bluuebunny/crossref_metadata_2025 huggingface dataset:
Renewal of the clinical‐phase dental curriculum to promote better learning at the University of Oulu
Authors: Hietala Eeva‐Liisa , Karjalainen Asko , Raustia Aune
Published: July 2004

The degree awarded to a dentist in Finland is Licentiate of Dentistry, and it takes 5 years to achieve it. The old curriculum at the Institute of Dentistry, University of Oulu, Finland, was based on the departmental division, and there was minimal integration between the disciplines. According to student feedback, the old curriculum was overloaded. The amount of contact teaching was up to 40 h per week throughout the academic year. Based on the workload regulation model launched at the University of Oulu, the actual workload of students for three clinical years was found to exceed the confirmed curriculum (40 study weeks per year for 3 years, representing 180 European Credit Transfer System (ECTS) credits) by 68 ECTS credits (representing 45.3 study weeks). Because of the heavy workload, students did not have time actively to deepen their scientific reasoning. To tackle this problem and to maintain the high academic standards, the Institute of Dentistry, University of Oulu, Finland, decided to change the dental curriculum. The properties and qualities of the competent dentist were listed and arranged in the corners of an octagonal to provide the model of the key dental competencies. Based on this, a thorough core analysis of the courses was carried out by the departments. The new curriculum consists of 10 broader integrative entities, so called dental teaching strands (DTSs), wherein the teaching given by the different departments has been combined. The effort was successful. We managed to remove overlap in the substance of the courses to reduce the students' actual workload by about 45 ECTS credits (representing 30 study weeks and 1200 h of studying) and to promote better scientific reasoning and learning results. The authentic learning and comprehensive patient care comprise the core of the clinical practice.
Simulation of patient encounters using a virtual patient in periodontology instruction of dental students: design, usability, and learning effect in history‐taking skills
Authors: Janda M. Schittek , Mattheos N. , Nattestad A. , Wagner A. , Nebel D. , Färbom C. , Lê D.‐H. , Attström R.
Published: July 2004

Simulations are important educational tools in the development of health care competence. This study describes a virtual learning environment (VLE) for diagnosis and treatment planning in oral health care. The VLE is a web‐based, database application where the learner uses free text communication on the screen to interact with patient data. The VLE contains forms for history taking, clinical images, clinical data and X‐rays. After reviewing the patient information, the student proposes therapy and makes prognostic evaluations of the case in free text. A usability test of the application was performed with seven dental students. The usability test showed that the software responded with correct answers to the majority of the free text questions. The application is generic in its basic functions and can be adapted to other dental or medical subject areas. A randomised controlled trial was carried out with 39 students who attended instruction in history taking with problem‐based learning cases, lectures and seminars. In addition, 16 of the 39 students were randomly chosen to practise history taking using the virtual patient prior to their first patient encounter. The performance of each student was recorded on video during the patient sessions. The type and order of the questions asked by the student and the degree of empathy displayed towards the patient were analysed systematically on the videos. The data indicate that students who also undertook history taking with a virtual patient asked more relevant questions, spent more time on patient issues, and performed a more complete history interview compared with students who had only undergone standard teaching. The students who had worked with the virtual patient also seemed to have more empathy for the patients than the students who had not. The practising of history taking with a virtual patient appears to improve the capability of dental students to take a relevant oral health history.
Assessment of ‘borderline’ clinical competence using generalisability and decision studies in dental skills training
Authors: Kropmans T. J. B. , Ćosić K.
Published: July 2004

Introduction:  Generalisability coefficients are widely used as a measure of reliability in educational sciences. However, coefficients do not inform about how much individual and/or educational variance is needed for borderline competence. Probing depth measurements were used as an example to demonstrate the use of generalisability and decision studies in educational decision‐making.

Method:  All six probing depths of seven elements of the first quadrant were assessed in a random crossed four‐way ‘elements’ (7), ‘probing depth’ (6) ‘observers’ (7–8) and ‘repetitions’ design for both students (8) and faculty staff (7). Borderline competence was assessed in four decision study designs.

Results:  In decision studies the generalisability coefficient varied from 0.31 to 0.88 for the first single and fourth repeated study design, respectively. The standard error of the measurement varied from 1.73 to 0.64 mm with a corresponding 95% confidence interval varying from 3 to 1 mm.

Conclusion:  Repeated measurement is not the most efficient way to improve educational decision‐making. What is new to this approach is that we used the 95% confidence interval of the standard error of measurement as a measure for ‘borderline competence’ expressed in the unity of the measurement instrument. Correctly performing the procedure of probing depth assessment is of clinical and educational importance in deciding whether further treatment is necessary and whether students fail or pass their exams.
Dental students, social policy students and learning disability: do differing attitudes exist?
Authors: Coyle C. , Saunderson W. , Freeman R.
Published: July 2004

Objectives:  To examine the attitudes of dental students and social policy students towards learning disabilities in order to identify whether attitudinal differences exist and to suggest recommendations in the dental undergraduate curriculum commensurate with Government legislation in the United Kingdom.

Design:  A cross‐sectional survey of all undergraduate dental students at Queen's University, Belfast and all undergraduate social policy students at University of Ulster.

Method:  A convenience sample of all undergraduate dental and social policy students was obtained. The students completed a questionnaire to assess attitude towards learning disability. The data were analysed using Cronbach's α, Student's t‐test and analysis of variance (one‐way fixed effect model). The level of statistical significance was set at 5%.

Results:  The response rate was 83% for dental students and 97% for social policy students. Dental students had significantly lower mean scores and hence less favourable attitudes to learning disability compared with social policy students. Female dental students had significantly higher mean scores and hence more favourable attitudes to learning disability compared with male students.

Conclusions:  The findings show that dental undergraduates compared with social policy students had less favourable attitudes towards those with learning disability. Dental students should receive training in learning disability and undergraduate programmes should be conceptualised as a spiral curriculum. It is proposed that social policy theory should be introduced into undergraduate dental curricula, that early exposure to learning disability in a community setting should be incorporated into the first undergraduate years and in later undergraduate clinical years students should treat patients with learning disability in order to promote experiential learning and reflective practice.
Hypoxic depression of melatonin secretion after simulated long duration flights in man
Authors: Coste Olivier , Beaumont Maurice , Batéjat Denise , Beers Pascal Van , Charbuy Henriette , Touitou Yvan
Published: July 2004

Abstract:  Fatigue is often reported after long duration flights. Mild hypobaric hypoxia caused by pressurization may be involved in this effect through disruption of circadian rhythms, independent of the number of time zones crossed. In this controlled crossover study we assessed the effects of two levels of hypoxia equivalent to 8000 and 12,000 ft on the rhythm of plasma melatonin concentrations, a marker of circadian rhythmicity. Sixteen healthy young male volunteers (23–39 years) were exposed in a hypobaric chamber for 8 hr (08:00–16:00 hours) to 8000 ft, followed 4 wk later by 12,000 ft. Plasma melatonin was assayed over two 24‐hr cycles (control and hypoxic exposure) every 2 hr in all subjects. We found a significant decrease in the nocturnal melatonin peak after hypoxic exposure at both altitudes, and we found that this effect was age dependent for the 12,000‐ft exposure: the decrease was only seen in the younger subjects (23–28 years). Analysis of heart rate variability allowed us to demonstrate that the older and less trained subjects (29–39 yr) in our study exhibited a far greater increase in sympathetic tone than the younger subjects during the 12,000‐ft exposure. These results show that hypoxic depression of melatonin secretion may be influenced by individual factors such as age, physical fitness and sympathetic reactivity to hypoxia. Our findings suggest that hypoxia may by itself contribute at least in part to postflight fatigue after long duration flights, and to the clinical disorders of jet lag in transmeridian flights through its effects on the circadian system.
Melatonin attenuates isoproterenol‐induced protein kinase A overactivation and tau hyperphosphorylation in rat brain
Authors: Wang Dan‐Ling , Ling Zhi‐Qun , Cao Fu‐Yuan , Zhu Ling‐Qiang , Wang Jian‐Zhi
Published: July 2004

Abstract:  Hyperphosphorylation of microtubule‐associated protein tau at specific sites is a recognized pathological process in Alzheimer's disease (AD), and protein kinase A (PKA) is a crucial kinase in AD‐like tau hyperphosphorylation. In the present study, isoproterenol (ISO) was injected bilaterally into hippocampus of rat brain; ISO is a specific PKA activator and it induces tau hyperphosphorylation. With this system, melatonin (MT) was shown to protect against ISO‐induced tau hyperphosphorylation. We found that hippocampal injection of ISO (0.02 μm) induced PKA overactivation and tau hyperphosphorylation at both paired helical filament (PHF)‐1 and tau‐1 sites. ISO injection also resulted in activation of superoxide dismutase (SOD) and elevation of malondialdehyde (MDA), parameters suggesting elevated oxidative stress. Preinfusion of MT intraperitoneally partially reversed ISO‐induced tau hyperphosphorylation at the PHF‐1 epitope (1 and 10 mg/kg continuously for 4 wk or 10 mg/kg for 1, 2 or 3 wk) and tau‐1 epitope (10 mg/kg for 2 wk). Furthermore, MT (10 mg/kg for 2 wk) obviously antagonized ISO‐induced PKA overactivation, as well as enhanced SOD activity and decreased the level of MDA. It is suggested from these data that ISO may induce abnormal hyperphosphorylation of tau through not only the activation of PKA but also because of the fact that it increases oxidative stress; MT may protect against ISO‐induced tau hyperphosphorylation through suppression of both PKA overactivation and oxidative stress.
Melatonin attenuates ifosfamide‐induced Fanconi syndrome in rats
Authors: Sener Goksel , Sehirli Özer , Yegen Berrak Ç. , Cetinel Sule , Gedik Nursal , Sakarcan Abdullah
Published: July 2004

Abstract:  Regarding the mechanisms of ifosfamide (IFO)‐induced nephrotoxicity and hemorrhagic cystitis, several hypotheses have been put forward, among which oxidative stress and depletion of glutathione (GSH) are suggested. This investigation elucidates the role of free radicals in IFO‐induced toxicity and the protection by melatonin. Wistar albino rats were injected intraperitoneally with saline (0.9% NaCl; control‐C group), melatonin (Mel group; 10 mg/kg daily for 5 days) or ifosfamide (50 mg/kg daily for 5 days; IFO group) or IFO + Mel. On the 5th day (120 hr) after the first IFO dose, animals were killed by decapitation and trunk blood was collected. Kidney and bladder tissues were obtained for biochemical and histological analysis. Urine was collected 24 hr before the rats were killed. The results demonstrated that IFO induced a Fanconi syndrome (FS) characterized by wasting of sodium, phosphate, and glucose, along with increased serum creatinine and urea. Melatonin markedly ameliorated the severity of renal dysfunction induced by IFO with a significant decrease in urinary sodium, phosphate, and glucose and increased creatinine excretion. Moreover, melatonin significantly improved the IFO‐induced GSH depletion, malondialdehayde accumulation and neutrophil infiltration in both renal and bladder tissues. In the kidney, Na+,K+‐ATPase activity which was significantly reduced by IFO, was increased with melatonin treatment. Increased collagen contents of the kidney and bladder tissues by IFO treatment were reversed back to the control levels with melatonin. Our results suggest that IFO causes oxidative damage in renal and bladder tissues and melatonin, via its antioxidant effects, protects these tissues. These data suggest that melatonin may be of therapeutic use in preventing acquired FS due to IFO toxicity.
Estrogen modulation of adrenoceptor responsiveness in the female rat pineal gland: differential expression of intracellular estrogen receptors
Authors: Sànchez Juan J. , Abreu Pedro , González‐Hernández Tomás , Hernández Alexis , Prieto Luis , Alonso Rafael
Published: July 2004

Abstract:  The effect of different doses of 17β‐estradiol (E2) on the pineal response to β‐adrenoceptor stimulation in female rats was examined. Pinealocytes from 21‐day‐old ovariectomized rats were exposed to different estrogen doses and treated with β‐adrenergic agonists. Estrogen treatment produced a dose‐dependent, biphasic response to β‐adrenoceptor‐induced accumulation of cAMP. This effect was inhibitory at estrogen doses up to 0.1 nm and fitted to a negative exponential curve, while at doses from 0.1 to 100 nm the effect was stimulatory and fitted to a standard positive hyperbola. For in vivo studies, ovariectomized rats were treated with equivalent estrogen concentrations plus a single dose of progesterone (250 μg per rat), and their pineals exposed in vitro to β‐adrenergic agonists. Low doses of E2 (0.1–100 ng per rat) reduced both pineal cAMP accumulation and N‐acetyltransferase activity after β‐adrenoceptor stimulation, while a high dose (10 μg per rat) induced the opposite response. Apparently, the final estrogen target was the pineal β‐adrenergic receptor, as a low dose of E2 (which had diminished cAMP accumulation after β‐adrenoceptor stimulation) also reduced its maximal binding capacity (Bmax) and its dissociation constant (Kd). We also found that the female rat pineal gland contains two different ER subtypes, α and β, which respond to estrogen exposure with nucleocytoplasmic shuttling. These results indicate that, in the female rat, estrogen directly modulates pineal sensitivity to adrenergic stimulation in a complex, dose‐dependent manner that may be related to differential expression and activity of two estrogen receptor subtypes within pineal cells.
Oral administration of melatonin reduces food intake and modifies macronutrient selection in European sea bass (Dicentrarchus labrax, L.)
Authors: Rubio V. C. , Sánchez‐Vázquez F. J. , Madrid J. A.
Published: July 2004

Abstract:  Seasonal and circadian changes have been observed in dietary selection and feeding behavior of fish. It is known that the light–dark cycle is the principal mediator of the production of pineal‐derived melatonin in fish, and also that the digestive tract synthesizes and secretes melatonin and indeed is the principal extrapineal source of this secretor product, suggesting that melatonin could be involved in the processes of feeding and/or digestion. Fish are capable of regulating their energy intake from separate sources of macronutrients, but the mechanisms of this selection process are unknown. In the present paper, we explored the effect of melatonin administered orally to European sea bass on their selection of encapsulated macronutrients. Melatonin doses of 0.1, 0.5, and 2.5 mg/kg body weight were administered in gelatin capsules. The voluntarily ingested melatonin was absorbed into the fish's plasma, 45 min after the administration reaching a level depending on the dose that was up to 26 times greater than the controls with the highest dose of melatonin. The indole produced a dose‐dependent inhibition of total food intake of 9, 26, and 34%, respectively, and also modified the pattern of macronutrient selection. Carbohydrate intake was significantly reduced (by 17, 33, and 42% for the three doses, respectively), but the observed reductions in fat and protein intake were not statistically significant. On the contrary, fat percentage significantly increased for the highest dose, but no changes were observed in the protein or carbohydrate percentages for any of the melatonin doses. In conclusion, orally administered melatonin affected both the amount of food consumed and the pattern of macronutrients selected. This is the first evidence for the existence of neurohumoral mediators involved in the selection of macronutrients in fish.
mRNA expression of nuclear receptor RZR/RORα, melatonin membrane receptor MT1, and hydroxindole‐O‐methyltransferase in different populations of human immune cells
Authors: Pozo David , García‐Mauriño Sofía , Guerrero Juan M. , Calvo Juan R.
Published: July 2004

Abstract:  We characterized the expression levels of the retinoid Z receptor α (RZR α), RORα mRNA isoforms (RORα1, RORα2, and RORα3), and both melatonin receptor MT1 and hydroxindole‐O‐methyltransferase (HIOMT) genes. For this purpose, the following human peripheral blood mononuclear cells populations were isolated: monocytes (CD14+ cells), B lymphocytes (CD19+ cells), T helper lymphocytes (CD14− CD4+), cytotoxic T lymphocytes (CD56− CD8+ cells), and natural killer (NK) lymphocytes (CD56+ cells). PBMCs subsets were obtained by Dynabeads M‐450 (Dynal) isolation procedure. We observed a strong gene expression signal for RZRα in all subpopulations studied, whereas both RORα1 and RORα2 transcripts were amplified only in CD8+ cells. Specific signal for RORα2 was obtained in all subpopulations studied, but we were not able to detect the RORα3 mRNA transcript in human immune cells studied. A weaker signal (especially in CD19+ cells) was also detected in all subsets of cells for the MT1 gene. With regard to HIOMT, a strong signal was achieved among all but one subpopulation of cells; the only exception was CD14+ cells. Thus, in addition to its classical function in the nervous and endocrine system, melatonin could act directly as a paracrine and/or autocrine agent in the human immune system.
Inter‐ and intra‐variability of pigmented skin lesions: could the ABCD rule be influenced by host characteristics?
Authors: Burroni Marco , Dell'Eva Giordana , Corona Rosamaria , Sera Francesco , Bono Riccardo , Sbano Paolo , Andreassi Lucio , Rubegni Pietro
Published: July 2004

Background/purpose: Many differences in color, shape and dimension exist between different moles even in the same individual. Major differences might be accounted for anatomical location, genetic factors and by environmental factors, mainly sunlight exposure. Therefore, it would be of great value, when evaluating skin lesions, to take into account the degree of intra‐ and inter‐variability of several diagnostic parameters. In order to assess the morphologic and chromatic differences between lesions belonging to different patients and between lesions belonging to the same individual, we examined objective digital parameters obtained with dermatoscopic analysis, using the DBDermo MIPS system (BIO MIPS Engineering, S.R.L, siena, Italy).

Methods: The automatic classifier inside the software is based on a ‘match by similarity’ algorithm, based on the measurement of the Euclidean distances of all variables considered from the reference image. Two‐hundred and four clinically benign pigmented lesion, belonging to 18 patients were examined, stored and automatically processed. For each lesion objective parameters related to geometry, color and texture were automatically evaluated.

Results: We found skin color (healthy skin) is objectively different from subject to subject and the lesion color is more similar among different lesions of the same patient than among lesions belonging to different individuals both in their darkest and slightly dark component. We also observed that lesion dimensions are individual correlates, i.e. the probability for a lesion to be large is higher when the other, in the same patient, is large.

Conclusion: Many parameters of pigmented skin lesions evaluated by digital dermoscopy analysis are similar in the same patient and different from those belonging to different individuals. This indicates that, when considering a lesion, we should take into account the peculiar patient's characteristics.
Methodological aspects of high‐frequency ultrasound of skin in children
Authors: Schou A. J. , Thomsen K. , Plomgaard A. M. , Wolthers O. D.
Published: July 2004

Background: High‐frequency ultrasound of the skin has recently been introduced for assessment of systemic effects in the cutis and subcutis of oral and inhaled glucocorticoids in children. However, the use of high‐frequency skin ultrasound in clinical trials is invalidated because important methodological aspects have not been addressed. The aim of the present study was to evaluate inter‐ and intraobserver, day to day and diurnal variations of measurement of thickness of cutis and subcutis, and the fraction of low echogenic pixels (fLEP) in the cutis and, furthermore, to assess effects of exercise on the cutis and subcutis and variations in subcutaneous thickness between anatomical locations in children with a high‐frequency B‐mode ultrasound scanning device.

Methods: Three studies were conducted, each including 10 healthy prepubertal children. High‐frequency skin ultrasound was performed with the 20 MHz Dermascan C® (Cortex Technology, Hadsund, Denmark). In study 1, the same observer performed five consecutive scannings to assess intraobserver variations. In study two different observers performed scannings at 2 h intervals between 08:00 and 20:00 h, whereby interobserver and diurnal variations were assessed. In study 3, the same observer performed scannings in different anatomical locations on five consecutive days, and on one of these days before and after exercise. Thus day‐to‐day variations and the effect of exercise were assessed.

Results: Low inter‐ and intraobserver variations were found on assessment of the thickness of cutis and subcutis, whereas high variations were found on evaluation of the dermal water content. Diurnal variations were absent, and day‐to‐day variations were low. Exercise caused significant increases in the thickness of cutis and subcutis on the thigh.

Conclusion: Low inter‐ and intraobserver variations make high‐frequency ultrasound a precise and reliable tool for assessment of the cutaneous and subcutaneous thickness in children. In future trials, repetitive scannings need not to be performed at the same time of the day, whereas strenuous physical activity should be avoided on days of examination.
Wound problems due to zinc deficiency
Authors: Patel Girish K , Harding Keith G
Published: July 2004

Zinc deficiency, though uncommon, can occasionally present in current medical practice. A 4.5‐year‐old boy with previous gastrointestinal surgery presented with diarrhoea, disinterest and dermatitis affecting the face and perineum. The clinical diagnosis was confirmed by the presence of a low serum zinc level. Administration of parenteral zinc led to rapid improvement in diarrhoea, demeanour and dermatitis. Further surgery was then undertaken, surgery had been postponed until normalisation of zinc levels due the association between zinc deficiency and poor postoperative wound healing.
Reepithelialisation and the possible involvement of the transcription factor, basonuclin
Authors: Matsuzaki Kyoichi , Inoue Hajime , Kumagai Norio
Published: July 2004

This article briefly summarises the basic mechanism of reepithelialisation and discusses the possible role of the cell‐type‐specific transcription factor, basonuclin. Reepithelialisation is initiated by a signal resulting from the absence of neighbouring cells at the wound edge. Basal cells at the wound edge become flattened and lose their intercellular desmosomes and substratum attachment. The amount of cytoplasmic actinomyosin filaments that insert into the new adhesion complexes is increased, and contraction of those filaments produces cell movement. The epithelial cells at the wound edge migrate on a provisional matrix using the newly expressed integrin receptors. Once reepithelialisation is complete, the epithelial cells revert to the normal phenotype of basal epidermal cells, firmly attach to the newly developed basement membrane zone through hemidesmosomes and resume standard differentiation. Protein synthesis increases in the epidermal cells at the wound edge during reepithelialisation. Active protein synthesis requires accelerated transcription of ribosomal RNA genes. The transcription factor basonuclin binds to the ribosomal RNA gene promoter and increases the transcription of the genes. Therefore, it is speculated that basonuclin in epithelial cells is required in the process of reepithelialisation.
Keloids – a frustrating hurdle in wound healing
Authors: Rekha Arcot
Published: July 2004

A balance between collagen formation and degradation is essential for normal wound healing. Inadequate wound healing results in wound breakdown, and exaggeration results in hypertrophic scars and keloids. We look at the aetiological factors, the biochemical alterations and the treatment modalities for keloids, in this clinical challenge.
Levosimendan Interacts with Potassium Channel Blockers in Human Saphenous Veins
Authors: Höhn József , Pataricza János , Petri András , Tóth Gábor K. , Balogh Ádám , Varr András , Papp Julius Gy.
Published: July 2004

Abstract: The involvement of potassium channels in the venodilating capacity of the inodilator levosimendan in human saphenous vein preparations was investigated. Levosimendan caused relaxation with 50% effective concentration (EC50) of 0.32±0.04 μM in isolated veins contracted by 5‐hydroxytryptamine. Fifteen μM glibenclamide, a blocker of the ATP‐sensitive potassium channels (KATP), partially inhibited the relaxing effect of the inodilator. In the presence of iberiotoxin, the selective blocker of large conductance calcium‐activated potassium channels (BKCa), levosimendan induced contraction with EC50 of 0.21±0.06 μM. We presume that levosimendan dilates human saphenous veins by interacting with hyperpolarizing potassium channels (KATP and BKCa).
Early Acute Necrosis and Delayed Apoptosis Induced by Methyl Mercury in Murine Peritoneal Neutrophils
Authors: Kuo Tsun‐Cheng , Lin‐Shiau Shoei‐Yn
Published: July 2004

Abstract: There is growing evidence that heavy metals in general, and mercurial compounds in particular, are immunotoxic. The purpose of this study was to explore the mechanism of MeHg in inducing cell death of mouse peritoneal neutrophils. In this paper we demonstrate that MeHg induces apoptosis and necrosis depending on MeHg concentration. In vitro exposure of mouse peritoneal neutrophils to MeHg resulted in a time‐ and concentration‐dependent cell death. MeHg (15 μM) induced neutrophil necrosis in 13 min. The type of cell death was attributed to necrosis based on cells permeable to the fluorescent dye, propidium iodide and DNA appeared as a smear. With fura‐2 microfluorimetric technique, we found that the entry of external Ca2+ into the cytosol played a crucial role in inducing cell necrosis by 15 μM MeHg. However, at lower concentrations, MeHg (10 μM)‐induced apoptosis is confirmed by the observation of morphological features characterised by apoptotic bodies and fragmented DNA ladder. MeHg (10 μM) caused an immediate fall in pHi as revealed by the pH‐sensitive fluorescent probe 2′7′‐bis (carboxyethyl)‐5(6)‐carboxyfluorescein. We have found that MeHg induced cellular acidification prior to DNA fragmentation so as the other two apoptosis‐inducing agents (ZnCl2 and EGTA). Furthermore, acid‐activated endonuclease was increased by MeHg in neutrophils, which we considered to play a possible role in chromatin digestion leading to apoptosis. Taken together, these findings indicate that MeHg induces necrosis at higher concentrations by a rapid increase of [Ca2+]i and apoptosis at lower concentrations by acid activation of endonuclease.
Cytotoxic and DNA‐Damaging Effects of Diterpenoid Quinones from the Roots of Salvia officinalis L. on Colonic and Hepatic Human Cells Cultured in vitro
Authors: Slameňová Darina , Mašterová Irena , Lábaj Juraj , Horváthová Eva , Kubala Pavol , Jakubíková Jana , Wsólová Ladislava
Published: July 2004

Abstract: Three diterpenoid quinones (royleanone – SAR 3, horminone – SAR 26, and acetyl horminone – SAR 43) isolated from the roots of Salvia officinalis L. were tested for their cytotoxic and DNA‐damaging activity in human colon carcinoma cells Caco‐2 and human hepatoma cells HepG2 cultured in vitro. Cytotoxicity was measured by the trypan blue exclusion technique and induction of apoptosis was evaluated by flow immunofluorocytometry after 30–300 min. exposure of HepG2 and Caco‐2 cells to diterpenoid quinones and following 24 hr post‐incubation in the culture medium. Induction of DNA breaks was measured after 60 min. exposure of cells to different concentrations of the compounds studied by the alkaline elution of DNA and by the Comet assay. Though all the quinones tested decreased the viability of the cells studied proportionally to the concentration and to the time of treatment (cytotoxicity=30–60%), the increased level of apoptotic nuclei comparable to the level of apoptotic nuclei induced by a topoisomerase I inhibitor was proved only in HepG2 cells treated with 1×10−4 mol/l SAR 26 or SAR 43. Either no or marginal increase of the level of apoptotic nuclei was observed in SAR 3‐treated HepG2 cells and in SAR 3‐, SAR 26‐ or SAR 43‐treated Caco‐2 cells. All compounds tested induced creation of DNA strand breaks in both cell types at concentrations >1×10−7–1×10−6 mol/l. The occurrence of DNA strand breaks at different pH values as well as the kinetics of DNA breaks rejoining were evaluated only in colonic cells Caco‐2. The Comet assay processed in parallel at pH 13.0 and pH 12.1 showed that strand breaks detected in SARs‐treated colonic Caco‐2 cells originated from alkali‐labile sites, as induced DNA lesions were converted to DNA strand breaks only under strong alkaline conditions. The kinetics of DNA rejoining revealed that SARs‐induced DNA breaks were repaired very slowly.
Comparative skin dose measurement in the treatment of anal canal cancer: Conventional versus conformal therapy
Authors: Devic Slobodan , Hegyi Gyorgy , Vuong Té , Muanza Thierry , Podgorsak Ervin B.
Published: July 2004

The subject of this work was to compare the effect of Conventional and Conformal techniques, used for anal canal cancer treatments, on the skin dose deposition. Skin dose was measured on a Rando phantom using XR‐T GAFCHROMIC® film. A skin surface dose histogram was constructed and a skin dose profile in the sagittal direction of the perineal region was measured, for both techniques. The measured skin dose in the anterior and posterior region of the skin exposed to radiation is from two to ten times higher when using a conventional technique. In the perineal region, an 85% of the prescription isodose line spreads over 25% of the perineum for conformal technique as compared to 65% with conventional techniques. In addition, conformal technique dose profiles confine better the anatomical position of the anal verge than conventional techniques. Results presented in this work confirm clinically observed improvement in the radiation‐induced dermatitis when using the conformal technique.
Classification of breast tissue density by optical transillumination spectroscopy: Optical and physiological effects governing predictive value
Authors: Blyschak Kristina , Simick Michelle , Jong Roberta , Lilge Lothar
Published: July 2004

Preventive oncology is in need of a risk assessment technique that can identify individuals at high risk for breast cancer and has the ability to monitor the efficacy of a risk reducing intervention. Optical transillumination spectroscopy (OTS) gives information about breast tissue composition and tissue density. OTS is noninvasive and in contrast to mammography, uses nonionizing radiation. It is safe and can be used frequently on younger women, potentially permitting early risk detection and thus increasing the time available for risk reduction interventions to assert their influence. Before OTS can be used as a risk assessment and/or monitoring technique, its predictive ability needs to be demonstrated and maximized through the construction of various mathematical models relating OTS and breast tissue density, and hence, risk. To establish a correlation between OTS and mammographic density principal components analysis (PCA), using risk classification, is calculated. The PCA scores are presented in three‐dimensional cluster plots and a plane of differentiation that separates the high and low tissue densities is used to calculate the predictive value. Stratification of PCA for measurement position on the breast in cranial‐caudal projection is introduced. Analysis of PCA scores as a function of the volunteer's age and body mass index (BMI) is examined. A small but significant correlation between the component scores and age or BMI is noted but the correlation is dependent on the tissue density category examined. Correction of the component scores for age and BMI is not recommended, since a priori knowledge of a woman's breast tissue density is required. Stratification for the center and distal measurement positions provide a predictive value for OTS above 96%.
Incorporation of an iterative, linear segmentation routine into a mammographic mass CAD system
Authors: Catarious David M. , Baydush Alan H. , Floyd Carey E.
Published: July 2004

In previous research, we have developed a computer‐aided detection (CAD) system designed to detect masses in mammograms. The previous version of our system employed a simple but imprecise method to localize the masses. In this research, we present a more robust segmentation routine for use with mammographic masses. Our hypothesis is that by more accurately describing the morphology of the masses, we can improve the CAD system's ability to distinguish masses from other mammographic structures. To test this hypothesis, we incorporated the new segmentation routine into our CAD system and examined the change in performance. The developed iterative, linear segmentation routine is a gray level‐based procedure. Using the identified regions from the previous CAD system as the initial seeds, the new segmentation algorithm refines the suspicious mass borders by making estimates of the interior and exterior pixels. These estimates are then passed to a linear discriminant, which determines the optimal threshold between the interior and exterior pixels. After applying the threshold and identifying the object's outline, two constraints on the border are applied to reduce the influence of background noise. After the border is constrained, the process repeats until a stopping criterion is reached. The segmentation routine was tested on a study database of 183 mammographic images extracted from the Digital Database for Screening Mammography. Eighty‐three of the images contained 50 malignant and 50 benign masses; 100 images contained no masses. The previously developed CAD system was used to locate a set of suspicious regions of interest (ROIs) within the images. To assess the performance of the segmentation algorithm, a set of 20 features was measured from the suspicious regions before and after the application of the developed segmentation routine. Receiver operating characteristic (ROC) analysis was employed on the ROIs to examine the discriminatory capabilities of each individual feature before and after the segmentation routine. A statistically significant performance increase was found in many of the individual features, particularly those describing the mass borders. To examine how the incorporation of the segmentation routine affected the performance of the overall CAD system, free‐response ROC (FROC) analysis was employed. When considering only malignant masses, the FROC performance of the system with the segmentation routine appeared better than the previous system. When detecting 90% of the malignant masses, the previous system achieved 4.9 false positives per image (FPpI) compared to the post‐segmentation system's 4.2 FPpI. At 80% sensitivity, the respective FPpI were 3.5 and 1.6.
A model to predict bladder shapes from changes in bladder and rectal filling
Authors: Lotz Heidi T. , Remeijer Peter , van Herk Marcel , Lebesque Joos V. , de Bois Josien A. , Zijp Lambert J. , Moonen Luc M.
Published: July 2004

The purpose of this study is to develop a model that quantifies in three dimensions changes in bladder shape due to changes in bladder and/or rectal volume. The new technique enables us to predict changes in bladder shape over a short period of time, based on known urinary inflow. Shortly prior to the treatment, the patient will be scanned using a cone beam CT scanner (x‐ray volume imager) that is integrated with the linear accelerator. After (automated) delineation of the bladder, the model will be used to predict the short‐term shape changes of the bladder for the time interval between image acquisition and dose delivery. The model was developed using multiple daily CT scans of the pelvic area of 19 patients. For each patient, the rigid bony structure in follow‐up scans was matched to that of the planning CT scan, and the outer bladder and rectal wall were delineated. Each bladder wall was subdivided in 2500 domains. A fixed reference point inside the bladder was used to calculate for each bladder structure a “Mercator‐like” 2D scalar map (similar to a height map of the globe), containing the distances from this reference point to each domain on the bladder wall. Subsequently, for all bladder shapes of a patient and for all domains on the wall individually, the distance to the reference point was fitted by a linear function of both bladder and rectal volume. The model uses an existing bladder structure to create a new structure via expansion (or contraction), until the expressed volume is reached. To evaluate the predictive power of the model, the jack‐knife method was used. The errors in the fitting procedure depended on the part of the bladder and range from 0 to 0.5 cm (0.2 cm on average). It was found that a volume increase of 150 cc can lead to a displacement up to about 2.5 cm of the cranial part of the bladder. With the model, the uncertainty in the position of the bladder wall can be reduced down to a maximum value of about 0.5 cm in case the bladder volume increase is known. Furthermore, it was found that a change in rectal filling causes a shift of the bladder, while its shape is hardly influenced. In conclusion, we developed a model that describes the bladder shape and position as a function of the bladder volume and the rectal filling. The model accurately describes the complex shape of the bladder as it works on each domain of the bladder separately.
Dosimetry of small x‐ray beams for stereotactic radiotherapy
Authors: McKerracher Carolyn
Published: July 2004

The dosimetry of small width) x‐ray beams, such as those used in stereotactic radiotherapy, is much more complex than that of those used in routine clinical treatments. A thorough understanding of the properties of both small beams and small detectors is necessary to determine the optimum detector to use in each measurement situation. Accurate and reproducible experimental methods must also be developed to measure absolute and relative doses, obtain precise beam data and subsequently verify the delivered treatment dose. This work is an investigation of the above aspects of small beam dosimetry, with particular reference to the types of small fields used for stereotactic radiotherapy in the Edinburgh Cancer Centre. These are fields formed by circular stereotactic collimators (12.5 to 40 mm diameter), used in conjunction with arc therapy for the treatment of small brain lesions. Several detectors were compared in the measurement of percentage depth doses, tissue maximum ratios, off axis ratios, head scatter and relative output factors, on a 6 MV linac. This included the testing of three new, commercially available detectors. Clinical beam data were obtained via detector comparison and recommendations made as to the best methodology for each measurement parameter. The most accurate and reproducible technique for head scatter factors was extended to smaller stereotactic collimators (5 to 10 mm diameter) and square fields with widths of 10 to 20 mm. These were shaped with both the movable linac collimators and the multileaf collimator and the results will be applied to the measurement of the small subfields used in intensity modulated radiotherapy (IMRT). A verification phantom was designed to be compatible with the stereotactic head frame and the properties of various small detectors were investigated for use in the phantom to measure point doses in both single arcs and multiple non‐coplanar plans. The recommendations on beam data acquisition and dose verification were applied to two additional linacs. On all machines, the dose to the isocenter was verified in several typical treatment plans to within 2% of the calculated dose, for all clinical collimators. The results confirm the accuracy of the measurement processes used. The verification technique also provides the basis for a proposed audit of dosimetry in all stereotactic centers in the UK.
A method to improve spatial resolution and smoothness of intensity profiles in IMRT treatment planning
Authors: Hou Qing , Zhang Conghua , Wu Zhangwen , Chen Yan
Published: July 2004

In IMRT optimization, the size of beamlets used for optimizing the beam intensity distributions is a planner‐selected parameter. The appropriate setting for the beamlet size is critical to the outcome of IMRT planning. With too small beamlets the dose calculation can be inaccurate, and the resulting intensity profiles can be unnecessarily complex and difficult to generate. Relatively simple intensity profiles can be obtained using large beamlets. However, this may compromise the conformity of the dose distribution. In this paper we present a method, in which multiple beamlet matrices displaced from each other by a shift in MLC leaf travel direction are used instead of the single beamlet matrix per beam in a conventional method, to achieve finer spatial resolution for the intensity distribution than the given beamlet size. Two test cases were used to assess the method by the resultant DVHs and dose distributions and characteristic indices of the intensity profiles. The results show that this method can produce optimized dose distributions that are similar to those produced by the conventional inverse planning method with the benefit of smoother intensity profiles that are easier to deliver with a computer controlled MLC.
A multimodality vascular imaging phantom with fiducial markers visible in DSA, CTA, MRA, and ultrasound
Authors: Cloutier Guy , Soulez Gilles , Qanadli Salah D. , Teppaz Pierre , Allard Louise , Qin Zhao , Cloutier François , Durand Louis‐Gilles
Published: July 2004

The objective was to design a vascular phantom compatible with digital subtraction angiography, computerized tomography angiography, ultrasound and magnetic resonance angiography (MRA). Fiducial markers were implanted at precise known locations in the phantom to facilitate identification and orientation of plane views from three‐dimensional (3‐D) reconstructed images. A vascular conduit connected to tubing at the extremities of the phantom ran through an agar‐based gel filling it. A vessel wall in latex was included around the conduit to avoid diffusion of contrast agents. Using a lost‐material casting technique based on a low melting point metal, geometries of pathological vessels were modeled. During the experimental testing, fiducial markers were detectable in all modalities without distortion. No leak of gadolinium through the vascular wall was observed on MRA after 5 hours. Moreover, no significant deformation of the vascular conduit was noted during the fabrication process (confirmed by microtome slicing along the vessel). The potential use of the phantom for calibration, rescaling, and fusion of 3‐D images obtained from the different modalities as well as its use for the evaluation of intra‐ and inter‐modality comparative studies of imaging systems are discussed. In conclusion, the vascular phantom can allow accurate calibration of radiological imaging devices based on x‐ray, magnetic resonance and ultrasound and quantitative comparisons of the geometric accuracy of the vessel lumen obtained with each of these methods on a given well defined 3‐D geometry.
Treatment plan optimization incorporating respiratory motion
Authors: Zhang Tiezhi , Jeraj Robert , Keller Harry , Lu Weiguo , Olivera Gustavo H. , McNutt Todd R. , Mackie Thomas R. , Paliwal Bhudatt
Published: July 2004

Similar to conventional conformal radiotherapy, during lung tomotherapy, a motion margin has to be set for respiratory motion. Consequently, large volume of normal tissue is irradiated by intensive radiation. To solve this problem, we have developed a new motion mitigation method by incorporating target motion into treatment optimization. In this method, the delivery‐breathing correlation is determined prior to treatment plan optimization. Beamlets are calculated by using the CT images at the corresponding breathing phases from a dynamic (four‐dimensional) image sequence. With the displacement vector fields at different breathing phases, a set of deformed beamlets is obtained by mapping the dose to the primary phase. Optimization incorporating motion is then performed by using the deformed beamlets obtained by dose mapping. During treatment delivery, the same breathing‐delivery correlation can be reproduced by instructing the patient to breathe following a visually displayed guiding cycle. This method was tested using a computer‐simulated deformable phantom and a real lung case. Results show that treatment optimization incorporating motion achieved similar high dose conformality on a mobile target compared with static delivery. The residual motion effects due to imperfect breathing tracking were also analyzed.
Practicability of protontherapy using compact laser systems
Authors: Malka Victor , Fritzler Sven , Lefebvre Erik , d'Humières Emmanuel , Ferrand Régis , Grillon Georges , Albaret Claude , Meyroneinc Samuel , Chambaret Jean‐Paul , Antonetti Andre , Hulin Danièle
Published: July 2004

Protontherapy is a well‐established approach to treat cancer due to the favorable ballistic properties of proton beams. Nevertheless, this treatment is today only possible with large scale accelerator facilities which are very difficult to install at existing hospitals. In this article we report on a new approach for proton acceleration up to energies within the therapeutic window between 60 and 200 MeV by using modern, high intensity and compact laser systems. By focusing such laser beams onto thin foils we obtained on target intensities of which is sufficient to produce a well‐collimated proton beam with an energy of up to 10 MeV. These results are in agreement with numerical simulations and indicate that proton energies within the therapeutic window should be obtained in the very near future using such economical and very compact laser systems. Hence, this approach could revolutionize cancer treatment by bringing the “lab to the hospital—rather than the hospital to the lab.”