bluuebunny/crossref_metadata_2025 huggingface dataset:
Quadriceps Weakness, Atrophy, and Activation Failure in Predicted Noncopers after Anterior Cruciate Ligament Injury
Authors: Williams Glenn N. , Buchanan Thomas S. , Barrance Peter J. , Axe Michael J. , Snyder-Mackler Lynn
Published: February 2005

Background

Quadriceps weakness is common after anterior cruciate ligament injury, especially in those who do not compensate well for the injury (“noncopers”). Both atrophy and activation failure have been demonstrated in this population but have not been directly related to quadriceps weakness.

Hypotheses

(1) Quadriceps strength, volumes, and cross-sectional areas of the noncopers would be smaller than those of the contralateral muscles, whereas other muscles would not demonstrate atrophy. (2) Quadriceps muscle activation deficits would be observed. (3) Atrophy and activation failure would account for the quadriceps weakness in these patients.

Study Design

Cross-sectional study, Level of evidence, 3.

Methods

Seventeen noncopers with isolated anterior cruciate ligament injury underwent burst-superimposition strength and activation testing of the quadriceps and magnetic resonance imaging of 12 muscles an average of 2 months after injury. Morphological characteristics was described by digitally reconstructing each muscle from the axial images and calculating muscle volume and peak cross-sectional area.

Results

The quadriceps muscles of the anterior cruciate ligament-deficient limb were significantly weaker (average 25%) than those of the uninjured side; activation failure (8%-10%) was observed for the quadriceps muscles of both limbs. The total quadriceps, vastus lateralis, and vastus intermedius volume and cross-sectional area were significantly smaller in the anterior cruciate ligament-deficient limb. There was no significant atrophy of any other muscle or muscle group. Atrophy and activation failure explained more than 60% of the variance in quadriceps weakness (P =. 004).

Conclusion

The quadriceps femoris weakens soon after acute anterior cruciate ligament injury. Activation deficits and atrophy occur and affect quadriceps strength. Rehabilitation techniques that address activation deficits as well as atrophy may be necessary to restore quadriceps strength.
De Quervain Disease in Volleyball Players
Authors: Rossi Costantino , Cellocco Paolo , Margaritondo Enrico , Bizzarri Francesco , Costanzo Giuseppe
Published: February 2005

Background

Chronic inflammatory tendon diseases in athletes are frequent, and they often result from modifications in normal kinematics of a tendon associated with a patient's anatomical determinants. De Quervain stenosing tenosynovitis is an inflammatory disease of tendons of the first dorsal compartment of the wrist. There is no literature about this disease concerning professional volleyball players.

Hypothesis

Limited, multiple trauma on the dorsal radial portion of the wrist, associated with long training times, can be involved in the pathogenetic process of de Quervain disease in professional volleyball players.

Study Design

Case series; Level of evidence, 4.

Materials and Methods

The authors studied 45 consecutively enrolled volleyball players (27 professional, 18 nonprofessional) satisfying clinical criteria for the diagnosis of de Quervain stenosing tenosynovitis. All patients were evaluated by questionnaire and physical examination. They were divided into group A (mild) and group B (severe) based on the severity of the symptoms and physical findings; they were followed for a mean of 37 months.

Results

Total training quantity (mean weekly training time multiplied by mean sports activity duration) in group A was 74, whereas it was 155 in group B (P <. 01). No neuropathies were found in group A, whereas they were found in 3 patients in group B. Fifty percent of surgical patients had a longitudinal fibrous septum, whereas 54% showed multiple tendon sheaths making up the abductor pollicis longus tendon.

Conclusions

This study shows that increased training time and consequent microtrauma associated with professional volleyball activity can increase the likelihood of de Quervain disease.
A Radiographic Investigation to Determine the Safety of Suture Anchor Systems for Pediatric Modified Broström Ankle Ligament Reconstruction
Authors: Hazratwala Kaushik , Best Alistair , Kopplin Matthew , Giza Eric , Sullivan Martin
Published: February 2005

Background

The modified Broström ligament reconstruction using anchor sutures has been performed in adults with clinical success; however, the safety parameters for the use of suture anchors in adolescent lateral ankle ligament reconstruction have not been established.

Purpose

To perform a radiographic analysis comparing the depth of penetration of suture anchors in adult ankle ligament reconstruction with the average distance of the physis from the tip of the fibula in adolescents.

Study Design

Cross-sectional study, Level of evidence, 4.

Methods

Forty postoperative ankle radiographs of adult patients who had a modified Broström procedure were compared with 40 normal adolescent ankle radiographs. In the adult group, the distance of the suture anchor penetration from the distal tip of the fibula was measured; in the adolescent group, the distance of the physis from the distal tip of the fibula was measured.

Results

The mean depth of the suture anchors was 17 mm (range, 14-21 mm) from the tip of the fibula in the adult group, and the mean distance of the growth plate was 23 mm (range, 18-29 mm) in the adolescent group. Eight radiographs from the adolescent group (20%) had a physis measurement of <22 mm on the anteroposterior or mortise view.

Conclusions

Using careful preoperative planning and intraoperative technique, it is possible to safely perform lateral ankle ligament repair in the skeletally immature patient using suture anchors.
Intrinsic Risk Factors for Inversion Ankle Sprains in Male Subjects: A Prospective Study
Authors: Willems Tine Marieke , Witvrouw Erik , Delbaere Kim , Mahieu Nele , De Bourdeaudhuij Llse , De Clercq Dirk
Published: February 2005

Background

Many variables have been retrospectively associated with ankle sprains. However, very little is known about factors predisposing people to these injuries.

Hypothesis

Measurable intrinsic factors might predispose male athletes to ankle sprains.

Study Design

Cohort study; Level of evidence, 2.

Methods

A total of 241 male physical education students were evaluated for possible intrinsic risk factors for inversion sprains at the beginning of their academic study. The evaluated intrinsic risk factors included anthropometrical characteristics, functional motor performances, ankle joint position sense, isokinetic ankle muscle strength, lower leg alignment characteristics, postural control, and muscle reaction time during a sudden inversion perturbation. Subjects were followed prospectively for 1 to 3 years.

Results

A total of 44 (18%) of the 241 male subjects sustained an inversion sprain; 4 sprained both ankles. Cox regression analysis revealed that male subjects with slower running speed, less cardiorespiratory endurance, less balance, decreased dorsiflexion muscle strength, decreased dorsiflexion range of motion, less coordination, and faster reaction of the tibialis anterior and gastrocnemius muscles are at greater risk of ankle sprains.

Conclusion

Based on our findings, it is suggested that running speed, cardiorespiratory endurance, balance, dorsiflexion strength, coordination, muscle reaction, and dorsiflexion range of motion at the ankle are associated with the risk of ankle inversion sprains in male subjects.
Pediatric Fractures during Skateboarding, Roller Skating, and Scooter Riding
Authors: Zalavras Charalampos , Nikolopoulou Georgia , Essin Daniel , Manjra Nahid , Zionts Lewis E.
Published: February 2005

Background

Skateboarding, roller skating, and scooter riding are popular recreational and sporting activities for children and adolescents but can be associated with skeletal injury. The purpose of this study is to describe the frequency and characteristics of fractures resulting from these activities.

Purpose

Fractures from skateboarding, roller skating, and scooter riding compose a considerable proportion of pediatric musculoskeletal injuries.

Study Design

Case series; Level of evidence, 4.

Methods

Demographic data and injury characteristics were analyzed for all patients who presented to the pediatric fracture clinic of the level I trauma center from January 2001 to May 2002 after sustaining fractures due to skateboarding, roller skating, and scooter riding.

Results

Among a total of 2371 fractures, the authors identified 325 fractures (13.7%) that occurred during one of these activities. There were 187 patients (mean age, 13 years; 95% male) who sustained 191 skateboard-related fractures, 64 patients (mean age, 10.8 years; 54% male) who sustained 65 fractures while roller skating, and 66 patients (mean age, 9.7 years; 64% male) who sustained 69 fractures while riding a scooter. The forearm was fractured most often, composing 48.2% of skate-boarding fractures, 63.1% of roller-skating fractures, and 50.7% of fractures due to scooter riding. Of the forearm fractures, 94% were located in the distal third. In the skateboarding group, 10 of 191 (5.2%) fractures were open injuries of the forearm, compared to 6 of 2046 (0.3%) fractures caused by other mechanisms of injury (significant odds ratio, 18.8).

Conclusions

Skateboarding, roller-skating, and scooter-riding accidents result in a large proportion of pediatric fractures. An open fracture, especially of the forearm, was more likely to be caused by skateboarding than by other mechanisms of injury. Use of wrist and forearm protective equipment should be considered in all children who ride a skateboard.
Prevalence of Jumper's Knee among Elite Athletes from Different Sports: A Cross-sectional Study
Authors: Lian Østein B. , Engebretsen Lars , Bahr Roald
Published: February 2005

Background

The prevalence of jumper's knee across different sports has not been examined, and it is not known if there is a gender difference. Data from surgical case series indicate that there may be a high prevalence in sports with high speed and power demands.

Hypothesis

The aim of this study was to estimate the prevalence of jumper's knee in different sports among female and male athletes and to correlate the prevalence to the loading characteristics of the extensor mechanism in these sports.

Study Design

Cross-sectional study; Level of evidence, 4.

Methods

The authors examined approximately 50 Norwegian male and female athletes at the national elite level from each of the following 9 sports: athletics (male athletes: high jump, 100- and 200-m sprint), basketball (male athletes), ice hockey (male athletes), volleyball (male athletes), orienteering (male athletes), road cycling (male athletes), soccer (male and female athletes), team handball (male and female athletes), and wrestling (male athletes). The examination included an interview on individual characteristics (weight, age, height, and training background), a clinical examination, and self-recorded Victorian Institute of Sport Assessment score from 0 (worst) to 100 (best).

Results

The overall prevalence of current jumper's knee was 14.2% (87 of 613 athletes), with a significant difference between sports with different performance characteristics (range, 0%-45%). In addition, 51 athletes (8%) reported previous symptoms. The prevalence of current symptoms was highest in volleyball (44.6% ± 6.6%) and basketball (31.9% ± 6.8%), whereas there were no cases in cycling or orienteering. The prevalence of current jumper's knee was lower among women (5.6% ± 2.2%) compared with men (13.5% ± 3.0%; χ2 test, P =. 042). The duration of symptoms among athletes with current jumper's knee (n = 87) was 32 ± 25 (standard deviation) months, with a Victorian Institute of Sport Assessment score of 64 ± 19.

Conclusion

The prevalence of jumper's knee is high in sports characterized by high demands on speed and power for the leg extensors. The symptoms are often serious, resulting in long-standing impairment of athletic performance.
Utility deregulation and business ethics: More openness through gaming/simulation
Authors: Tsuchiya Shigehisa
Published: February 2005

Deregulation in the utilities industry is putting pressure on the utility companies to operate more efficiently. This efficiency drive seems to have had an impact on commitment to established safety procedures and ethical standards. Analyzing three major corporate accidents in the nuclear power generation industry, the author came to the conclusion that the lowering of ethical standards was the root cause of the accidents, resulting in severe damage to public image and profit. The author also found that maintaining effective communication through openness is the main leverage in preventing deterioration of ethical standards and practices and, thus, reducing the risk of major accidents occurring. The approach selected for teaching and training of business ethics and openness was learning by doing with the help of gaming/simulation. By using this approach, the author developed two gaming/simulation exercises, the RESCUE TEAM and the KING OF FISHERMEN.
Deregulation of utility industries and roles of simulation
Authors: Wenzler Ivo , Kleinlugtenbelt Wouter Jan , Mayer Igor
Published: February 2005

The authors describe why and how different types of simulations can be used to understand and support the challenges of utility deregulation. They present an overview of liberalization and deregulation efforts in three utility markets—electricity, natural gas, and drinking water—and describe the main challenges and opportunities for regulators and business managers. A general classification of seven different types of simulation is presented, including market simulations, policy simulations, dynamic business simulations, capability simulations, day-in-a-life simulations, performance simulations, and gaming simulations. The authors reflect on the role of these simulations for utility deregulation and give examples.
Murine hematopoietic stem cells change their surface phenotype during ex vivo expansion
Authors: Zhang Cheng Cheng , Lodish Harvey F.
Published: February 2005

Ex vivo expansion of hematopoietic stem cells (HSCs) is important for many clinical applications, and knowledge of the surface phenotype of ex vivo–expanded HSCs will be critical to their purification and analysis. Here, we developed a simple culture system for bone marrow (BM) HSCs using low levels of stem cell factor (SCF), thrombopoietin (TPO), insulin-like growth factor 2 (IGF-2), and fibroblast growth factor-1 (FGF-1) in serum-free medium. As measured by competitive repopulation analyses, there was a more than 20-fold increase in numbers of long-term (LT)–HSCs after a 10-day culture of total BM cells. Culture of BM “side population” (SP) cells, a highly enriched stem cell population, for 10 days resulted in an approximate 8-fold expansion of repopulating HSCs. Similar to freshly isolated HSCs, repopulating HSCs after culture were positive for the stem cell markers Sca-1, Kit, and CD31 and receptors for IGF-2. Surprisingly, prion protein and Tie-2, which are present on freshly isolated HSCs, were not on cultured HSCs. Two other HSC markers, Endoglin and Mpl, were expressed only on a portion of cultured HSCs. Therefore, the surface phenotype of ex vivo–expanded HSCs is different from that of freshly isolated HSCs, but this plasticity of surface phenotype does not significantly alter their repopulation capability.
Identification of a transiently exposed VE-cadherin epitope that allows for specific targeting of an antibody to the tumor neovasculature
Authors: May Chad , Doody Jacqueline F. , Abdullah Rashed , Balderes Paul , Xu Xiaohong , Chen Chien Peter , Zhu Zhenping , Shapiro Lawrence , Kussie Paul , Hicklin Daniel J. , Liao Fang , Bohlen Peter
Published: February 2005

VE-cadherin is an adhesion molecule localized at the adherens junctions of endothelial cells. It is crucial for the proper assembly of vascular structures during angiogenesis and maintaining vascular integrity. We have studied 3 monoclonal antibodies (mAbs) against murine VE-cadherin that inhibit angiogenesis and tumor growth. Two of these, BV13 and 10G4, also disrupted normal vessels, resulting in severe vascular leakage, whereas the third, E4G10, did not. The goal of the current report was to identify the epitope of E4G10 and distinguish it from those of the disruptive mAbs. We mapped the epitope of E4G10 to within the first 10 amino acids of mature VE-cadherin and demonstrated that conserved tryptophan residues in this sequence are required for VE-cadherin–mediated trans-adhesion. The disruptive mAbs target a different epitope within amino acids 45 to 56, which structural homology modeling suggests is not involved in trans-adhesion. From our studies, we hypothesize that E4G10 can only bind the neovasculature, where VE-cadherin has not yet engaged in trans-adhesion and its epitope is fully exposed. Thus, E4G10 can inhibit junction formation and angiogenesis but is unable to target normal vasculature because its epitope is masked. In contrast, BV13 and 10G4 bind an epitope that is accessible regardless of VE-cadherin interactions, leading to the disruption of adherens junctions. Our findings establish the immediate N-terminal region of VE-cadherin as a novel target for inhibiting angiogenesis.
Src homology 2 domain-containing inositol-5-phosphatase 1 (SHIP1) negatively regulates TLR4-mediated LPS response primarily through a phosphatase activity- and PI-3K-independent mechanism
Authors: An Huazhang , Xu Hongmei , Zhang Minghui , Zhou Jun , Feng Tao , Qian Cheng , Qi Runzi , Cao Xuetao
Published: February 2005

Src homology 2 (SH2) domain-containing inositol-5-phosphatase 1 (SHIP1) plays important roles in negatively regulating the activation of immune cells primarily via the phosphoinositide 3-kinase (PI-3K) pathway by catalyzing the PI-3K product PtdIns-3,4,5P3 (phosphatidylinositol-3,4,5-triphosphate) into PtdIns-3,4P2. However, the role of SHIP1 in Toll-like receptor 4 (TLR4)-mediated lipopolysaccharide (LPS) response remains unclear. Here we demonstrate that SHIP1 negatively regulates LPS-induced inflammatory response via both phosphatase activity-dependent and -independent mechanisms in macrophages. SHIP1 becomes tyrosine phosphorylated and up-regulated upon LPS stimulation in RAW264.7 macrophages. SHIP1-specific RNA-interfering and SHIP1 overexpression experiments demonstrate that SHIP1 inhibits LPS-induced tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) production by negatively regulating the LPS-induced combination between TLR4 and myeloid differentiation factor 88 (MyD88); activation of Ras (p21ras protein), PI-3K, extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun NH2-terminal kinase (JNK); and degradation of IκB-α. SHIP1 also significantly inhibits LPS-induced mitogen-activated protein kinase (MAPK) activation in TLR4-reconstitited COS7 cells. Although SHIP1-mediated inhibition of PI-3K is dependent on its phosphatase activity, phosphatase activity-disrupted mutant SHIP1 remains inhibitory to LPS-induced TNF-α production. Neither disrupting phosphatase activity nor using the PI-3K pathway inhibitor LY294002 or wortmannin could significantly block SHIP1-mediated inhibition of LPS-induced ERK1/2, p38, and JNK activation and TNF-α production, demonstrating that SHIP1 inhibits LPS-induced activation of MAPKs and cytokine production primarily by a phosphatase activity- and PI-3K-independent mechanism. (Blood. 2005;105:4685-4692)
Extent of exposure to environmental tobacco smoke (ETS) and its dose-response relation to respiratory health among adults
Authors: Maziak Wasim , Ward Kenneth D , Rastam Samer , Mzayek Fawaz , Eissenberg Thomas
Published: February 2005

Background

There is a dearth of standardized studies examining exposure to environmental tobacco smoke (ETS) and its relationship to respiratory health among adults in developing countries.

Methods

In 2004, the Syrian Center for Tobacco Studies (SCTS) conducted a population-based survey using stratified cluster sampling to look at issues related to environmental health of adults aged 18–65 years in Aleppo (2,500,000 inhabitants). Exposure to ETS was assessed from multiple self-reported indices combined into a composite score (maximum 22), while outcomes included both self-report (symptoms/diagnosis of asthma, bronchitis, and hay fever), and objective indices (spirometric assessment of FEV1 and FVC). Logistic and linear regression analyses were conducted to study the relation between ETS score and studied outcomes, whereby categorical (tertiles) and continuous scores were used respectively, to evaluate the association between ETS exposure and respiratory health, and explore the dose-response relationship of the association.

Results

Of 2038 participants, 1118 were current non-smokers with breath CO levels ≤ 10 ppm (27.1% men, mean age 34.7 years) and were included in the current analysis. The vast majority of study participants were exposed to ETS, whereby only 3.6% had ETS score levels ≤ 2. In general, there was a significant dose-response pattern in the relationship of ETS score with symptoms of asthma, hay fever, and bronchitis, but not with diagnoses of these outcomes. The magnitude of the effect was in the range of twofold increases in the frequency of symptoms reported in the high exposure group compared to the low exposure group. Severity of specific respiratory problems, as indicated by frequency of symptoms and health care utilization for respiratory problems, was not associated with ETS exposure. Exposure to ETS was associated with impaired lung function, indicative of airflow limitation, among women only.

Conclusions

This study provides evidence for the alarming extent of exposure to ETS among adult non-smokers in Syria, and its dose-response relationship with respiratory symptoms of infectious and non-infectious nature. It calls for concerted efforts to increase awareness of this public health problem and to enforce regulations aimed at protecting non-smokers.
Recent Hits Acquired by BLAST (ReHAB): A tool to identify new hits in sequence similarity searches
Authors: Whitney Joe , Esteban David J , Upton Chris
Published: February 2005

Background

Sequence similarity searching is a powerful tool to help develop hypotheses in the quest to assign functional, structural and evolutionary information to DNA and protein sequences. As sequence databases continue to grow exponentially, it becomes increasingly important to repeat searches at frequent intervals, and similarity searches retrieve larger and larger sets of results. New and potentially significant results may be buried in a long list of previously obtained sequence hits from past searches.

Results

ReHAB (Recent Hits Acquired from BLAST) is a tool for finding new protein hits in repeated PSI-BLAST searches. ReHAB compares results from PSI-BLAST searches performed with two versions of a protein sequence database and highlights hits that are present only in the updated database. Results are presented in an easily comprehended table, or in a BLAST-like report, using colors to highlight the new hits. ReHAB is designed to handle large numbers of query sequences, such as whole genomes or sets of genomes. Advanced computer skills are not needed to use ReHAB; the graphics interface is simple to use and was designed with the bench biologist in mind.

Conclusions

This software greatly simplifies the problem of evaluating the output of large numbers of protein database searches.
Genetic variation analysis of the Bali street dog using microsatellites
Authors: Irion Dawn N , Schaffer Alison L , Grant Sherry , Wilton Alan N , Pedersen Niels C
Published: February 2005

Background

Approximately 800,000 primarily feral dogs live on the small island of Bali. To analyze the genetic diversity in this population, forty samples were collected at random from dogs in the Denpasar, Bali region and tested using 31 polymorphic microsatellites. Australian dingoes and 28 American Kennel Club breeds were compared to the Bali Street Dog (BSD) for allelic diversity, heterozygosities, F-statistics, GST estimates, Nei's DA distance and phylogenetic relationships.

Results

The BSD proved to be the most heterogeneous, exhibiting 239 of the 366 total alleles observed across all groups and breeds and had an observed heterozygosity of 0.692. Thirteen private alleles were observed in the BSD with an additional three alleles observed only in the BSD and the Australian dingo. The BSD was related most closely to the Chow Chow with a FST of 0.088 and also with high bootstrap support to the Australian dingo and Akita in the phylogenetic analysis.

Conclusions

This preliminary study into the diversity and relationship of the BSD to other domestic and feral dog populations shows the BSD to be highly heterogeneous and related to populations of East Asian origin. These results indicate that a viable and diverse population of dogs existed on the island of Bali prior to its geographic isolation approximately 12,000 years ago and has been little influenced by domesticated European dogs since that time.
The mannose receptor is expressed by subsets of APC in non-lymphoid organs
Authors: Linehan Sheena A
Published: February 2005

Background

The mannose receptor (MR) is an endocytic receptor of Mφ and endothelial cell subsets whose natural ligands include both self glycoproteins and microbial glycans. It is also expressed by immature cultured dendritic cells (DC), where it mediates high efficiency uptake of glycosylated antigens, yet its role in antigen handling in vivo is unknown. Knowledge of which APC subsets express MR will assist the design of experiments to address its immunological functions. Here the expression of MR by MHC class II positive APC in non-lymphoid organs of the mouse is described.

Results

MR positive APC were identified in several peripheral organs: skin, liver, cardiac and skeletal muscle and tongue. MR positive cells in salivary gland, thyroid and pancreas coexpressed MHC class II and the myeloid markers macrosialin and sialoadhesin, but not the dendritic cell markers CD11c or DEC-205. MR and MHC class II colocalised in confocal microscope images, implying that antigen capture may be the primary role of MR in these cells. Distinct ligands of MR were found in salivary gland and pancreas tissue lysates that are candidate physiological ligands of MR positive APC in these organs.

Conclusions

The tissue and subcellular distribution of MR suggest it is appropriately located to serve as a high efficiency antigen uptake receptor of APC.
Quantitative evaluation and modeling of two-dimensional neovascular network complexity: the surface fractal dimension
Authors: Grizzi Fabio , Russo Carlo , Colombo Piergiuseppe , Franceschini Barbara , Frezza Eldo E , Cobos Everardo , Chiriva-Internati Maurizio
Published: February 2005

Background

Modeling the complex development and growth of tumor angiogenesis using mathematics and biological data is a burgeoning area of cancer research. Architectural complexity is the main feature of every anatomical system, including organs, tissues, cells and sub-cellular entities. The vascular system is a complex network whose geometrical characteristics cannot be properly defined using the principles of Euclidean geometry, which is only capable of interpreting regular and smooth objects that are almost impossible to find in Nature. However, fractal geometry is a more powerful means of quantifying the spatial complexity of real objects.

Methods

This paper introduces the surface fractal dimension (D
s
) as a numerical index of the two-dimensional (2-D) geometrical complexity of tumor vascular networks, and their behavior during computer-simulated changes in vessel density and distribution.

Results

We show that D
s
significantly depends on the number of vessels and their pattern of distribution. This demonstrates that the quantitative evaluation of the 2-D geometrical complexity of tumor vascular systems can be useful not only to measure its complex architecture, but also to model its development and growth.

Conclusions

Studying the fractal properties of neovascularity induces reflections upon the real significance of the complex form of branched anatomical structures, in an attempt to define more appropriate methods of describing them quantitatively. This knowledge can be used to predict the aggressiveness of malignant tumors and design compounds that can halt the process of angiogenesis and influence tumor growth.
Cardiovascular comorbidities among public health clinic patients with diabetes: the Urban Diabetics Study
Authors: Robbins Jessica M , Webb David A , Sciamanna Christopher N
Published: February 2005

Background

We sought to determine the frequency and distribution of cardiovascular comorbidities in a large cohort of low-income patients with diabetes who had received primary care for diabetes at municipal health clinics.

Methods

Outpatient data from the Philadelphia Health Care Centers was linked with hospital discharge data from all Pennsylvania hospitals and death certificates.

Results

Among 10,095 primary care patients with diabetes, with a mean observation period of 4.6 years (2.8 after diabetes diagnosis), 2,693 (14.3%) were diagnosed with heart disease, including 270 (1.4%) with myocardial infarction and 912 (4.8%) with congestive heart failure. Cerebrovascular disease was diagnosed in 588 patients (3.1%). Over 77% of diabetic patients were diagnosed with hypertension. Incidence rates of new complications ranged from 0.6 per 100 person years for myocardial infarction to 26.5 per 100 person years for hypertension. Non-Hispanic whites had higher rates of myocardial infarction, and Hispanics and Asians had fewer comorbid conditions than African Americans and non-Hispanic whites.

Conclusion

Cardiovascular comorbidities were common both before and after diabetes diagnosis in this low-income cohort, but not substantially different from mixed-income managed care populations, perhaps as a consequence of access to primary care and pharmacy services.
Deciphering structure and topology of conserved COG2042 orphan proteins
Authors: Armengaud Jean , Dedieu Alain , Solques Olivier , Pellequer Jean-Luc , Quemeneur Eric
Published: February 2005

Background

The cluster of orthologous group COG2042 has members in all sequenced Eukaryota as well as in many Archaea. The cellular function of these proteins of ancient origin remains unknown. PSI-BLAST analysis does not indicate a possible link with even remotely-related proteins that have been functionally or structurally characterized. As a prototype among COG2042 orthologs, SSO0551 protein from the hyperthermophilic archaeon Sulfolobus solfataricus was purified to homogeneity for biophysical characterization.

Results

The untagged protein is thermostable and behaves as a monomeric protein in gel filtration experiment. Several mass spectrometry-based strategies were combined to obtain a set of low resolution structural information. Kinetic data from limited proteolysis with various endoproteases are concordant in pointing out that region Glu73-Arg78 is hyper-sensitive, and thus accessible and flexible. Lysine labeling with NHS-biotin and cross-linking with DTSSP revealed that the 35 amino acid RLI motif at the N terminus is solvent exposed. Cross-links between Lys10-Lys14 and Lys23-Lys25 indicate that these residues are spatially close and in adequate conformation to be cross-linked. These experimental data have been used to rank multiple three-dimensional models generated by a de novo procedure.

Conclusion

Our data indicate that COG2042 proteins may share a novel fold. Combining biophysical, mass-spectrometry data and molecular model is a useful strategy to obtain structural information and to help in prioritizing targets in structural genomics programs.
Interactions between xenoestrogens and ketoconazole on hepatic CYP1A and CYP3A, in juvenile Atlantic cod (Gadus morhua)
Authors: Hasselberg Linda , Grøsvik Bjørn E , Goksøyr Anders , Celander Malin C
Published: February 2005

Background

Xenoestrogens and antifungal azoles probably share a common route of metabolism, through hepatic cytochrome P450 (CYP) enzymes. Chemical interactions with metabolic pathways may affect clearance of both xenobiotics and endobiotics. This study was carried out to identify possible chemical interactions by those substances on CYP1A and CYP3A, in Atlantic cod liver. We investigated effects of two xenoestrogens (nonylphenol and ethynylestradiol) and of the model imidazole ketoconazole, alone and in combination.

Results

Treatment with ketoconazole resulted in 60% increase in CYP1A-mediated ethoxyresorufin-O-deethylase (EROD) activity. Treatment with nonylphenol resulted in 40% reduction of CYP1A activity. Combined exposure to ketoconazole and nonylphenol resulted in 70% induction of CYP1A activities and 93% increase in CYP1A protein levels. Ketoconazole and nonylphenol alone or in combination had no effect on CYP3A expression, as analyzed by western blots. However, 2-dimensional (2D) gel electrophoresis revealed the presence of two CYP3A-immunoreactive proteins, with a more basic isoform induced by ketoconazole. Treatment with ketoconazole and nonylphenol alone resulted in 54% and 35% reduction of the CYP3A-mediated benzyloxy-4-[trifluoromethyl]-coumarin-O-debenzyloxylase (BFCOD) activity. Combined exposure of ketoconazole and nonylphenol resulted in 98% decrease in CYP3A activity. This decrease was greater than the additive effect of each compound alone. In vitro studies revealed that ketoconazole was a potent non-competitive inhibitor of both CYP1A and CYP3A activities and that nonylphenol selectively non-competitively inhibited CYP1A activity. Treatment with ethynylestradiol resulted in 46% decrease in CYP3A activity and 22% decrease in protein expression in vivo. In vitro inhibition studies in liver microsomes showed that ethynylestradiol acted as a non-competitive inhibitor of CYP1A activity and as an uncompetitive inhibitor of CYP3A activity.

Conclusions

Ketoconazole, nonylphenol and ethynylestradiol all interacted with CYP1A and CYP3A activities and protein expression in Atlantic cod. However, mechanisms of interactions on CYP1A and CYP3A differ between theses substances and combined exposure had different effects than exposure to single compounds. Thus, CYP1A and CYP3A mediated clearance may be impaired in situations of mixed exposure to those types of compounds.
Remembering George L. Wied, M.D., February 7, 1921-July 25, 2004
Authors: Rosenthal Dorothy L
Published: February 2005

A personal tribute to George L. Wied, M.D., a founder of the medical subspecialty, cytopathology, who died July 25, 2004.
A conditional-lethal vaccinia virus mutant demonstrates that the I7L gene product is required for virion morphogenesis
Authors: Byrd Chelsea M , Hruby Dennis E
Published: February 2005

A conditional-lethal recombinant virus was constructed in which the expression of the vaccinia virus I7L gene is under the control of the tetracycline operator/repressor system. In the absence of I7L expression, processing of the major VV core proteins is inhibited and electron microscopy reveals defects in virion morphogenesis subsequent to the formation of immature virion particles but prior to core condensation. Plasmid-borne I7L is capable of rescuing the growth of this virus and rescue is optimal when the I7L gene is expressed using the authentic I7L promoter. Taken together, these data suggest that correct temporal expression of the VV I7L cysteine proteinase is required for core protein maturation, virion assembly and production of infectious progeny.
Development of the methodology to improve automotive door closing sound
Authors: Cheng C C , Wu F T , Yang K W , Lin F Y , Pan K L , Chen Y Y
Published: February 2005

A systematic method for improving the door closing sound (DCS) of vehicles is developed. Two vehicles are chosen. One is the target used for modification and the other is the competitor for comparison. The primary focus of this paper is to assimilate the DCS of this target vehicle to that of the competitor systematically. Several parameters are developed specifically to represent the DCS quantitatively during the assimilating procedure. These parameters are used to represent the DCS of the target and competitive vehicles and the discrepancy between them. Contribution analysis based on Maxwell reciprocity is proposed to rank the critical components that have the most impact on the DCS of the target vehicle. Therefore the DCS of the target vehicle can be improved by choosing the proper component for modification while taking cost into consideration. Finally, several examples of component modifications are demonstrated to show that the DCS of the target vehicle can be tailored to be close to that of the competitor in a cost effective way based on the proposed methodology and parameters of the DCS.
A Two-Moment Approximation for the GI/G/c Queue with Finite Capacity
Authors: Choi Dae W. , Kim Nam K. , Chae Kyung C.
Published: February 2005

In this paper, we consider the steady-state queue length of the multiserver finite-capacity GI/G/c/c+r queue. As a result, we first obtain an exact transform-free expression for the steady-state queue-length distribution. Making use of this result, we then present a simple two-moment approximation for the queue-length distribution. From this, approximations for some important performance measures, such as the loss probability, the mean queue length, and the mean waiting time, are also obtained. In addition, we propose an approximation for the minimal buffer size that keeps the loss probability below an acceptable level. Extensive numerical experiments show that our approximation is extremely simple yet fairly good in its performance.
Role of Pentoxifylline and Vitamin E in Attenuation of Radiation-Induced Fibrosis
Authors: Chiao Teresa B , Lee Audrey J
Published: February 2005

OBJECTIVE:

To evaluate the use of pentoxifylline and vitamin E as monotherapy and in combination for the treatment of radiation-induced fibrosis (RIF).

DATA SOURCES:

Literature retrieval was performed through MEDLINE (1966–March 2004) using the terms vitamin E, α-tocopherol, pentoxifylline, radiation-induced fibrosis, and radiation injury.

DATA SYNTHESIS:

Few treatments exist for managing RIF of soft tissues. Due to its antioxidant properties, vitamin E may reduce the oxidative damage induced by radiation. The precise mechanism of action for pentoxifylline in management of RIF remains unclear. Uncontrolled studies evaluating vitamin E or pentoxifylline as monotherapy in RIF have shown modest improvement in clinical regression of fibrosis. However, controlled data are needed to verify these benefits. Studies involving pentoxifylline plus vitamin E demonstrated regression in RIF. The combination was more effective than placebo and may be superior to monotherapy with either agent. Adverse effects were rarely reported in the studies and consisted mainly of gastrointestinal and nervous system effects.

CONCLUSIONS:

Overall, pentoxifylline is well tolerated and is one of the few commercially available drugs with clinical data for management of RIF. Despite a lack of large, well-designed clinical trials, pentoxifylline plus vitamin E should be considered as an option in patients with symptomatic RIF.
Hyperglycemia in the Hospital Setting: The Case for Improved Control among Non-Diabetics
Authors: Conner Therese M , Flesner-Gurley Kelly R , Barner Jamie C
Published: February 2005

OBJECTIVE:

To review studies on the role of hyperglycemia in acutely ill adults, regardless of diabetes diagnosis, and the impact of glucose control on health outcomes.

DATA SOURCES:

Searches on Ovid MEDLINE, Ovid Evidence-Based Medicine (EBM), and PubMed MEDLINE, limited to articles written in English, trials conducted on adult subjects, and material published between 1994 and April 2004. Search words included the major MeSH term hyperglycemia and title words glucose, hyperglycemia/hyperglycemic, or insulin therapy, with text words admission, hospitalized, inhospital, or inpatient.

STUDY SELECTION AND DATA EXTRACTION:

All articles identified from the data sources were evaluated, and all information deemed relevant was included in this review.

DATA SYNTHESIS:

Hyperglycemia, even in patients without diabetes, has been shown to be detrimental among inpatients in medical and surgical units, as well as in critical care. A review of 25 outcomes studies indicated that the majority of research on this topic used retrospective or prospective cohort designs; only 2 were conducted as randomized controlled studies. In general, the findings demonstrated negative impact on outcomes among various patient populations with hyperglycemia including increased lengths of stay, health complications, utilization of resources, and risk of mortality.

CONCLUSIONS:

Studies report that hyperglycemia is a common but detrimental condition and that better control in the hospital setting decreases short- and long-term risk of mortality, illness complications, hospital lengths of stay, and healthcare costs. Increased efforts to treat hyperglycemia and screen for diabetes are needed in the hospital setting. Future studies on cost-effective approaches to glucose control are recommended.
Adverse Drug Reaction and Medication Error Reporting by Pharmacy Students
Authors: Sears Erin L , Generali Joyce A
Published: February 2005

BACKGROUND:

The reporting of adverse drug reactions (ADRs) and medication errors is the responsibility of all who are involved, particularly pharmacists. Since pharmacists are often privy to information surrounding ADRs and medication errors, it is of utmost importance that they are educated regarding the procedures of reporting.

OBJECTIVE:

To determine pharmacy students' knowledge of and ability to report ADRs and medication errors.

METHODS:

A total of 1322 students from 9 colleges of pharmacy were surveyed.

RESULTS:

The largest group of respondents was fifth-year pharmacy students (38%) followed by third-, fourth-, and sixth-year students (28%, 26%, and 8%, respectively). The majority of students reported learning about ADR and medication error reporting programs via didactic experiences. In comparison, fewer students cited alternative mechanisms of learning, including experiential rotations and work experience. Overall, respondents demonstrated the most experience with MedWatch and the least experience with the Vaccine Adverse Event Reporting System (VAERS). As students progressed through pharmacy curricula, there was a positive trend in the ability to locate and complete MedWatch forms. For VAERS and Medication Error Reporting (MER) program forms, however, this positive trend was broken at year 4. For all programs, significantly fewer students demonstrated appropriate use of the forms compared with those indicating familiarity with the programs.

CONCLUSIONS:

This study demonstrated that students are becoming familiar with ADR and MER programs via the college curriculum; however, there is opportunity for greater exposure and understanding. Colleges of pharmacy should continually seek methods to strengthen the education provided to pharmacy students regarding these programs.
Dramatic Improvement in down Syndrome—Associated Cognitive Impairment with Donepezil
Authors: Kondoh Tatsuro , Amamoto Nagisa , Doi Tomoki , Hamada Hitomi , Ogawa Yoji , Nakashima Mikiro , Sasaki Hitoshi , Aikawa Katsuyo , Tanaka Tatsuhiko , Aoki Mizue , Harada Junji , Moriuchi Hiroyuki
Published: February 2005

OBJECTIVE:

To report 2 cases of patients with Down syndrome and severe cognitive impairment who gained dramatic improvements in quality of life (QOL) upon donepezil treatment.

CASE SUMMARIES:

Case 1. A 38-year-old woman with Down syndrome, diagnosed with secondary progressive dementia when her mental state had deteriorated rapidly after graduation from junior high school, started donepezil treatment. The loading dose was 3 mg/day and was increased to 5 mg/day for maintenance. One month after the dose was increased, adverse effects such as soft stool and urinary incontinence appeared. These adverse effects disappeared when the dose was decreased again to 3 mg/day. Her QOL improved dramatically with this minimal dose. She recovered verbal and written communication skills that she had lost for the past 21 years. Case 2. A 22-year-old man with Down syndrome, who had been diagnosed as having severe mental retardation, was put on donepezil therapy. Both loading and maintenance doses were 3 mg/day. His QOL had also dramatically improved, with some recovery in verbal communication. Transient agitation/violence and transient muscle weakness appeared during the first few months of treatment.

DISCUSSION:

Patients with Down syndrome may be more sensitive to donepezil therapy than others and may benefit from this medicine, although they may also have adverse effects more frequently.

CONCLUSIONS:

Donepezil may be a useful medicine for some patients with Down syndrome with severe cognitive impairment or mental retardation if the adverse effects are manageable.
Clarithromycin—Nifedipine Interaction as Possible Cause of Vasodilatory Shock
Authors: Gerónimo-Pardo Manuel , Cuartero-del-Pozo Ana B , Jiménez-Vizuete José M , Cortiñas-Sáez Manuel , Peyró-García Ramón
Published: February 2005

OBJECTIVE:

To report a case of vasodilatory shock possibly resulting from a clarithromycin—nifedipine interaction.

CASE SUMMARY:

A 77-year-old male with uncontrollable hypertension developed shock, heart block, and multiorgan failure 2 days after clarithromycin was added to his antihypertensive treatment (nifedipine, captopril, doxazosin). Invasive monitoring revealed hyperdynamic shock with decreased systemic vascular resistances.

DISCUSSION:

Nifedipine is metabolized by isoenzyme CYP3A4. This metabolic pathway is inhibited by clarithromycin, thus potentially increasing the plasma nifedipine concentration, which may lead to excessive calcium-channel blocker effects. Clinical manifestations of excessive calcium-channel blockade comprise hypotension or vasodilatory shock and heart block, as in our case. An objective causality assessment revealed that this drug interaction was the possible cause of these adverse effects. Because of an initial diagnosis of septic shock, suspicion of this entity was delayed and specific diagnostic and treatment were not possible.

CONCLUSIONS:

This life-threatening clinical picture, including shock and heart block, was possibly the result of a pharmacokinetic interaction between clarithromycin and nifedipine.
Impact of Topiramate on Serum Bicarbonate Concentrations in Adults
Authors: Garris Shauna S , Oles Karen S
Published: February 2005

BACKGROUND:

Topiramate is an antiepileptic medication with multiple pharmacologic effects, including inhibition of carbonic anhydrase activity. It is associated with metabolic acidosis in both children and adults.

OBJECTIVE:

To evaluate the incidence and magnitude of the effect of topiramate on serum bicarbonate concentrations in an adult population.

METHODS:

This was a retrospective cohort study. Data were evaluated to assess the relationship between serum bicarbonate concentrations before and during topiramate therapy.

RESULTS:

Fifty-four patients (40 females) with a mean age of 47.6 years (range 19–89) were included in the study. Mean ± SD serum bicarbonate concentrations before and during topiramate therapy were 26.8 ± 2.9 mEq/L (range 21–36) and 21.7 ± 3.6 mEq/L (range 13–29), respectively, with a mean difference of 5.1 (95% CI 3.7 to 6.5; p < 0.001). Twenty-six patients (48%) had low serum bicarbonate concentrations while on topiramate, with a mean concentration of 18.8 mEq/L (range 13–21).

CONCLUSIONS:

Topiramate was associated with metabolic acidosis in 48% of the patients studied, which did not result in clinically significant problems.