bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of psychiatric comorbidity in alcohol‐dependent subjects in a representative population survey on treatment utilization and natural recovery
Authors: Bischof G. , Rumpf H.‐J. , Meyer C. , Hapke U. , John U.
Published: February 2005

Background  It is well known that only a minority of alcohol‐dependent subjects seek help and that the majority of alcohol‐dependent individuals recover without utilization of formal help. Psychiatric comorbidity is highly prevalent among alcohol‐dependent individuals. However, no data are available on the impact of psychiatric comorbidity on natural recovery.

Aims  To analyse the impact of non‐psychotic psychiatric comorbid Axis I disorders on remission rate and utilization of formal help in alcohol‐dependent individuals drawn from a representative general population sample in northern Germany (response rate: 70.2%, n = 4075). Psychiatric diagnoses and utilization of help were assessed in a personal interview using standardized instruments. One hundred and fifty‐three life‐time alcohol‐dependent individuals were assessed, among whom 98 fulfilled the criteria for sustained long‐term remission according to the Diagnostic and Statistical Manual version II (DSM‐IV) criteria. Any coincidence of DSM‐IV non‐psychotic Axis I disorders with alcohol dependence was counted as comorbidity. Comorbidity rate in the whole sample was 36.1%.

Results  The rate of individuals who remitted from alcohol dependence without formal help was 36.9% in the non‐comorbid and 42.6% in the comorbid group. Utilization of formal help was unrelated to comorbidity. Dually diagnosed subjects without a history of help‐seeking showed minor differences concerning reasons for not seeking help. Seeking help was not related to schooling, severity of dependence and gender.

Conclusion  Data reveal that remission without formal help is equally prevalent among non‐comorbid as among comorbid alcohol‐dependent individuals. Axis I comorbidity is not related directly to utilization of alcohol‐related help. Negative prognoses for untreated comorbid alcohol‐dependent individuals are not justified from an epidemiological point of view.
Postprandial changes in LDL phenotypes in patients with myocardial infarction
Authors: Koba S. , Tsunoda F. , Hirano T. , Iso Y. , Suzuki H. , Geshi E. , Katagiri T.
Published: February 2005

Background  Low‐density lipoprotein (LDL) particle size is strongly affected by both fasting and postprandial triglyceride levels. We report here that the LDL phenotype shifts toward the smaller phenotype during oral fat tolerance tests (OFTTs) in some patients with myocardial infarction (MI); a condition closely associated with postprandial increases of triglyceride and remnant‐like particles (RLPs).

Methods  Oral fat tolerance tests were performed on 63 MI patients with fasting serum triglyceride levels of less than 2·25 mmol L−1 (= 200 mg dL−1). Remnant‐like particles and other serum lipids were compared among patients characterized by three LDL phenotypes based on nondenaturing gradient gel electrophoresis: pattern A (large LDLs, peak LDL particle size ≥ 260 Å), pattern I (intermediate‐sized LDLs, LDL size > 255 Å, < 260 Å), and pattern B (small, dense LDLs, LDL size ≤ 255 Å).

Results  The LDL size decreased significantly in patients with the highest tertile of areas under the incremental curves (AUICs) of triglycerides above the fasting levels. The LDL phenotype shifted toward the smaller phenotype after a fat load in three of eight patients with pattern A and in seven of 35 patients with pattern I. The AUICs of triglyceride‐rich lipoproteins were significantly higher in these patients than in the patients exhibiting little change in LDL size, whereas the fasting metabolic parameters were similar among the patients of the same LDL phenotype in the fasting state.

Conclusion  These results suggest that alimentary lipaemia plays an important role in the remodeling of LDL particles into the more atherogenic small, dense LDLs in patients with MI.
Female Preference Intensities on Different Call Characteristics and Symmetry of Preference Above and Below the Mean in the Iberian Midwife Toad Alytes cisternasii
Authors: Bosch Jaime , Márquez Rafael
Published: February 2005

The intensity of female preference for call characteristics is measured in two‐speaker playback tests with female Iberian midwife toads ‘Alytes cisternasii’ using an experimental design that allows quantitative comparisons across characters. Female preferences do not appear to be symmetrical above and below the population mean, female preference being more efficient at discriminating against low quality competing males that at selecting optimum males among good ones. Female preference is significantly more effective selecting males calling at higher call rates (a highly variable call characteristic probably related to the physical state of the male) rather than selecting calls of low dominant frequency (a characteristic of low intra‐individual variation, related to male size and age).
Tonkean Macaques Orient Their Food Search From Olfactory Cues Conveyed by Conspecifics
Authors: Chauvin C. , Thierry B.
Published: February 2005

We investigated the ability of monkeys to use referential information about environmental resources from cues passively transmitted by conspecifics. The subjects and their companions were four young males belonging to a group of semifree‐ranging Tonkean macaques (Macaca tonkeana) raised in a 2‐acre wooded park. In a first experiment, a subject had to orient its search strategy from the information obtained from a conspecific. It first had to smell the mouth of a companion having just eaten a food item, and then search for same quality food in the field. The results showed that subjects adjusted their foraging speed according to the value of the reward to be found. They were able to recognize the food resource on the basis of the item previously eaten by their companion. In a second experiment, we asked whether the subjects could anticipate a given food quantity from smelling a companion associated with that given food quantity. When testing whether subjects oriented their search strategy on the basis of companion's identity, they did not appear to use it as a referential cue to food quantity. They nonetheless adapted their foraging speed according to food value. Both experiments indicated that macaques are liable to assess and select food from information extracted from conspecifics, and hence avoid some costs associated with individual food searching.
Intestinal pseudo‐obstruction complicating multiple sclerosis
Authors: Lane S. W. , Pender M. P.
Published: February 2005

Three patients with intestinal pseudo‐obstruction secondary to multiple sclerosis are reported. This is a serious complication with significant morbidity and mortality, which is infrequently recognized in clinical practice and rarely reported in the medical literature. (Intern Med J 2005; 35: 191–192)
Selecting the future doctors: the role of graduate medical programmes
Authors: Elliott S. L. , Epstein J.
Published: February 2005

Abstract

Graduate‐entry medical programmes have been introduced in many Australian states. This has coincided with the introduction of learner‐centred, problem‐orientated medical courses and has resulted in a need to develop new selection pathways. Medical schools have complemented their primary selection tool of academic performance with tests of personal attributes considered important in future doctors. Schools with graduate‐entry programmes now employ a combination of the results of the applicant's undergraduate degree, a semistructured interview and a psychometric test (the Graduate Australian Medical School Admissions Test) to select students. Rationale for the change to graduate entry and the outcomes of this change will be discussed. (Intern Med J 2005; 35: 174–177)
Modulation of glycine receptor subunits and gephyrin expression in the rat facial nucleus after axotomy
Authors: Eleore Lyndell , Vassias Isabelle , Vidal Pierre‐Paul , Triller Antoine , De Waele Catherine
Published: February 2005

In the last decade, numerous studies have investigated molecular changes in excitatory glutamatergic receptors in axotomized motoneurons, but few data are available concerning the modulation of inhibitory amino acid receptors. We report here the effect of axotomy on the expression of glycine receptors, gephyrin, vesicular inhibitory amino acid transporter (VIAAT) and synapsin I in rat facial motor neurons as demonstrated by in situ hybridization and immunohistochemistry. The facial nerve trunk was sectioned unilaterally and rats were killed 1, 3, 8, 30 or 60 days after surgery. We investigated the mechanisms underlying the changes in production of these proteins following axotomy by perfusing the facial nerve with colchicine or tetrodotoxin, and injecting cardiotoxin or botulinum toxin independently and unilaterally into the whisker pads of normal rats. Animals were killed 8 days later and processed for immunohistochemistry. The abundance of GlyR subunits and gephyrin fell sharply in the axotomized facial nucleus. This decrease began 1 day after axotomy and was lowest at 8 days, with protein levels returning to normal by day 60. Abnormal synapsin immunolabelling was also observed between days 8 and 60 after axotomy but we detected no change in VIAAT immunoreactivity. The effect of colchicine was similar to, but weaker than, that of axotomy. In contrast, tetrodotoxin, cardiotoxin and botulinum toxin had no significant effect. Thus, axotomy‐induced changes probably resulted from a loss of trophic factor transported from the periphery or a positive injury signal, or both. They did not seem to depend on the disruption of activity.
Increased spinal cord phosphorylation of extracellular signal‐regulated kinases mediates micturition overactivity in rats with chronic bladder inflammation
Authors: Cruz Célia D. , Avelino António , McMahon Stephen B. , Cruz Francisco
Published: February 2005

Spinal processing of somatosensory and viscerosensory information is greatly facilitated in some persistent pain states. Growing evidence suggests that the so‐called central sensitization depends in part on intracellular activation and signalling via specific MAP kinases. Here we studied the expression of phosphorylated extracellular signal‐regulated kinases 1 and 2 (phosphoERK), the active form of these kinases, in spinal neurons following innocuous and noxious distension of non‐inflamed and cyclophosphamide (CYP)‐inflamed rat urinary bladders. Additionally, we investigated the nature of bladder primary afferents responsible for spinal ERK activation. Finally, we used a specific inhibitor of ERK phosphorylation to study the influence of these kinases on the bladder reflex activity of normal and inflamed bladders. Results indicated that, in non‐inflamed rats, noxious but not innocuous bladder distension significantly increased spinal phosphoERK immunoreactivity from its normal very low level. However, in CYP‐inflamed rats, innocuous and noxious bladder distension significantly increased the number of spinal neurons immunoreactive to phosphoERK. ERK activation was rapid (within minutes) and transient. Desensitization of vanilloid‐sensitive afferents by intravesical resiniferatoxin, a capsaicin analogue, did not decrease phosphoERK immunoreactivity in normal or CYP‐inflamed rats. ERK inhibition by intrathecal PD 98059 had no effect on bladder reflex contractions of non‐inflamed bladders but significantly decreased its frequency in inflamed animals. Our results suggest that spinal ERK intervene in acute and chronic inflammatory pain perception and mediate bladder reflex overactivity accompanying chronic bladder inflammation. In addition, bladder noxious input conveyed in vanilloid‐resistant primary afferents is important to spinal ERK phosphorylation in both noninflamed and CYP‐inflamed animals.
Dopamine modulation of spike dynamics in bursting neurons
Authors: Szücs Attila , Abarbanel Henry D. I. , Rabinovich Michail I. , Selverston Allen I.
Published: February 2005

The pyloric network of the lobster stomatogastric ganglion is a prime example of an oscillatory neural circuit. In our previous study on the firing patterns of pyloric neurons we observed characteristic temporal structures termed ‘interspike interval (ISI) signatures’ which were found to depend on the synaptic connectivity of the network. Dopamine, a well‐known modulator of the pyloric network, is known to affect inhibitory synapses so it might also tune the fine temporal structure of intraburst spikes, a phenomenon not previously investigated. In the recent work we study the DA modulation of ISI patterns of two identified pyloric neurons in normal conditions and after blocking their glutamatergic synaptic connections. Dopamine (10–50 µm) strongly regularizes the firing of the lateral pyloric (LP) and pyloric dilator (PD) neurons by increasing the reliability of recurrent spike patterns. The most dramatic effect is observed in the LP, where precisely replicated spike multiplets appear in a normally ‘noisy’ neuron. The DA‐induced regularization of intraburst spike patterns requires functional glutamatergic inputs to the LP neuron and this effect cannot be mimicked by simple intracellular depolarization. Inhibitory synaptic inputs arriving before the bursts are important factors in shaping the intraburst spike dynamics of both the PD and the LP neurons. Our data reveal a novel aspect of chemical neuromodulation in oscillatory neural networks. This effect sets in at concentrations lower than those affecting the overall burst pattern of the network. The sensitivity of intraburst spike dynamics to preceding synaptic inputs also suggests a novel method of temporal coding in neural bursters.
Zinc accumulation after target loss: an early event in retrograde degeneration of thalamic neurons
Authors: Land Peter W. , Aizenman Elias
Published: February 2005

Accumulation of cytoplasmic zinc is linked with a cascade of events leading to neuronal death. In many in vivo models of zinc‐induced cell death, toxic concentrations of synaptically released zinc enter vulnerable neurons via neurotransmitter‐ or voltage‐gated ion channels. In vitro studies demonstrate, in addition, that zinc can be liberated from intracellular stores following oxidative stress and contribute to cell death processes, including apoptosis. Here we describe accumulation of intracellular zinc in an in vivo model of cell death in the absence of presynaptic zinc release. We focused on the lateral geniculate nucleus (LGN) because LGN neurons undergo apoptosis when separated from their target, the primary visual cortex (V1), and the LGN is mostly devoid of zinc‐containing presynaptic terminals. Infant and adult rats and adult mice received unilateral ablation of V1, either by aspiration or kainate injection. One to 14 days later, brain sections were stained with selenium autometallography or fluorescently labeled to localize zinc, or stained immunochemically for activated caspase‐3. V1 lesions led to zinc accumulation in LGN neurons in infant and adult subjects. Zinc‐containing neurons were evident 1–3 days after aspiration lesions, depending on age, but not until 14 days after kainate injection. Zinc accumulation was followed rapidly by immunostaining for activated caspase‐3. Our data indicate that like neurotrauma and excitotoxicity, target deprivation leads to accumulation of zinc in apoptotic neurons. Moreover, zinc accumulation in vivo can occur in the absence of presynaptic zinc release. Together these findings suggest that accumulation of intracellular zinc is a ubiquitous component of the cell death cascade in neurons.
Simple rules for the coexistence and competitive dominance of plants mediated by mycorrhizal fungi
Authors: Umbanhowar James , McCann Kevin
Published: February 2005

Mycorrhizal fungi have been demonstrated to be important in the makeup of plant communities. Likely, their most important role is in altering mineral nutrition of plants, which, in turn, is thought to be among the most important determinants of plant competitive ability. Using mathematical models we examine what role these fungi can play in determining the competitive outcome between two plants in competition for one mineral resource. Depending on different relationships between the benefit accrued to the plant and the fungi, the presence of mycorrhizal fungi can (i) have no impact on which plant wins in competition, (ii) change the order of competitive dominance or (iii) enable coexistence when compared with the system in the absence of mycorrhizal fungi. Furthermore, environmental conditions, such as light and nutrient levels, can determine if coexistence is possible. We describe the necessary biological trade‐offs for coexistence and experimental tests for these trade‐offs.
Ecological speciation
Authors: Rundle Howard D. , Nosil Patrik
Published: February 2005

Ecological processes are central to the formation of new species when barriers to gene flow (reproductive isolation) evolve between populations as a result of ecologically‐based divergent selection. Although laboratory and field studies provide evidence that ‘ecological speciation’ can occur, our understanding of the details of the process is incomplete. Here we review ecological speciation by considering its constituent components: an ecological source of divergent selection, a form of reproductive isolation, and a genetic mechanism linking the two. Sources of divergent selection include differences in environment or niche, certain forms of sexual selection, and the ecological interaction of populations. We explore the evidence for the contribution of each to ecological speciation. Forms of reproductive isolation are diverse and we discuss the likelihood that each may be involved in ecological speciation. Divergent selection on genes affecting ecological traits can be transmitted directly (via pleiotropy) or indirectly (via linkage disequilibrium) to genes causing reproductive isolation and we explore the consequences of both. Along with these components, we also discuss the geography and the genetic basis of ecological speciation. Throughout, we provide examples from nature, critically evaluate their quality, and highlight areas where more work is required.
Resources and global avian assemblage structure in forests
Authors: Pautasso Marco , Gaston Kevin J.
Published: February 2005

Explaining spatial variation in a number of bird species, particularly from temperate to tropical regions, has been a longstanding challenge. We test at a global scale whether species‐rich forest assemblages are associated with division of a larger resource pool, a finer division of that pool, or some combination of the two. Species richness increases with increasing assemblage abundance, biomass and energy use. As assemblage abundance, biomass and energy use increase with increasing energy availability, and as per species numbers of individuals, biomass and energy use do not decrease with increasing energy availability, we provide direct evidence that the avian species–energy relationship in forests is associated foremost with an increase in the size of the resource pool and not with a finer level of its subdivision.
Children, play, and computers in pre‐school education
Authors: Plowman Lydia , Stephen Christine
Published: February 2005

The paper reports a study designed to inform the development of an information and communication technology strategy for the pre‐school years of education. The main methods of collecting evidence were observations at seven pre‐school settings and interviews with at least two practitioners and a number of children at each site. Practitioners generally referred to children “playing with the computer”. We describe some of the problems to be found in the emphasis on free play in nurseries and play groups when this means children are using computers as complete novices. There were few examples of peer support; adults rarely intervened or offered guidance and the most common form of intervention was reactive supervision. Interaction with a computer was therefore a limited experience for most children, but we provide examples of guided interaction that suggest a way forward for professional development.
Biological energy requirements as quantitative boundary conditions for life in the subsurface
Authors: HOEHLER T. M.
Published: February 2005

All life requires energy, which must be extracted from the environment. For all known life, free energy must be available at finite minimum levels in order to be usefully harnessed and must be delivered at finite minimum rates in order to support basic biochemical integrity and function. While seldom tested in the high energy light‐ and oxygen‐based metabolisms of the surface biosphere, the magnitude of these requirements – the biological energy quantum (BEQ) and maintenance energy (ME) requirements, respectively – is considerable with respect to the potential metabolisms and energy sources that characterize the deep subsurface realm. As such, they constitute a fundamental constraint on the possible nature, distribution, and activity of microbial life in that environment. Because the energy released in a chemical transformation can be equated to the concentrations of substrates and products, both the BEQ and ME requirements define the minimum substrate concentration and minimum substrate production rate that must be sustained by a given environment for it to be capable of supporting life. The magnitudes of the BEQ and ME requirements are sensitive to a range of environmental parameters that may vary significantly in the subsurface. Temperature exerts a particularly strong control and is among the most important parameters to be considered in evaluating the energetic habitability of subsurface environments.
Outcome of Older Patients with Severe Pneumonia Predicted by Recursive Partitioning
Authors: El‐Solh Ali A. , Sikka Pawan , Ramadan Fadi
Published: February 2005

OBJECTIVES: To develop a prognostic model to predict outcome of older patients with severe pneumonia requiring mechanical ventilation.

DESIGN: A nonconcurrent prospective study.

SETTING: A 24‐bed intensive care unit (ICU) within two university‐affiliated tertiary care hospitals.

PARTICIPANTS: All patients age 75 and older with severe pneumonia between June 1996 and September 1999 were included. Demographic data including activities of daily living (ADL) index score before admission, and clinical and laboratory data were collected in the first 24 hours of admission to the ICU. One hundred four patients (mean age ± standard deviation (SD) 82.3 ± 5.5 years) met the inclusion criteria.

MEASUREMENTS: A classification tree was developed using binary recursive partitioning to predict hospital discharge. The model was compared with a logistic regression model using variables selected by the tree analysis and with the Acute Physiologic and Chronic Health Evaluation (APACHE) II.

RESULTS: Outcome predictors for the classification tree were use of vasopressors, presence of multilobar pneumonia on chest radiograph, ratio of blood urea nitrogen to creatinine, Glasgow Coma Scale, urine output, and ADL score before admission. The tree achieved a sensitivity of 83.8% (95% confidence interval (CI) 69.2–92.4) and a specificity of 93.3% (95% CI 83–98.1). The predictive accuracy as assessed by the area under the curve (c‐index ± standard error) was significantly higher with the classification tree (0.932 ± 0.03) than with logistic regression and APACHE II, (0.801 ± 0.028 and 0.711 ± 0.049, respectively (P < .05).

CONCLUSIONS: The classification tree model demonstrated a superior predictive accuracy to that of logistic regression and APACHE II. If validated prospectively, the classification tree can be used as a tool to assess the outcome of older patients with severe pneumonia requiring mechanical ventilation on admission to the ICU. In addition, the classification tree can be used to assist healthcare workers in providing a concise summary of local outcome experience and prognostic information to patients and their surrogates.
Ability of Fat and Fat‐Free Mass Percentages to Predict Functional Disability in Older Men and Women
Authors: Broadwin Julie , Goodman‐Gruen Deborah , Slymen Don
Published: February 2005

OBJECTIVES: Previous studies suggest an association between body composition and declining functional ability in older people. This study examined the relation between functional disability and percentage of fat mass (FM) and percentage of fat‐free mass (FFM) in older men and women.

DESIGN: Cross‐sectional and prospective.

SETTING: Rancho Bernardo, California.

PARTICIPANTS: Subjects consisted of 1,051 ambulatory, community‐dwelling Caucasian men and women, age 55 to 92, who attended a clinic visit between 1988 and 1992 and a subsequent clinic visit between 1992 and 1996.

MEASUREMENTS: Measured at both visits, percentage of fat mass and percentage of lean body mass were estimated by bioelectric impedance analysis and functional disability was ascertained by self‐administered questionnaire. Functional disability was dichotomized into those having any difficulty with a set of tasks versus those having no difficulty with the tasks. Two measures of functional disability were used: “lower body” disability, consisting of two lower motor tasks (walking 2–3 blocks and climbing up 10 stairs) and “overall” disability, consisting of nine tasks representing upper and lower body function and mobility.

RESULTS: Compared with men, women were more likely to report both lower body and overall functional disability (P = .001). Cross‐sectionally, a significant positive association was shown between fat mass and overall functional disability and a significant negative association was shown between FFM and overall functional disability in both men and women. Prospectively, increased percentage of body fat and decreased percentage of FFM were significantly associated with decreased functional ability in both women and men. All results were adjusted for age, smoking, alcohol use, physical activity, current estrogen use, depression, chronic disease, and education.

CONCLUSION: Increased percentage of fat mass and decreased percentage of FFM are associated with greater functional disability in older men and women. Further research is needed to assess the relative importance of decreasing fat percentage or increasing fat‐free percentage to preserve or improve functional ability in older people.
True Right Bundle Branch Block Masking the Typical ECG in Brugada Syndrome
Authors: ROLF SASCHA , HAVERKAMP WILHELM , ECKARDT LARS
Published: February 2005

A patient with a family history of sudden cardiac death and a structurally normal heart presented with a resting ECG intermittently displaying a saddle‐type Brugada‐ECG, which could be reproducibly converted to a coved‐type ECG pattern suggestive of Brugada syndrome. However, no ST‐segment changes occurred in the presence of a true right bundle branch block (RBBB) in the same patient. In consideration of the inalienable diagnostic criterion of dynamic ECG abnormalities in the right precordial leads in Brugada syndrome, setting the diagnosis in patients with true RBBB may be unattainable.
The Impact of Supraventricular Tachycardias on Driving Ability in Patients Referred for Radiofrequency Catheter Ablation
Authors: WALFRIDSSON ULLA , WALFRIDSSON HÅKAN
Published: February 2005

Aim: The aim of the present study was to evaluate the occurrence of arrhythmia‐related symptoms in patients with supraventricular tachycardia (SVT) referred for radiofrequency catheter ablation (RF ablation) with special focus on driving ability.

Methods and Results: Of the 301 patients referred for RF ablation between November 1998 and December 2000 due to SVT 226 were active drivers. The present study is an interview study with structured questions. Hemodynamic symptoms were frequently encountered during tachycardia. The symptoms occurred irrespective of driving. In the 226 active drivers, fatigue was reported in 77%, dizziness in 47%, breaking into a cold sweat in 52%, near‐syncope in 50%, and syncope in 14%. Women experienced all symptoms more frequently than men: fatigue (P < 0.05), dizziness (P < 0.01), cold sweat (P < 0.05), near‐syncope (P < 0.001), and syncope (P < 0.01). Fifty‐seven percent of the patients had experienced tachycardia while driving, and 42% of those patients had to stop because of it. Twenty‐four of all patients considered their tachycardia as an obstacle to driving. There was a significant correlation (P < 0.001) between having experienced near‐syncope and considering the risk for tachycardia as an obstacle.

Conclusions: SVT frequently occurs during driving and is often associated with hemodynamic symptoms including near‐syncope and syncope. Women reported tachycardia‐related hemodynamic symptoms more often than men. There is a correlation between having experienced near‐syncope and considering tachycardia as an obstacle to driving. The risk for serious tachycardia‐related symptoms should be considered, especially in occupational drivers.
Improved Extraction of ePTFE and Medical Adhesive Modified Defibrillation Leads from the Coronary Sinus and Great Cardiac Vein
Authors: WILKOFF BRUCE L. , BELOTT PETER H. , LOVE CHARLES J. , SCHEINER AVRAM , WESTLUND RANDY , RIPPY MARIAN , KRISHNAN MOHAN , NORLANDER BARRY E. , STEINHAUS BRUCE , EMMANUEL JANSON , ZELLER PETER J.
Published: February 2005

Background: Permanent leads with shocking coils for defibrillation therapy are sometimes implanted in the coronary sinus (CS) and great cardiac vein (GCV). These shocking coils, as documented by pathologic examination of animal investigations, often become tightly encapsulated by fibrosis and can be very difficult to remove.

Methods: One of three configurations of the Guidant model 7109 Perimeter® coronary sinus shocking lead was implanted into the distal portion of the GCV of 24 sheep for up to 14 months. Group 1 had unmodified coils (control), group 2 had coils backfilled with medical adhesive (MA), and Group 3 had coils coated with expanded polytetrafluoroethylene (ePTFE). Eighteen leads, three from each group at 6 and 14 months were transvenously extracted from the left jugular vein. The remaining six animals were not subject to extraction. All animals were euthanized for pathological and microscopic examination.

Results: All six of the control, three of the MA, and one of the ePTFE leads required the use of an electrosurgical dissection sheath (EDS) for extraction. Five control, two MA, and none of the ePTFE leads had significant fibrotic attachments to the shocking coils. Significant trauma was observed at necropsy for those leads requiring the use of the EDS for extraction.

Conclusions: Tissue ingrowth is a major impediment to the removal of defibrillation leads implanted in the CS and GCV of sheep. Reduction of tissue ingrowth by coating the shocking coils with ePTFE or by backfilling with MA facilitates transvenous lead removal with reduced tissue trauma.
The Use of in vitro Data in Risk Assessment
Authors: Bernauer Ulrike , Oberemm Axel , Madle Stephan , Gundert‐Remy Ursula
Published: February 2005

Abstract: Describing the toxicological profile of a substance is the first step required for risk assessment. Although a wide range of in vitro methods are widely used to characterise toxicological properties including toxicokinetics, regulatory acceptance is mainly confined to in vitro tests which investigate genotoxic end‐points. In vitro tests have been proposed for the endpoints acute toxicity, repeated dose toxicity and toxicity to reproduction which encompass the minimum requirements in the OECD SIDS programme. However, until now, limitations of the proposed tests preclude their application in a regulatory framework. Presently, in vitro tests play a major role in obtaining information on mechanism of toxicity with the perspective to be able to identify pathways of toxic responses by applying toxicogenomics techniques. Physiologically based toxicokinetic modelling is using data from in vitro studies to build up the model for a specific compound. Information from both areas is incorporated into the risk assessment to derive compound‐specific safety factors, which account for species differences and for the variability among the human population, including possible sensitive subpopulations. Future developments to further enhance the use of in vitro methods in regulatory toxicology include the development of (Q)SAR approaches supplemented by mechanisms of toxicity, which can be addressed by developing methods of molecular toxicology.
Application of Full Physiological Models for Pharmaceutical Drug Candidate Selection and Extrapolation of Pharmacokinetics to Man
Authors: Parrott Neil , Jones Hannah , Paquereau Nicolas , Lavé Thierry
Published: February 2005

Abstract: This paper describes how we are applying physiologically based models of pharmacokinetics as an integrated part in the research and preclinical development of novel drugs. The modeling and simulation tools and techniques used are briefly reviewed and the strategy for application in drug research is described. Three examples illustrate how such models may be applied at different stages ranging from early application prior to in vivo studies, through clinical candidate selection to the estimation of human kinetics and dose selection prior to clinical studies. Although there are obvious restrictions related to limited input data at the earlier stages, the examples illustrate some of the advantages of the approach compared to other more empirical methods. These advantages will be fully exploited with more widespread use of physiological models as powerful and user‐friendly software make them accessible to non‐specialists.
Synchronization of enteric neuronal firing during the murine colonic MMC
Authors: Spencer Nick J. , Hennig Grant W. , Dickson Eamonn , Smith Terence K.
Published: February 2005

DiI (1,1′didodecyl‐3,3,3′,3′‐tetramethylindocarbecyanine perchlorate) retrograde labelling and intracellular electrophysiological techniques were used to investigate the mechanisms underlying the generation of spontaneously occurring colonic migrating myoelectric complexes (colonic MMCs) in mice. In isolated, intact, whole colonic preparations, simultaneous intracellular electrical recordings were made from pairs of circular muscle (CM) cells during colonic MMC activity in the presence of nifedipine (1–2 μm). During the intervals between colonic MMCs, spontaneous inhibitory junction potentials (IJPs) were always present. The amplitudes of spontaneous IJPs were highly variable (range 1–20 mV) and occurred asynchronously in the two CM cells, when separated by 1 mm in the longitudinal axis. Colonic MMCs occurred every 151 ± 7 s in the CM and consisted of a repetitive discharge of cholinergic rapid oscillations in membrane potential (range: 1–20 mV) that were superimposed on a slow membrane depolarization (mean amplitude: 9.6 ± 0.5 mV; half‐duration: 25.9 ± 0.7 s). During the rising (depolarizing) phase of each colonic MMC, cholinergic rapid oscillations occurred simultaneously in both CM cells, even when the two electrodes were separated by up to 15 mm along the longitudinal axis of the colon. Smaller amplitude oscillations (< 5 mV) showed poor temporal correlation between two CM cells, even at short electrode separation distances (i.e. < 1 mm in the longitudinal axis). When the two electrodes were separated by 20 mm, all cholinergic rapid oscillations and IJPs in the CM (regardless of amplitude) were rarely, if ever, coordinated in time during the colonic MMC. Cholinergic rapid oscillations were blocked by atropine (1 μm) or tetrodotoxin (1 μm). Slow waves were never recorded from any CM cells. DiI labelling showed that the maximum projection length of CM motor neurones and interneurones along the bowel was 2.8 mm and 13 mm, respectively. When recordings were made adjacent to either oral or anal cut ends of the colon, the inhibitory or excitatory phases of the colonic MMC were absent, respectively. In summary, during the colonic MMC, cholinergic rapid oscillations of similar amplitudes occur simultaneously in two CM cells separated by large distances (up to 15 mm). As this distance was found to be far greater than the projection length of any single CM motor neurone, we suggest that the generation of each discrete cholinergic rapid oscillation represents a discreet cholinergic excitatory junction potential (EJP) that involves the synaptic activation of many cholinergic motor neurones simultaneously, by synchronous firing in many myenteric interneurones. Our data also suggest that ascending excitatory and descending inhibitory nerve pathways interact and reinforce each other.
Crystal Structure of the Malaria Vaccine Candidate Apical Membrane Antigen 1
Authors: Pizarro Juan Carlos , Normand Brigitte Vulliez-Le , Chesne-Seck Marie-Laure , Collins Christine R. , Withers-Martinez Chrislaine , Hackett Fiona , Blackman Michael J. , Faber Bart W. , Remarque Edmond J. , Kocken Clemens H. M. , Thomas Alan W. , Bentley Graham A.
Published: February 2005

Apical membrane antigen 1 from
Plasmodium
is a leading malaria vaccine candidate. The protein is essential for host-cell invasion, but its molecular function is unknown. The crystal structure of the three domains comprising the ectoplasmic region of the antigen from
P. vivax
, solved at 1.8 angstrom resolution, shows that domains I and II belong to the PAN motif, which defines a superfamily of protein folds implicated in receptor binding. We also mapped the epitope of an invasion-inhibitory monoclonal antibody specific for the
P. falciparum
ortholog and modeled this to the structure. The location of the epitope and current knowledge on structure-function correlations for PAN domains together suggest a receptor-binding role during invasion in which domain II plays a critical part. These results are likely to aid vaccine and drug design.
Complex head and neck specimens and neck dissections. How to handle them
Authors: Slootweg P J
Published: February 2005

Dissecting surgical specimens from the upper aerodigestive tract is often difficult because of their complicated anatomy. The local environment dictates the routes of tumour spread and surgical margins at risk, and these features differ for various subsites within this part of the body. The examination of surgical specimens of the upper aerodigestive tract should disclose whether postoperative adjuvant treatment is needed and allow the evaluation of preoperatively performed diagnostic imaging. The aim of this article is to provide a concise guideline for the dissection of specimens from this part of the body.
Development of a quantitative assay for SARS coronavirus and correlation of GAPDH mRNA with SARS coronavirus in clinical specimens
Authors: Wong S C C , Chan J K C , Lee K C , Lo E S F , Tsang D N C
Published: February 2005

Aims:To develop a quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR) for severe acute respiratory syndrome coronavirus (SARS-CoV) detection and explore the potential of using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA as an internal control to exclude false negative results.

Methods:SARS-CoV and GAPDH mRNA were both measured in 26 specimens from 16 patients with SARS, 40 follow up specimens from the same batch of patients, and appropriate control subjects. The relation between SARS positivity and GAPDH mRNA concentration was investigated using the χ2test. Increasing the sensitivity for SARS-CoV and GAPDH mRNA detection was investigated in follow up specimens in which SARS-CoV and GAPDH mRNA were not detected initially.

Results:Varying amounts of SARS-CoV were found in the 26 SARS-CoV positive specimens and SARS-CoV was not detected in the 40 follow up specimens and controls. In addition, concentrations of GAPDH mRNA were significantly different between the patients with SARS, follow up specimens, and healthy controls (Kruskal-Wallis test, p<0.05). Moreover, GAPDH mRNA concentrations were highly correlated with SARS-CoV positivity (χ2 = 5.43; p<0.05). Finally, SARS-CoV and GAPDH mRNA were both detected in three follow up urine specimens that were initially negative when the amount of cDNA used was increased from 5 μl to 10 and 15 μl.

Conclusions:This Q-RT-PCR assay can be used to detect SARS-CoV. Moreover, GAPDH mRNA may be useful to rule out false negative results in SARS-CoV detection, and the current extraction method for urine may not be sensitive enough to detect low titres of SARS-CoV.
Is endomyometrial injury during termination of pregnancy or curettage following miscarriage the precursor to placenta accreta?: Table 1
Authors: Beuker J M , Erwich J J H M , Khong T Y
Published: February 2005

Aims:To determine the frequency with which myometrium is removed during vacuum terminations of pregnancy or dilatation and curettage after miscarriage, and to relate these findings to subsequent placenta accreta or its proxies.

Methods:Archival tissues from vacuum termination of pregnancy or dilatation and blunt curettage after miscarriage were examined for the presence of myometrium. The subsequent obstetric histories were scrutinised for manual removal of placenta, postpartum haemorrhage, or retained placenta. A retrospective study comparing the frequency of miscarriage and termination in women who had or did not have a manual removal was also performed.

Results:Myometrium was seen in the products of conception in 44% and 35% of termination and miscarriage tissues, respectively. One of nine women with myometrium at miscarriage had a postpartum haemorrhage in a subsequent pregnancy whereas, of the 21 women without myometrium at miscarriage, three required manual removal and seven had a postpartum haemorrhage afterwards. A past history of termination and/or miscarriage was more frequent in multigravid women who had a manual removal than those who did not.

Conclusions:Endomyometrial injury is frequent at termination or dilatation and curettage after miscarriage, but the relation to subsequent placenta accreta remains unclear. Women requiring a manual removal of the placenta were likely to have had a past history of termination and/or miscarriage.
Phenotypic plasticity of life-history characters in response to different germination timing in two annual weeds
Authors: Zhou Daowei , Wang Tianhui , Valentine Ian
Published: February 2005

An experimental manipulation was conducted to test whether germination timing influences the post-germination life-history characters in Amaranthus retroflexus L. and Chenopodium glaucum L. Seeds were sown in spring, late spring, and summer. Life-history characters of both phenology and morphology were measured, and dry masses of roots, stems, leaves, and reproductive organs were determined. Life-history characters showed high plasticity in response to different sowing dates. Later germinating plants had relatively faster growth rates and smaller sizes at reproduction than earlier germinating plants. Delaying germination led to relatively earlier reproduction and a relatively greater allocation to reproduction. Much of the variation (60%) could be explained by a single axis of a principal component analysis. The attributes on this axis were similar to the CR axis of Grime's CSR model. Further, the sowing dates of these two species were aggregated on this axis such that spring germinators tended towards the competitor strategy (C), late-spring germinators tended towards a mixed competitiveruderal strategy (CR), and summer germinators tended towards a ruderal strategy (R). Different germination timing led to different life-history strategies in the established phase. This kind of phenotypic plasticity in life history results from the plant adapting to regeneration strategies of different germination timing.Key words: Amaranthus retroflexus, Chenopodium glaucum, phenotypic plasticity, life-history characters, plant strategies, germination timing.
Morphological and molecular characterization of mycorrhizal fungi isolated from neotropical orchids in Brazil
Authors: Pereira Olinto Liparini , Kasuya Maria Catarina Megumi , Borges Arnaldo Chaer , Araújo Elza Fernandes de
Published: February 2005

To initiate a conservation program of the Orchidaceae from the Brazilian Atlantic rain forest with the purpose of ex situ conservation or reintroduction in the State of Minas Gerais, seven mycorrhizal Rhizoctonia-like fungal strains were isolated from roots of seven neotropical orchid species from three different Atlantic rain forest fragments. Taxonomic studies revealed that the isolates belong to the genera Ceratorhiza and Epulorhiza. The Epulorhiza isolates were identified as Epulorhiza repens (N. Bernard) R.T. Moore and Epulorhiza epiphytica Pereira, Rollemberg et Kasuya. RAPD analysis indicated higher polymorphism between Epulorhiza epiphytica and Epulorhiza repens than found in the PCRRFLP analysis. RAPD and morphological analyses indicated a degree of relatedness among the Ceratorhiza isolates obtained from the roots of different Oncidium species. A combination of morphological and molecular characterizations permitted integration of fungal strain identification with genetic relatedness among the isolates, thus allowing some inferences to be made on specificity of these endosymbionts under field conditions.Key words: biodiversity, Ceratorhiza, Epulorhiza, orchid mycorrhiza, Rhizoctonia-like, symbiosis, specificity.
Effect of the arbuscular mycorrhizal fungus Glomus intraradices on expression of cytoskeletal proteins in tomato roots
Authors: Timonen S , Smith S E
Published: February 2005

The expression patterns of the cytoskeletal proteins α-, β-, and γ-tubulin, actin, and myosin were investigated in young tomato roots and older roots at different intensities of mycorrhizal colonization. The relative level of cytoskeletal proteins was estimated by protein blotting and immunostaining. The contribution of plant α-, β-, and γ-tubulin to the total protein pool was higher in uncolonized 2-week-old roots than in 10-week-old roots, whereas the contribution of actin remained constant. The level of plant tubulin expression was clearly higher in mycorrhizal root systems than in uncolonized older root systems. These results indicate that tubulins are more involved in plant cell differentiation than actin. Myosin of approximately 230 kDa was expressed in the roots of 10-week-old wild-type tomato but not in young or mycorrhizal tomatoes. In contrast, a smaller ca. 170 kDa myosin was consistently present in all root samples. Indirect immunofluorescence microscopy showed that plant myosin was located particularly along the periarbuscular membranes surrounding the arbuscule branches. In uncolonized roots, myosin was associated mainly with membranes adjacent to plant cell walls. These data provide novel evidence that myosin expression and localization in root cells responds to mycorrhizal colonization.Key words: actin, myosin, arbuscular mycorrhizal fungi, protein expression, tubulin.