bluuebunny/crossref_metadata_2025 huggingface dataset:
Transesophageal Echocardiography in Patients with Atrial Fibrillation
Authors: ASHER CRAIG R. , KLEIN ALLAN L.
Published: December 2004

Over the past decade transesophageal echocardiography (TEE) has become an integral tool in the management of patients with AF. Thrombi can be readily detected and the function of the left atrium and left atrial appendage (LAA) can be easily assessed by this modality. With this knowledge, informed decisions regarding anticoagulation, cardioversion, and the likelihood of restoring and maintaining sinus rhythm can be made. An alternative TEE‐guided strategy for achieving sinus rhythm in patients with AF is now available with efficacy and safety similar to the conventional approach. Refinements of this strategy may include the use of low molecular weight heparin to avoid hospitalization in patients planned for cardioversion. Further uses of TEE in patients with AF are in their early stages including evaluation of patients following pulmonary vein radiofrequency ablation and those undergoing percutaneous or surgical closure of the LAA. (PACE 2003; 26[Pt. II]:1597–1603)
Contemporary Surgical Treatment for Atrial Fibrillation
Authors: GILLINOV A. MARC , MCCARTHY PATRICK M. , MARROUCHE NASSIR , NATALE ANDREA
Published: December 2004

Traditional surgical treatment of AF is the Cox‐Maze III procedure. The Cox‐Maze III procedure cures AF in >90% of patients and virtually eliminates the risk of stroke. Recent understanding of the importance of the pulmonary veins and left atrium in the pathogenesis of AF has resulted in the development of new surgical approaches. New operations to ablate AF use alternate energy sources (radiofrequency, microwave, cryothermy) and simplified left atrial lesion sets. These operations cure AF in 70–80% of patients. This article describes contemporary and emerging surgical approaches to AF, synthesizes results of these operations, and proposes a strategy for choice of operation based on patient presentation. (PACE 2003; 26[Pt. II]:1641–1644)
The Second Vasovagal Pacemaker Study (VPSII)
Authors: Connolly Stuart J. , Sheldon Robert , Thorpe Kevin E. , Roberts Robin S. , Ellenbogen Kenneth A. , Wilkoff Bruce L. , Morillo Carlos , Gent Michael ,   VPS II investigators
Published: December 2004

The Second Vasovagal Pacemaker Study (VPSII): A double‐blind randomized controlled trial of pacemaker therapy for the prevention of syncope in patients with recurrent severe vasovagal syncope. Three previous small randomized trials have reported that pacemaker therapy is very beneficial for patients with severe recurrent vasovagal syncope. However these trials were not double blind and were thus at risk of bias in assessment of outcomes and of a ‘placebo‐effect’ of surgery. To determine if pacing therapy reduces the risk of syncope in patients with vasovagal syncope. A double‐blind randomized trial of pacemaker therapy was performed. After implantation of a dual chamber pacemaker, 100 patients from 15 centres were randomized, double blind, to receive dual chamber pacing (DDD) with rate drop response or to have only sensing with no pacing (ODO). Patients were followed for up to 6 months and the primary outcome of the study was time to first recurrence of syncope. Results: Patients were well matched as to baseline characteristics. In the year prior to randomization patients had had a median of 4 episodes of syncope. No patients were lost to follow up. Of the patients randomized to ODO, 22 of 52 (42%) had recurrent syncope within 6 months, compared to 16 of 48 (33%) of the patients in the DDD group. The cumulative risk of syncope at 6 months was 40% (95% confidence interval 25%, 52%) for the ODO group and was 31% (95% confidence interval 17%, 43%) for the DDD group. The relative risk reduction in time to syncope with DDD pacing was 30% (95% confidence interval −33%, 63%, p = 0.14 one‐sided). Lead dislodgement or repositioning occurred in 7 patients, one patient had vein thrombosis and another had pericardial tamponade leading to removal of the pacemaker system. One patient had infection involving the pacemaker generator. Conclusions: This double blind randomized trial does not confirm the results of earlier smaller unblinded randomized trials. Because of the weak evidence of efficacy of pacemaker therapy and the risk of complications, pacemaker therapy should not be recommended as first line therapy for patients with recurrent vasovagal syncope.
The Role of Multisite Atrial Pacing in Rhythm Control in AF: Insights from Sub‐analyses of the Dual Site Atrial Pacing for Prevention of Atrial Fibrillation Study
Authors: Saksena Sanjeev
Published: December 2004

Novel pacing modes are being proposed for the prevention or reversion of atrial fibrillation (AF). High right atrial (RA) pacing and septal pacing have not individually reduced arrhythmic events in patients with AF in controlled trials. The DAPPAF trial compared the effectiveness of overdrive high right atrial single and dual site right atrial pacing as compared to demand pacing in prevention of recurrent symptomatic AF in patients with AF & bradyarrhythmias. Methods: From September 1996 to November 2000, 120 patients with documented symptomatic AF were enrolled and followed in a prospective randomized single blind crossover multicenter trial. 73 males & 45 females, mean age 66 ± 11 yrs with recurrent symptomatic AF (paroxysmal in 82 pts, persistent >72 hrs in 30 pts & persistent >30 days in 6 pts) were enrolled. Baseline AF event frequency was ≥1/day in 40 pts, 1/week in 43 pts, <1/week in 30 pts, & unknown in 5 pts. Patients were implanted with dual site right atrial pacing systems and randomly assigned to six‐month treatment periods in overdrive dual, overdrive single or demand pacing. Three primary endpoints (time to first AF recurrence, patient quality of life & tolerance/safety) and several secondary endpoints (device detected sustained AF, atrial & ventricular function indices, & composite endpoints) were examined. Results: Only DAP was significantly effective in preventing recurrent AF and prolonging time to first symptomatic AF recurrence in the presence of class 1 & 3 antiarrhythmic drug therapy; it was more effective than H.A. pacing in reducing asymptomatic AF event frequency; DAY alone prevented left ventricular and left atrial dilatation seen with D'ETRE pacing in this population due to improved left atrial transport; in patients with persistent AF or after Sawtell therapy, DAY maintained efficacy while H.A. pacing showed attrition in effectiveness. DAY was better tolerated than H.A. pacing, with fewer crossovers and comparable safety to H.A. pacing. Conclusions: DAY is an important therapeutic tool in an “hybrid” strategy for management of drug‐refractory AF. It offers antiarrhythmic and hemodynamic benefits and can have therapeutic effects on symptomatic and asymptomatic paroxysmal and persistent AF. It can facilitate efficacy of other antiarrhythmic therapies in AF. Further study of its antiarrhythmic effects with hybrid drug and ablation therapies is now in progress, and long‐term use in an “hybrid” strategy has been reported in large pilot studies.
Trial to Evaluate the Management of PSVT During Electrophysiologic Study with Tecadenoson (TEMPEST)
Authors: O'Neill Gearoid ,   TEMPEST Study Group
Published: December 2004

Introduction: Tecadenoson, a selective A1 adenosine derivative,prolongs AV nodal conduction without A2‐mediated reductions in BP or A2B/A3‐mediated bronchospasm. The primary study objective was to assess the rate of therapeutic conversion of PSVT without high degree AV block. Methods: This randomized, double‐blind, placebo‐controlled study enrolled PSVT patients in need of electrophysiologic study. PSVT was induced, sustained for ≥2 minutes and first IV bolus of study drug administered. If PSVT persisted after 1 minute, a second bolus was administered. The five tecadenoson regimens were 75μg/150μg (A), 150μg/300μg (B), 300μg/600μg (C), 450μg/900μg (D), 900μg/900μg (E) vs placebo. Results: Therapeutic conversion rate of each tecadenoson regimen was statistically significant versus placebo (ITT; n = 181; p < 0.0005). Higher regimens converted PSVT after the first dose in most patients (p < 0.001). Median time to conversion was ≤1 minute. No apparent dose‐dependent increase in AE frequency was observed. Conclusion: Each tecadenoson regimen rapidly converted PSVT to sinus rhythm in a dose‐dependent manner. In TEMPEST, tecadenoson regimens were identified that rapidly converted 90% of patients without significant adverse symptoms or hemodynamic effects.
The Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial
Authors: Wilkoff Bruce L. ,   DAVID Trial Investigators
Published: December 2004

Introduction: The devices used to prove the benefit of ICD therapy had only VVI pacing but most current ICD devices provide dual chamber pacing therapy. The DAVID trial sought to measure the impact of dual chamber pacing at 70 bpm (DDDR‐70) vs. ventricular backup pacing at 40 bpm (VVI‐40) in patients with standard indications for ICD implantation but without indications for bradycardia pacing. Methods: This single‐blind, multicenter, parallel‐group, randomized clinical trial enrolled 506 patients with indications for ICD therapy between 10/2000 and 9/2002. All patients had an LVEF ≤0.40, no indication for pacemaker therapy and no persistent atrial arrhythmias. ICDs with dual chamber, rate‐responsive pacing capability were implanted and programmed to VVI‐40 or DDDR‐70. Results: The combined endpoint of mortality or hospitalization for congestive heart failure (CHF) at one year was 16.1% (VVI‐40) vs. 26.7% (DDDR‐70), (p ∼ 0.03), mortality 6.5% vs. 10.1% (p ∼ 0.15) and CHF hospitalization 13.3% vs. 22.5% (p ∼ 0.07). Conclusion: For ICD patients, DDDR‐70 pacing exhibits no clinical advantage over VVI‐40 pacing and may increase CHF and mortality.
The use of floral homeotic mutants as a novel way to obtain durable resistance to insect pests
Authors: Kater Martin M. , Franken John , Inggamer Hein , Gretenkort Marie , Van Tunen Arjen J. , Mollema Chris , Angenent Gerco C.
Published: December 2004

We have developed a novel strategy for the introduction of durable insect resistance in crops. This strategy was based on intervention in the natural relationship between plants and insects. For many insects, including pests such as thrips (Frankliniella occidentalis), the flower is an important factor in their life cycle, serving either as a food source or as a place for mating. The insects are attracted to the flower by scent, which is mainly produced by the petals, and by the bright colour of these floral organs. We therefore anticipated that removal or changing the identity of the petals would significantly reduce the attractiveness of the flower to thrips. To test this hypothesis, we used cucumber as a model species because most modern varieties are parthenocarpic, in which the fruit develops without fertilization. The cucumber mutant green petals, in which the petals are homeotically transformed into green sepals, was particularly useful for this study. The susceptibility of the cucumber plants to damage by thrips was determined by recording thrip numbers and by measuring leaf damage. Large differences were observed when greenhouse compartments with either wild‐type or green petal mutant plants were compared. The rate of population growth of the insects on the mutant plants was significantly reduced and the leaves were almost undamaged. These results demonstrate that alterations in the structure of flowers may interfere with the life cycle of insects, providing the means for a novel and natural strategy for obtaining insect resistance.
Criteria for high‐level expression of a fungal laccase gene in transgenic maize
Authors: Hood Elizabeth E. , Bailey Michele R. , Beifuss Katherine , Magallanes‐Lundback Maria , Horn Michael E. , Callaway Evelyn , Drees Carol , Delaney Donna E. , Clough Richard , Howard John A.
Published: December 2004

Expression of industrial enzymes in transgenic plants offers an alternative system to fungal fermentation for large‐scale production. Very high levels of expression are required to make the enzymes cost‐effective. We tested several parameters to determine the best method for achieving high levels of expression for a fungal laccase gene. Transgenic maize plants were generated using an Agrobacterium‐mediated system. The molecular parameters that induced the highest expression were the maize embryo‐preferred globulin 1 promoter and targeting of the protein to the cell wall. Two independent transgenic events that yielded multiple clonal plants were characterized in detail. Independent transgenic events 01 and 03 contained two or one copies of T‐DNA, respectively. Plants derived from a single transgenic event varied in expression level, and the variation in expression levels was heritable. Within the seed, expression in these plants was primarily within the embryo, and was associated with seed browning and limited germination. High oil germplasm was used to increase germination, as well as to assist in increasing expression 20‐fold in five generations through breeding and selection.
Haplotyping and mapping a large cluster of downy mildew resistance gene candidates in sunflower using multilocus intron fragment length polymorphisms
Authors: Slabaugh Mary B. , Yu Ju‐Kyung , Tang Shunxue , Heesacker Adam , Hu Xu , Lu Guihua , Bidney Dennis , Han Feng , Knapp Steven J.
Published: December 2004

Downy mildew (Plasmopara halstedii (Farl.) Berlese et de Toni) is a serious foliar pathogen of cultivated sunflower (Helianthus annuus L.). Genetic resistance is conditioned by several linked downy mildew resistance gene specificities in the HaRGC1 cluster of TIR‐NBS‐LRR resistance gene candidates (RGCs) on linkage group 8. The complexity and diversity of the HaRGC1 cluster was assessed by multilocus intron fragment length polymorphism (IFLP) genotyping using a single pair of primers flanking a hypervariable intron located between the TIR and NBS domains. Two to 23 bands were amplified per germplasm accession. The size of the included intron ranged from 89 to 858 nucleotides. Forty‐eight unique markers were distinguished among 24 elite inbred lines, six partially isogenic inbred lines, nine open‐pollinated populations, four Native American land races, and 20 wild H. annuus populations. Nine haplotypes (based on 24 RGCs) were identified among elite inbred lines and were correlated with known downy mildew resistance specificities. Sixteen out of 39 RGCs identified in wild H. annuus populations were not observed in elite germplasm. Five partially isogenic downy mildew resistant lines developed from wild H. annuus and H. praecox donors carried eight RGCs not found in other elite inbred lines. Twenty‐four HaRGC1 loci were mapped to a 2–4 cM segment of linkage group 8. The multilocus IFLP marker and duplicated, hypervariable microsatellite markers tightly linked to the HaRGC1 cluster are powerful tools for distinguishing downy mildew resistance gene specificities and identifying and introgressing new downy mildew resistance gene specificities from wild sunflowers.
Over‐expression of hydroxynitrile lyase in transgenic cassava roots accelerates cyanogenesis and food detoxification
Authors: Siritunga Dimuth , Arias‐Garzon Diana , White Wanda , Sayre Richard T.
Published: December 2004

Cassava (Manihot esculenta, Crantz) roots are the primary source of calories for more than 500 million people, the majority of whom live in the developing countries of Africa. Cassava leaves and roots contain potentially toxic levels of cyanogenic glycosides. Consumption of residual cyanogens (linamarin or acetone cyanohydrin) in incompletely processed cassava roots can cause cyanide poisoning. Hydroxynitrile lyase (HNL), which catalyses the conversion of acetone cyanohydrin to cyanide, is expressed predominantly in the cell walls and laticifers of leaves. In contrast, roots have very low levels of HNL expression. We have over‐expressed HNL in transgenic cassava plants under the control of a double 35S CaMV promoter. We show that HNL activity increased more than twofold in leaves and 13‐fold in roots of transgenic plants relative to wild‐type plants. Elevated HNL levels were correlated with substantially reduced acetone cyanohydrin levels and increased cyanide volatilization in processed or homogenized roots. Unlike acyanogenic cassava, transgenic plants over‐expressing HNL in roots retain the herbivore deterrence of cyanogens while providing a safer food product.
New Ways of Specifying Data Edits
Authors: Petrakos George , Conversano Claudio , Farmakis Gregory , Mola Francesco , Siciliano Roberta , Stavropoulos Photis
Published: December 2004

Data editing is the process by which data that are collected in some way (a statistical survey for example) are examined for errors and corrected with the help of software. Edits, the logical conditions that should be satisfied by the data, are specified by subject-matter experts with a procedure which could be tedious and could lead to mistakes with practical implications. To render the process of edit specification more efficient we provide a new step—the definition of the so-called abstract data model of a survey—which describes the structure of the phenomenon that is studied in a survey. The existence of this model enables experts to identify all combinations of variables which should be checked by edits and to avoid the definition of conflicting edits. Furthermore, we introduce an automatic data validation strategy—TREEVAL—that consists of fast tree growing to derive automatically the functional form of edits and of a statistical criterion to clean the incoming data. The TREEVAL strategy is cast within a total quality management framework. The application of the methodologies proposed is demonstrated with the help of a real life application.
Production of external mycelium by ectomycorrhizal fungi in a norway spruce forest was reduced in response to nitrogen fertilization
Authors: Nilsson Lars Ola , Wallander Håkan
Published: December 2004

A field study was carried out to evaluate the influence of N fertilization on the growth of the external mycelium of ectomycorrhizal (EM) fungi in a Norway spruce forest in SW Sweden.

Nylon mesh bags filled with sand were buried in the soil for 6–18 months and the ingrowth of mycelium was used as an estimate of EM mycelial growth. Root‐isolated, trenched plots were used to estimate background growth of saprotrophic fungi.

Mycelial growth of EM fungi in N‐treated plots was reduced to c. 50% of that in nonfertilized plots. Local addition of apatite stimulated the EM mycelial growth in N‐treated plots.

The negative influence of N on the growth of external EM mycelium observed earlier in laboratory studies was confirmed in the present field study. The growth of EM mycelia was not directly related to N concentration in the soil but rather to the N status of the trees, although other factors induced by the N treatment may also have influenced EM mycelial growth.
Changes in leaf hydraulic conductance during leaf shedding in seasonally dry tropical forest
Authors: Brodribb T. J. , Holbrook N. M.
Published: December 2004

The hydraulic conductance of leaves (kleaf) was examined to determine whether this little understood component of the water transport pathway plays a role in governing leaf phenology of two deciduous dry forest trees (Calycophyllum candidissimum and Rhedera trinervis).

kleaf was monitored in parallel with stem hydraulic conductivity (Kstem) during the transition from wet to dry season. The relationships between declining photosynthetic quantum yield during senescence and declining kleaf and Kstem were compared.

Divergent patterns were observed in the response of Kstem to seasonal drying; however, the behaviour of kleaf was essentially similar in both species. Large (five‐ to ten‐fold) decreases in leaf hydraulic conductance occurred before, and during the later stages of leaf senescence. During senescence, declining kleaf, which continued until leaves were ultimately shed, was associated with a concomitant decline in quantum yield.

We conclude that, in these species, the loss of hydraulic conductance of the leaf vascular system is linked to, and possibly responsible for, the loss of photosynthetic capacity during leaf senescence.
Inter‐ and intraspecific variation of homologous hydrophobin (H1) gene sequences amongXanthoriaspp. (lichen‐forming ascomycetes)
Authors: Scherrer Sandra , Honegger Rosmarie
Published: December 2004

Inter‐ and intra‐specific variability of the hydrophobin geneH1was investigated in a range ofXanthoriaspecies collected in their natural habitat.

On Southern blots theXEH1probe (fromXanthoria ectaneoides) hybridized under standard conditions to the genomic DNA ofXanthoria calcicola, Xanthoria parietinaandXanthoria flammea. The correspondingH1genes in these and additional species (Xanthoria turbinata, Xanthoriaspp.), and ribosomal gene regions (ITS 1 and 2, 5.8S rDNA) were amplified with polymerase chain reaction, sequenced and similarities calculated. Restriction fragment length polymorphism and cleaved amplified polymorphic sequence analyses provided molecular tools for species delimitation.

Ribosomal gene data were largely in parallel with the hydrophobinH1sequence data, the protein‐codingH1sequence being even more variable as the noncoding rDNA regions.

Very low intraspecific variation was detected in theH1gene ofX. parietinasamples collected on four continents, with the highest variability occurring among Mediterranean samples.Xanthoria ectaneoidesfrom Brittany, France, andX. calcicolaappear to be coastal and inland forms of the same fungal species but differ from SicilianX. ectaneoides. The AfricanX. flammeaandX. turbinataare related to theX. parietinacluster.
Differential heavy metal tolerance of Arabidopsis halleri and Arabidopsis thaliana: a leaf slice test
Authors: Cho Misuk , Chardonnens Agnes N. , Dietz Karl‐Josef
Published: December 2004

Here, a short‐term leaf tissue tolerance test was designed to determine the distinct Zn‐, Cd‐ and Ni‐tolerance levels for leaves of the Zn‐hyperaccumulating plant Arabidopsis halleri compared with Arabidopsis thaliana.

Leaf slices were incubated in different metal concentrations for 2 h. Quantum yield of photosystem II was used as a parameter dependent on heavy metal concentrations in the incubation medium.

The half effective concentration values (EC50) showed that A. halleri was extremely tolerant to Zn (EC50 » 1 m), whereas A. thaliana had an EC50 of only 2.5 mm. For Cd, the EC50 values were 40 mm and 1.9 mm for A. halleri and A. thaliana, respectively. No differential tolerance was observed for Ni between the two species. Determination of heavy metal uptake by leaf slices under the same conditions revealed decreased uptake rates for A. halleri, suggesting that low metal influx from the apoplast, probably combined with efficient intracellular compartmentation, constitutes the mechanistic basis for Zn‐ and Cd‐hyperaccumulation. It is also shown that pre‐exposure of A. halleri with Zn during growth affects tolerance in the subsequent leaf slice test.

The leaf slice test presented here provides a quick and reliable method for estimating heavy metal tolerance levels in individual plants.
Expression of the OsPI1 gene, cloned from rice roots using cDNA microarray, rapidly responds to phosphorus status
Authors: Wasaki Jun , Yonetani Ryoma , Shinano Takuro , Kai Motoshi , Osaki Mitsuru
Published: December 2004

Plants have developed several methods of adapting to conditions of low phosphorus (P). However, details of the regulation of the gene expression system that responds to P status of plants is unknown. Here, a phosphorus limitation inducible novel gene was isolated and characterized to provide further information of plant adaptation to low P.

Rice plants (Oryza sativa) were grown hydroponically with or without P. A novel gene was isolated by cDNA microarray analysis and designated as OsPI1 (Oryza sativaPhosphate‐limitation Inducible Gene 1). mRNA accumulation was examined by Northern blot and quantitative real time PCR.

The OsPI1 gene was rapidly induced by phosphate starvation in both shoots and roots. When phosphate was supplied to phosphate‐deficient plants, the OsPI1 transcripts rapidly disappeared. OsPI1 cDNA consisted of 375 bp and contained several small open reading frames (ORFs). The OsPI1 gene shows the same characteristics as the TPSI1/Mt4 family (the phosphate starvation inducible novel gene family).

It is suggested that OsPI1 acts as riboregulator, that is, it binds with other molecules under phosphate starvation and regulates their function.
Early neural activity in Necker‐cube reversal: Evidence for low‐level processing of a gestalt phenomenon
Authors: Kornmeier Jürgen , Bach Michael
Published: December 2004

Normally we experience the visual world as stable. Ambiguous figures provide a fascinating exception: On prolonged inspection, the “Necker cube” undergoes a sudden, unavoidable reversal of its perceived front‐back orientation. What happens in the brain when spontaneously switching between these equally likely interpretations? Does neural processing differ between an endogenously perceived reversal of a physically unchanged ambiguous stimulus and an exogenously caused reversal of an unambiguous stimulus? A refined EEG paradigm to measure such endogenous events uncovered an early electrophysiological correlate of this spontaneous reversal, a negativity beginning at 160 ms. Comparing across nine electrode locations suggests that this component originates in early visual areas. An EEG component of similar shape and scalp distribution, but 50 ms earlier, was evoked by an external reversal of unambiguous figures. Perceptual disambiguation seems to be accomplished by the same structures that represent objects per se, and to occur early in the visual stream. This suggests that low‐level mechanisms play a crucial role in resolving perceptual ambiguity.
Stimulus modality, perceptual overlap, and the go/no‐go N2
Authors: Nieuwenhuis Sander , Yeung Nick , Cohen Jonathan D.
Published: December 2004

Stimuli that elicit a prepotent but incorrect response are typically associated with an enhanced electrophysiological N2 that is thought to index the operation of a control process such as inhibition or conflict detection. However, recent studies reporting the absence of the N2 modulation in go/no‐go tasks involving auditory stimuli challenge this view: It is not clear why inhibition or conflict detection should be sensitive to the modality of the stimulus. Here we present electrophysiological data from a go/no‐go task suggesting that the relative size of the N2 modulation in visual and auditory tasks depends on the perceptual overlap between the go and no‐go stimuli. Stimuli that looked similar but sounded different were associated with a typical visual N2 modulation and the absence of an auditory N2 modulation, consistent with previous findings. However, when we increased the perceptual overlap between the auditory stimuli, a large no‐go N2 was observed. These findings are discussed in terms of existing hypotheses of the N2, and clarify why previous studies have not found an N2 modulation in auditory go/no‐go tasks.
Awareness of sleepiness when driving
Authors: Horne James A. , Baulk Stuart D.
Published: December 2004

The extent to which sleepy drivers are aware of sleepiness has implications for the prevention of sleep‐related crashes, especially for drivers younger than 30 years old who are most at risk. Using a real car interactive simulator, we report on EEG, subjective sleepiness, and lane drifting (sleepiness‐related driving impairment) from 38 sleep‐restricted, healthy young adults undergoing nontreatment control conditions from three (unpublished) investigations using the same experimental protocols for assessing various drinks intended to alleviate sleepiness. Participants drove 2 h during midafternoon under monotonous conditions. For all studies, subjective sleepiness and EEG activity indicative of sleepiness were highly correlated, with both changing concomitantly, along with lane drifting. Drivers had knowledge of their physiological sleepiness. There were indications that sugar content of these drinks may additionally affect sleepiness.
Insulin Autoantibodies and Insulin Antibodies Have Similar Binding Characteristics
Authors: Brooks‐Worrell Barbara M. , Nielson Dave , Palmer Jerry P.
Published: December 2004

Type 1 diabetes is an autoimmune disease characterized by immune‐mediated destruction of the pancreatic beta cells. Insulin autoantibodies (IAAs) develop in many subjects at high risk for developing type 1 diabetes prior to onset of clinical disease and exposure to exogenous insulin, whereas insulin antibodies (IAs) commonly develop in patients treated with exogenous insulin. To investigate whether the binding characteristics of IAA and IA are similar, we measured eight different binding characteristics of IAAs from 19 insulin‐naive first‐degree relatives of type 1 diabetes patients and compared these to the binding characteristics of IAs from 19 type 1 diabetes patients treated with exogenous insulin. IAA and IA samples were matched for percentage insulin binding. Scatchard analysis revealed that IAAs have a two‐slope representation similar to IAs—that is, two populations of antibodies, a high‐affinity low‐cpaacity population and a low‐affinity high‐cpaacity population. Binding properties of the two respective populations were found to be similar for IAAs and IAs. Sipps’ equation was used to generate a Hill plot and produce an index of heterogeneity, which showed further similarity between IAAs and IAs. These results suggest that the IAAs found in subjects at increased risk for type 1 diabetes, like IAs, are likely to be polyclonal in nature. The similarities between IAAs and IAs support the hypothesis that both are induced by insulin presentation to the immune system.
Treatment for Drug Dependence
Authors: Jarlais Donald C. Des , Hubbard Robert
Published: December 2004

Drug abuse treatment is a major method for reducing the health and social problems associated with dependence on psychoactive drugs. Drug dependence is very well established in the United States, where cyclical rises and falls in the use of different drugs often occur. Heroin and cocaine use are spreading rapidly throughout the world as a whole, particularly in developing countries. The need for effective treatments for drug dependence is likely to increase in the foreseeable future. Currently three major forms of long‐term drug abuse treatment exist: methadone maintenance, in which an agonist medication is used to normalize physiological functioning; residential therapeutic communities, which are based on “resocializing” the drug user; and outpatient drug‐free programs, which utilize a wide variety of counseling and psychotherapy approaches. Multiple large treatment outcome studies have been conducted among persons receiving treatment for drug dependence and have shown consistent effects in reducing the use of psychoactive drugs, though complete elimination of drug use is an infrequent outcome. Length of time in drug treatment is the best single predictor of positive post‐treatment outcomes. HIV infection has become an extremely important adverse consequence associated with the injection of psychoactive drugs. Multiple studies have shown that drug abuse treatment is an effective method for preventing HIV infection among injecting drug users.
Tobacco and Alcohol Abuse: Clinical Opportunities for Effective Intervention
Authors: Fiore Michael C. , Fleming Michael F. , Burns Marguerite E.
Published: December 2004

No behaviors are more costly to the United States from a health or economic perspective than tobacco and alcohol use. One of the primary strategies available to mitigate this exacting toll is to identify and clinically treat the 25% of adults in America who smoke and the 20% of adults who drink alcohol above recommended limits. During the last two decades, researchers have identified a series of brief clinical interventions that can markedly reduce alcohol and tobacco use and significantly decrease the health burdens resulting from such use. This review outlines office‐based clinical interventions and the organizational policies that support these interventions that have been shown to decrease tobacco and alcohol use.
Mortality and Morbidity Attributable to Use of Addictive Substances in the United States
Authors: McGinnis J. Michael , Foege William H.
Published: December 2004

Addiction to tobacco, alcohol, and other drugs inflicts a substantial toll on Americans, measurable in terms of deaths and illnesses, social costs, and economic costs. With approximately 60 million smokers, 14 million dependent on alcohol, and 14 million users of illicit drugs, more than one fourth of Americans over age 15 has a physiological dependence on at least one addictive substance. As a result, nearly 590,000 deaths—about a quarter of all deaths in the United States—are caused by addictive substances: 105,000 from alcohol abuse, 446,000 from tobacco use, and 39,000 from addictive drugs in 1995. The magnitude of addiction’s impact on morbidity is also great, causing approximately 40 million illnesses and injuries each year. The economic burden of addiction is estimated at greater than $400 billion every year, including health care costs, lost worker productivity, and crime. Less quantifiable, but equally important, are the social costs to families and communities of addiction. Children of substance‐abusing parents are more likely as adults to become plagued by addiction and its related problems. Passive exposure to tobacco smoke affects nonsmokers; drug and alcohol abuse are risk factors for crime and incarceration, family violence, fatal and permanently disabling accidents, birth defects, and divorce. Combined, the effects of tobacco, alcohol, and drugs inflict a greater toll on the health and well‐being of Americans than any other single preventable factor.
Inherited Variability of Tumor Necrosis Factor Production and Susceptibility to Infectious Disease
Authors: Knight Julian C. , Kwiatkowski Dominic
Published: December 2004

Tumor necrosis factor (TNF) is a critical mediator of host defense against infection but may cause severe pathology when produced in excess. Individuals vary in the amount of TNF produced when their peripheral blood mononuclear cells are stimulated in vitro, and family studies indicate that much of this variability is genetically determined. Since the TNF response to infection is partly regulated at the transcriptional level, TNF promoter polymorphisms have been the subject of intense interest as potential determinants of disease susceptibility. A single nucleotide polymorphism at nucleotide –308 relative to the transcriptional start site has been associated with susceptibility to severe malaria, leishmaniasis, scarring trachoma, and lepromatous leprosy. Some experimental data indicate that this polymorphism acts to upregulate TNF transcription, but this remains controversial. Detailed analysis of multiple genetic markers at this locus and more sophisticated investigations of TNF transcriptional regulation, in different cell types and with a wide range of stimuli, are required to understand the molecular basis of these disease associations.
Enterococci: New Aspects of an Old Organism
Authors: Murray Barbara E. , Weinstock George M.
Published: December 2004

Enterococci are a long‐known cause of bacterial endocarditis and a more recently recognized cause of nosocomial infection and superinfection. While much is known about the many antibiotic resistances of enterococci, less is known about the organism itself and how it causes disease. This article presents a brief overview of enterococci and its possible virulence factors and summarizes the authors’ efforts to understand the features of this organism that may contribute to its disease potential.
Understanding the Genetic Basis of Susceptibility to Mycobacterial Infection
Authors: Levin Michael , Newport Melanie
Published: December 2004

Genetic factors have long been suspected of determining susceptibility and resistance to mycobacterial infection. The recent identification of families with a unique susceptibility to mycobacterial infection, and the identification of mutations in the genes for either the interferon‐γ (IFN‐γ) receptor or the interleukin (IL)‐12 receptor as the cause of the defect, has provided an important clue to the pathways critical for resistance to mycobacterial infection in humans. Although the genetically determined absence of key cytokines or their receptors results in susceptibility to lethal mycobacterial infections in early childhood, it is likely that more subtle mutations that result in only partial dysfunction of macrophage upregulation pathways may play a role in susceptibility to tuberculosis (TB) and leprosy in the general population.
The Genes of Systemic Autoimmunity
Authors: Theofilopoulos Argyrios N. , Kono Dwight H.
Published: December 2004

Autoimmune diseases include a wide spectrum of disorders, which have been divided into systemic and organ‐specific disorders. Lupus, the prototypic systemic autoimmune disease, is characterized by female predominance, multiorgan pathology, and autoantibodies, primarily directed against nuclear antigens. The disease is heterogeneous, with variable organ involvement, serology, and clinical course. Susceptibility to lupus is inherited as a polygenic trait with added contributions from environmental and stochastic variance. Concerted efforts have recently been made by several laboratories to define the genetic basis of this disease in predisposed mice and humans. The identification of the Fas/FasL defects in lpr and gld lupus mice was the first example of spontaneous mutations of apoptosis‐promoting genes being associated with systemic autoimmunity. This research was instrumental in clarifying the roles of these genes in tolerance and immunoregulation, and in extrapolating these results to other autoimmune diseases, as well as cancer and transplantation. To these findings have been added those from transgenic and gene knockout mouse studies that have helped to define the systemic autoimmunity‐inducing or ‐modifying effects of specific genes in normal background and lupus‐congenic mice. In addition, the findings from genome‐wide searches have begun to identify predisposing loci (and ultimately genes) for the spontaneous lupus‐like diseases in various mouse strains and in humans. The emerging picture is that multiple genetic contributions can independently lead to systemic autoimmunity in mice, which reinforces the view that human lupus may be similarly composed of diverse genotypes. This complexity underscores the importance of defining the predisposing alleles and mechanisms of action, an undertaking that is certainly feasible given current technologies and future advances in the definition of mammalian genomes.
Physiology and Pathophysiology of Nitric Oxide in Chronic Renal Disease
Authors: Noris Marina , Remuzzi Giuseppe
Published: December 2004

Nitric oxide (NO), an L‐arginine derivative, exerts a variety of renal and extrarenal physiological and pathophysiological effects. NO is generated by three isoforms of nitric oxide synthases (NOS): two acutely responsive, constitutive isoforms, neuronal NOS (nNOS) and endothelial NOS (ecNOS), and the slower, more persistent, inducible NOS (iNOS). NO regulates glomerular ultrafiltration, tubular reabsorption, and intrarenal renin secretion. A number of recent studies, most of them in the experimental model of renal mass reduction (RMR) in rats, have raised the hypothesis that an impaired NO synthetic pathway could have a key role in mediating the complex renal hemodynamic and nonhemodynamic disorders associated with the progression of renal disease. Thus, kidneys from rats with RMR produce less NO than normal rats, and NO generation negatively correlates with markers of renal damage. The abnormality is due to a defect in iNOS in the kidney. Data are also available showing that drugs capable of enhancing renal NO activity may be renoprotective in a variety of experimental renal diseases, particularly those characterized by derangements of glomerular hemodynamics. Fewer studies are available in humans and these have shown less than conclusive results.
Asthma Therapy with Agents Preventing Leukotriene Synthesis or Action
Authors: Drazen Jeffrey M.
Published: December 2004

Elucidation of the biochemistry of leukotriene production and the pharmacology of its actions has led to the development of a number of therapeutic agents shown to be of value in the treatment of asthma. These agents either prevent the synthesis of the leukotrienes, by preventing the action of the 5‐lipoxygenase‐activating protein or the catalytic action of the 5‐lipoxygenase, or by inhibiting the action of leukotrienes at the CysLT1 receptor. Numerous clinical trials in exercise‐induced asthma, allergen‐induced asthma, aspirin‐induced asthma, and spontaneously occurring asthmatic episodes have indicated that these agents are safe and effective asthma treatments.
Proceedings of the 1998 Meeting of the Society for Pediatric Dermatology
Authors: Duarte Ana M. , GREVELINK SUZANNE
Published: December 2004

The Society for Pediatric Dermatology held its annual meeting in Cambridge, Massachusetts, on July 23–26, 1998. Selected summaries of presentations at the meeting follow.
Collodion Baby Associated with Asymmetric Crying Facies: A Case Report
Authors: Akcakus Mustafa , Gunes Tamer , Kurtoglu Selim , Ozturk Adnan
Published: December 2004

Abstract: Collodion baby is a distinct subset of neonatal erythroderma that can be a clinical marker for a variety of underlying abnormalities. The phenotype includes parchment‐like hyperkeratosis, pseudocontractures, ectropion, eclabium, absence of eyebrows, and sparse hair. Asymmetric crying facies is caused by congenital hypoplasia or agenesis of the depressor anguli oris muscle. Associations of this facial defect with major congenital anomalies have been reported, most commonly in the cardiovascular system, less frequently involving the genitourinary, musculoskeletal, cervicofacial, and respiratory systems, and rarely the endocrine system. We report a newborn with a collodion membrane and asymmetric crying facies. To the best of our knowledge, this association has not been previously published.
Mucinous Eccrine Nevus: An Unusual Lesion in a Child
Authors: Llombart B. , Molina I. , Monteagudo C. , Ramón D. , Martín J. M. , Sanchez R. , Jordá E.
Published: December 2004

Abstract: Mucinous eccrine nevus has been described as a variant of eccrine nevus. Only one instance of this variant, diagnosed in a 47‐year‐old woman, has been reported. We report a 2‐year‐old girl who had two 1 cm, asymptomatic, brownish nodules. Histologic analysis revealed a dermal lobulated proliferation of eccrine structures surrounded by a prominent mucinous stroma. This is thus, to the best of our knowledge, the first case of this extremely rare entity in a child.
Xp22.3 Microdeletion in a 19‐Year‐Old Girl with Clinical Features of MLS Syndrome
Authors: Enright F. , Campbell P. , Stallings R. L. , Hall K. , Green A. J. , Sweeney E. , Barnes L. , Watson R.
Published: December 2004

Abstract: We describe a 19‐year‐old girl who has clinical features of microphthalmia with linear skin defects (MLS) syndrome caused by a microdeletion of Xp22.3. In addition to the classical ocular abnormalities and linear skin defects she has other features not previously described. She was previously reported in this journal in 1990 as poikiloderma congenitale, but her true diagnosis of an Xp22.3 microdeletion was clarified when fluorescent in situ hybridization (FISH) analysis indicated that one of her X chromosomes had a microdeletion including the KAL gene. We describe this patient with an Xp22.3 microdeletion to heighten awareness among dermatologists of this syndrome and to underscore the difficulties in diagnosing MLS syndrome.
Palmar‐Plantar Keratoderma of Unna Thost Associated with Atopic Dermatitis: An Underrecognized Entity?
Authors: Loh Teck‐Hiong , Yosipovitch Gil , Tay Yong‐Kwang
Published: December 2004

Abstract: We report six cases of palmar‐plantar keratoderma of Unna Thost (PPKUT) associated with atopic dermatitis. All had typical features of PPKUT with diffuse, yellowish thickening on the palms and soles with a well‐defined erythematous rim of demarcation on the sides associated with palmar‐plantar hyperhidrosis. The changes were obvious since birth or arose during early life, and were persistent. We believe that the association between the two disorders is not coincidental but an underrecognized entity that may shed light on the underlying pathogenesis of these two conditions.
Gangrenous Cutaneous Mucormycosis in a Child with a Solid Organ Transplant: A Case Report and Review of the Literature
Authors: Boyd Alan S. , Wiser Britt , Sams Hunter H. , King Lloyd E.
Published: December 2004

Abstract: Infections by members of the Phycomycetes class of fungi typically arise in patients with substantial underlying immunosuppression. Several clinical presentations, including that of gangrenous cellulitis, have been described. In the pediatric population, critically ill premature newborns and older children with underlying hematopoietic malignancies and/or bone marrow transplantation are affected. Presentation in children with solid organ transplants is rare. Successful therapy for this condition includes aggressive debridement of infected tissue and systemic administration of amphotericin B.
Sarcoidosis in a Preschooler with Only Skin and Joint Involvement
Authors: Fetil Emel , Özkan Şebnem , İlknur Turna , Kavukçu Salih , Kuşku Ergün , Lebe Banu
Published: December 2004

Abstract: Sarcoidosis is a multisystemic granulomatous disease of unknown etiology. It is relatively rare in children less than 15 years of age and especially in those less than 5–6 years of age. Sarcoidosis characteristically involves the skin, eyes, and synovial tissues in patients less than 5–6 years of age. We report a 3‐year‐old boy with sarcoidosis who had cutaneous findings with joint symptoms. Dermatologic examination revealed lichenoid, erythematous, 2–3 mm papules, some of them grouped, all over his extremities and trunk. There were symmetric swellings on his ankles and wrists without erythema or pain which did not interfere with function. However, until now, no eye involvement had been detected in the patient.
Andogsky Syndrome Variant: Atopic Dermatitis Associated with Bilateral Cataracts and Retinal Degeneration with Left Retinal Detachment
Authors: Margolin Leon , Hershko Klilah , Garcia‐Rojas Miguel , Ingber Arieh
Published: December 2004

Abstract: A 15‐year‐old girl had a new variation of Andogsky syndrome (unilateral cataract and atopic dermatitis) in which atopic dermatitis was associated with primary bilateral cataracts and retinal degeneration with primary left retinal detachment before cataract surgery. She had no history of systemic steroid treatment.
Tuberculosis in a Child Presenting as Asymptomatic Oropharyngeal and Laryngeal Lesions
Authors: Magina S. , Lisboa C. , Resende C. , Azevedo F. , Amado F. , Cardoso V. , Almeida F. , Mesquita‐Guimarães J.
Published: December 2004

Abstract: We describe an 11‐year‐old boy who had several, asymptomatic, erythematous papules in the oropharynx and larynx with recent onset, two cervical lymphadenopathies, and a painless, erythematous plaque on the right wrist with a 2.5‐year history of slow growth. Histologic examination of the mucocutaneous lesions revealed a submucous infiltrate of lymphocytes and Langhans giant cells in the papules and granulomatous dermatitis in the plaque. The cervical lymph node was biopsied and on the surgical scar, an erythematous, nodular lesion developed. A biopsy specimen of this lesion showed tuberculoid granulomas with prominent caseation necrosis, and culture was positive for Mycobacterium tuberculosis. The Mantoux test was strongly positive with a vesicular response. A diagnosis of mucocutaneous lupus vulgaris and scrofuloderma secondary to cervical tuberculous lymphadenitis was made. Two months after initiation of antituberculosis therapy there was a complete resolution of mucous lesions and healing with atrophic scars on the neck and wrist. This is a rare presentation in the literature and reminds clinicians that tuberculosis should be kept in mind in the differential diagnosis of oral cavity lesions.