bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a sequence‐specific PCR marker linked to the Ku gene which removes the vernalization requirement in narrow‐leafed lupin
Authors: Boersma J. G. , Buirchell B. J. , Sivasithamparam K. , Yang H.
Published: March 2007

Wild types of Lupinus angustifolius require vernalization to promote flowering. Modern domesticated cultivars carry the early‐flowering gene Ku which removes this requirement. A microsatellite‐anchored fragment length polymorphism marker was identified as co‐segregating with the Ku gene in a recombinant inbred line (RIL) population derived from a domesticated × wild‐type cross. DNA sequencing showed that the marker contained a 7 bp insertion/deletion polymorphism, as well as a single nucleotide polymorphism. A pair of sequence‐specific primers was designed and successfully converted the size polymorphism into a simple polymerase chain reaction based co‐dominant marker. This marker is closely linked to the Ku gene, as it co‐segregates with the Ku phenotyping in a population consisting of 106 RILs.
Propofol‐ketamine vs propofol‐fentanyl for sedation during pediatric upper gastrointestinal endoscopy
Authors: TOSUN ZEYNEP , AKSU RECEP , GULER GULEN , ESMAOGLU ALIYE , AKIN AYNUR , ASLAN DURAN , BOYACI ADEM
Published: March 2007

Background:  The aim of this study was to compare the clinical efficacy and safety of propofol‐ketamine with propofol‐fentanyl in pediatric patients undergoing diagnostic upper gastrointestinal endoscopy (UGIE).

Methods:  This was a prospective, randomized, double blinded comparison of propofol‐ketamine with propofol‐fentanyl for sedation in patients undergoing elective UGIE. Ninety ASA I–II, aged 1 to 16‐year‐old patients were included in the study. Heart rate (HR), systolic arterial pressure, peripheral oxygen saturation, respiratory rate (RR) and Ramsey sedation scores of all patients were recorded perioperatively. Patients were randomly assigned to receive either propofol‐ketamine (PK; n = 46) or propofol‐fentanyl (PF; n = 44). PK group received 1 mg·kg−1 ketamine + 1.2 mg·kg−1 propofol, and PF group received 1 μg·kg−1 fentanyl + 1.2 mg·kg−1 propofol for sedation induction. Additional propofol (0.5–1 mg·kg−1) was administered when a patient showed discomfort in either group.

Results:  The number of patients who needed additional propofol in the first minute after sedation induction was eight in Group PK (17%), and 22 in Group PF (50%) (P < 0.01) and those who did not need additional propofol throughout the endoscopy were 14 in Group PK (30%) and three in Group PF (7%) (P < 0.01). HR and RR values after induction in Group PF were significantly lower than Group PK (P < 0.01).

Conclusions:  Both PK and PF combinations provided effective sedation in pediatric patients undergoing UGIE, but the PK combination resulted in stable hemodynamics and deeper sedation though more side effects.
Decrease in functional residual capacity and ventilation homogeneity after neuromuscular blockade in anesthetized preschool children in the lateral position1
Authors: VON UNGERN‐STERNBERG BRITTA S. , REGLI ADRIAN , FREI FRANZ J. , HAMMER JÜRG , JORDI RITZ EVA‐MARIA , ERB THOMAS O.
Published: March 2007

Background:  While functional residual capacity (FRC) is reduced in children undergoing general anesthesia, the lateral position leads to an increase in FRC compared with the supine position. The impact of neuromuscular blockade remains unknown. We tested the hypothesis that neuromuscular blockade leads to a decrease in FRC and increase in lung clearance index (LCI) while the application of positive endexpiratory pressure (PEEP) of 6 cmH2O leads to a restoration in both parameters.

Methods:  After approval of the local Ethics Committee, we studied 18 preschool children (2–6 years) without cardiopulmonary disease, who were scheduled for elective surgery. Anesthesia was standardized using propofol and fentanyl. FRC and LCI were calculated by a blinded observer using a SF6 multibreath washout technique with an ultrasonic transit‐time airflow meter (Exhalyzer D). Measurements were taken in the left lateral position (PEEP 3 cmH2O) after 1. intubation with a cuffed tracheal tube, 2. neuromuscular blockade with rocuronium, and 3. the additional application of PEEP (6 cmH2O).

Results:  Functional residual capacity mean (sd) decreased from 31.6 (4.4) ml·kg−1 to 27.6 (4.2) ml·kg−1 (P < 0.001) following neuromuscular blockade while the LCI increased from 6.54 (0.6) to 7.0 (0.6) (P ≤ 0.001). After the application of PEEP (6 cmH2O), FRC increased to 32.4 (5.0) ml·kg−1 whereas the LCI decreased to 6.58 (0.5) showing no significant changes from baseline measurements.

Conclusions:  In the lateral position, neuromuscular blockade led to a significant decrease in FRC associated with a small increase in ventilation inhomogeneity. FRC and LCI were restored to baseline levels with the application of PEEP 3 cmH2O that is in addition to a background of PEEP 3 cmH2O giving a total of 6 cmH2O PEEP.
Fine‐touch pressure thresholds in the adult penis
Authors: Sorrells Morris L. , Snyder James L. , Reiss Mark D. , Eden Christopher , Milos Marilyn F. , Wilcox Norma , Van Howe Robert S.
Published: March 2007

OBJECTIVE

To map the fine‐touch pressure thresholds of the adult penis in circumcised and uncircumcised men, and to compare the two populations.

SUBJECTS AND METHODS

Adult male volunteers with no history of penile pathology or diabetes were evaluated with a Semmes‐Weinstein monofilament touch‐test to map the fine‐touch pressure thresholds of the penis. Circumcised and uncircumcised men were compared using mixed models for repeated data, controlling for age, type of underwear worn, time since last ejaculation, ethnicity, country of birth, and level of education.

RESULTS

The glans of the uncircumcised men had significantly lower mean (sem) pressure thresholds than that of the circumcised men, at 0.161 (0.078) g (P = 0.040) when controlled for age, location of measurement, type of underwear worn, and ethnicity. There were significant differences in pressure thresholds by location on the penis (P < 0.001). The most sensitive location on the circumcised penis was the circumcision scar on the ventral surface. Five locations on the uncircumcised penis that are routinely removed at circumcision had lower pressure thresholds than the ventral scar of the circumcised penis.

CONCLUSIONS

The glans of the circumcised penis is less sensitive to fine touch than the glans of the uncircumcised penis. The transitional region from the external to the internal prepuce is the most sensitive region of the uncircumcised penis and more sensitive than the most sensitive region of the circumcised penis. Circumcision ablates the most sensitive parts of the penis.
Epigenetic events, remodelling enzymes and their relationship to chromatin organization in prostatic intraepithelial neoplasia and prostatic adenocarcinoma
Authors: Mohamed Mahmoud A. , Greif Philipp A. , Diamond James , Sharaf Osama , Maxwell Perry , Montironi Rodolfo , Young Robert A.M. , Hamilton Peter W.
Published: March 2007

OBJECTIVE

To explore the nuclear chromatin phenotype, overall epigenetic mechanisms, chromatin remodelling enzymes and their role as diagnostic biomarkers in prostate lesions, using high‐resolution computerized quantitative digital image analysis (DIA).

MATERIALS AND METHODS

A tissue microarray (TMA) was constructed using paraffin wax‐embedded prostatic tissues from 78 patients, containing 30 cores of benign prostatic hyperplasia (BPH), 10 of low‐grade prostatic intraepithelial neoplasia (LGPIN), 38 of prostate adenocarcinoma, 20 of BPH tissue excised at 0.6–1 mm from LGPIN lesions, and 10 of BPH prostatic tissues obtained 0.6–1 mm from high‐grade PIN (HGPIN) lesions. Chromatin phenotype was assessed on haematoxylin‐stained sections using high‐resolution texture analysis. For quantitative immunohistochemistry, antibodies raised against acetylated histone H3 lysine 9 (AcH3K9), 5′methylcytidine (5MeC) and the chromatin remodelling ATPase ISWI (SNF2H and SNF2L) were used. The immunodensity was measured using DIA to determine the epigenetic profile of the cases. At least 60 nuclei were measured from each case.

RESULTS

There were many statistically significant differences in staining intensity and nuclear distribution patterns in chromatin phenotype and immunostaining (p ≤ 0.001). These changes allowed the differentiation between the various pathological subgroups with a classification accuracy of 76–100% using chromatin phenotype or immunostaining measuring epigenetic and chromatin remodelling changes (5MeC, AcH3K9 and ISWI). In PIN lesions, there was a high chromatin content with DNA‐hypermethylation, while in prostatic adenocarcinoma there was a lower chromatin content with DNA‐hypomethylation and H3K9‐hypoacetylation. There was significantly more ISWI protein in neoplastic tissues. There were malignancy‐associated changes (MAC) in chromatin phenotype and overall epigenetic events in BPH tissues adjacent to PIN lesions.

CONCLUSIONS

The present study confirms the ability of high‐resolution computerized digital imaging of nuclear texture features to detect changes in chromatin phenotype, epigenetic events and the presence of chromatin remodelling, factors that can be used to distinguish between different prostatic pathologies, i.e. BPH, LGPIN, HGPIN and prostate adenocarcinoma, and further allow the detection of MAC near PIN lesions. These results provide a base for future diagnostic applications of DIA combined with immunohistochemistry. Our experiments underscore the importance of epigenetic mechanisms during carcinogenesis. Further studies are needed to elucidate the complex interplay between chromatin structure, its modifications and the progression of prostate cancer.
Association of vitamin‐D receptor (Fok‐I) gene polymorphism with bladder cancer in an Indian population
Authors: Mittal Rama D. , Manchanda Parmeet K. , Bhat Sanjay , Bid Hemant K.
Published: March 2007

OBJECTIVE

To explore the association of vitamin‐D receptor (VDR) genotypes and haplotypes (variants at the Fok‐I, and Taq‐I sites) with the risk of bladder cancer, as vitamin D is antiproliferative and reported to induce apoptosis in human bladder tumour cells in vitro.

PATIENTS, SUBJECTS AND METHODS

A case‐control study using polymerase chain reaction‐restriction fragment length polymorphism was conducted in 130 patients with bladder cancer and 346 normal healthy individuals in a north Indian population. Patients were also categorized according to grade and stage of tumour.

RESULTS

There was a significant difference in genotype and allelic distribution of VDR (Fok‐I) polymorphism in the patients (P = 0.033 and = 0.017, respectively). The FF genotype was associated with twice the risk for bladder cancer (odds ratio 2.042, 95% confidence interval, CI, 0.803–5.193). There was no significant difference in genotypic distribution or allelic frequencies of the VDR (Taq‐I) polymorphism (P = 0.477 and 0.230) when compared with the controls. The stage and grade of the bladder tumours had no association with VDR (Fok‐I and Taq‐I) genotypes. There was a significant difference in the frequency distribution of the haplotypes FT and fT (P < 0.001); these haplotypes had a protective effect in the control group (odds ratio 0.167, 95% CI 0.096–0.291, and 0.079, 0.038–0.164).

CONCLUSION

These data suggest that VDR (Fok‐I) polymorphism is associated with the risk of bladder cancer. Further, the results for the haplotype FT and fT indicate that patients with this haplotype have a lower risk of developing bladder cancer than those with other haplotypes.
Cerebral mechanisms and voiding function
Authors: DasGupta Ranan , Kavia Rajesh B. , Fowler Clare J.
Published: March 2007

Some of the most recent work investigating the cerebral mechanisms involved in bladder control has been very helpful in adding to our understanding of bladder dysfunction. The group behind this work, from London, presents a mini‐review which will help to update our knowledge in this area.

Authors from Australia present a review describing the interactions between bone and prostate cancer cells in metastatic disease. This area has generated much interest and is something for which we should develop a full understanding, to optimise our treatments for this condition.
THE NATURE OF CITIES AND THE ANALYSIS OF THEIR CULTURAL PROBLEMS
Authors: CLAVAL PAUL
Published: March 2007

Urban geographers had for a long time mainly approached culture through its material aspects. The situation changed with the cultural turn of the discipline. As a result a re‐evaluation of the former results was made. The basic concepts of community and society are taking a new significance at the time of globalisation. An increasing attention is devoted to counter‐cultures and cultures of resistance. Landscapes have ceased to appear essentially as expressions of urban functions. They play a fundamental role in the assertion of identities: hence the harsh competition for the control of public space. In contemporary urban archipelagos, culture has become a key factor in shaping forms. It often expresses deep conflicts and feelings of frustration.
Concordant molecular and phenotypic data delineate new taxonomy and conservation priorities for the endangered mountain yellow‐legged frog
Authors: Vredenburg V. T. , Bingham R. , Knapp R. , Morgan J. A. T. , Moritz C. , Wake D.
Published: March 2007

The mountain yellow‐legged frogRana muscosa sensu lato, once abundant in the Sierra Nevada of California and Nevada, and the disjunct Transverse Ranges of southern California, has declined precipitously throughout its range, even though most of its habitat is protected. The species is now extinct in Nevada and reduced to tiny remnants in southern California, where as a distinct population segment, it is classified as Endangered. Introduced predators (trout), air pollution and an infectious disease (chytridiomycosis) threaten remaining populations. A Bayesian analysis of 1901 base pairs of mitochondrial DNA confirms the presence of two deeply divergent clades that come into near contact in the Sierra Nevada. Morphological studies of museum specimens and analysis of acoustic data show that the two major mtDNA clades are readily differentiated phenotypically. Accordingly, we recognize two species,Rana sierrae, in the northern and central Sierra Nevada, andR. muscosa, in the southern Sierra Nevada and southern California. Existing data indicate no range overlap. These results have important implications for the conservation of these two species as they illuminate a profound mismatch between the current delineation of the distinct population segments (southern California vs. Sierra Nevada) and actual species boundaries. For example, our study finds that remnant populations ofR. muscosaexist in both the southern Sierra Nevada and the mountains of southern California, which may broaden options for management. In addition, despite the fact that only the southern California populations are listed as Endangered, surveys conducted since 1995 at 225 historic (1899–1994) localities from museum collections show that 93.3% (n=146) ofR. sierraepopulations and 95.2% (n=79) ofR. muscosapopulations are extinct. Evidence presented here underscores the need for revision of protected population status to include both species throughout their ranges.
AUTONOMIC CORRELATES OF THE SPONTANEOUS K‐COMPLEX
Authors: Johnson Laverne , Karpan Wayne E.
Published: March 2007

Spontaneous K‐complexes during stage 2 sleep were scored on nine subjects to study 1) rate of occurrence and 2) autonomic correlates, specifically the heart rate response, number of finger vasoconstrictions, number of galvanic skin responses, and number of skin potential responses. Records for two nights of sleep were available for five subjects.

Spontaneous K‐complexes occur with considerable regularity at a rate of 1.21 per minute with a range over subjects from. 75 to 1.93 per minute. There was no significant change in this rate over six hours of sleep nor was there a significant difference over two nights of sleep.

When compared with control portions of the record, spontaneous K‐complexes were significantly associated on both nights one and two with an increase in heart rate, increased frequency of vasoconstrictions, an increase in number of GSRs, and an increase in number of skin potential responses. There were no autonomic changes associated with isolated sleep spindles.
SELECTIVE ATTENTION AND INSTRUMENTAL MODIFICATION OF THE GSR
Authors: Martin Randall , Dean Sanford , Shean Glenn
Published: March 2007

A series of experiments were conducted on instrumental modification of the Galvanic Skin Response (GSR) in a discrimination procedure where preparatory signals indicated which discriminative stimulus was to occur. When shock avoidance was contingent upon the presence of a response the GSR was enhanced; when shock avoidance was contingent upon the inhibition of a response there was a decrement in reactivity. Heart rate acceleration occurred to Respond stimuli while deceleration occurred to Inhibit stimuli. Various types of cognitive strategies were reported by the subjects from attempts to control attention by attending less to stimuli associated with inhibition to attempts to arouse a response by thinking of exciting events and to inhibit by thinking of calming events. Postexperimental recognition of words tended to be negatively related to magnitude of response. When the verbal stimuli served directly as discriminative stimuli, however, these relationships tended to be reversed.
Selective processing of two‐dimensional visual stimuli in young and old subjects: Electrophysiological analysis
Authors: KENEMANS J. LEON , SMULDERS FREN T. Y. , KOK ALBERT
Published: March 2007

In this study, we compared selection of conjunctions of spatial frequency and orientation in young and old subjects, using performance and event‐related brain potential (ERP) measures. Responses to target conjunctions were slightly but significantly slower in older subjects; lateralized readiness potential (LRP) onsets did not differ between groups. Older subjects made more false‐positive responses to stimuli sharing only spatial frequency with the target. Difference waves associated with selection of separate dimensions included frontal positivity and occipital and central negativity and were 20–50 ms slower in older subjects. Later parts of these difference waves had smaller amplitudes in older subjects. Sensory discrimination, assessed through the effects of physical stimulus parameters on ERPs, was not clearly affected by age. Data are interpreted in terms of a relationship in older subjects between longer latencies of difference waves but equal LRP onsets and a higher false‐alarm rate.
Event‐related potentials to airway occlusion in young and old subjects
Authors: HARVER ANDREW , SQUIRES NANCY K. , BLOCH‐SALISBURY ELISABETH , KATKIN EDWARD S.
Published: March 2007

Event‐related potentials (ERPs) were recorded to both inspiratory and expiratory airway occlusion in young (21‐28 years) and old (55–67 years) subjects under both attend and ignore conditions. Early and late components of the ERP (N1, P2, N2, P3) were observed to both types of occlusions in both conditions. Variations in these components were consistent in both direction and degree with those observed in oddball tasks employing exteroceptive stimuli. ERPs for breathing may serve to clarify sensory attributes of respiratory stimuli in humans and to identify central processing abnormalities in patient populations.
Temporal stability of heart period variability during a resting baseline and in response to psychological challenge
Authors: SLOAN R. P. , SHAPIRO P. A. , BAGIELLA E. , GORMAN J. M. , BIGGER J. T.
Published: March 2007

Central to the psychophysiologic reactivity hypothesis of the etiology of coronary artery disease is the assumption that reactivity is an individual characteristic that is stable over time. Although heart rate (HR) and blood pressure reactivity appear to meet this criterion, temporal stability of cardiac autonomic control as measured by analysis of heart period variability (HPV) has not been assessed. In this study, we tested the stability of HPV, measured in both the time and frequency domain, during a quiet, resting baseline and in response to 5‐min mental arithmetic and reaction time tasks, in 20 normal subjects measured in three testing sessions during a 9‐month period. Stability, assessed by the intraclass correlation coefficient (ICC), was excellent for resting baseline measures of HR and HPV, with ICCs of 0.68–0.86. However, HR and HPV reactivity to either arithmetic or reaction time tasks generally was less stable, with ICCs of 0.17–0.73, in contrast to results of previous studies demonstrating long‐term Stability of HR responses to psychological challenge. Stability of aggregated reactivity scores was only slightly improved. Whether for individual tasks or aggregated measures, reactivity of total and low‐frequency measures of HPV was moderately stable but stability of high‐frequency HPV reactivity was poor.
Neural mechanisms of detecting and orienting attention toward unattended threatening somatosensory target stimuli. II. Intensity effects
Authors: Dowman Robert
Published: March 2007

Negative potentials evoked by painful electrical stimulation of the sural nerve that occur at 100–180 ms poststimulus over the contralateral temporal scalp (CTN100‐180) and at 130–200 ms over the fronto‐central scalp (FCN130‐200) exhibit unusual attention effects. That is, their amplitudes are larger when the painful evoking stimulus is unattended than when it is attended. In this experiment, I show that attention has no effect on the CTN100‐180 evoked by a weak, nonthreatening sural nerve electrical stimulus. These data suggest that the generators of the CTN100‐180, which include the somatosensory association areas in the parietal operculum, are specifically involved in detecting threatening somatosensory stimuli. The FCN130‐200 showed a small increase in the unattended condition, which is consistent with the role of its medial prefrontal cortex generators in monitoring any situation that might require a change in attentional control.
Crossmodal effect with rubber hand illusion and gamma‐band activity
Authors: Kanayama Noriaki , Sato Atsushi , Ohira Hideki
Published: March 2007

The integration of multimodal stimuli has been regarded as important for the promotion of adaptive behavior. Although recent work has identified brain areas that respond to multimodal stimuli, the temporal features are not clear yet. Earlier event‐related potential studies revealed crossmodal attention effects, but did not focus on mechanisms underlying crossmodal integration. Here, electroencephalography (EEG) activity in the gamma band was considered as a correlate of multimodal integration. Participants localized a tactile stimulus on their fingers while seeing visual stimuli on rubber hands with the same posture as their hands. EEG analyses using wavelet transform suggested that interelectrode phase synchrony in the gamma‐band range (40–50 Hz) was related to behavioral indices of the intermodal illusion under consideration. The findings suggest a role of high‐frequency oscillations in the integrative processing of stimuli across modalities.
VASCULAR CALCIFICATION IN PATIENTS WITH KIDNEY DISEASE: Techniques and Technologies to Assess Vascular Calcification
Authors: Bellasi Antonio , Raggi Paolo
Published: March 2007

Cardiovascular calcification (CV) is highly prevalent in chronic kidney disease stage V and has been associated with an increased risk for all‐cause as well as cardiovascular mortality. A number of noninvasive imaging techniques are available to screen for the presence of CV—plain x‐rays of the abdomen and extremities to identify macroscopic calcifications of aorta and peripheral arteries; echocardiography for assessment of valvular calcification; two‐dimensional ultrasound for calcification of carotid arteries, femoral arteries and aorta, and computed tomography technologies that constitute the gold standard for quantification of coronary artery and aorta calcification. Some of these modalities are also useful to monitor calcification progression and to assess the effect of different therapeutic strategies directed at modifying calcification progression. In this article we review the strengths and limitations of the most common noninvasive techniques employed for the imaging of vascular calcification.
VASCULAR CALCIFICATION IN PATIENTS WITH KIDNEY DISEASE: Cardiovascular Calcification in Nondialyzed Patients with Chronic Kidney Disease
Authors: Qunibi Wajeh Y.
Published: March 2007

Chronic kidney disease (CKD) has become a major health‐care problem of global proportions. Progression to end‐stage renal disease (ESRD), the need for renal replacement therapy, and the high annual death rate of dialysis patients are the most noticeable outcomes of CKD. Less appreciated, however, is the fact that most patients with CKD actually die mainly from cardiovascular disease, rather than progress to ESRD. Coronary artery calcification (CAC), a surrogate marker of atherosclerosis, is common in dialysis and CKD patients. Coronary artery calcium scores, as measured by ultrafast computed tomography, is an independent predictor of future cardiac events. Using this technique, several studies have documented extensive calcification in dialysis patients, a subject of several exhaustive reviews. Unfortunately, much less attention has been paid to calcification in nondialyzed patients with CKD. In this review, I will emphasize the fact that CVC is common in patients with CKD not yet on dialysis, develops early in the course of CKD, and worsens with the decline in renal function particularly among diabetics who progressed to ESRD. I will also discuss the pathogenesis of CVC in CKD patients and highlight the lack of a major role for abnormalities of mineral metabolism in the pathogenesis of calcification in CKD patients. In addition to the high prevalence of traditional risk factors for CAD, the presence of proteinuria, reduced renal function, diabetic nephropathy, and the rate of progression to ESRD may represent the main uremia‐related factors that increase the risk for calcification in CKD. Finally, I will review the protective role of inhibitors of calcification in CKD.
New Roles for Interleukin-1 Beta in the Mechanisms of Epilepsy
Authors: Vezzani Annamaria , Baram Tallie Z.
Published: March 2007

The mechanisms that transform a normal brain to an epileptic one are not fully understood. Interleukin-1 beta (IL-1β) contributes to neuronal degeneration observed in several neurological disorders and recently has been implicated in neuronal injury that may accompany the process of epileptogenesis. This review presents the hypothesis that IL-1β may contribute to the development of epilepsy via several mechanisms, including classical effects on neuronal survival and transcription pathways; novel rapid effects on receptor-gated ion channels; and long-lasting effects on expression of selective gene families. Thus, evidence that IL-1β actions in epilepsy can be independent from the neurotoxic effects of this cytokine is presented.
Means, Motive, and Opportunity: Establishing Culpability in Pharmacoresistant Epilepsy
Authors: Sills Graeme J.
Published: March 2007

Inhibition of the Multidrug Transporter P-Glycoprotein Improves Seizure Control in Phenytoin-Treated Chronic Epileptic Rats. van Vliet EA, van Schaik R, Edelbroek PM, Redeker S, Aronica E, Wadman WJ, Marchi N, Vezzani A, Gorter JA. Epilepsia 2006;47:672–680.

Purpose

Overexpression of multidrug transporters such as P-glycoprotein (P-gp) may play a significant role in pharmacoresistance, by preventing antiepileptic drugs (AEDs) from reaching their targets in the brain. Until now, many studies have described increased P-gp expression in epileptic tissue or have shown that several AEDs act as substrates for P-gp. However, definitive proof showing the functional involvement of P-gp in pharmacoresistance is still lacking. Here we tested whether P-gp contributes to pharmacoresistance to phenytoin (PHT) by using a specific P-gp inhibitor in a model of spontaneous seizures in rats.

Methods

The effects of PHT on spontaneous seizure activity were investigated in the electrical post-status epilepticus rat model for temporal lobe epilepsy, before and after administration of tariquidar (TQD), a selective inhibitor of P-gp.

Results

A 7-day treatment with therapeutic doses of PHT suppressed spontaneous seizure activity in rats, but only partially. However, an almost complete control of seizures by PHT (93% μ 7%) was obtained in all rats when PHT was coadministered with TQD. This specific P-gp inhibitor was effective in improving the anticonvulsive action of PHT during the first 3–4 days of the treatment. Western blot analysis confirmed P-gp upregulation in epileptic brains (140–200% of control levels), along with approximately 20% reduced PHT brain levels. Inhibition of P-gp by TQD significantly increased PHT brain levels in chronic epileptic rats.

Conclusions

These findings show that TQD significantly improves the anticonvulsive action of PHT, thus establishing a proof-of-concept that the administration of AEDs in combination with P-gp inhibitors may be a promising therapeutic strategy in pharmacoresistant patients.
Higher cortisol awakening response in young adolescents with persistent anxiety problems
Authors: Greaves‐Lord K. , Ferdinand R. F. , Oldehinkel A. J. , Sondeijker F. E. P. L. , Ormel J. , Verhulst F. C.
Published: March 2007

Objective:  The aims of the present study were to test the association between current anxiety problems and basal cortisol levels in a large population sample of young preadolescents, and to test if HPA‐axis activity differs between individuals with no, only current, or persistent anxiety problems.

Method:  Cortisol levels of 10‐ to 12‐year olds (n = 1768) from the general population were measured on three time points during the day. A self‐report questionnaire (RCADS) was used to assess current anxiety, a parent‐report questionnaire (TPBQ) to assess anxiety problems at age 4.

Results:  Associations between cortisol levels and current anxiety problems were not found. However, individuals with persistent anxiety problems had higher morning cortisol levels and a higher cortisol awakening response.

Conclusion:  Apparently, only persistent, and not current, anxiety problems are associated with higher HPA‐axis activity. Alterations in HPA‐axis activity might underlie persistent anxiety problems, or result from the stress accompanied by persistent anxiety problems.
Oral health of children in South Australia by socio‐demographic characteristics and choice of provider
Authors: Gaughwin Anne , Spencer A. John , Brennan David S. , Moss John
Published: March 2007

Abstract –

Australia has a highly developed school dental program for providing dental care to schoolchildren which operates alongside well‐established private practice delivery of dental care. While free school‐based dental care has high utilisation where offered, little is known about the oral health outcomes of groups of children across different providers of dental care, or patterns of service use. This paper investigates the effects of socio‐demographic characteristics and choice of dental provider on oral health amongst a random sample of secondary school students residing in Adelaide, South Australia. Objectives: To describe the oral health of children by different dental provider groups; to describe the association of socio‐demographic characteristics with oral health outcomes; and to describe the differences in oral health that remained after controlling for socio‐demographic confounding, by dental provider group. Methods: The study included metropolitan Adelaide schoolchildren from Year 9 and 10 school grades (n=373). Results: Children who received care from the School Dental Service (SDS) and from both the SDS and private dentists (Mixed) had significantly lower caries experience (DMFS) than children who received care from private dentists (Private) or who had not received any care for at least 2 years (No Recent Care). There were differences in the socio‐demographic characteristics between children who used different dental providers, and these socio‐demographic characteristics were significantly associated with levels of decayed, missing and filled surfaces and surfaces which had been fissure sealed. After controlling for socio‐demographic characteristics using multiple regression, significant differences were seen in mean caries experience (DMFS) and mean numbers of decayed surfaces and filled surfaces. Conclusion: Although from less advantaged backgrounds, children seen through the SDS had more favourable oral health outcomes than children seen by a private dentist.
Fluoride supplements and caries in a non‐fluoridated child population
Authors: Wang N. J. , Riordan P. J.
Published: March 2007

Abstract –

In Norway, there is no water fluoridation and little naturally occurring fluoride in drinking water. Fluoride toothpaste is used by 95% of the population and there is a long tradition of use of fluoride supplements. The purpose of this study was to analyse whether children who used fluoride toothpaste regularly and complied with the recommendations for use of fluoride supplements had less caries than other children at the age of 8 years. Most fluoride supplements sold in Norway are lozenge‐type tablets, which allow for extended enamel exposure to fluoride. All children (n=551) born in 1988 living in a suburban community in Norway were invited to participate. In those who participated (n=470), caries was registered clinically and radiographically and parents provided data on use of supplements. Thirty‐eight percent of the children had used fluoride supplements regularly during the period 0.5 to 4.0 years of age and 66% used supplements regularly at the age of 6 to 8 years. Multivariate analyses showed that the children complying with the recommendations for use of fluoride supplements during the period 0.5 to 4.0 years of age had lower caries experience (dmfs) and fewer decayed surfaces (ds) in primary teeth than other children. No significant associations were found between supplement use in childhood and caries prevalence (DMFS) or number of decayed surfaces (DS) in permanent teeth at the age of 8 years. Supplement use from 6 to 8 years of age was not associated with caries occurrence either in primary or in permanent teeth. Both mother's education and the quality of dental hygiene were inversely associated with caries occurrence.
Treatment practices in caries prevention for 6‐year‐olds in Finland
Authors: Varsio Sinikka , Vehkalahti Miira , Murtomaa Heikki
Published: March 2007

Abstract– Objectives: To evaluate caries‐preventive treatment practices in relation to caries state and eruption of first permanent molars (FPMs) among 6‐year‐olds (n=3489) examined and treated in public dental clinics in Helsinki during 1992. Methods: The study subjects were selected on the basis of their caries state using a two‐point study design: the high‐caries group (n=99) had the greatest number of DT+dt, the cavity‐free group (n=32) had neither past nor present caries. Evaluation of dentists ‘caries‐preventive treatment decisions was based on data from detailed personal oral health records. Results: In total, 22% of the high‐caries patients (mean DT+dt 8.7; range 4–18) had been judged by their dentists as high‐risk patients. Eruption of FPMs had no influence on dentists' judgement on caries risk. A subjects number of DT+dt had no influence on the intensity of preventive treatment given, but those with a high‐risk judgement from a dentist received more preventive measures per visit than did other high‐caries patients. For high‐caries patients with erupting FPMs, three visits in 10 included preventive intervention other than sealants, compared to nine in the cavity‐free group. Intensity of oral hygiene instruction correlated with presence of erupting FPMs, yet 86% of the patients with erupting FPMs had received no oral hygiene instruction. Conclusions: Dentists should be encouraged to use standardized criteria, including data on caries state and eruption stage, in judging each patients's risk of caries to provide intensified caries‐preventive treatment to those most in need.
Is ART really atraumatic?
Authors: van Amerongen W. Evert , Rahimtoola Salim
Published: March 2007

Abstract– Atraumatic restorative treatment (ART) is an approach to the management of carious lesions that uses only hand instruments to remove carious tissue and to restore the tooth involved. The name ART implies that the approach is atraumatic to both the patient and the tooth. This study set out to evaluate whether ART is atraumatic in terms of both patient discomfort and tooth tissue conservation. Three hundred and fifty‐nine patients were divided in two groups: one group was treated with hand instruments and the other with rotary equipment. Each patient received two restorations: one using amalgam and one using glass ionomer as the restorative material, placed without the use of anaesthesia. Less discomfort was reported with the ART approach compared to conventional restorations made using rotary instruments and amalgam. Moreover, preparations with hand instruments were smaller than those produced with rotary instruments. Reported discomfort was associated with the size of the preparation, although the influence of the operator on both criteria was considerable. A patient effect was also observed since patients who reported discomfort during the first treatment were more likely to report discomfort after the second treatment. In conclusion, the choice of the term “ART” as an atraumatic procedure is defensible.
The residual caries dilemma
Authors: Weerheijm Karin L. , Groen Henk J.
Published: March 2007

Abstract– Restorative dentistry is based on the assumption that bacterial infection of demineralized dentine should prompt operative intervention. One of the concepts of practical dentistry is to create a favourable environment for caries arrest with minimal operative intervention. The progress of remaining primary caries is key to any discussion of this concept. This discussion is important for the atraumatic restorative treatment (ART) approach, since the removal of all carious dentine is sometimes difficult using hand instruments only. In this paper the results of possible measures to guard against the effects of residual carious and its consequences are reviewed, in order to obtain an impression of the justification for (in)complete excavation of occlusal dentinal caries. Three types of measure are considered: isolating the caries process from the oral environment, excavating the carious dentine, and using a cariostatic filling material. Each of these measures contributes to the arrest of the caries process. However, none of these measures can arrest this process by itself. A combination of all three seems necessary. It is concluded that although residual caries does not seem to be the criterion for re‐restoration, one has to strive for as complete caries removal as possible. If this cannot be fulfilled the sealing capacities of the filling material seem to be more important than its cariostatic properties.
Does ART have a place in preservative dentistry?
Authors: Anusavice Kenneth J.
Published: March 2007

Abstract– The ART technique consists of hand excavating carious tissue and placing a highly viscous glass ionomer cement as a restoration material and as a sealant. Although the results of several studies are promising, the retention rates of these restorations for primary teeth are not impressive. Materials and methods that yield greater success rates are needed to improve long‐term caries management outcomes. In principle, ART should yield outcomes similar to those associated with preservative dentistry, including the potential for minimal surgical intervention, conservation of sound tooth structure, avoidance of pain and need for local anesthetic injections, reduced risk for subsequent endodontics and tooth extraction, and increased survival time of the affected teeth. The ideal direct‐filling ART material would be biocompatible and tooth colored; “forgiving” in its handling properties; insensitive to moisture or desiccation; hardenable without special equipment; able to form stable bonds to enamel and dentin; able to seal marginal gaps against bacteria; capable of releasing fluoride or remineralization and antibacterial agents when demineralization is most likely; and resistant to chemical attack. The highly viscous glass ionomer materials currently used for ART meet several of this criteria, though they may be deficient in their ability to seal marginal gaps against bacteria and in their sensitivity to desiccation. Furthermore, although they release fluoride over the lifetime of the restoration, this fluoride release alone may not prevent caries progression in all cases. It is necessary for cases of high caries risk to use chlorhexidine in conjunction with fluoride to achieve caries arrest and remineralization of adjacent areas of the affected teeth. Thus, while the ART technique offers some benefits in restoring function and reducing the rate of caries progression, it is unlikely that current materials will be able to arrest caries progression completely in high‐risk persons.
Scaled Healing Assessment Index: a novel method for measuring the degree of wound bed preparation
Authors: Shai Avi , Avrin Vadim , Zvulunov Alex , Dinstein Its'hak
Published: March 2007

Background/purpose: The color of a wound bed reflects its degree of ‘cleanness’ and serves as an indicator in evaluating the progression of wounds toward healing. We were aiming to develop a standard tool, for use in clinical research studies, which would analyze and provide objective data as to the color distribution of wound surfaces. To this end, we designed the ‘Scaled Healing Assessment Index’ algorithmic tool to provide a scoring system to determine the average color of wound surfaces.

Methods: The scale is graded from 1 to 10, with 1 representing the most unclean yellow wound, and 10 representing the optimal red wound. In order to test the accuracy of the software, 102 chronic wounds in 88 patients were examined. Each wound was assessed using a grading from 1 to 10, according to its color, using three separate methods: (1) by three dermatologists [average clinical score (ACS)] in the outpatient clinic; (2) by three other dermatologists with the same wounds presented on a computer screen [average photo score (APS)]; and (3) by the Scaled Healing Assessment Index [software score (SS)]. The results of the three methods were examined statistically using Pearson's correlation.

Results: We found a high correlation between the ACSs and the SSs (0.86), between the APSs and the SSs (0.863), as well as the ACSs with the APSs (0.95).

Conclusion: The Scaled Healing Assessment Index algorithm provides objective and reliable data, and can be used in research studies aimed at examining the beneficial effect of products intended for wound healing.
Mechanisms that play a role in the maintenance of the calcium gradient in the epidermis
Authors: Cornelissen Lisette H. , Oomens Cees W. J. , Huyghe Jacques M. , Baaijens Frank P. T.
Published: March 2007

Background/purpose: Calcium regulates the proliferation and differentiation of keratinocytes and plays a role in restoration of the epidermal barrier function. The factors that maintain the calcium gradient in vivo are still unknown. A numerical model may give more insight into transport processes that maintain the epidermal calcium gradient.

Methods: In this study, transport of free calcium in the epidermis is described with diffusion, convection and electrophoresis. Binding and release of calcium results in equilibrium between free and bound calcium. The physiological epidermal calcium gradient as well as the calcium concentration in a damaged epidermis are modeled.

Results: The typical shape of the calcium gradient in the epidermis, as found in experimental studies, was maintained when separate formulations were used for free and bound calcium. Application of damage results in a decrease of the calcium concentration, especially in the upper living epidermis. Using this model, an estimate could be made about the fraction bound calcium in the epidermis.

Conclusion: The typical shape of the gradient is predominantly determined by the bound calcium concentration. For both a normal and a damaged epidermis, the concentration of free calcium is mainly determined by electrophoresis in the living epidermis, whereas in the largest part of the stratum corneum diffusion is the most important factor. The convection that was determined by the transepidermal water loss did not have an effect on the calcium concentration.
Cytokines at different stratum corneum levels in normal and sodium lauryl sulphate‐irritated skin
Authors: De Jongh Cindy M. , Verberk Maarten M. , Spiekstra Sander W. , Gibbs Susan , Kezic Sanja
Published: March 2007

Background/purpose: Cytokines play an important role in inflammatory and repair processes occurring in the skin. The objectives of this study were to determine the amounts of cytokines and protein isolated by tape stripping in the different layers of the stratum corneum (SC), and to compare normal skin with skin exposed in vivo to the irritant sodium lauryl sulphate (SLS).

Methods: In eight volunteers, we determined the amount of total and soluble protein and also interleukin‐1α (IL‐1α) in pooled tape strips obtained from the upper, intermediate and lower parts of the SC. Three different types of tape were compared (Diamond®, D‐squame® or Sentega® tape). In a separate study, 20 volunteers were repeatedly exposed to 0.1% SLS over a 3‐week period. The amounts of IL‐1α, IL‐1RA and IL‐8 in strips obtained from the three different SC levels of SLS‐exposed skin were compared with an unexposed site.

Results: For normal skin, the amounts of soluble protein and IL‐1α were similar for the three tapes. Diamond® tape showed the highest yield of total protein. The total protein yield per strip decreased to lower SC levels, whereas soluble protein and IL‐1α normalized by soluble protein did not change across the SC. After SLS induced skin irritation, IL‐1α decreased and IL‐1RA and IL‐8 increased at increasing depth into the SC.

Conclusions: Tape stripping is a suitable method to determine SC cytokine concentrations in human skin. With this technique, it is possible to study changes in cytokine concentrations at different SC layers after skin irritation.
Protection effect of cosmetics on human skin under simulated rigorous environment
Authors: Cheng Yan , Dong Yi‐yang , Dong Mei‐xian , Wang Chao , Su Ning , Sun Yuan‐tao , Liu Juan , Zheng Hong‐yan , Schrader Andreas , Rohr Mathias , Liu Wei
Published: March 2007

Background/purpose: The efficacy of cosmetics on human skin measured under normal mild laboratory environment might be discounted by exterior environment factors such as wind, UV exposure, etc. Few studies have focused on the ‘genuine’ efficacy of cosmetics on human skin during exposure to external rigorous environment. The aim of this study was to develop a model for the evaluation of the efficacy of cosmetics on human skin under simulated rigorous environment.

Methods: We measured skin water content and transepidermal water loss (TEWL) before and after products application under simulated windy and sub‐erythema UV exposure treatment in a constant temperature and humidity laboratory.

Results: The results showed that the products had higher water content and lower TEWL at 2, 4 and 8 h of products application, and ameliorated the skin moisturization situation after a 3‐week continuous use of the products. In addition, the products might protect the skin to maintain the normal water content and TEWL under the simulated windy or sub‐erythema UV exposure treatment in our laboratory when compared with untreated area.

Conclusion: Our data indicate that this model may provide a more accurate evaluation for the genuine moisturizing effect of cosmetics under external natural climate.