Ecchordosis Physaliphora: Does It Even Exist?

The term ecchordosis physaliphora (EP) has been used historically to describe a benign notochordal remnant with no growth potential, most commonly occuring in the central clivus. Unfortunately, the radiologic appearance of EP overlaps considerably with the appearance of low-grade chordomas, which do have the potential for growth. In this article, we review new pathologic terminology that better describes this family of diseases, and we propose new radiologic terms that better address the uncertainty of the radiologic diagnosis. The surgical importance of accurate terminology and the implications for patient care are discussed.

Projected decrease in trail access in the Arctic.

Transportation systems in northern Canada are highly sensitive to climate change. We project how access to semi-permanent trails on land, water, and sea ice might change this century in Inuit Nunangat (the Inuit homeland in northern Canada), using CMIP6 projections coupled with trail access models developed with community members. Overall trail access is projected to diminish, with large declines in access for sea ice trails which play a central role for Inuit livelihoods and culture; limits to adaptation in southern regions of Inuit Nunangat within the next 40 years; a lengthening of the period when no trails are accessible; and an unequal distribution of impacts according to the knowledge, skills, equipment, and risk tolerance of trail users. There are opportunities for adaptation through efforts to develop skillsets and confidence in travelling in more marginal environmental conditions, which can considerably extend the envelope of days when trails are accessible and months when this is possible. Such actions could reduce impacts across emissions scenarios but their potential effectiveness declines at higher levels of global warming, and in southern regions only delays when sea ice trails become unusable.

Discerning the dietary habits of the smooth butterfly ray Gymnura lessae using two distinct methods, otolith identification and metagenetics.

Two different methods, metagenetics and free-otolith identification, were used to identify prey in the stomach contents of 531 Gymnura lessae captured by trawling in Mobile Bay, Alabama 2016-2018. Both methods were found to produce analogous results and were therefore combined into a single complete dataset. All prey were teleosts; the families Sciaenidae and Engraulidae were the most important prey (prey specie index of relative importance 89.3% IPSRI ). Multivariate analyses indicated that the diet of G. lessae varied with sex and seasonality. Specifically, variability was probably due to morphologically larger females consuming larger teleost prey species compared with males, whereas seasonal variability was probably due to changes in the available prey community composition. The findings indicate that both metagenetics and free otolith identification, used independently or complementarily, offer robust means of characterising dietary habits for teleost-specialised species such as G. lessae, which may play an important role in the structure and maintenance of coastal food webs such as those in Mobile Bay.

The role of environmental factors in search and rescue incidents in Nunavut, Canada.

OBJECTIVES: Unintentional injury is a leading cause of morbidity and mortality in Nunavut, where the importance of land-based activities and reliance on semi-permanent trails create unique risk profiles. Climate change is believed to be exacerbating these risks, although no studies have quantitatively examined links between environmental conditions and injury and distress in the Canadian Arctic. We examine the correlation between environmental conditions and land-based search and rescue (SAR) incidents across Nunavut. STUDY DESIGN: Case study. METHODS: Case data were acquired from the Canadian National Search and Rescue Secretariat. Gasoline sales from across the territory are then used to model land-use and exposure. We compare weather and ice conditions during 202 SAR incidents to conditions during 755 non-SAR days (controls) between 2013 and 2014. RESULTS: We show daily ambient temperature, ice concentration, ice thickness, and variation in types of ice to be correlated with SAR rates across the territory during the study period. CONCLUSIONS: These conditions are projected to be affected by future climate change, which could increase demand for SAR and increase injury rates in the absence of targeted efforts aimed at prevention and treatment. This study provides health practitioners and public health communities with clearer understanding to prepare, respond to, and prevent injuries across the Arctic.

Biosynthetic infochemical communication.

There is an ever-increasing demand for data to be embedded in our environment at ever-decreasing temporal and spatial scales. Whilst current communication and storage technologies generally exploit the electromagnetic properties of media, chemistry offers us a new alternative for nanoscale signaling using molecules as messengers with high information content. Biological systems effectively overcome the challenges of chemical communication using highly specific biosynthetic pathways for signal generation together with specialized protein receptors and nervous systems. Here we consider a new approach for information transmission based upon nature's quintessential example of infochemical communication, the moth pheromone system. To approach the sensitivity, specificity and versatility of infochemical communication seen in nature, we describe an array of biologically-inspired technologies for the production, transmission, detection, and processing of molecular signals. We show how it is possible to implement each step of the moth pheromone pathway for biosynthesis, transmission, receptor protein binding/transduction, and antennal lobe processing of monomolecular and multimolecular signals. For each implemented step, we discuss the value, current limitations, and challenges for the future development and integration of infochemical communication technologies. Together, these building blocks provide a starting point for future technologies that can utilize programmable emission and detection of multimolecular information for a new and robust means of communicating chemical information.

Comparative effectiveness of alternative clinical pathways for primary hip and knee joint replacement patients: a pragmatic randomized, controlled trial.

OBJECTIVE: Total hip replacement (THR) and total knee replacement (TKR) (arthroplasty) surgery for end-stage osteoarthritis (OA) are ideal candidates for optimization through an algorithmic care pathway. Using a comparative effectiveness study design, we compared the effectiveness of a new clinical pathway (NCP) featuring central intake clinics, dedicated inpatient resources, care guidelines and efficiency benchmarks vs. the standard of care (SOC) for THR or TKR. METHODS: We compared patients undergoing primary THR and TKR who received surgery in NCP vs. SOC in a randomised controlled trial within the trial timeframe. 1,570 patients (1,066 SOC and 504 NCP patients) that underwent surgery within the study timeframe from urban and rural practice settings were included. The primary endpoint was improvement in Western Ontario and McMaster University osteoarthritis index (WOMAC) overall score over 12 months post-surgery. Secondary endpoints were improvements in the physical function (PF) and bodily pain (BP) domains of the Short Form 36 (SF-36). RESULTS: NCP patients had significantly greater improvements from baseline WOMAC scores compared to SOC patients after adjusting for covariates (treatment effect=2.56; 95% confidence interval (CI) [1.10-4.01]). SF-36 BP scores were significantly improved for both hip and knee patients in the NCP (treatment effect=3.01, 95% CI [0.70-5.32]), but SF-36 PF scores were not. Effects of the NCP were more pronounced in knee patients. CONCLUSION: While effect sizes were small compared with major effects of the surgery itself, an evidence-informed clinical pathway can improve health related quality of life (HRQoL) of hip and knee arthroplasty patients with degenerative joint disorder in routine clinical practice for up to 12 months post-operatively. CLINICALTRIALS.GOV IDENTIFIER: NCT00277186.

Bone metastases from prostate, breast and multiple myeloma: differences in lesion conspicuity at short-tau inversion recovery and diffusion-weighted MRI.

OBJECTIVES: The objective of this study was to compare the relative conspicuity of bone metastases on short-tau inversion recovery (STIR) and diffusion-weighted MRI (DWI) whole-body MR sequences for breast, prostate and myeloma malignancies. METHODS: 44 whole-body MRI scans were reviewed retrospectively (coronal T(1) weighted, STIR and DWI with b=800). On each scan, up to four of the largest bone lesions were identified on T(1) weighting, and the region of interest signal intensity was measured on STIR and DWI, as well as the background signal intensity. The mean lesion signal to background ratio was calculated for each patient and then for each malignancy group. RESULTS: In prostate cancer patients, the DWI signal/background ratio was greater than that of STIR in 22 out of 24 patients (mean DWI lesion/background ratio 3.91, mean STIR lesion/background ratio 2.31; p=0.0001). In multiple myeloma, the DWI ratio was higher in 6/7 patients (DWI group mean ratio 7.59, STIR group mean ratio 3.7; p=0.0366). In 13 breast cancer patients, mean STIR and DWI signal/background were similar (DWI group mean ratio 4.13, group mean STIR ratio 4.26; p=0.8587). CONCLUSION: Bone lesion conspicuity measured by lesion/background signal intensity was higher on DWI b=800 than on STIR in patients with prostate cancer and multiple myeloma. DWI should be used in whole-body MR oncology protocols in these conditions to maximise lesion detection.

First Report of a 16SrII-D Subgroup Phytoplasma Associated with Pale Purple Coneflower Witches'-Broom Disease in Australia.

Pale purple coneflower, Echinacea pallida (Nutt.) Nutt., is an herbaceous perennial cultivated for its ornamental and medicinal properties. In 2005, phytoplasma-like symptoms, including virescence, phyllody, and chlorotic leaves, were first observed in coneflower fields in northern Tasmania, Australia. During the 2010-2011 growing season, the incidence of affected plants was estimated to be 12% within a single field. Total DNA was extracted from symptomatic plants with a DNeasy Plant Mini Kit (QIAGEN Inc., Valencia, CA) according to the manufacturer's instructions. DNA was also extracted, as described above, from asymptomatic coneflower seedlings obtained by germinating surface-sterilized seed on water agar. DNA was amplified via a nested PCR using universal primer pairs P1/P7 followed by R16F2n/R16R2 to detect putative phytoplasmas (2). Amplifications yielded expected products of 1.8 and 1.2 kb, respectively, only from symptomatic samples. Subsequently, PCR products from six arbitrarily selected samples were used for sequencing (Genome Lab Dye Terminator Cycling Sequence with Quick Start Chemistry) and read in a CEQ8000 sequencer (Beckman Coulter Inc., Brea, CA). Sequence homology indicated 100% similarity between isolates designated EWB1 to EWB4 (GenBank Accession Nos. JF340075 and JF340077 to JF340079) and between EWB5 and EWB6 (JF340076 and JF40080). Sequence homology between the two observed groups was 99.7%, resulting from a 4-bp difference in the R16F2n primer region. Blast search revealed isolates EWB1 to EWB4 were 100% homologous with Catharanthus roseus phytoplasma (EU096500.1), Tomato big bud phytoplasma (EF193359.1), Scaevola witches'-broom phytoplasma (AB257291.1), and Mollicutes sp. (Y10097.1 and Y10096.1). Moreover, isolates EWB5 and EWB6 shared 99% sequence identity with the above isolates. iPhyClassifier (4) was used to perform sequence similarity and generate virtual restriction fragment length polymorphism (RFLP) profiles. The 16S rDNA sequence of isolates EWB1 to EWB4 and EWB5 to EWB6 shared 100 and 99.7% similarity, respectively, to the 'Candidatus Phytoplasma australasiae' reference strain (Y10097). RFLP profiles from all isolates suggested that they belonged to the 16SrII-D subgroup. To our knowledge, this is the first report of a 16SrII-D subgroup phytoplasma infecting E. pallida in Australia. Aster yellow phytoplasmas (16SrI-C subgroup) infections of E. purpurea have been recorded in Slovenia (3) and southern Bohemia (1). References: (1) J. Franova et al. Eur. J. Plant Pathol. 123:85, 2009. (2) I. M. Lee et al. Int. J. Syst. Bacteriol. 48:1153, 1998. (3) S. Radisek et al. Plant Pathol. 58:392, 2009. (4) Y. Zhao et al. Int. J. Syst. Evol. Microbiol. 59:2582, 2009.

Multilayer PDMS microfluidic chamber for controlling brain slice microenvironment.

A novel three-layer microfluidic polydimethylsiloxane (PDMS) device was constructed with two fluid chambers that holds a brain slice in place with microposts while maintaining laminar perfusate flow above and below the slice. Our fabrication technique permits rapid production of PDMS layers that can be applied to brain slices of different shapes and sizes. In this study, the device was designed to fit the shape and thickness (530-700 microm) of a medullary brain slice taken from P0-P4 neonatal rats. Medullary slices in this chamber spontaneously produced rhythmic, respiratory-related motor output for up to 3 h, thereby demonstrating that brain slice viability was maintained for prolonged periods. This design is unique in that it achieves independent control of fluids through multiple channels in two separate fluid chambers. The laminar flow exhibited by the microfluidic chamber allows controlled solutions to target specific areas of the brain slice based on the input flow rates. To demonstrate this capability, a stream of Na(+)-free solution was focused on one half of a medullary slice to abolish spontaneous neural activity in only that half of the brain slice, while the other half remained active. We also demonstrated that flow of different solutions can be focused over the midline of the brain slice. The multilayer brain slice chamber design can integrate several traditional types of electrophysiology tools that are commonly used to measure neurophysiological properties of brain slices. Thus, this new microfluidic chamber is advantageous for experiments that involve controlled drug or solution delivery at high spatiotemporal resolution.

Towards a truly biomimetic olfactory microsystem: an artificial olfactory mucosa.

Today, the capability of the human olfactory system is still, in many ways, superior to that of the electronic nose. Although electronic noses are often compared with their biological counterpart, they neither mimic its neural architecture nor achieve its discriminating performance. Experimental studies on the mammalian olfactory system suggest that the nasal cavity, comprising of the mucous layer and the olfactory epithelium, performs a degree of chromatographic separation of complex mixtures. Thus receptor cells distributed beneath the mucous layer provide both spatial and temporal chemosensory information. Here we report on the development of an artificial olfactory microsystem that replicates this basic structure. This contains an integrated channel to emulate the nasal cavity and coated with a polymer to mimic the partitioning mucous layer, which is positioned directly over a sensor array. Our system employs an 80 element chemoresistive microsensor array with carbon black/polymer odour-sensitive films combined with a microfluidic package fabricated by micro-stereolithography. Results show that this biomimetic system generates both spatial and temporal odorant signals, with a temporal chemical retention period of up to 170 s. Data analysis has revealed improvements in its ability to discriminate between two simple odours and a set of complex odours. We believe such emulation of the olfactory system can lead to improved odour discrimination within the field of electronic noses.

Alternative clinical end points in rectal cancer--are we getting closer?

BACKGROUND: In rectal cancer a high risk of local recurrence has been reported for patients treated by surgery alone. It is also recognised that 20%-40% of rectal cancer patients continue to develop distant metastases and die, even when a very low risk of local recurrence has been achieved with the use of preoperative radiotherapy and total mesorectal excision (TME). Hence, the current design of randomised trials in rectal cancer continues to use the standard end points of local control and survival. This strategy is time-consuming. The recently published EORTC 22921 trial, which compared radiotherapy with chemoradiotherapy and tested the role of postoperative adjuvant chemotherapy, has taken 14 years from planning to results. The aim of this review was to use the evidence from both phase II and phase III trials to provide a comprehensive survey of alternative clinical trial end points in rectal cancer, where preoperative chemoradiation has now become the standard treatment. We describe their strengths and weaknesses. Some are clearly defined, easy to assess and can be obtained early, because surgical resection usually takes place within 6-8 weeks of the completion of treatment. Some pathological response end points reflect biological activity, although their effect on survival has yet to be validated in randomised controlled trials. We will propose measurement and analytical techniques for minimising bias and intra- and inter-observer variability of the non-validated end points in the hope of basing these judgements on as firm a ground as possible. METHODS: A literature search identified both randomised and non-randomised trials of preoperative radiation therapy (RT) and chemoradiation therapy (CRT) in rectal cancer from 1993 to 2005. The aim was to find those studies that documented potential alternative end points. RESULTS: Pathological parameters have been used as early end points to compare studies of preoperative radiotherapy or chemoradiation. In the light of the German CAO/ARO/AIO-94 study, which demonstrated an improved therapeutic ratio for preoperative treatment, enthusiasm for preoperative chemoradiation in the management of rectal cancer is increasing. Current evidence cannot indicate whether the degree of response to chemoradiation (e.g. complete pathological response; downsizing the primary tumour; sterilizing the regional nodes; tumour regression grades or residual cell density) or the achievement of a curative resection (CRM/R0 resection) is the best early clinical end point. Problems with these end points include lack of structured measurement and analysis techniques to control for intra- and inter-observer variation and lack of validation as surrogates for long-term clinical end points such as local control and survival. However, retrospective studies in rectal cancer have confirmed a strong association between the presence of microscopic tumour cells within 1 mm of the CRM and increased risks of both local recurrence and distant metastases. Further end points of current clinical relevance for which adequate methodologies for assessment are lacking include sphincter sparing end points, and assessment of long-term toxicities, ano-rectal function and their specific impact on quality of life. Recommendations are made as to the most appropriate information, which should be documented in future trials. CONCLUSIONS: Pathological complete response following preoperative chemoradiation does not reliably predict late outcome. There are other events not mediated through this end point and there are also unintended effects (often an excess of non-cancer related deaths). Disease-free survival currently remains the best (because it is relatively quick) primary end point in designing randomised phase III studies of preoperative chemoradiation in rectal cancer, although it is necessary to control for postoperative adjuvant chemotherapy. However, the CRM status can substantially account for effects on disease-free and overall survival after chemoradiation, radiation or surgery alone. Hopefully, randomised controlled trials, which utilise these alternative clinical end points, will in future determine the precise percentages of the effect of different chemoradiation schedules on disease-free and overall survival.

Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn's disease.

INTRODUCTION: Interferon gamma is a potent proinflammatory cytokine implicated in the inflammation of Crohn's disease (CD). We evaluated the safety and efficacy of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe CD. METHODS: A total of 133 patients with Crohn's disease activity index (CDAI) scores between 250 and 450, inclusive, were randomised to receive placebo or fontolizumab 4 or 10 mg/kg. Forty two patients received one dose and 91 patients received two doses on days 0 and 28. Investigators and patients were unaware of assignment. Study end points were safety, clinical response (decrease in CDAI of 100 points or more), and remission (CDAI < or =150). RESULTS: There was no statistically significant difference in the primary end point of the study (clinical response) between the fontolizumab and placebo groups after a single dose at day 28. However, patients receiving two doses of fontolizumab demonstrated doubling in response rate at day 56 compared with placebo: 32% (9/28) versus 69% (22/32, p = 0.02) and 67% (21/31, p = 0.03) for the placebo, and 4 and 10 mg/kg fontolizumab groups, respectively. Stratification according to elevated baseline C reactive protein levels resulted in a decreased placebo response and pronounced differences in clinical benefit. Two grade 3 adverse events were reported and were considered to be related to CD. One death (during sleep) and one serious adverse event (an elective hospitalisation) occurred, both considered unrelated. CONCLUSION: Treating active CD with fontolizumab was well tolerated and resulted in increased rates of clinical response and remission compared with placebo.

A dose escalating, placebo controlled, double blind, single dose and multidose, safety and tolerability study of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease.

INTRODUCTION: This study was designed to evaluate the safety of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease (CD). PATIENTS AND METHODS: Forty five patients with a CD activity index (CDAI) of 250-450 were randomised in a double blind, placebo controlled, dose escalating fashion to receive single doses of fontolizumab (0.1, 1.0, and 4.0 mg/kg) or placebo. By day 29, patients with clinical response were re-randomised to receive three additional doses of one half their initial fontolizumab dose or placebo at four weekly intervals. Primary objectives were safety and tolerability. Secondary outcomes included assessments of immunogenicity, clinical activity, and potential pharmacodynamic surrogates. RESULTS: Treatment was generally well tolerated. There were slightly more reports of chills, flu-like syndrome, asthenia, nausea, and vomiting in the 1.0 mg and 4.0 mg/kg fontolizumab cohorts. Two serious adverse events rated as worsening of CD occurred under fontolizumab. Antibodies to fontolizumab were confirmed in one patient. No differences in clinical activity parameters were noted between any of the active treatment groups and placebo, with the placebo group having a particularly favourable outcome (60% response and 40% remission). By day 29, a more enhanced decrease in median Crohn's disease endoscopic index of severity (p = 0.02) and serum C reactive protein (p<0.001) was observed in the 4.0 mg/kg (n = 14) fontolizumab cohort compared with placebo (n = 10). Pharmacodynamic effects were observed by immunohistochemistry. CONCLUSIONS: Fontolizumab was well tolerated with minimal immunogenicity at doses of up to 4.0 mg/kg in patients with CD. A biological activity of fontolizumab is suggested.

Dynamic control of extracellular environment in in vitro neural recording systems.

A technique is presented for rapid fabrication of microfluidic channels on top of multichannel in vitro neural recording electrode arrays. The channels allow dynamic control of transient flow over localized areas of the array. Dorsal root ganglion neurons were integrated into the system. The device was used to demonstrate precise control of the extracellular microenvironment of individual cells on the array. Because the methods presented here are not specific to a particular cell type or neural recording system, the technique is amenable to a wide range of applications within the neuroscience field.

Elitek-rasburicase: an effective means to prevent and treat hyperuricemia associated with tumor lysis syndrome, a Meeting Report, Dallas, Texas, January 2002.

Renal precipitation of uric acid associated with tumor lysis syndrome (TLS) is a major complication in the management of leukemia, lymphoma, and other drug-sensitive cancers. Management of hyperuricema has historically consisted of administration of allopurinol, hydration, alkalinization to maintain pH between 7.0 and 7.3, and in some cases diuresis. Allopurinol, a xanthine analogue, blocks xanthine oxidase and formation of uric acid. Urate oxidase converts uric acid to allantoin, which is 5-10 times more soluble than uric acid. Homo sapiens cannot express urate oxidase because of a nonsense mutation. Urate oxidase was initially purified from Aspergillus flavus fungus. Treatment with this nonrecombinant product had been effective in preventing renal precipitation of uric acid in cancer patients, but was associated with a relatively high frequency of allergic reactions. This enzyme was recently cloned from A. flavus and is now manufactured as a recombinant protein. Clinical trials have shown this drug to be more effective than allopurinol for prevention and treatment of hyperuricemia in leukemia and lymphoma patients. This drug has been approved in Europe as well as the US and several clinical trials are in progress to further determine its clinical utility in other patient subsets. The purpose of this meeting was to discuss usefulness of recombinant urate oxidase, also known as rasburicase, Fasturtec, and Elitek, for the management of TLS in certain cancer patients.

Psychotherapeutic approaches to children in foster care: guidance from attachment theory.

The diverse psychological and emotional problems of foster children are reviewed, and an explanatory, interactional model based upon the key concepts of developmental psychopathology is described. The constructs of the internal working model and interpersonal schema, derived from attachment theory, are pathogenic mechanisms that contribute to the emergence of psychopathology in this population. The paper presents a general orientation to therapeutic work with foster children and describes some specific interventions based upon this interactional model. While attachment theory has much to offer clinicians, insecure attachment is just one of a number of risk factors; a comprehensive approach, both in terms of conceptualizing foster childrens' problems and treating them, is essential.

Optical multibead arrays for simple and complex odor discrimination.

A fiber optic bead-based sensor array platform has been employed to discriminate between six different odors and air carrier gas. Six different bead sensor types, with over 250 replicates of each, were monitored before, during, and after odor exposure to produce time-dependent fluorescence response patterns that were unique for each sensor-analyte combination. A total of 2,683 sensors were analyzed with respect to changes in their fluorescence, and signals from identical sensor beads were averaged to improve signal-to-noise ratios. Analyte classification rates of 100% were achieved for three complex (coffee bean) odors and three pure (simple) odors (toluene, acetone, 1,3-dinitrotoluene) measured at their highest relative concentrations. When lower odor concentrations were employed, the system exhibited better than 85% classification rates for analyte discrimination. Sensor response repeatability to these odor stimuli has also been quantified statistically, which is vital in defining the detection limit of the overall system. These results demonstrate, for the first time, the utility of our bead array technology for discriminating between different odor types at various dilution levels.

Phase I/II study of the P-glycoprotein modulator PSC 833 in patients with acute myeloid leukemia.

PURPOSE: To determine the maximum-tolerated dose, pharmacokinetic interaction, and activity of PSC 833 compared with daunorubicin (DNR) and cytarabine in patients with poor-risk acute myeloid leukemia. PATIENTS AND METHODS: Patients received ara-C 3 g/m(2)/d on 5 consecutive days, followed by an IV loading dose of PSC 833 (1.5 mg/kg) and an 84-hour continuous infusion escalating from 6, 9, or 10 mg/kg/d. Daunorubicin was administered as a 72-hour continuous infusion at 34 or 45 mg/m2/d [corrected]. Responding patients received consolidation chemotherapy with DNR pharmacokinetics performed without PSC-833 on day 1, and with PSC-833 on day 4. Response was correlated with expression of P-glycoprotein and lung resistance protein (LRP), and in vitro sensitization of leukemia progenitors to DNR cytotoxicity by PSC 833. RESULTS: All 43 patients are assessable for toxicity and response. Grade 3 or greater hyperbilirubinemia (70%) was the only dose-dependent toxicity. Four patients (9%) succumbed to treatment-related complications. Twenty-one patients (49%) achieved a complete remission or restored chronic phase, including 10 of 20 patients treated at the maximum-tolerated dose of 10 mg/kg/d of PSC-833 and 45 mg/m(2) of DNR. The 95% confidence interval for complete response was 33.9% to 63.7%. Administration of PSC 833 did not alter the mean area under the curve for DNR, although clearance decreased approximately two-fold (P =.04). Daunorubicinol clearance decreased 3.3-fold (P =.016). Remission rates were not effected by mdr-1 expression, but LRP overexpression was associated with chemotherapy resistance. CONCLUSION: Combined treatment with infused PSC 833 and DNR is well tolerated and has activity in patients with poor risk acute myeloid leukemia. Administration of PSC 833 delays elimination of daunorubicinol, but yields variable changes in DNR systemic exposure.

Subtalar joint movement: clinical and computed tomography scan correlation.

The purpose of this study was to compare subtalar motion measured externally (representing clinical assessment) with subtalar motion measured by computed tomography (CT), in normal individuals. Ten recreationally active subjects (20 lower extremities), aged 20 to 35 years with no lower extremity pathologic condition, were involved in the study. External subtalar inversion and eversion was assessed using a goniometer. By overlaying CT images of the subtalar joint in inversion and eversion on neutral images, angular subtalar motion was measured directly. Subtalar motion measured by CT ranged from 5 degrees to 16 degrees (mean, 11 degrees). External subtalar motion ranged from 39 degrees to 54 degrees (mean, 46 degrees), overestimating CT measurement of subtalar motion by approximately three-fold. This discrepancy is probably secondary to soft tissue motion and talocrural motion that is not isolated from subtalar motion at clinical examination. This solidifies our belief that clinical assessment of subtalar motion should no longer be used to determine or document the measurement of subtalar motion.