly water-soluble compounds like silver.
Antipneumococcal Activities of Two Novel Macrolides, GW 773546 and GW 708408, Compared with Those of Erythromycin, Azithromycin, Clarithromycin, Clindamycin, and Telithromycin
Authors: Matic Vlatka , Kosowska Klaudia , Bozdogan Bulent , Kelly Linda M. , Smith Kathy , Ednie Lois M. , Lin Gengrong , Credito Kim L. , Clark Catherine L. , McGhee Pamela , Pankuch Glenn A. , Jacobs Michael R. , Appelbaum Peter C.
Published: October 2004

The MICs of GW 773546, GW 708408, and telithromycin for 164 macrolide-susceptible and 161 macrolide-resistant pneumococci were low. The MICs of GW 773546, GW 708408, and telithromycin for macrolide-resistant strains were similar, irrespective of the resistance genotypes of the strains. Clindamycin was active against all macrolide-resistant strains except those with
erm
(B) and one strain with a 23S rRNA mutation. GW 773546, GW 708408, and telithromycin at two times their MICs were bactericidal after 24 h for 7 to 8 of 12 strains. Serial passages of 12 strains in the presence of sub-MICs yielded 54 mutants, 29 of which had changes in the L4 or L22 protein or the 23S rRNA sequence. Among the macrolide-susceptible strains, resistant mutants developed most rapidly after passage in the presence of clindamycin, GW 773546, erythromycin, azithromycin, and clarithromycin and slowest after passage in the presence of GW 708408 and telithromycin. Selection of strains for which MICs were ≥0.5 μg/ml from susceptible parents occurred only with erythromycin, azithromycin, clarithromycin, and clindamycin; 36 resistant clones from susceptible parent strains had changes in the sequences of the L4 or L22 protein or 23S rRNA. No
mef
(E) strains yielded resistant clones after passage in the presence of erythromycin and azithromycin. Selection with GW 773546, GW 708408, telithromycin, and clindamycin in two
mef
(E) strains did not raise the erythromycin, azithromycin, and clarithromycin MICs more than twofold. There were no change in the ribosomal protein (L4 or L22) or 23S rRNA sequences for 15 of 18 mutants selected for macrolide resistance; 3 mutants had changes in the L22-protein sequence. GW 773546, GW 708408, and telithromycin selected clones for which MICs were 0.03 to >2.0 μg/ml. Single-step studies showed mutation frequencies <5.0 × 10
−10
to 3.5 × 10
−7
for GW 773546, GW 708408, and telithromycin for macrolide-susceptible strains and 1.1 × 10
−7
to >4.3 × 10
−3
for resistant strains. The postantibiotic effects of GW 773546, GW 708408, and telithromycin were 2.4 to 9.8 h.