bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacogenetics of cytochrome P4502D6: genetic background and clinical implication
Authors: Cascorbi I. 
Published: October 2003

AbstractInterindividual differences in the pharmacokinetics of a number of drugs are often due to hereditary polymorphisms of drug‐metabolizing enzymes. Most important is cytochrome P4502D6 (CYP2D6), also known as debrisoquine/sparteine hydroxylase. It catalyzes hydroxylation or demethylation of more than 20% of drugs metabolized in the human liver, such as neuroleptics, antidepressants, some β‐blockers and many others like codeine. About 7%−10% of Caucasians lack any CYP2D6 activity due to deletions and frame‐shift or splice‐site mutations of the gene. About 1%−3% of Middle‐Europeans, but up to 29% of Ethiopians display gene duplications, leading to elevated so‐called ultrarapid metabolization rates. Meanwhile there is now a much better understanding of the genetic background of poor, intermediate, extensive and ultrarapid metabolizers, enabling a more precise DNA genotyping‐based prediction of plasma levels. Since there is evidence that deteriorated drug elimination partly accounts for drug side‐effects, CYP2D6 genotyping could contribute to an individualized and therefore optimized drug therapy.
Importance of P‐glycoprotein for drug disposition in humans
Authors: Fromm M. F. 
Published: October 2003

AbstractThe ATP‐binding cassette transporter P‐glycoprotein is now recognized as an important determinant for disposition of multiple drugs. The use of P‐glycoprotein‐expressing cell lines, the generation of P‐glycoprotein knockout mice as well as studies in animals and humans contributed to a better understanding on the role of active transport processes for drug disposition. P‐glycoprotein is located in tissues with excretory function such as intestine, liver and kidney. Moreover, due to its expression in important blood–tissue barriers (blood–brain and blood–testis barriers), in lymphocytes and in placenta it limits tissue penetration of its substrates. Induction and inhibition of P‐glycoprotein have now been identified as important underlying mechanisms of drug interactions in humans. Using selected examples, this review summarizes currently available data on the impact of P‐glycoprotein for bioavailability of drugs, drug interactions and drug effects.
Organic anion‐transporting polypeptide (OATP) transporter family and drug disposition
Authors: Kim R. B. 
Published: October 2003

AbstractDrug transporters are increasingly recognized as a key determinant of drug disposition. Recent studies have revealed that targeted expression of drug uptake and efflux transporters to specific cell membrane domains allows for the efficient directional movement of many drugs in clinical use. While the role of certain efflux transporters such as MDR1 (P‐glycoprotein) in drug disposition has been extensively studied, emerging evidence suggests that uptake transporters may also be important to the intestinal absorption and renal or hepatic elimination of drugs. Members of the organic anion‐transporting polypeptide (OATP) family of drug uptake transporters have been found capable of transporting a large array of structurally divergent drugs. Moreover, expression of OATP isoforms in the gastrointestinal tract, liver and kidney, as well as at the level of the blood–brain barrier, has important implications for our understanding of the factors governing drug absorption, elimination and tissue penetration.
Clinical relevance of genetic polymorphisms in the human CYP2C9 gene
Authors: Schwarz U. I. 
Published: October 2003

AbstractCytochrome P450 (CYP) 2C9 hydroxylates about 16% of drugs in current clinical use. Of special interest are those with a narrow therapeutic index, such as S‐warfarin, tolbutamide and phenytoin, where impairment in CYP2C9 metabolic activity might cause difficulties in dose adjustment as well as toxicity. Single‐nucleotide polymorphisms (SNP) in the CYP2C9 gene have increasingly been recognized as determinants of the metabolic phenotype that underlies interindividual and ethnic differences. Apart from the wild‐type protein CYP2C9*1 at least five allelic variants produce allozymes with reduced or deficient metabolic activity. Among white populations only CYP2C9*2 and CYP2C9*3 variants are of significance, with allelic frequencies of 0·08–0·14 and 0·04–0·16, respectively. In contrast, in Africans (African‐Americans and Ethiopians) and Asians both variants are much less frequent (0·005–0·04), and CYP2C9*2 has not yet been detected in Asians. CYP2C9*4 has been exclusively identified in Japanese patients, and CYP2C9*5 and *6 were only found among African‐Americans with a low allelic frequency of 0·017 and 0·006, respectively. Furthermore in Japanese a CYP2C9 promotor variant of four linked SNPs was correlated with reduced intrinsic clearance of phenytoin in vitro. Subjects who are carriers of one or more variant alleles may be at risk for adverse drug reactions/toxicities when prescribed drugs extensively metabolized by CYP2C9.
Orthograde retreatment and apexification after unsuccessful endodontic treatment, retreatment and apicectomy
Authors: Sedgley C. M. , Wagner R. 
Published: October 2003

AbstractAim  To describe a case where a second orthograde retreatment was successful in the management of an infected mandibular right first molar that previously had received both orthograde and retrograde treatments.Summary  Periapical surgery is unlikely to be successful unless the root canal system has been adequately debrided and sealed. A case is described where orthograde endodontic treatment, retreatment and apicectomy were unsuccessful in the management of an infected mandibular right first molar. The periapical radiolucency eventually disappeared following a second orthograde retreatment. The second retreatment included 12 months of intracanal calcium hydroxide placement to promote apexification, thus allowing subsequent controlled obturation with gutta percha and AH26. At a 5‐year review following completion of treatment, the tooth remained asymptomatic and was in normal function.Key learning points

Orthograde retreatment is a treatment option to manage refractory lesions in teeth that have previously received endodontic treatment, retreatment and apicectomy.
Orthograde retreatment using long‐term intracanal calcium hydroxide can help promote root‐end closure of a resected apex.
Comparative study of root‐canal preparation using Lightspeed and Quantec SC rotary NiTi instruments
Authors: Hülsmann M. , Herbst U. , Schäfers F. 
Published: October 2003

AbstractAim  To compare several parameters of root‐canal preparation using two different rotary nickel–titanium (NiTi) instruments: Lightspeed (Lightspeed Inc, San Antonio, TX, USA) and Quantec SC (Tycom, Irvine, USA).Methodology  Fifty extracted mandibular molars with root‐canal curvatures between 20° and 40° were embedded into a muffle system. All root canals were prepared to size 45 followed by a stepback in 1‐mm increments to size 70 (Lightspeed) or 45 (Quantec SC), using a high‐torque motor at 1300 or 350 r.p.m. respectively. In both groups, irrigation was performed with 2 mL NaOCl (3%) after each instrument size. RC‐Prep (Premier, PA, USA) was used as a chelating agent. The following parameters were evaluated: straightening of curved root canals, postoperative root‐canal diameter, working safety (instrument fractures, perforations, apical blockages, loss of working length (WL)), cleaning ability and working time. Cleanliness of the root‐canal walls was investigated under SEM using 5‐score indices for debris and smear layer. Statistical analysis was performed using the Wilcoxon's test (P < 0.05) for straightening and Fisher's exact test (P < 0.05) for comparison of cross‐sections, contact between pre‐ and postoperative diameter, root‐canal cleanliness and working time.Results  Both NiTi systems maintained the curvature well: the mean degree of straightening was 1.8° for Lightspeed and 1.7° for Quantec SC; differences were not significant. Procedural incidents occurred with Quantec SC in 12 root canals (three fractures, four apical blockages and five cases of loss of WL), preparation with Lightspeed resulted in five fractures, one apical blockage and five cases of loss of WL (11 incidents). Following preparation with Lightspeed, 55.5% of the root canals had a round diameter, 25% an oval and 19.5% an irregular diameter; Quantec SC preparations resulted in a round diameter in 51.5%, oval shape in 33.3% and irregular cross‐sections in 15.2% of the cases. Mean working time was similar for Quantec SC (161 s) and Lightspeed (155 s); the difference was not significant. For debris, Lightspeed and Quantec achieved 64 and 63% for scores 1 and 2, respectively. For smear layer, Lightspeed and Quantec achieved only 13.3 and 27.4% for scores 1 and 2, respectively. Differences were not significant for either debris or smear layer.Conclusions  Both systems respected original root‐canal curvature well and prepared acceptable diameter forms. The cleaning ability was judged not satisfactory for both systems. Both systems showed deficiencies in working safety.
Coronal pulp size in molars: a study of bitewing radiographs
Authors: Chandler N. P. , Pitt Ford T. R. , Monteith B. D. 
Published: October 2003

AbstractAim  To: (i) study coronal pulp dimensions in human first molar teeth; (ii) investigate the effects of restorations on pulp size; (iii) determine differences in dimensions between teeth of Mongoloid patients and teeth of other ethnic groups; and (iv) record the presence of pulp stones.Methodology  Bitewing radiographs of 121 subjects (mean age, 20.9 years) were taken under standardized conditions. The films were digitally scanned and nine measurements were made from the image of each first molar. The data were analysed in terms of presence or absence of restorations and in terms of racial group. Differences were examined using Student's t‐test, Pearson correlations and Levene's test.Results  A total of 445 teeth were analysed. Large crowns were correlated to large pulps. Teeth restored with occlusal and proximal restorations had significantly smaller pulps (P = 0.044 and 0.004, respectively), but no difference was found in pulp area in the clinical crown between the restoration types. Mongoloid crowns were shorter and more bulbous. Pulp areas of maxillary molars and pulp widths at the cervix of mandibular molars were significantly larger in Mongoloids. The pulp area in the clinical crown correlated to pulp horn height for Mongoloids and others and for maxillary and mandibular teeth. No differences were found between the heights of pulp horns in the Mongoloid and other teeth. Four of the pulp measurements demonstrated sexual dimorphism. Stones were present in almost 10% of the subjects, representing 4% of the tooth pulps examined.Conclusion  Even teeth with shallow occlusal restorations had reduced pulp spaces. There were significant differences in pulp and crown dimensions between the teeth of Mongoloid patients and those of other patients.
An in vitro study of the torsional properties of new and used K3 instruments
Authors: Yared G. , Kulkarni G. K. , Ghossayn F. 
Published: October 2003

AbstractAim  To compare torque and angle of rotation at fracture of new and used K3 rotary instruments. The relation between size of instrument and torque at fracture was also investigated.Methodology  Nickel–titanium (Ni‐Ti) .06 K3 rotary instruments were used in a crown‐down manner at 300 r.p.m. to prepare canals in resin blocks. The torque and angle of rotation at fracture of new and the used Ni‐Ti .06 K3 rotary instruments (sizes 15–40) were determined according to ANSI/ADA Specification no. 28. Analysis of variance was used to compare the torque and angle of rotation at fracture amongst the different sizes of the new instruments and between new instruments and instruments of the same size, which had been used in resin blocks (α = 0.05). The relationship between torque at fracture and size of instrument was subjected to regression analysis.Results  Torque at fracture of the new instruments increased significantly with the diameter. The used instruments (sizes 15, 20, 30, 35 and 40) had lower torque at fracture compared to the new ones (P < 0.0001). The means of angle of rotation at fracture between the different sizes of new instruments were significantly different (P < 0.0001) except for sizes 15–20 (P = 0.2561). The used instruments (sizes 20–40) had lower angle of rotation at fracture compared to the new ones (P < 0.05). A linear relationship was found between the size of the file and the torque at fracture for the new instruments (r2 = 0.84; P < 0.0001) and the used ones (r2 = 0.82; P < 0.0001).Conclusions  In general, the results suggested that the torque and angle of rotation at fracture were significantly affected by the repeated use of .06 K3 instruments in resin blocks.
In vitro fracture resistance of root‐filled teeth using new‐generation dentine bonding adhesives
Authors: Hürmüzlü F. , Serper A. , Siso Ş. H. , Er K. 
Published: October 2003

AbstractAim  To compare the fracture resistance of root‐filled premolar teeth restored with new‐generation dentine bonding adhesives.Methodology  Sixty extracted single‐rooted human maxillary premolar teeth were used. Access cavities were prepared, and the roots were instrumented with K‐files to an apical size 50 using a step‐back technique. Root fillings were accomplished using gutta percha (Sure‐Endo, Seoul, Korea) and AH Plus root canal sealer (Dentsply DeTrey, Konstanz, Germany) using the lateral condensation technique. The teeth were then randomly divided into six groups of 10 teeth each. A mesiodistocclusal (MOD) cavity was prepared in the teeth to the level of the canal orifices so that the thickness of the buccal wall of the teeth measured 2 mm at the occlusal surface and 3 mm at the cemento‐enamel junction. Preparations were restored using the following adhesive systems: Etch & Prime 3.0 (Degussa AG, Hanau, Germany), Clearfil SE Bond (Kuraray, Osaka, Japan), Prompt L‐Pop (ESPE, Seefeld, Germany), Panavia F (Kuraray, Osaka, Japan), Optibond Plus (Kerr, Orange, CA, USA) and Admira Bond (Voco, Cuxhaven, Germany); all preparations except those of the Panavia F and Admira Bond groups were further restored with resin composites. The Panavia F group was restored with amalgam and the Admira Bond group with Ormocer (Voco, Cuxhaven, Germany). The teeth were mounted in a Universal Testing Machine (Hounsfield, Surrey, UK), and the buccal walls were subjected to a slowly increasing compressive force until fracture occurred. The force of fracture of the walls of each tooth was recorded and the results in the various groups were compared. Statistical analysis of the data was accomplished using one‐way anova.Results  There was no significant difference in the fracture resistance of any of the test groups.Conclusions  In this laboratory study, the type of dentine bonding agents had no influence in the fracture resistance of teeth.
Minor illness education for parents of young children
Authors: Robbins Helen , Hundley Vanora , Osman Liesl M 
Published: October 2003

Background. A number of previous studies on minor illness have concentrated on nurse‐led clinics and the role of nurse practitioners. This study examines the effect of a minor illness education programme which aimed to increase parents’ confidence and knowledge in managing childhood illnesses.Aim. The primary aim of this study was to evaluate the effectiveness of a home visit and booklet in providing education to parents about minor infant illnesses.Design. A randomized controlled trial was conducted. The intervention involved a home visit to discuss parents’ concerns and provide advice and information, and a booklet advising parents what to do and when to consult about infant illnesses.Method. A total of 120 parents of 6 week old babies were identified over a 6 month period, using health visitors’ caseloads, and randomized to an intervention group (60), that received a visit and a booklet, or a control group (60) that received standard care. Groups were compared on entry to the study and at 7 months, in terms of parental knowledge and confidence about childhood illnesses, the intended use of home care activities, intention to consult professionals and actual use of health services. Data were collected by self‐completed questionnaire and case note review.Findings. The educational intervention resulted in a reduction in visits to the child health clinic but had little effect on use of other services. Parents in the intervention group showed a general trend towards greater certainty about the home care options they would choose, and a reduction in intention to consult a doctor. However, they also indicated a feeling of reduced confidence and knowledge.Conclusion. The trial showed no effect on use of services but did demonstrate reduction in parents’ intentions to consult a doctor, which appeared to be because of increased certainty about home care. However, it is of concern that they indicated feeling less confident and knowledgeable. It is not possible to clarify whether this represented anxiety that was constructive, enhancing decision‐making or was destructive. Further work into the role of education in parental decision‐making, anxiety levels and enhancement of confidence is required.
Early detection and treatment of postnatal depression in primary care
Authors: Davies Bronwen R. , Howells Sarah , Jenkins Meryl 
Published: October 2003

Background. Postnatal depression has a relatively high incidence and gives rise to considerable morbidity. There is sound evidence supporting the use of the Edinburgh Postnatal Depression Scale as a screening tool for possible postnatal depression.Aim. This paper reports on a project developed by two health visitors and a community mental health nurse working in the United Kingdom. The aim of the project was to improve the early detection and treatment of postnatal depression in the population of the general practice to which they were attached.Method. The health visitors screened for postnatal depression in the course of routine visits on four occasions during the first postpartum year. Women identified as likely to be suffering from postnatal depression were offered ‘listening visits’ as a first‐line intervention, with referral on to the general practitioner and/or community mental health nurse if indicated.Findings. Data collected over 3 years showed that the project succeeded in its aim of enhancing early detection and treatment of postnatal depression. These findings replicate those of other studies. The data also showed that a substantial number of women were identified for the first time as likely to be suffering from postnatal depression at 12 months postpartum. Women screened for the first time at 12 months were at greater risk than those who had been screened earlier than this.Conclusions. Health visitors should screen for postnatal depression throughout the period of their contact with mothers, not solely in the immediate postnatal period. It is particularly important to screen women who, for whatever reason, were not screened when their child was younger. The knowledge and skills needed to use the Edinburgh Postnatal Depression Scale and provide first‐line intervention and onward referral can be developed at practitioner level through close collaborative working.
Adherence to diabetes control recommendations: impact of nurse telephone calls
Authors: Kim Hee‐Seung , Oh Jeong‐Ah 
Published: October 2003

Background. Type 2 diabetes mellitus is increasing in incidence and research has shown that normalization of blood glucose levels can moderate the risk of microvascular and neurological complications.Aim. The purpose of this study was to investigate the effect of nurse telephone calls on glycosylated haemoglobin (HbA1c) levels and adherence to diabetes control recommendations.Methods. A randomized design with control and experimental groups being assessed pre‐ and postintervention was used to assess the effectiveness of nurse telephone calls. Twenty patients were randomly assigned to an intervention group and 16 to a control group. The goal of the intervention was to keep blood glucose concentrations close to the normal range (HbA1c < 7%). The intervention was applied to the intervention group for 12 weeks, and consisted of continued education and reinforcement of diet, exercise, medication adjustment recommendations, as well as frequent self‐monitoring of blood glucose levels. Telephone intervention was performed twice per week for the first month and then weekly for the second and third month. Participants were requested to write self‐management logs including blood glucose levels, diet and an exercise diary. A dietitian analysed the diet diaries and participants were informed about their results by telephone or mail. All medication adjustments were communicated to participants’ doctors. The HbA1c and diabetes adherence were measured before and after the intervention.Results. Patients in the intervention group had a mean decrease of 1·2% in HbA1c levels and those in the control group had a mean increase of 0·6% in HbA1c levels. The intervention group had greater diet and blood glucose testing adherence than the control group.Conclusion. These findings indicate that a nurse telephone intervention can improve HbA1c, and diet and blood glucose testing adherence.
Anxiety and well‐being in older people after discharge from hospital
Authors: Kvaal Kari , Laake Knut 
Published: October 2003

Background. A previous study using the State‐Trait Anxiety Inventory (STAI) has documented a very high prevalence of anxiety symptoms among older inpatients. The STAI produced two main concepts on factor analysis –‘Nervousness’ and ‘Well‐being’– and high scores on both caused the high overall score in these patients.Aim. To investigate how the scorings on the STAI evolve after discharge in older patients in order to understand better the reasons for their high scorings while in hospital.Methods. Sixty‐three patients who had been scored on the STAI during their stay in an elder care department were followed up at 1–3 and 12 months after discharge. Data were analysed by ancova for unbalanced designs.Results. The mean STAI sum score increased significantly (3·5 points adjusted for the baseline scoring, age and gender, P < 0·001) from the first follow‐up while in hospital to 1–3 months after discharge, with no significant change between the second and the last follow‐up. This increase resulted primarily from a significant worsening of the score on ‘well‐being’. The score on ‘nervousness’ remained unchanged. Age did not influence the scores, while females scored higher. No interaction effects were observed, indicating that the evolvement of nervousness and anxiety after discharge is independent of gender and age. Item analysis showed that the worsening of the score on ‘well‐being’ in these patients during the first 1–3 months after discharge was primarily caused by a lower score on the item ‘I feel secure’.Conclusion. The study does not support the hypothesis that a high level of nervousness and lack of well‐being among hospitalized older patients results from acute illness and hospitalization. The worsening in the score on well‐being after discharge of such patients is primarily caused by low levels of feelings of security. This represents a challenge to nurses providing home‐based care.