bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin secretion-independent effects of GLP-1 on canine liver glucose metabolism do not involve portal vein GLP-1 receptors
Authors: Dardevet Dominique , Moore Mary Courtney , DiCostanzo Catherine A. , Farmer Ben , Neal Doss W. , Snead Wanda , Lautz Margaret , Cherrington Alan D.
Published: July 2005

Whether glucagon-like peptide (GLP)-1 requires the hepatic portal vein to elicit its insulin secretion-independent effects on glucose disposal in vivo was assessed in conscious dogs using tracer and arteriovenous difference techniques. In study 1, six conscious overnight-fasted dogs underwent oral glucose tolerance testing (OGTT) to determine target GLP-1 concentrations during clamp studies. Peak arterial and portal values during OGTT ranged from 23 to 65 pM and from 46 to 113 pM, respectively. In study 2, we conducted hyperinsulinemic-hyperglycemic clamp experiments consisting of three periods (P1, P2, and P3) during which somatostatin, glucagon, insulin and glucose were infused. The control group received saline, the PePe group received GLP-1 (1 pmol·kg−1·min−1) peripherally, the PePo group received GLP-1 (1 pmol·kg−1·min−1) peripherally (P2) and then intraportally (P3), and the PeHa group received GLP-1 (1 pmol·kg−1·min−1) peripherally (P2) and then through the hepatic artery (P3) to increase the hepatic GLP-1 load to the same extent as in P3 in the PePo group ( n = 8 dogs/group). Arterial GLP-1 levels increased similarly in all groups during P2 (∼50 pM), whereas portal GLP-1 levels were significantly increased (2-fold) in the PePo vs. PePe and PeHa groups during P3. During P2, net hepatic glucose uptake (NHGU) increased slightly but not significantly (vs. P1) in all groups. During P3, GLP-1 increased NHGU in the PePo and PeHa groups more than in the control and PePe groups (change of 10.8 ± 1.3 and 10.6 ± 1.0 vs. 5.7 ± 1.0 and 5.4 ± 0.8 μmol·kg−1·min−1, respectively, P < 0.05). In conclusion, physiological GLP-1 levels increase glucose disposal in the liver, and this effect does not involve GLP-1 receptors located in the portal vein.
Protection of HIF-1-deficient primary renal tubular epithelial cells from hypoxia-induced cell death is glucose dependent
Authors: Biju Mangatt P. , Akai Yasuhiro , Shrimanker Nikita , Haase Volker H.
Published: July 2005

Ischemic acute renal failure is a frequent clinical problem in hospitalized patients and is associated with significant mortality. Hypoxia-inducible factor 1 (HIF-1) mediates cellular adaptation to hypoxia by regulating biological processes important for cell survival, which include glycolysis, angiogenesis, erythropoiesis, apoptosis, and proliferation. To investigate the role of HIF-1 in hypoxia-induced renal epithelial cell death, we generated mice that allow inactivation of HIF-1α by tetracycline-inducible Cre-loxP-mediated recombination in primary renal proximal tubule cells (PRPTC), resulting in a suppression of HIF-1-mediated gene transcription during oxygen deprivation. In the absence of glucose, the onset and the degree of hypoxia-induced cell death in HIF-1-deficient PRPTC were comparable to wild-type cells. However, when glucose availability was limited, the onset of cell death was delayed in either PRPTC that were HIF-1 deficient or in wild-type PRPTC when glycolysis or glucose uptake was partially inhibited. Our findings suggest in an in vitro genetic model that 1) the generation of adequate energy levels for the maintenance of PRPTC viability under hypoxia does not require HIF-1 and 2) that HIF-1 regulates the timing of hypoxia-induced cell death and apoptosis onset through its effects on glucose consumption.
Role of heme oxygenase-1 in endotoxemic acute renal failure
Authors: Poole Brian , Wang Wei , Chen Yung-Chang , Zolty Einath , Falk Sandor , Mitra Amitabha , Schrier Robert
Published: July 2005

The pathogenesis of septic acute renal failure (ARF) involves systemic vasodilation with compensatory upregulation of vasoconstrictors. This can lead to renal vasoconstriction and ARF. Heme oxygenase (HO) is the rate-limiting step in heme metabolism and produces carbon monoxide (CO) and biliverdin. HO-1 is an inducible form of the enzyme and is expressed in response to cell injury. It was hypothesized in endotoxemia, induction of HO-1 would lead to increased production of the vasodilator CO, lower blood pressure, and decrease renal function. The role of HO-1 was therefore examined in a mouse model of endotoxemia. One group of mice received LPS alone and were compared with mice that received LPS in addition to an inhibitor of HO-1, zinc protoporphyrin (ZnPP). Treatment of mice with LPS resulted in significant increases in the protein expression of HO-1 compared with controls treated with vehicle. Immunohistochemical analysis localized this upregulation to both the proximal and distal tubules as well as the vasculature. Hemodynamic studies were performed during endotoxemia and the mean arterial pressure (MAP) was found to be significantly higher in the HO-1 inhibitor-treated compared with vehicle-treated mice (78 ± 3 vs. 64 ± 2 mmHg, P < 0.01). It was found that the inhibitor group had higher renal blood flows (RBF) also during endotoxemia (1.8 ± 0.2 vs. 0.68 ± 0.1 ml/min, P < 0.01). Furthermore, when renal vascular resistance (RVR) was calculated, there was a significant decrease in RVR in the inhibitor group (43.5 ± 3.4 vs. 95.9 ± 11.3 mmHg·ml−1·min−1, P < 0.01). In concert with the hemodynamic data, glomerular filtration rate (GFR), as measured by inulin clearance, was higher in the HO inhibitor compared with the vehicle controls during endotoxemia (111.5 ± 19.5 vs. 66.0 ± 3.5 μl/min, P < 0.05). In summary, during endotoxemia ARF, inhibiting HO-1 with ZnPP resulted in the protection of renal function. The renal protection was associated with significantly improved systemic hemodynamics, less renal vasoconstriction, and a higher GFR.
Computer Simulation of Stepping in the Hind Legs of the Cat: An Examination of Mechanisms Regulating the Stance-to-Swing Transition
Authors: Ekeberg Örjan , Pearson Keir
Published: July 2005

Physiological studies in walking cats have indicated that two sensory signals are involved in terminating stance in the hind legs: one related to unloading of the leg and the other to hip extension. To study the relative importance of these two signals, we developed a three-dimensional computer simulation of the cat hind legs in which the timing of the swing-to-stance transition was controlled by signals related to the force in ankle extensor muscles, the angle at the hip joint, or a combination of both. Even in the absence of direct coupling between the controllers for each leg, stable stepping was easily obtained using either a combination of ankle force and hip position signals or the ankle force signal alone. Stable walking did not occur when the hip position signal was used alone. Coupling the two controllers by mutual inhibition restored stability, but it did not restore the correct timing of stepping of the two hind legs. Small perturbations applied during the swing phase altered the movement of the contralateral leg in a manner that tended to maintain alternating stepping when the ankle force signal was included but tended to shift coordination away from alternating when the hip position signal was used alone. We conclude that coordination of stepping of the hind legs depends critically on load-sensitive signals from each leg and that mechanical linkages between the legs, mediated by these signals, play a significant role in establishing the alternating gait.
Activity-Independent Coregulation of IA and Ih in Rhythmically Active Neurons
Authors: MacLean Jason N. , Zhang Ying , Goeritz Marie L. , Casey Richard , Oliva Ricardo , Guckenheimer John , Harris-Warrick Ronald M.
Published: July 2005

The fast transient potassium or A current ( IA) plays an important role in determining the activity of central pattern generator neurons. We have previously shown that the shal K+ channel gene encodes IA in neurons of the pyloric network in the spiny lobster. To further study how IA shapes pyloric neuron and network activity, we microinjected RNA for a shal-GFP fusion protein into four identified pyloric neuron types. Neurons expressing shal-GFP had a constant increase in IA amplitude, regardless of cell type. This increase in IA was paralleled by a concomitant increase in the hyperpolarization-activated cation current Ih in all pyloric neurons. Despite significant increases in these currents, only modest changes in cell firing properties were observed. We used models to test two hypotheses to explain this failure to change firing properties. First, this may reflect the mislocalization of the expressed shal protein solely to the somata and initial neurites of injected neurons, rendering it electrically remote from the integrating region in the neuropil. To test this hypothesis, we generated a multicompartment model where increases in IA could be localized to the soma, initial neurite, or neuropil/axon compartments. Although spike activity was somewhat more sensitive to increases in neuropil/axon versus somatic/primary neurite IA, increases in IA limited to the soma and primary neurite still evoked much more dramatic changes than were seen in the shal-GFP–injected neurons. Second, the effect of the increased IA could be compensated by the endogenous increase in Ih. To test this, we modeled the compensatory increases of IA and Ih with a cycling two-cell model. We found that the increase in Ih was sufficient to compensate the effects of increased IA, provided that they increase in a constant ratio, as we observed experimentally in both shal-injected and noninjected neurons. Thus an activity-independent homeostatic mechanism maintains constant neuronal activity in the face of dramatic increases in IA.
Evoked H-Reflex and V-Wave Responses During Maximal Isometric, Concentric, and Eccentric Muscle Contraction
Authors: Duclay Julien , Martin Alain
Published: July 2005

This study was designed to investigate the modulations of H-reflex and V-wave responses during passive and maximal active dynamic actions. Experiments were performed on 16 healthy males [age: 24 ± 4 (SD) yr]. Maximal H-reflexes ( Hmax) and M-waves ( MmaxR) were evoked at the same muscle length during passive isometric, shortening and lengthening actions and during maximal voluntary isometric, concentric, and eccentric plantar-flexion. In all contraction types, supra-maximal stimulus intensity was used to evoke the superimposed maximal M wave ( MmaxA) and V wave ( V) of the soleus muscle. At rest, the Hmax/ MmaxR ratio was significantly reduced during lengthening with respect to isometric and shortening actions ( P < 0.05). For each action type, the ratio between H reflex superimposed to the contraction ( Hsup) and MmaxA was not different from Hmax/ MmaxR ratio. When plantar flexors were maximally voluntary activated, the Hsup/ MmaxA ratio was still lower during eccentric contraction as compared with isometric and concentric efforts (0.33 ± 0.03 vs. 0.47 ± 0.02 and 0.50 ± 0.03, P < 0.001), whereas V/ MmaxA ratios were similar for all contraction types (isometric 0.26 ± 0.02; concentric 0.23 ± 0.03, and eccentric 0.24 ± 0.02; P > 0.05). The V/ MmaxA ratio was significantly lower than Hsup/ MmaxA during isometric and concentric MVC ( P < 0.001). No difference was observed between V/ MmaxA and Hsup/ MmaxA ratios during eccentric efforts. The H-reflex modulations, present during lengthening actions, were mainly attributed to presynaptic inhibition of Ia afferents and to homosynaptic postactivation depression. Results on V wave and H reflex suggest that during eccentric MVC, the spinal loop is specifically modulated by the supra-spinal centers and/or neural mechanisms at spinal level.
How to Think about Rules and Rule Following
Authors: Stueber Karsten R.
Published: July 2005

This article will discuss the difficulties of providing a plausible account of rule following in the social realm. It will show that the cognitive model of rule following is not suited for this task. Nevertheless, revealing the inadequacy of the cognitive model does not justify the wholesale dismissal of understanding human practices as rule-following practices, as social theorists like Bourdieu or Dreyfus have argued. Instead it will be shown that rule-following behavior is best understood as being based on a set of complex dispositions. In this manner one is able to account for the causal explanatory role of the notion of a rule.
Norms, Invariance, and Explanatory Relevance
Authors: Henderson David
Published: July 2005

Descriptions of social norms can be explanatory. The erotetic approach to explanation provides a useful framework. I describe one very broad kind of explanation-seeking why-question, a genus that is common to the special sciences, and argue that descriptions of norms can serve as an answer to such why-questions. I draw upon Woodward’s recent discussion of the explanatory role of generalizations with a significant degree of invariance. Descriptions of norms provide what is, in effect, a generalization regarding the kind of historically contingent system— a group or society, a generalization with a significant degree of invariance.
Three Grades of Normative Involvement: Risjord, Stueber, and Henderson on Norms and Explanation
Authors: Roth Paul A.
Published: July 2005

What makes for a good explanation of a person’s actions? Their reasons, or soa natural reply goes. But how do reasons function as part of explanations, that is, within an account of the causes of action? Here philosophers divide concerning the logical relation in which reasons stand to actions. For, tradition holds, reasons evaluatively characterized must be causally inert, inasmuch as the normative features cannot be found in any account of the empirical/descriptive. To countenance reasons as causes thus seems to imply some degree of normative involvement in causal explanation. Mark Risjord opts for full normative involvement while David Henderson insistently denies a role to norms in explanation. Stueber occupies an intermediate position here. I question just whether there exists some “special” problem regarding norms, at least in the form which, I take it, all three of the authors I discuss assume there to be one.
Developmental Factors Related to Deviant Sexual Preferences in Child Molesters
Authors: Lussier Patrick , Beauregard Eric , Proulx Jean , Nicole Alexandre
Published: July 2005

The aim of this study was to investigate the relationship between developmental factors and deviant sexual preferences in child molesters. In total, 146 adult males having committed a sexual offence against a child were included in the study. Three types of factors were investigated: negative experiences during childhood, behavior problems during adolescence, and sexual criminal activity in adulthood. Negative experiences and behavior problems were assessed through a semistructured interview. The sexual criminal activity was determined using police records. Sexual preferences towards children were assessed using phallometric assessment. Hierarchical regression analyses suggested the presence of two developmental pathways. The psychosocial deficits pathway is related to a sexual interest for nonviolent sexual stimuli involving children. The sexualization pathway is associated with a sexual interest for violent sexual stimuli involving children. These two pathways are discussed in light of previous empirical findings related to the development of deviant sexual preferences in child molesters.
Courtship Violence Using Couple Data
Authors: Perry Andrea R. , Fromuth Mary Ellen
Published: July 2005

This study examined courtship violence using couple data. Participants were 50 heterosexual dating couples with at least one member of the couple being a university student. Using the Conflict Tactics Scales 2 (CTS2), both members of a couple reported on received and inflicted physical and psychological violence. The prevalence of physical aggression depended on how violence was defined. On the CTS2, 60% of couples were considered physically violent when within-couple agreement was not considered; this dropped to as low as 28% when agreement had to be present. Women were more likely than men to report inflicting psychological aggression and to report aggressing against their partner with a playful intent. Taken together, these findings demonstrate the need to continue to examine courtship violence, especially by utilizing responses from both members of a couple.
Working Positively With Sexual Offenders
Authors: Marshall William L. , Ward Tony , Mann Ruth E. , Moulden Heather , Fernandez Yolanda M. , Serran Geris , Marshall Liam E.
Published: July 2005

In this article, the authors draw on literatures outside sexual offending and make suggestions for working more positively and constructively with these offenders. Although the management of risk is a necessary feature of treatment, it needs to occur in conjunction with a strength-based approach. An exclusive focus on risk can lead to overly confrontational therapeutic encounters, a lack of rapport between offenders and clinicians, and fragmented and mechanistic treatment delivery. The authors suggest that the goals of sexual offender treatment should be the attainment of good lives, which is achieved by enhancing hope, increasing self-esteem, developing approach goals, and working collaboratively with the offenders. Examples are provided of how these targets may be met. When this is done within a therapeutic context where the treatment providers display empathy and warmth and are rewarding and directive, the authors suggest that treatment effects will be maximized.
Managing Citizen Fears
Authors: West Darrell M. , Orr Marion
Published: July 2005

The authors examine public attitudes toward urban terrorism, focusing on whether emotion or reason is a more important determinant of how people feel. Using the results of a public opinion survey in a large, northeastern city, the authors find that both emotion and reason affect people’s reactions to terrorist attacks. However, this relationship is affected by personal conversation. The more people talk about terrorism, the greater the chance reason rather than fear will dictate reactions. These results have important ramifications for how urban officials deal with homeland security and assuage citizens whose excessive concerns about terrorism have led to costly security expenditures.
Cities and Diversity
Authors: Fainstein Susan S.
Published: July 2005

Diversity has become the new orthodoxy of city planning. The term has several meanings: a varied physical design, mixes of uses, an expanded public realm, and multiple social grouping sexercising their “right to the city.” Its impetus lies in the postmodernist/poststructuralist critique of modernism’s master narratives and more specifically in reactions to the urban landscape created by segregation, urban renewal, massive housing projects, and highway building programs. Privileging diversity raises significant issues. Can planned environments produce diversity or only a “staged authenticity”? Does emphasizing diversity obscure the economic structure? Is there a connection between diversity and economic innovation? Does social diversity necessarily contribute to equity and a broadly satisfying public realm? Rather than setting diversity as the principal goal of city planning, I argue for the model of the just city, based on Nussbaum’s concept of capacities and a recognition of the inevitable trade-offs among equity, diversity, growth, and sustainability.
Information theory-based algorithm for in silico prediction of PCR products with whole genomic sequences as templates
Authors: Cao Youfang , Wang Lianjie , Xu Kexue , Kou Chunhai , Zhang Yulei , Wei Guifang , He Junjian , Wang Yunfang , Zhao Liping
Published: July 2005

Background

A new algorithm for assessing similarity between primer and template has been developed based on the hypothesis that annealing of primer to template is an information transfer process.

Results

Primer sequence is converted to a vector of the full potential hydrogen numbers (3 for G or C, 2 for A or T), while template sequence is converted to a vector of the actual hydrogen bond numbers formed after primer annealing. The former is considered as source information and the latter destination information. An information coefficient is calculated as a measure for fidelity of this information transfer process and thus a measure of similarity between primer and potential annealing site on template.

Conclusion

Successful prediction of PCR products from whole genomic sequences with a computer program based on the algorithm demonstrated the potential of this new algorithm in areas like in silico PCR and gene finding.
Computational tradeoffs in multiplex PCR assay design for SNP genotyping
Authors: Rachlin John , Ding Chunming , Cantor Charles , Kasif Simon
Published: July 2005

Background

Multiplex PCR is a key technology for detecting infectious microorganisms, whole-genome sequencing, forensic analysis, and for enabling flexible yet low-cost genotyping. However, the design of a multiplex PCR assays requires the consideration of multiple competing objectives and physical constraints, and extensive computational analysis must be performed in order to identify the possible formation of primer-dimers that can negatively impact product yield.

Results

This paper examines the computational design limits of multiplex PCR in the context of SNP genotyping and examines tradeoffs associated with several key design factors including multiplexing level (the number of primer pairs per tube), coverage (the % of SNP whose associated primers are actually assigned to one of several available tube), and tube-size uniformity. We also examine how design performance depends on the total number of available SNPs from which to choose, and primer stringency criterial. We show that finding high-multiplexing/high-coverage designs is subject to a computational phase transition, becoming dramatically more difficult when the probability of primer pair interaction exceeds a critical threshold. The precise location of this critical transition point depends on the number of available SNPs and the level of multiplexing required. We also demonstrate how coverage performance is impacted by the number of available snps, primer selection criteria, and target multiplexing levels.

Conclusion

The presence of a phase transition suggests limits to scaling Multiplex PCR performance for high-throughput genomics applications. Achieving broad SNP coverage rapidly transitions from being very easy to very hard as the target multiplexing level (# of primer pairs per tube) increases. The onset of a phase transition can be "delayed" by having a larger pool of SNPs, or loosening primer selection constraints so as to increase the number of candidate primer pairs per SNP, though the latter may produce other adverse effects. The resulting design performance tradeoffs define a benchmark that can serve as the basis for comparing competing multiplex PCR design optimization algorithms and can also provide general rules-of-thumb to experimentalists seeking to understand the performance limits of standard multiplex PCR.
Genotyping of Mycobacterium tuberculosis clinical isolates in two cities of Turkey: Description of a new family of genotypes that is phylogeographically specific for Asia Minor
Authors: Zozio Thierry , Allix Caroline , Gunal Selami , Saribas Zeynep , Alp Alpaslan , Durmaz Riza , Fauville-Dufaux Maryse , Rastogi Nalin , Sola Christophe
Published: July 2005

Background

Population-based bacterial genetics using repeated DNA loci is an efficient approach to study the biodiversity and phylogeographical structure of human pathogens, such asMycobacterium tuberculosis, the agent of tuberculosis. Indeed large genetic diversity databases are available for this pathogen and are regularly updated. No population-based polymorphism data were yet available forM. tuberculosisin Turkey, at the crossroads of Eurasia.

Results

A total of 245 DNAs fromMycobacterium tuberculosisclinical isolates from tuberculosis patients residing in Turkey (Malatya n = 147 or Ankara n = 98) were genotyped by spoligotyping, a high-throughput genotyping method based on the polymorphism of the Direct Repeat locus. Thirty-three spoligotyping-defined clusters including 206 patients and 39 unique patterns were found. The ST41 cluster, as designated according to the international SpolDB3 database project, represented one fourth and when gathered to three genotypes, ST53, ST50 and ST284, one half of all the isolates. Out of 34 clinical isolates harboring ST41 which were further genotyped by IS6110and by MIRU-VNTR typing, a typical 2-copy IS6110-RFLP pattern and a "215125113322" MIRU-VNTR pattern were observed among 21 clinical isolates. Further search in various databases confirms the likely Turkish-phylogeographical specificity of this clonal complex.

Conclusion

We described a new phylogeographically-specific clone ofM. tuberculosis, designated LAM7-TUR. Further investigations to assess its frequency within all regions of Turkey and its phylogeographical origin and phylogenetic position within the globalM. tuberculosisphylogenetic tree will shed new light on its endemicity in Asia Minor.
Patients' views on outcome following head injury: a qualitative study
Authors: Morris Paul Graham , Prior Lindsay , Deb Shoumitro , Lewis Glyn , Mayle Wendy , Burrow Caroline E , Bryant Eleanor
Published: July 2005

Background

Head injuries are a common occurrence, with continuing care in the years following injury being provided by primary care teams and a variety of speciality services. The literature on outcome currently reflects areas considered important by health-care professionals, though these may differ in some respects from the views of head injured individuals themselves. Our study aimed to identify aspects of outcome considered important by survivors of traumatic head injury.

Methods

Thirty-two individuals were interviewed, each of whom had suffered head injury between one and ten years previously from which they still had residual difficulties. Purposive sampling was used in order to ensure that views were represented from individuals of differing age, gender and level of disability. These interviews were fully transcribed and analysed qualitatively by a psychologist, a sociologist and a psychiatrist with regular meetings to discuss the coding.

Results

Aspects of outcome mentioned by head injury survivors which have received less attention previously included: specific difficulties with group conversations; changes in physical appearance due to scarring or weight change; a sense of loss for the life and sense of self that they had before the injury; and negative reactions of others, often due to lack of understanding of the consequences of injury amongst both family and general public.

Conclusion

Some aspects of outcome viewed as important by survivors of head injury may be overlooked by health professionals. Consideration of these areas of outcome and the development of suitable interventions should help to improve functional outcome for patients.
Preconception care by family physicians and general practitioners in Japan
Authors: Kitamura Kazuya , Fetters Michael D , Ban Nobutaro
Published: July 2005

Background

Preconception care provided by family physicians/general practitioners (FP/GPs) can provide predictable benefits to mothers and infants. The objective of this study was to elucidate knowledge of, attitudes about, and practices of preconception care by FP/GPs in Japan.

Methods

A survey was distributed to physician members of the Japanese Academy of Family Medicine. The questionnaire addressed experiences of preconception education in medical school and residency, frequency of preconception care in clinical practice, attitudes about providing preconception care, and perceived need for preconception education to medical students and residents.

Results

Two hundred and sixty-eight of 347 (77%) eligible physicians responded. The most common education they reported receiving was about smoking cessation (71%), and the least was about folic acid supplementation (12%). Many participants reported providing smoking cessation in their practice (60%), though only about one third of respondents advise restricting alcohol intake. Few reported advising calcium supplementation (10%) or folic acid supplementation (4%). About 70% reported their willingness to provide preconception care. Almost all participants believe medical students and residents should have education about preconception care.

Conclusion

FP/GPs in Japan report little training in preconception care and few currently provide it. With training, most participants are willing to provide preconception care themselves and think medical students and residents should receive this education.
L-Glutamine therapy reduces endothelial adhesion of sickle red blood cells to human umbilical vein endothelial cells
Authors: Niihara Yutaka , Matsui Neil M , Shen Yamin M , Akiyama Dean A , Johnson Cage S , Sunga M Alenor , Magpayo John , Embury Stephen H , Kalra Vijay K , Ho Cho Seong , Tanaka Kouichi R
Published: July 2005

Background

We have previously demonstrated that therapy with orally administered L-glutamine improves nicotinamide adenosine dinucleotide (NAD) redox potential of sickle red blood cells (RBC). On further analysis of L-glutamine therapy for sickle cell anemia patients, the effect of L-glutamine on adhesion of sickle RBC to human umbilical vein endothelial cells (HUVEC) was examined.

Methods

The first part of the experiment was conducted with the blood samples of the 5 adult sickle cell anemia patients who had been on L-glutamine therapy for at least 4 weeks on a dosage of 30 grams per day compared to those of patient control group. In the second part of the experiment 6 patients with sickle cell anemia were studied longitudinally. Five of these patients were treated with oral L-glutamine 30 grams daily and one was observed without treatment as the control. t-test and paired t-test were used for determination of statistical significance in cross-sectional and longitudinal studies respectively.

Results

In the first study, the mean adhesion to endothelial cells with the autologous plasma incubated cells were 0.97 ± 0.45 for the treated group and 1.91 ± 0.53 for the nontreated group (p < 0.02). Similarly with lipopolysaccharide (LPS) incubated cells the mean adhesion to endothelial cells were 1.39 ± 0.33 for the treated group and 2.80 ± 0.47 for the untreated group (p < 0.001). With the longitudinal experiment, mean decrease in the adhesion to endothelial cells was 1.13 ± 0.21 (p < 0.001) for the 5 treated patients whereas the control patient had slight increase in the adhesion to endothelial cells.

Conclusion

In these studies, oral L-glutamine administration consistently resulted in improvement of sickle RBC adhesion to HUVEC. These data suggest positive physiological effects of L-glutamine in sickle cell disease.
Off-trial evaluation of bisphosphonates in patients with metastatic breast cancer
Authors: Liauw Winston , Segelov Eva , Lih Anna , Dunleavy Ms Ruth , Links Matthew , Ward Robyn
Published: July 2005

Background

Bisphosphonate therapy has been readily accepted as standard of care for individuals with bone metastases from breast cancer. In this study we determined whether the proportion of patients experiencing a skeletal related event (SRE) in a clinical practice population was similar to that observed in phase III randomized controlled studies.

Methods

A retrospective chart review was conducted of 110 patients receiving intravenous bisphosphonates for advanced breast cancer. The proportion of patients experiencing at least one SRE after 12 months of therapy was determined. SRE included vertebral or non-vertebral fracture, cord compression, surgery and/or radiotherapy to bone.

Results

The proportion of patients who had an SRE was 30% (28 individuals) and the median time to first event was greater than 350 days. Non-vertebral events and radiotherapy were the most frequent type of SRE, while cord compression and hypercalcaemia were rare (1%). Most patients in the study had bone-only disease (58.2%) and most had multiple bone lesions. In the first 12 months the mean duration of exposure to intravenous bisphosphonates was 261 days and most patients remained on treatment until just before death (median 27 days).

Conclusion

This study suggests that the rate of clinically relevant SREs is substantially lower than the event rate observed in phase III clinical trials. We attribute this lower rate to observational bias. In the clinical trial setting it is possible that over-detection of skeletal events occurs due to the utilisation of regular skeletal survey or radionucleotide bone scan, whereas these procedures are not routine in clinical practice. Phase IV observational studies need to be conducted to determine the true benefits of bisphosphonate therapy in order to implement rationale use of bisphosphonates.
Palmoplantar keratoderma is associated with esophagus squamous cell cancer in Van region of Turkey: a case control study
Authors: Ilhan Mahmut , Erbaydar Tugrul , Akdeniz Necmettin , Arslan Sevket
Published: July 2005

Background

Esophagus squamous cell cancer (ESCC) is the most common cancer in women with 20.2% and second in men with 10.7% relative frequency among all cancer cases diagnosed in Van Region in the east of Turkey. Ninety percent of all esophageal cancer cases are ESCC and 20–30% of them have family history of esophageal cancer. The most clear defined hereditary predisposition associated with ESCC is palmoplantar keratoderma (PPK). To examine the relationship between ESCC and PPK, we have carried out this case control study.

Methods

The case group consisted of 48 subjects who had new diagnosis of ESCC and did not receive any chemo or radiotherapy. The control group consisted of 96 healthy individuals who were visitors of their relatives in the hospital. Two control persons who matched for age, gender, living place (urban /rural) and region were selected for each case. All subjects were evaluated for PPK by dermatologist. Evaluation was graded as none, mild, evident and severe. None and mild subjects were classified as negative for PPK; and others as positive. Relationship between ESCC and PPK was evaluated with odds ratios and confidence intervals for cases with or without family history of ESCC.

Results

The PPK frequencies were 92.3% in ESCC cases with family history, 62.5% in ESCC cases without family history, 70.8% in all ESCC cases, and 28.1% in the control group. Odds ratios for cases with or without family history of esophageal cancer, and for the whole case group were found as 30.7 (95%CI = 3.8–247.4), 4.3 (95%CI = 1.9–9.8) and 6.2 (95%CI = 2.9–13.3) respectively.

Conclusion

Presence of PPK lesions represents genetic susceptibility for ESCC. This susceptibility for ESCC is the highest among those who have PPK lesions and a positive family history of esophageal cancer. Furthermore, a PPK sufferer has an increased risk of developing ESCC even if there is no family history of esophageal cancer.
Intensity modulated radiotherapy for high risk prostate cancer based on sentinel node SPECT imaging for target volume definition
Authors: Ganswindt Ute , Paulsen Frank , Corvin Stefan , Eichhorn Kai , Glocker Stefan , Hundt Ilse , Birkner Mattias , Alber Markus , Anastasiadis Aristotelis , Stenzl Arnulf , Bares Roland , Budach Wilfried , Bamberg Michael , Belka Claus
Published: July 2005

Background

The RTOG 94-13 trial has provided evidence that patients with high risk prostate cancer benefit from an additional radiotherapy to the pelvic nodes combined with concomitant hormonal ablation. Since lymphatic drainage of the prostate is highly variable, the optimal target volume definition for the pelvic lymph nodes is problematic. To overcome this limitation, we tested the feasibility of an intensity modulated radiation therapy (IMRT) protocol, taking under consideration the individual pelvic sentinel node drainage pattern by SPECT functional imaging.

Methods

Patients with high risk prostate cancer were included. Sentinel nodes (SN) were localised 1.5–3 hours after injection of 250 MBq 99mTc-Nanocoll using a double-headed gamma camera with an integrated X-Ray device. All sentinel node localisations were included into the pelvic clinical target volume (CTV). Dose prescriptions were 50.4 Gy (5 × 1.8 Gy / week) to the pelvis and 70.0 Gy (5 × 2.0 Gy / week) to the prostate including the base of seminal vesicles or whole seminal vesicles. Patients were treated with IMRT. Furthermore a theoretical comparison between IMRT and a three-dimensional conformal technique was performed.

Results

Since 08/2003 6 patients were treated with this protocol. All patients had detectable sentinel lymph nodes (total 29). 4 of 6 patients showed sentinel node localisations (total 10), that would not have been treated adequately with CT-based planning ('geographical miss') only. The most common localisation for a probable geographical miss was the perirectal area. The comparison between dose-volume-histograms of IMRT- and conventional CT-planning demonstrated clear superiority of IMRT when all sentinel lymph nodes were included. IMRT allowed a significantly better sparing of normal tissue and reduced volumes of small bowel, large bowel and rectum irradiated with critical doses. No gastrointestinal or genitourinary acute toxicity Grade 3 or 4 (RTOG) occurred.

Conclusion

IMRT based on sentinel lymph node identification is feasible and reduces the probability of a geographical miss. Furthermore, IMRT allows a pronounced sparing of normal tissue irradiation. Thus, the chosen approach will help to increase the curative potential of radiotherapy in high risk prostate cancer patients.
Adenomyoepithelial tumours and myoepithelial carcinomas of the breast – a spectrum of monophasic and biphasic tumours dominated by immature myoepithelial cells
Authors: Hungermann Daniela , Buerger Horst , Oehlschlegel Christian , Herbst Hermann , Boecker Werner
Published: July 2005

Background

Adenomyoepithelial tumours and myoepithelial carcinomas of the breast are primarily defined by the presence of neoplastic cells with a myoepithelial immunophenotype. Current classification schemes are based on purely descriptive features and an assessment of individual prognosis is still problematic.

Methods

A series of 27 adenomyoepithelial tumours of the breast was analysed immunohistochemically with antibodies directed against various cytokeratins, p63, smooth muscle alpha-actin (SMA) and vimentin. Additionally, double immunofluorescence and comparative genomic hybridisation (CGH) was performed.

Results

Immunohistochemically, all the tumours showed a constant expression of high molecular weight cytokeratins (Ck) Ck5 and Ck14, p63, SMA and vimentin. With exception of one case diagnosed as myoepithelial carcinoma, all tested tumours expressed low molecular weight cytokeratin Ck18 in variable proportions of cells. Even in monophasic tumours lacking obvious glandular differentiation in conventional staining, a number of neoplastic cells still expressed those cytokeratins. Double immunofluorescence revealed tumour cells exclusively staining for Ck5/Ck14 in the presence of other cell populations that co-expressed high molecular weight Ck5/Ck14 as well as either low molecular weight Ck8/18 or SMA. Based on morphology, we assigned the series to three categories, benign, borderline and malignant. This classification was supported by a stepwise increase in cytogenetic alterations on CGH.

Conclusion

Adenomyoepithelial tumours comprise a spectrum of neoplasms consisting of an admixture of glandular and myoepithelial differentiation patterns. As a key component SMA-positive cells co-expressing cytokeratins could be identified. Although categorisation of adenomyoepithelial tumours in benign, borderline and malignant was supported by results of CGH, any assessment of prognosis requires to be firmly based on morphological grounds. At present it is not yet clear, if and to what extent proposed Ck5-positive progenitor cells contribute to the immunohistochemical and morphological heterogeneity of these neoplasms of the breast.
Internet-based search of randomised trials relevant to mental health originating in the Arab world
Authors: Takriti Yahya , El-Sayeh Hany G , Adams Clive E
Published: July 2005

Background

The internet is becoming a widely used source of accessing medical research through various on-line databases. This instant access to information is of benefit to busy clinicians and service users around the world. The population of the Arab World is comparable to that of the United States, yet it is widely believed to have a greatly contrasting output of randomised controlled trials related to mental health. This study was designed to investigate the existence of such research in the Arab World and also to investigate the availability of this research on-line.

Methods

Survey of findings from three internet-based potential sources of randomised trials originating from the Arab world and relevant to mental health care.

Results

A manual search of an Arabic online current contents service identified 3 studies, MEDLINE, EMBASE, and PsycINFO searches identified only 1 study, and a manual search of a specifically indexed, study-based mental health database, PsiTri, revealed 27 trials.

Conclusion

There genuinely seem to be few trials from the Arab world and accessing these on-line was problematic. Replication of some studies that guide psychiatric/psychological practice in the Arab world would seem prudent.
Pilot survey of oral health-related quality of life: a cross-sectional study of adults in Benin City, Edo State, Nigeria
Authors: Okunseri Christopher , Chattopadhyay Amit , Lugo R Iván , McGrath Colman
Published: July 2005

Background

Oral health studies conducted so far in Nigeria have documented prevalence and incidence of dental disease using traditional clinical measures. However none have investigated the use of an oral health-related quality of life (OHRQoL) instrument to document oral health outcomes. The aims of this study are: to describe how oral health affects and impacts quality of life (QoL) and to explore the association between these affects and the oral health care seeking behavior of adults in Benin City, Edo State, Nigeria.

Methods

A cross-sectional survey recruited 356 adults aged 18–64 years from two large hospital outpatient departments and from members of a university community. Closed-ended oral health questionnaire with "effect and impact" item-questions from OHQoL-UK© instrument was administered by trained interviewers. Collected data included sociodemographic, dental visits, and effects and impact of oral health on QoL. Univariate and bivariable analyses were done and a chi-square test was used to test differences in proportions. Multivariable analyses using ANOVA examined the association between QoL factors and visits to a dentist.

Results

Complete data was available for 83% of the participants. About 62% of participants perceived their oral health as affecting their QoL. Overall, 82%, 63%, and 77% of participants perceived that oral health has an effect on their eating or enjoyment of food, sleep or ability to relax, and smiling or laughing, respectively. Some 46%, 36%, and 25% of participants reported that oral health impact their daily activities, social activities, and talking to people, respectively. Dental visits within the last year was significantly associated with eating, speech, and finance (P < 0.05). The summary score for the oral health effects on QoL ranged from 33 to 80 with a median value of 61 (95% CI: 60, 62) and interquartile range of 52–70. Multivariable modeling suggested a model containing only education (F = 6.5, pr>F = 0.0111). The mean of effects sum score for those with secondary/tertiary education levels (mean = 61.8; 95% CI: 60.6, 62.9) was significantly higher than those with less than secondary level of education (mean = 57.2; 95% CI: 57.2, 60.6).

Conclusion

Most adults in the study reported that oral health affects their life quality, and have little/no impact on their quality of life. Dental visits within the last year were associated with eating, speech, and finance.
Evaluating teaching effectiveness in nursing education:An Iranian perspective
Authors: Salsali Mahvash
Published: July 2005

Background

The main objective of this study was to determine the perceptions of Iranian nurse educators and students regarding the evaluation of teaching effectiveness in university-based programs.

Methods

An exploratory descriptive design was employed. 143 nurse educators in nursing faculties from the three universities in Tehran, 40 undergraduate, and 30 graduate students from Tehran University composed the study sample. In addition, deans from the three nursing faculties were interviewed. A researcher-developed questionnaire was used to determine the perceptions of both faculty and students about evaluating the teaching effectiveness of nurse educators, and an interview guide was employed to elicit the views of deans of faculties of nursing regarding evaluation policies and procedures. Data were analyzed using parametric and nonparametric statistics to identify similarities and differences in perceptions within the Iranian nurse educator group and the student group, and between these two groups of respondents.

Results

While faculty evaluation has always been a major part of university based nursing programs, faculty evaluation must be approached more analytically, objectively, and comprehensively to ensure that all nursing educators receive the fairest treatment possible and that the teaching-learning process is enhanced.

Conclusion

Educators and students stressed that systematic and continuous evaluation as well as staff development should be the primary goals for the faculty evaluation process. The ultimate goals is the improvement of teaching by nurse educators.
The GuideLine Implementability Appraisal (GLIA): development of an instrument to identify obstacles to guideline implementation
Authors: Shiffman Richard N , Dixon Jane , Brandt Cynthia , Essaihi Abdelwaheb , Hsiao Allen , Michel George , O'Connell Ryan
Published: July 2005

Background

Clinical practice guidelines are not uniformly successful in influencing clinicians' behaviour toward best practices. Implementability refers to a set of characteristics that predict ease of (and obstacles to) guideline implementation. Our objective is to develop and validate a tool for appraisal of implementability of clinical guidelines.

Methods

Indicators of implementability were identified from the literature and used to create items and dimensions of the GuideLine Implementability Appraisal (GLIA). GLIA consists of 31 items, arranged into 10 dimensions. Questions from 9 of the 10 dimensions are applied individually to each recommendation of the guideline. Decidability and Executability are critical dimensions. Other dimensions are Global, Presentation and Formatting, Measurable Outcomes, Apparent Validity, Flexibility, Effect on Process of Care, Novelty/Innovation, and Computability. We conducted a series of validation activities, including validation of the construct of implementability, expert review of content for clarity, relevance, and comprehensiveness, and assessment of construct validity of the instrument. Finally, GLIA was applied to a draft guideline under development by national professional societies.

Results

Evidence of content validity and preliminary support for construct validity were obtained. The GLIA proved to be useful in identifying barriers to implementation in the draft guideline and the guideline was revised accordingly.

Conclusion

GLIA may be useful to guideline developers who can apply the results to remedy defects in their guidelines. Likewise, guideline implementers may use GLIA to select implementable recommendations and to devise implementation strategies that address identified barriers. By aiding the design and operationalization of highly implementable guidelines, our goal is that application of GLIA may help to improve health outcomes, but further evaluation will be required to support this potential benefit.