Cucullanus pinnai pinnai and C. pinnai pterodorasi (Nematoda Cucullanidae): what does the integrative taxonomy tell us about these species and subspecies classification?

Cucullanus pinnai has been divided in two subspecies (C. pinnai pinnai and C. pinnai pterodorasi) based on the morphology of oesophastome. While C. pinnai pinnai apparently shows low host specificity and broad geographic occurrence, with certain morphological variations, C. pinnai pterodorasi was reported once, parasitizing Pterodoras granulosus. We used an integrative taxonomic approach to evaluate whether or not populations of C. pinnai pinnai from Trychomycterus spegazzinii (Escoipe River, Argentina) and Pimelodus fur (Miranda River, Brazil), and of C. pinnai pterodorasi from Pterodoras granulosus (Miranda River, Brazil) are conspecific. Parasites were observed using light microscopy and genetically characterized based on partial sequences of the 18S and 28S rDNA, ITS1-5.8S-ITS2, and COI mtDNA. Phylogenies were reconstructed and the Generalized Mixed Yule Coalescent (GMYC), Poisson Tree Process (bPTP), and Automatic Barcode Gap Discovery (ABGD) were used for species delimitation purposes. The present samples formed well-supported monophyletic assemblages, corroborating in part the results of morphological analyses; however, they grouped according to geographic origin. Species delimitation suggested conspecificity of C. pinnai pinnai with C. pinnai pterodorasi from Brazil; consequently, the morphology of oesophastome may be an intraspecific variation. Results also indicated that C. pinnai may represent a species complex as samples from Argentina were suggestive of an independent specific entity. However, definitive affirmations are premature, since there is no autapomorphy for separating C. pinnai from Brazil and Argentina and sampling was limited to three host species from two river basins. The phylogenetic reconstructions also confirmed the artificiality of some genera within Cucullanidae.

Integrative taxonomy of Sprentascaris mahnerti and phylogeny of raphidascaridid nematodes (Nematoda: Ascaridoidea: Raphidascarididae) suggest the monophyly of Sprentascaris.

Sprentascaris mahnerti (Nematoda: Raphidascarididae) collected from Loricariichthys labialis (Siluriformes: Loricariidae) in the Pantanal wetlands, State of Mato Grosso do Sul (Brazil), was redescribed using light and scanning electron microscopy (SEM), and genetically characterised along with two other raphidascaridids: Raphidascaroides brasiliensis and Ro. moraveci. Due to the systematic discussion regarding Raphidascaris and Sprentascaris, as well as the poor knowledge about the phylogenetic relationships within Raphidascarididae, phylogenies were reconstructed based on partial sequences of the 18S and 28S nuclear rRNA gene, the nuclear ITS1-5.8S-ITS2 and the cytochrome c oxidase subunit I (cox1) mtDNA. Morphological study of S. mahnerti, confirmed some previously described features, revealed new characteristics and permitted to elucidate some inconsistencies noted in the literature. Morphological and genetic characterisation of S. mahnerti supported its validity. Phylogenetic reconstructions supported the monophyly of Sprentascaris, which has three pairs of interlabial conspicuous cuticular projections as a synapomorphy. The relationships among several lineages of raphidascaridids were unsolved, albeit Goezia and Ichthyascaris formed well-supported monophyletic assemblages, in which the first included species with no relations regarding the habitat of hosts and the geographic origin. The present findings represent one more step towards the understanding of the interrelationships of raphidascaridid nematodes. In this sense, Sprentascaris should be considered valid as an independent lineage from Raphidascaris.

Palisaded encapsulated neuroma clinically mimicking a mucocele: report of a case / Neuroma encapsulado em paliçada mimetizando mucocele: relato de caso

ABSTRACT We report the case of a 21-year-old female patient with the chief complaint of a small tumor on the lower left lip. Intraoral examination revealed a two-month evolution nodular lesion on the left labial mucosa, of resilient consistency and asymptomatic. A history of prior trauma was reported by the patient. A provisional diagnosis of mucocele was established, and an excisional biopsy was performed. The diagnosis was palisaded encapsulated neuroma (PEN). As PEN is considered underdiagnosed by many authors, a discussion on the morphologic diagnostic criteria of this lesion will be provided.

RESUMO Relatamos o caso de uma paciente de 21 anos de idade, com queixa principal de um pequeno nódulo no lábio inferior esquerdo. O exame intraoral revelou lesão nodular na mucosa labial esquerda de consistência resiliente, assintomática, com evolução de dois meses. Histórico de trauma prévio foi relatado pela paciente. Diagnóstico provisório de mucocele foi estabelecido; realizou-se biópsia excisional. O diagnóstico foi neuroma encapsulado em paliçada (NEP). Como o NEP é considerado subdiagnosticado por muitos autores, será fornecida uma discussão sobre os critérios morfológicos de diagnóstico dessa lesão.

Chondroblastic osteosarcoma of the mandible: case report / Osteossarcoma condroblástico em mandíbula: relato de caso

ABSTRACT We report the case of a 32-year-old male patient, who was subjected to cone-beam tomography for planning the removal of an unerupted tooth. Cone-beam CT scans revealed the presence of a mixed lesion with poorly defined limits in the left posterior mandibular region, with "sun-ray" periosteal reaction. An incisional biopsy was performed and the diagnosis was chondroblastic osteosarcoma. In this paper, a discussion of the differential diagnosis criteria and treatment of this unusual malignant neoplasm is performed. Thus, it is intended to provide information that will help in the study of management protocols for the increasingly effective treatment of gnathic osteosarcomas.

RESUMO Relatamos o caso de um paciente do sexo masculino, 32 anos de idade, que realizou tomografia cone-beam para planejamento de remoção de dente incluso. O exame revelou presença de lesão mista de limites mal definidos na região posterior mandibular esquerda, com reação periosteal em "raios de sol". Foi realizada biópsia incisional, e o diagnóstico foi de osteossarcoma condroblástico. Neste trabalho, será realizada uma discussão dos critérios de diagnóstico diferencial e do tratamento dessa neoplasia maligna. Pretende-se, dessa forma, trazer informações que auxiliem no estudo de protocolos de conduta para o tratamento cada vez mais efetivo dos osteossarcomas gnáticos.

Behaviour of NBD-head group labelled phosphatidylethanolamines in POPC bilayers: a molecular dynamics study.

A complete homologous series of fluorescent phosphatidylethanolamines (diCnPE), labelled at the head group with a 7-nitrobenz-2-oxa-1,3-diazo-4-yl(NBD) fluorophore and inserted in 1-palmitoyl, 2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers, was studied using atomistic molecular dynamics simulations. The longer-chained derivatives of NBD-diCnPE, with n = 14, 16, and 18, are commercially available, and widely used as fluorescent membrane probes. Properties such as location of atomic groups and acyl chain order parameters of both POPC and NBD-diCnPE, fluorophore orientation and hydrogen bonding, membrane electrostatic potential and lateral diffusion were calculated for all derivatives in the series. Most of these probes induce local disordering of POPC acyl chains, which is on the whole counterbalanced by ordering resulting from binding of sodium ions to lipid carbonyl/glycerol oxygen atoms. An exception is found for NBD-diC16PE, which displays optimal matching with POPC acyl chain length and induces a slight local ordering of phospholipid acyl chains. Compared to previously studied fatty amines, acyl chain-labelled phosphatidylcholines, and sterols bearing the same fluorescent tag, the chromophore in NBD-diCnPE locates in a similar region of the membrane (near the glycerol backbone/carbonyl region) but adopts a different orientation (with the NO2 group facing the interior of the bilayer). This modification leads to an inverted orientation of the P-N axis in the labelled lipid, which affects the interface properties, such as the membrane electrostatic potential and hydrogen bonding to lipid head group atoms. The implications of this study for the interpretation of the photophysical properties of NBD-diCnPE (complex fluorescence emission kinetics, differences with other NBD lipid probes) are discussed.

Incidence and treatment of delayed symptoms of CSF leak following lumbar spinal surgery.

PURPOSE: Dural tear (DT) resulting in cerebrospinal fluid (CSF) leak is a common complication of spinal surgery. Most cases of DT are recognised and addressed intraoperatively; however, a small percentage of cases may present at a later stage with delayed symptoms of CSF leak, either due to an unrecognised intraoperative DT or as a result of a de novo delayed DT. Apart from few reports describing delayed symptomatic CSF leaks, most studies tend not to separate intraoperatively recognised DTs from delayed symptomatic CSF leaks. To our knowledge, there are no long-term studies describing specifically the incidence and management of this complication. The aim of this study is to determine the incidence of late presentation of dural tear (LPDT) following lumbar spinal surgery, its treatment, associated complications and clinical outcomes from long-term follow-up in a consecutive series of patients. METHODS: A retrospective review was conducted on 2052 consecutive patients who underwent spinal surgery by two spinal surgeons from 2000 to 2005 and 2007 to 2013 at two institutions. RESULTS: A total of 2052 patient records were reviewed. Seventeen patients (0.83%) were found to have LPDT, unrecognised intraoperatively. Fifteen patients required surgical intervention, one patient was treated with insertion of a subarachnoid drain and only one patient settled with conservative measures. Out of the 15 patients who underwent surgery, two patients required another operation and 2 patients were treated with a subarachnoid drain. At 9 months mean follow-up, there was no significant difference in outcome in cases with LPDT compared to those without. CONCLUSION: A delayed symptomatic presentation of DT unrecognised intraoperatively is a specific complication that needs to be recognised and treated appropriately. A high suspicion and vigilance can help discover and address delayed CSF leaks with no long-term sequelae.

Virtual reality in the rehabilitation of the arm after hemiplegic stroke: a randomized controlled pilot study.

OBJECTIVE: To assess the feasibility of a trial to investigate the effectiveness of virtual reality-mediated therapy compared to conventional physiotherapy in the motor rehabilitation of the arm following stroke, and to provide data for a power analysis to determine numbers for a future main trial. DESIGN: Pilot randomized controlled trial. SETTING: Clinical research facility. PARTICIPANTS: Eighteen people with a first stroke, 10 males and 8 females, 7 right and 2 left side most affected. Mean time since stroke 10.8 months. INTERVENTIONS: Participants were randomized to a virtual reality group or a conventional arm therapy group for nine sessions over three weeks. MAIN MEASURES: The upper limb Motricity Index and the Action Research Arm Test were completed at baseline, post intervention and six weeks follow-up. RESULTS: Outcome data were obtained from 95% of participants at the end of treatment and at follow-up: one participant withdrew. Compliance was high; only two people reported side-effects from virtual reality exposure. Both groups demonstrated small (7-8 points on upper limb Motricity Index and 4 points on the Action Research Arm Test), but non-significant, changes to their arm impairment and activity levels. CONCLUSION: A randomized controlled trial of virtual reality-mediated therapy comparable to conventional therapy would be feasible, with some suggested improvements in recruitment and outcome measures. Seventy-eight participants (39 per group) would be required for a main trial.

Diagnostic accuracy of limited-volume cone-beam computed tomography in the detection of periapical bone loss: 360° scans versus 180° scans.

AIM: To investigate the effect of reducing limited-volume cone-beam computed tomographs arc of rotation from 360° to 180° on the ability to diagnose small, artificially created apical lesions. METHODOLOGY: Small, artificial apical bone lesions were prepared with a bur in the apical region of the distal root of ten mandibular first molars, in human dry mandibles. The jaws were scanned in a fixed position with limited-volume CBCT making a 360° and 180° arc of rotation, before and after each periapical lesion had been created. A 4 × 4 cm field of view was used at 90 kV, with a current of 4 mA. Ten examiners blinded to the scan parameters and controls scored the presence/absence of bone lesions. Intra-examiner reliability was determined after 2 weeks, reviewing half the data set. Statistical analyses with paired t-tests determined the diagnostic accuracy of the two modalities (360° vs. 180°) in terms of sensitivity, specificity, receiver operating characteristic area under the curve, positive predictive values and negative predictive values. RESULTS: The mean values for sensitivity of the 360° and 180° scans were 0.91 and 0.89, respectively; their mean specificities were 0.73. No significant differences were reflected in the statistical analyses. CONCLUSIONS: Both 360° and 180° cone-beam computed tomography scans yielded similar accuracy in the detection of artificial bone lesions. The use of 180° scans might be advisable to reduce the radiation dose to the patient in line with the ICRP guidance to use as low a dosage as reasonably achievable.

What treatment packages do UK physiotherapists use to treat postural control and mobility problems after stroke?

OBJECTIVE: The aim of this study was to identify the treatment packages (combinations of interventions) used to treat postural control and mobility problems for patients with stroke. METHOD: A convenience sample of 74 physiotherapists from 34 National Health Service hospitals recorded the interventions used to treat postural control and mobility problems for 251 patients with stroke in 1156 treatment sessions using the Stroke Physiotherapy Intervention Recording Tool (Tyson and Selley, Disabil Rehabil 2004;26:1184 - 1188). Descriptive statistics assessed the frequency with which the interventions were used and geometric coding identified treatment packages. RESULTS: The most frequently used interventions involved facilitation, practice of activities and their components and mobilisations. The least frequently used interventions involved the provision of equipment, teaching carers or professionals and exercise. Two treatment packages were identified; one involving the facilitation (of activities and their components) and the other involving whole activities (facilitation and practice). CONCLUSIONS: Interventions are often combined in two treatment packages to treat postural control and mobility problems after stroke. One involved facilitation (of whole and component activities) and the other involved practice and facilitation of whole activities. Future research in which conventional or standard UK stroke physiotherapy is delivered should focus on these interventions and exclude atypically used interventions.

Oseltamivir oral suspension and capsules are bioequivalent for the active metabolite in healthy adult volunteers.

AIMS: The objective of this study was to assess the relative bioavailability of oseltamivir carboxylate (active metabolite) following oral administration of the market suspension, the clinical trial suspension and the market capsule formulations of oseltamivir (prodrug) in healthy subjects. METHODS: In this single-center, open-label, three-period crossover study, 24 healthy adult volunteers were randomized to receive one dose (150 mg oseltamivir) of each of the three formulations (market suspension, clinical trial suspension, market capsule formulation), with a 7-day washout period between each administration. Blood samples, collected for up to 48 h post-dosing, were analyzed for plasma oseltamivir and oseltamivir carboxylate. Adverse events were monitored. RESULTS: Pharmacokinetic parameters for oseltamivir and oseltamivir carboxylate were similar for the three formulations. Bioequivalence for oseltamivir carboxylate was demonstrated between the market capsule and the two suspensions: 90% confidence intervals for the log-transformed Cmax, AUClast and AUCinf ratios fell within the 80 - 125% criteria. Similarly, the two suspensions were also demonstrated as bioequivalent for oseltamivir carboxylate. Oseltamivir was well tolerated. The majority of adverse events observed were mild in intensity, with the most common being nausea and headache. CONCLUSIONS: This study demonstrates that the market suspension, the clinical trial suspension and the market capsule formulations of oseltamivir are bioequivalent for the active metabolite, oseltamivir carboxylate. Based on this finding, the market suspension may be used to achieve comparable exposure in patients unable to take capsules.

Low back pain in people with a stoma: a postal survey.

PURPOSE: To investigate whether low back pain (LBP) is a problem for people with a stoma. METHOD: Following ethical approval, a postal questionnaire was sent to the Ileostomy Association of Northern Ireland (n = 402). RESULTS: The response rate was 81.6%. Two hundred ninety three (72.8%) were included in the analysis. The participants fell into three groups: those who never had LBP (n = 102, 34.8%), those who had LBP but not within the last 6 months (n = 26, 8.9%) and those who had LBP within the last 6 months (n = 165, 56.3%). Participants with LBP (n = 165) compared the ease with which they could carry out everyday tasks: 'before' and 'since' surgery. There was a mean increased difficulty of between 1.75 and 2.26 points across all tasks. The Roland Morris Disability Questionnaire scores ranged from 0 to 24 with 50% having a score of 8/24 or higher. Some participants (n = 76, 46.1%) believed that the stoma surgery was the reason for their back pain, followed by 27.9% (n = 46) blaming weak muscles. Others (53.3%) thought their back pain was worsening. There was a significant rise in the incidence of first episode back pain within a year of surgery. CONCLUSIONS: These results suggest that LBP is a problem for people with a stoma.

What is Bobath? A survey of UK stroke physiotherapists' perceptions of the content of the Bobath concept to treat postural control and mobility problems after stroke.

OBJECTIVE: The aim of this study was to identify which interventions used to treat postural control and mobility are considered part of the Bobath concept (BC). DESIGN. Hospital-based UK stroke physiotherapists identified interventions which they perceived to be part of the BC from a pre-published list of interventions used to treat postural control and mobility problems. Interventions that > 75% of participants felt were part of the BC were classified as 'definitely Bobath'. Interventions that < 25% felt were part of the BC were classified as 'definitely not Bobath'. Other interventions were classified as 'unsure'; those indentified by 50-74% of participants as part of the BC were classified as 'probably Bobath' and those indentified 26-49% were classified as 'probably not Bobath'. RESULTS: Seventy-four physiotherapists from 33 hospitals participated. Facilitation, mobilizations and practicing components of activities were most strongly associated with the BC. Exercise and the use of equipment were identified as 'not' or 'probably not Bobath'. There was uncertainty about practicing activities, teaching patients and carers and arranging independent practice. CONCLUSIONS: UK stroke physiotherapists perceive that the BC involves interventions that focus on facilitating movement, mobilization, practicing components of activities and some whole activities. Their views about what is not part of the BC and the areas where they are uncertain contrast with British and international teachers of the BC. Consequently, it was not possible to define a 'typical package' of treatment for postural control and mobility that represents the BC. Future research into the BC should focus on the effectiveness of specific, well-defined interventions.

Low back pain in people with a stoma: patients' views.

PURPOSE: Low back pain (LBP) is a major health problem in western society. Stoma surgery, which involves creating a permanent opening in the abdominal wall, may interfere with the function of the abdominal muscles. Therefore people with a stoma may be at greater risk of developing LBP. A literature review revealed no research exploring a possible link between stoma formation and LBP, nor any study involving patients' perceptions. Therefore, the aims of this study were to determine (1) whether people with a stoma have LBP, (2) whether people with LBP and a stoma perceive that the conditions are linked, and (3) what issues regarding LBP should be included in a large survey of persons with a stoma. METHODS: Members of the Ileostomy Association of Northern Ireland volunteered to participate in a focus group study. Events from this group were recorded, transcribed, and validated. Thematic analysis was performed. RESULTS: Three themes were identified: (1) the presence of LBP, (2) a perceived link between LBP and a stoma, and (3) relevant issues for LBP. Ten of the 11 participants had experienced at least one episode of LBP, however 5 (50%) emphasized that they did not have a back problem. Six participants had no LBP prior to their surgery, but have experienced episodes of LBP since. The majority thought that the stoma and their LBP experience were linked. Suggested reasons for this link were changes in muscle strength, posture, and activities. Others included having an epidural or a pouching system that did not optimally suit their needs. CONCLUSIONS: The results suggest that LBP is a problem for some people with an abdominal stoma and support the need for further study in this population. Two possible areas of future study are an investigation of what the term low back pain means to this population, and further study of the mechanisms that may link stoma surgery to an increased risk of LBP.

Virtual reality in stroke rehabilitation: still more virtual than real.

PURPOSE: To assess the utility of virtual reality (VR) in stroke rehabilitation. METHOD: The Medline, Proquest, AMED, CINAHL, EMBASE and PsychInfo databases were electronically searched from inception/1980 to February 2005, using the keywords: Virtual reality, rehabilitation, stroke, physiotherapy/physical therapy and hemiplegia. Articles that met the study's inclusion criteria were required to: (i) be published in an English language peer reviewed journal, (ii) involve the use of VR in a stroke rehabilitation setting; and (iii) report impairment and/or activity oriented outcome measures. Two assessors independently assessed each study's quality using the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) grading system. RESULTS: Eleven papers met the inclusion criteria: Five addressed upper limb rehabilitation, three gait and balance, two cognitive interventions, and one both upper and lower limb rehabilitation. Three were judged to be AACPDM Level I/Weak, two Level III/Weak, three Level IV/Weak and three Level V quality of evidence. All articles involved before and after interventions; three randomized controlled trials obtained statistical significance, the remaining eight studies found VR-based therapy to be beneficial. None of the studies reported any significant adverse effects. CONCLUSION: VR is a potentially exciting and safe tool for stroke rehabilitation but its evidence base is too limited by design and power issues to permit a definitive assessment of its value. Thus, while the findings of this review are generally positive, the level of evidence is still weak to moderate, in terms of research quality. Further study in the form of rigorous controlled studies is warranted.

Brownian diffusion and surface kinetics of liposome and viral particle uptake by human lung cancer cells in-vitro.

In this study, the simultaneous roles of transport, diffusion, and surface kinetic uptake of liposome (Lip-FD), adenoviral (AD-Cy2), and liposome-adenoviral complex (lip-FD-Ad) particles by a non-small cell human lung cancer (A549) were examined through a coupling of in vitro experimental and mathematical modeling techniques. Experimentally, quantitative fluorescence spectroscopy was used to monitor time dependent particle uptake rates including low temperature (5 degrees C) conditions where endocytosis could be inhibited. Mathematically, analytic solutions to the Brownian particle diffusion equation with Langmuir type boundary conditions for the adsoprtion, desorption, and endocytosis process, were obtained for both unsteady and steady-state (no endocytosis) conditions. By direct comparisons of experimental data to model solutions, the adsorption constants, desorption constants, and number of cell surface receptor sites were determined for all particle types considered. It was found that the particle adsorption and desorption constants were of the same order of magnitude compared to earlier studies (Singh, M., T. Ghose, G. Faulkner, and M. Mezei. Cancer Res. 49:3976-3984, 1990.) using different cell lines, particle types, and methodologies. Also in agreement with previous studies using differing cell lines and methodologies (Miller, C. R., B. Boundurant, S. D. McLeon, K. A. McGovern, and D. F. O'Brien. Biochemistry 37:12875-12883, 1998; Perry, D. G., and W. J. Martin II. J. Immunol. Methods 181:269-285, 1995; Muller, W. J., K. Zen, A. B. Fisher, and H. Shuman. Am. J. Physiol. L11-L19, 1995), the number of cell surface receptor sites was predicted to be several orders of magnitude higher for liposome and liposome-viral complex than for viral particles alone, suggesting a nonspecific or nonrestrictive binding pattern for liposomes and liposome complexes and a specific or restrictive binding pattern for viral particles. The surface kinetic constants obtained here for the A549 cells may be useful in physiological modeling or pharmacokinetic applications of chemical or genetic carrying particles in the treatment of lung cancer and other lung diseases. Furthermore, the methodologies given here are straightforward and can be applied to other particle-cell uptake systems.

Virtual reality in the rehabilitation of the upper limb after stroke: the user's perspective.

Our group has developed a relatively low-cost virtual reality (VR) system for rehabilitation of the upper limb following stroke. Our system is immersive in that the participant views a representation of their arm and hand, reaching and retrieving objects in the virtual environment (VE), through a head-mounted display (HMD). This is thought to increase the participant's sense of presence in the VE and may lead to improved rehabilitation outcomes. However, use of immersion, particularly with our low-cost system, may increase the incidence of side effects reported. Therefore, the aim of this project was to assess the interaction of healthy users and those following stroke, in terms of their experience of presence in the VE and the rate of self-reported side effects. Differences in rates of perceived exertion, levels of enjoyment, and sense of control between both groups were also explored.

Effect of a casein/calcium phosphate-containing tooth cream and fluoride on enamel erosion in vitro.

The aim of this study was to determine whether a tooth cream containing casein/calcium phosphate (CasCP) protects enamel against erosion. Sixty bovine enamel specimens were prepared for profilometry and distributed into five groups. Specimens were rinsed with artificial saliva interrupted by 1% citric acid (pH 2.3) for 30 s 6 times daily for 14 days. Group 1 (n=12) was not treated (control); in group 2 (n=12) CasCP was applied for 120 s twice daily; in group 3 (n=12) 250 ppm fluoride as NaF was applied for 120 s twice daily; in group 4 (n=12) CasCP was applied for 120 s, then 250 ppm fluoride for 120 s twice daily, and in group 5 (n=12) amine fluoride (AmF) gel (12,500 ppm fluoride) was applied for 120 s twice daily. Differences between groups with respect to erosive enamel loss (profilometrically determined depth after 7 and 14 days) were tested by the Mann-Whitney test (alpha=0.05). After 7/14 days' erosive cycling, specimens treated with AmF gel showed significantly less enamel loss (18.5/35.5 microm; medians) than those treated with CasCP (25.5/46.9 microm), 250 ppm fluoride (25.0/ 40.9 microm), CasCP and 250 ppm fluoride (23.9/47.4 microm) or with no treatment (26.3/49.8 microm). It is concluded that highly fluoridated acidic AmF gel can protect enamel against erosion while CasCP, 250 ppm fluoride or a combination of CasCP and 250 ppm fluoride provide little protection.

Intravenous busulfan in adults prior to haematopoietic stem cell transplantation: a population pharmacokinetic study.

An IV form of busulfan (IV Bu) has recently become available for high dose conditioning regimen before haematopoietic stem cell transplantation (HSCT). This IV form is expected to reduce the high pharmacokinetic variability exhibited with oral busulfan and as a result, to better target the plasma area under the curve (AUC). Pharmacokinetics (PK) of IV Bu was investigated on 127 adult patients (333 PK administrations) who received 0.8 mg.kg-1 of Bu as a 2-h infusion every 6 h over 4 days, followed by cyclophosphamide (60 mg.kg-1 day-1x2). A retrospective population PK analysis was carried out to search for important predictive factors of IV Bu PK and to develop a limited sampling strategy (LSS) through Bayesian methodology. The analysis was conducted using the Non Linear Mixed Effect methodology and included a validation process on an independent data set. Adjusted Ideal Body Weight (AIBW) and Body Surface Area (BSA) were the best covariates to explain the inter-patient variability. The final inter-patient variability (CV=16%) in IV Bu clearance (Cltot) was estimated close to the intra-patient variability (CV=13%). There was neither age-dependency nor gender effect. IV Bu Cltot was not affected by elevated hepatic enzymes or by co-administration of either fluconazole or acetaminophen, and was not altered in heavily pre-treated or pre-transplanted patients. Normalised Cltot based on either AIBW or BSA was comparable between normal and obese patients (BMI=18-26.9 kg.m-2, >26.9 kg.m-2, respectively) whereas significant differences existed when based on either actual (ABW) or ideal body weight (IBW). As a consequence, no dose adjustment is required in obese patients when using a AIBW- or BSA-based dose calculation. A fixed dose of 0.80 mg.kg-1 of AIBW or 29 mg.m-2 of BSA yielded an average AUC of 1,200 microM.min, with 80% of patients within the "therapeutic" AUC range of 900-1,500 microM.min. Alternatively, 0.80 mg.kg-1 based on either ABW or IBW for normal patients and on AIBW for obese patients would achieve the same performance. A limited sampling strategy based on a Bayesian methodology was developed and validated on an independent dataset: AUCs obtained from one to two samplings were demonstrated to be reliably estimated.