Colorectal Serrated Neoplasia: An Institutional 12-Year Review Highlights the Impact of a Screening Programme.

BACKGROUND: As the malignant potential of sessile serrated lesions/polyps (SSL/Ps) and traditional serrated adenomas (TSAs) has been clearly demonstrated, it is important that serrated polyps are identified and correctly classified histologically. AIM: Our aim was to characterize the clinicopathological features of a series of SSL/Ps & TSAs, to assess the accuracy of the pathological diagnosis, the incidence, and the rate of dysplasia in SSL/Ps & TSAs. METHODS: We identified all colorectal serrated polyps between 01/01/2004 and 31/05/2016, by searching the laboratory information system for all cases assigned a "serrated adenoma" SNOMED code. All available and suitable slides were reviewed by one pathologist, who was blinded to the original diagnosis and the site of the polyp. Subsequently discordant cases, SSL/Ps with dysplasia, and all TSAs were reviewed by a second pathologist. RESULTS: Over a 149-month period, 759 "serrated adenoma" polyps were identified, with 664 (from 523 patients) available for review. 41.1% were reviewed by both pathologists; 15.1% (100/664) were reclassified, with the majority being changed from SSL/P to hyperplastic polyp (HYP) (66/664; 9.9%). 80.3% of these HYPs were located in the left colon, and the majority exhibited prolapse effect. There were 520 SSL/Ps (92.2%) & 40 TSAs (7.1%). The majority of SSL/Ps were in the right colon (86.7%) and were small (64.5% <1 cm), while most TSAs were in the left colon (85.7%) and were large (73.1%≥1 cm). 6.7% of SSL/Ps exhibited dysplasia, the majority of which were large (66.7%≥1 cm). Following consensus review, 13/520 (2.5%) SSL/Ps were downgraded from SSL/P with dysplasia to SSL/P without dysplasia. Detection of SSL/Ps peaked in the most recent years reviewed (87.5% reported between 2013 and 2016, inclusive), coinciding with the introduction of "BowelScreen" (the Irish FIT-based colorectal cancer screening programme). CONCLUSIONS: Awareness of, and adherence to, diagnostic criteria is essential for accurate classification of colorectal polyps.

Reducing febrile neutropenia rates in early breast cancer. Experience of two UK cancer centres.

PURPOSE: Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) is used in many institutions across the UK due to unacceptable febrile neutropenia (FN) rates with FEC-D (fluorouracil, epirubicin, cyclophosphamide-docetaxel). The resultant reduction in FN rate is thought to maintain dose intensity and improve patient experience. This retrospective study was performed to assess whether the addition of G-CSF primary prophylaxis into daily clinical practice has achieved these aims. METHODS: Collaborative audit performed in two UK cancer centres before and after the integration of G-CSF primary prophylaxis with FEC-D. The primary objective was FN rate. RESULTS: Data from 342 patients were analysed, 151 before routine use of primary G-CSF and 191 after. The FN rates were 30 and 11%, respectively. Despite the 99% adherence to primary G-CSF policy, there were more dose reductions (8 increased to 13%) and dose delays (11 increased to 23%) following the use of G-CSF primary prophylaxis. This appeared to be due to non-FN toxicities. Inpatient days decreased substantially from 93 to 16 and antibiotic courses from 28 to 13 (per hundred patients). CONCLUSIONS: Near universal adherence to the G-CSF policy in FEC-D treatment has led to a reduction in FN rate and inpatient days but has not translated into improved dose intensity. This collaborative audit allows sufficient data to give insight into current practice and generate hypotheses for further investigation.

Phylogenetic patterns of skeletal morphometrics and pelvic traits in relation to locomotor mode in frogs.

Frogs are one of the most speciose groups of vertebrate tetrapods (> 6200sp) with a diverse array of locomotor behaviours. Despite the impressive diversity in frog locomotor behaviours, there remains a paucity of information on the relationship between skeletal variation and locomotor mode in frogs and the evolutionary patterns in which these relationships are framed across the frog phylogeny. Our current understanding of the evolution of frog locomotion shows that hopping transitioned into jumping within the Neobatrachia where a variety of pelvic/hindlimb length patterns and locomotor niches have appeared, but this has yet to be studied over a broad taxonomic sample of frogs. Although limb length remains as the primary predictor of leaping performance, pelvic and sacral morphometrics have not been quantified in relation to limb proportions, body size and locomotor mode and previous studies have not sampled more than 24 families. We present a large-scale phylogenetic comparison of skeletal morphometrics in relation to locomotor mode in 188 genera from 37 families. Osteological variation in limb/pelvic girdle morphometrics and pelvic traits that are posited to be associated with locomotor mode were analysed to identify which aspects of the frog skeleton are the best descriptors of locomotor mode. Our results, contrary to previous work, reveal that the greatest axis of variation in frogs is represented by the shape of the sacrum with two pelvic morphologies evident in qualitative and quantitative ancestral trait reconstructions. Limb morphology was not significantly different across most locomotor modes, but we identified several outliers in hindlimb phylomorphospace. Patterns of sacral evolution together with hindlimb length outliers reveal how the general bauplan of this successful group of vertebrate tetrapods is constrained, has radiated and has converged on certain phenotypes to fill an array of locomotor modes.

Adjuvant epirubicin followed by cyclophosphamide, methotrexate and fluorouracil (CMF) vs CMF in early breast cancer: results with over 7 years median follow-up from the randomised phase III NEAT/BR9601 trials.

BACKGROUND: The National Epirubicin Adjuvant Trial (NEAT) and BR9601 trials tested the benefit of epirubicin when added to cyclophosphamide, methotrexate and 5-fluorouracil (E-CMF) compared with standard CMF in adjuvant chemotherapy for women with early breast cancer. This report details longer follow-up with interesting additional time-dependent analyses. METHODS: National Epirubicin Adjuvant Trial used epirubicin (E) 3-weekly for four cycles followed by classical (c) CMF for four cycles (E-CMF) compared with cCMF for six cycles. BR9601 used E 3-weekly for four cycles followed by CMF 3-weekly for four cycles, compared with CMF 3-weekly for eight cycles. RESULTS: In all, 2391 eligible patients were randomised and with a median 7.4-year follow-up, E-CMF confirmed a significant benefit over CMF in both relapse-free survival (RFS) (78% vs 71% 5 years RFS, respectively, hazard ratio (HR)=0.75 (95% CI: 0.65-0.86), P<0.0001) and overall survival (OS) (84% vs 78% 5 years OS, respectively, HR=0.76 (95% CI: 0.65-0.89), P=0.0007). Interaction of treatment effect and prognostic factors was demonstrated for duplication of chromosome 17 centromeric enumeration (Ch17CEP) as previously reported. Poor prognostic factors at diagnosis (ER and PR negative and HER2 positive) showed time-dependent annual hazard rates for RFS and OS. In univariate analysis, these factors demonstrated more favourable HRs for RFS after 5 years. Treatment effects also suggested a differential benefit for E-CMF within the first 5 years for poor prognosis tumours. CONCLUSION: Longer follow-up has confirmed E-CMF as significantly superior to CMF for all patients. Ch17CEP duplication was the only biomarker that demonstrated significant treatment interaction. Standard poor prognostic factors at diagnosis were time-dependent, and after 5 years disease-free, poor prognosis patients demonstrated favourable HRs for survival.

Vinorelbine and infusional 5-fluorouracil in anthracycline and taxane pre-treated metastatic breast cancer.

AIMS: To evaluate the efficacy and toxicity of a combination of intravenous vinorelbine and 5-fluorouracil (5-FU) given by continuous infusion in the treatment of metastatic breast cancer previously treated with anthracyclines and taxanes. MATERIALS AND METHODS: Sixty-one patients with metastatic breast cancer were treated with intravenous vinorelbine 30 mg/m2 on days 1 and 8 of each 21-day cycle together with 5-FU 200 mg/m2/day by continuous infusion. All had previously been treated with an anthracycline and 41% had also been previously treated with a taxane. All had normal haematological, renal and hepatic function and all but three had an Eastern Cooperative Oncology Group performance score of 2 or better. RESULTS: The overall response rate by World Health Organization criteria was 46% (28 patients); excluding nine non-evaluable patients gave a response rate of 54%. In patients who had previously been treated with both an anthracycline and a taxane, a response rate of 50% was observed (12 of 24 patients). Severe toxicity was uncommon, as was toxicity attributable to infusional 5-FU. Myelosuppression was rarely severe, but was common and led to delay or dose reduction in 38% of treatments. Eleven patients (18%) were admitted with fever and/or neutropenia and one patient died. The median received dose intensity was vinorelbine 16 mg/m2/week and 5-FU 143 mg/m2/day. CONCLUSIONS: The combination of vinorelbine and infusional 5-FU is active in metastatic breast cancer, including in patients previously treated with an anthracycline and a taxane. Toxicity is generally manageable, but myelosuppression is significant at this dose regimen. Recommended doses for routine clinical use are 5-FU 200 mg/m2/day and intravenous vinorelbine 30 mg/m2 days 1 and 15 on a 28-day cycle.

Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up.

OBJECTIVE: To test the effectiveness and long term safety of cannabinoids in multiple sclerosis (MS), in a follow up to the main Cannabinoids in Multiple Sclerosis (CAMS) study. METHODS: In total, 630 patients with stable MS with muscle spasticity from 33 UK centres were randomised to receive oral Delta(9)-tetrahydrocannabinol (Delta(9)-THC), cannabis extract, or placebo in the main 15 week CAMS study. The primary outcome was change in the Ashworth spasticity scale. Secondary outcomes were the Rivermead Mobility Index, timed 10 metre walk, UK Neurological Disability Score, postal Barthel Index, General Health Questionnaire-30, and a series of nine category rating scales. Following the main study, patients were invited to continue medication, double blinded, for up to 12 months in the follow up study reported here. RESULTS: Intention to treat analysis of data from the 80% of patients followed up for 12 months showed evidence of a small treatment effect on muscle spasticity as measured by change in Ashworth score from baseline to 12 months (Delta(9)-THC mean reduction 1.82 (n = 154, 95% confidence interval (CI) 0.53 to 3.12), cannabis extract 0.10 (n = 172, 95% CI -0.99 to 1.19), placebo -0.23 (n = 176, 95% CI -1.41 to 0.94); p = 0.04 unadjusted for ambulatory status and centre, p = 0.01 adjusted). There was suggestive evidence for treatment effects of Delta(9)-THC on some aspects of disability. There were no major safety concerns. Overall, patients felt that these drugs were helpful in treating their disease. CONCLUSIONS: These data provide limited evidence for a longer term treatment effect of cannabinoids. A long term placebo controlled study is now needed to establish whether cannabinoids may have a role beyond symptom amelioration in MS.

Oral antibiotics with early hospital discharge compared with in-patient intravenous antibiotics for low-risk febrile neutropenia in patients with cancer: a prospective randomised controlled single centre study.

Neutropenic sepsis remains a potentially life-threatening complication of anticancer chemotherapy. However, it is possible to identify patients who are at low risk for serious complications and for whom less-intensive, more-convenient treatment may be appropriate. The aim of this study was to assess the efficacy and safety of oral antibiotics in conjunction with early hospital discharge in comparison with standard in-patient intravenous antibiotics in patients with low-risk neutropenic fever. In all, 126 episodes of low-risk neutropenic fever occurred in 102 patients. Patients were randomised to receive either: an oral regimen of ciprofloxacin (750 mg 12 hourly) plus amoxicillin-clavulanate (675 mg 8 hourly) for a total of 5 days, or a standard intravenous regimen of gentamicin and tazocin (piperacillin/tazobactam) until hospital discharge. Patients randomised to oral antibiotics were eligible for discharge following 24 h of hospitalisation, if clinically stable and symptomatically improved. The efficacy of the two arms was similar: initial treatment was successful without antibiotic modification in 90% of episodes in the intravenous arm and 84.8% of episodes in the oral arm, P=0.55, absolute difference between the groups 5.2%; 95% confidence interval (CI) for the difference -7 to 17.3%. Only one episode in the oral arm was associated with significant clinical deterioration: this occurred within the initial in-patient assessment period. The median in-patient stay was 4 days in the intravenous arm (range 2-8) and 2 days in the oral arm (range 1-16 days), P&<0.0005. The reduction in hospital stay led to significant cost-savings in the oral arm. In conclusion, this study suggests that oral antibiotics in conjunction with early hospital discharge for patients who remain stable after a 24 h period of in-patient monitoring offers a feasible and cost-effective alternative to conventional management of low-risk neutropenic fever.

Randomised, phase II trial comparing oral capecitabine (Xeloda) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines.

Capecitabine, an oral fluoropyrimidine carbamate, was designed to generate 5-fluorouracil preferentially at the tumour site. This randomised, phase II trial evaluated the efficacy and safety of capecitabine or paclitaxel in patients with anthracycline-pretreated metastatic breast cancer. Outpatients with locally advanced and/or metastatic breast cancer whose disease was unresponsive or resistant to anthracycline therapy were randomised to 3-week cycles of intermittent oral capecitabine (1255 mg m(-2) twice daily, days 1-14, (22 patients)) or a reference arm of i.v. paclitaxel (175 mg m(-2), (20 patients)). Two additional patients were initially randomised to continuous capecitabine 666 mg m(-2) twice daily, but this arm was closed following selection of the intermittent schedule for further development. Overall response rate was 36% (95% CI 17-59%) with capecitabine (including three complete responses) and 26% (95% CI 9-51%) with paclitaxel (no complete responses). Median time to disease progression was similar in the two treatment groups (3.0 months with capecitabine, 3.1 months with paclitaxel), as was overall survival (7.6 and 9.4 months, respectively). Paclitaxel was associated with more alopecia, peripheral neuropathy, myalgia and neutropenia, whereas typical capecitabine-related adverse events were diarrhoea, vomiting and hand-foot syndrome. Twenty-three per cent of capecitabine-treated patients and 16% of paclitaxel-treated patients achieved a > or =10% improvement in Karnofsky Performance Status. Oral capecitabine is active in anthracycline-pretreated advanced/metastatic breast cancer and has a favourable safety profile. Furthermore, capecitabine provides a convenient, patient-orientated therapy.

Prey processing in amniotes: biomechanical and behavioral patterns of food reduction.

In this paper we examine the biomechanics of prey processing behavior in the amniotes. Whether amniotes swallow prey items whole or swallow highly processed slurries or boluses of food, they share a common biomechanical system where hard surfaces (teeth or beaks) are brought together on articulated jaws by the actions of adductor muscles to grasp and process food. How have amniotes modified this basic system to increase the chewing efficiency of the system? To address this question we first examine the primitive condition for prey processing representative of many of the past and present predatory amniotes. Because herbivory is expected to be related to improved prey processing in the jaws we review patterns of food processing mechanics in past and present herbivores. Herbivory has appeared numerous times in amniotes and several solutions to the task of chewing plant matter have appeared. Birds have abandoned jaw chewing in favor of a new way to chew--with the gut--so we will detour from the jaws to examine the appearance of gut chewing in the archosaurs. We will then fill in the gaps among amniote taxa with a look at some new data on patterns of prey processing behavior and jaw mechanics in lizards. Finally, we examine evolutionary patterns of amniote feeding mechanism and how correlates of chewing relate to the need to increase the efficiency of prey processing in order to facilitate increased metabolic rate and activity.

Bone density in asthmatic children treated with inhaled corticosteroids.

Volumetric trabecular bone mineral density of the lumbar spine (vTBMD) and distal radius (rTBMD) were measured in 20 prepubertal white asthmatic children treated with moderate to high doses of inhaled corticosteroids. The median standard deviation score for vTBMD (0.20, -0.56 to 2.09) and rTBMD (-0.04, -0.82 to 1.39) were within the normal range.

[A comparative randomized phase-II study of Xeloda (capecitabine) and paclitaxel in patients with breast cancer progressing after anthracycline antibiotics]. / Sravnitel'noe randomizirovannoe issledovanie po II faze kselody (kapetsitabina) i paklitaksela u bol'nykh rakom molochnoi zhelezy, progressiruiushchikh posle antratsiklinovykh antibiotikov.

A randomized study of the effectiveness of treatment with capecitabine (Xeloda) (22) and paclitaxel (taxol) (19) was carried out in breast cancer patients resistant to anthracycline antibiotic drugs. Capecitabine and paclitaxel showed comparable effectiveness, although the former appeared less toxic, particularly, in hematologic complication situations. Therefore, it may be administered to out-patients who previously received several courses of chemotherapy.

Low-dose continuous-infusion ceftazidime monotherapy in low-risk febrile neutropenic patients.

One hundred and thirty-five cancer patients admitted with low-risk neutropenic fever received a low-dose schedule of ceftazidime as infusional monotherapy over a total of 180 episodes. Ceftazidime was administered as a 1-g bolus followed by a continuous infusion of 2 g per day. In this patient population the ceftazidime was both practical and well tolerated. Sixty-eight percent of patients responded with clinical improvement and complete resolution of fever within 48 h. Overall, 95% of patients responded, although 18% subsequently required antibiotic modification for persistent fever. Only 5% of episodes were considered failures due to clinical deterioration, and over the study period there was only 1 fatality due to respiratory failure. The median duration of hospitalisation was only 4 days (2-20). In conclusion, monotherapy with low-dose infusional ceftazidime appears safe and highly effective in this low-risk population of neutropenic patients and may reduce antibiotic costs appreciably.

Locomotion in the quail (Coturnix japonica): the kinematics of walking and increasing speed.

Hindlimb segmental kinematics and stride characteristics are quantified in several quail locomoting on a treadmill over a six-fold increase in speed. These data are used to describe the kinematics of a walking stride and to identify which limb elements are used to change stride features as speed increases. In quail, the femur does not move during locomotion and the tarsometatarsus-phalangeal joint is a major moving joint; thus, quail have lost the most proximal moving joint and added one distally. The tibiotarsus and tarsometatarsus act together as a fixed strut swinging from the knee during stance phase (the ankle angle remains constant at a given speed) and the tarsometatarsus-phalangeal joint appears to have a major role in increasing limb length during the propulsive phase of the stride. Speed is increased with greater knee extension and by lengthening the tibiotarsus/tarsometatarsus via increased ankle extension at greater speeds. Because the femur is not moved and three distal elements are, quail move the limb segments through a stride and increase speed in a way fundamentally different from other nonavian vertebrates. However, the three moving joints in quail (the knee, ankle, and tarsometatarsophangeal joint) have strikingly similar kinematics to the analogous moving joints (the hip, knee, and ankle) in other vertebrates. Comparisons to other vertebrates indicate that birds appear to have two modes of limb function (three- and four-segment modes) that vary with speed and locomotory habits.

Early evaluation of tumour metabolic response using [18F]fluorodeoxyglucose and positron emission tomography: a pilot study following the phase II chemotherapy schedule for temozolomide in recurrent high-grade gliomas.

Quantitation of metabolic changes in tumours may provide an objective measure of clinical and subclinical response to anticancer therapy. This pilot study assesses the value of quantitation of metabolic rate of glucose (MRGlu) measured in mmol min(-1) ml(-1) to assess early subclinical response to therapy in a relatively non-responsive tumour. Nine patients receiving the CRC Phase II study schedule of temozolomide were assessed with [18F]fluorodeoxyglucose ([18F]FDG) dynamic positron emission tomography (PET) scans prior to and 14 days after treatment with temozolomide given as 750-1000 mg m(-2) over 5 days every 28 days. Tumour MRGlu was calculated and compared with objective response at 8 weeks. Pretreatment MRGlu was higher in responders than non-responders. The responding patient group had a greater than 25% reduction in MRGlu in regions of high focal tumour uptake (HFU). Whole tumour changes in MRGlu did not correlate with response. Percentage change in HFU standardized uptake value (SUV) did discriminate the responding from the non-responding patients, but not as well as with MRGlu. Large differences also occurred in the normal brain SUV following treatment. Thus, MRGlu appeared to be a more sensitive discriminator of response than the simplified static SUV analysis. Changes in MRGlu may reflect the degree of cell kill following chemotherapy and so may provide an objective, quantitative subclinical measure of response to therapy.

Prey transport kinematics in Tupinambis teguixin and Varanus exanthematicus: conservation of feeding behavior in 'chemosensory-tongued' lizards.

Although lizards have been predicted to show extensive intraoral prey-processing behaviors, quantitative analyses of the types of prey-processing behavior they demonstrate and of their kinematics have been limited. The more basal lizard lineages (Iguanians) have undergone some study, but the prey-processing repertoires of crown taxa have not been thoroughly examined and quantitative comparisons of behaviors within or among species have not been made. In this study, the prey transport behavior of the savannah monitor (Varanus exanthematicus) and gold tegu (Tupinambis teguixin) are described. Although these two lineages have independently evolved tongues that are highly specialized for chemoreception, we found that they share the same three distinct types of transport behavior. These behavior patterns are (i) a purely inertial transport, (ii) an inertial transport with use of the tongue, and (iii) a non-inertial lingual transport. The tongue is used extensively in both the inertial and the purely lingual transport behaviors. More than 75 % of all transport behaviors involved tongue movements. These species appear to exhibit a conservation of feeding kinematics compared with patterns known for basal lizards. A hypothesis for the evolution of inertial feeding is proposed.

Health problems associated with international business travel. A critical review of the literature.

1. Few studies examine the travel related health problems of international business travelers (IBTs). Research exists for other travelers, such as tourists, which begins to help clinicians understand the potential health problems faced by IBTs. 2. A review of the literature reveals 36% to 54% of travelers experience physical health problems such as traveler's diarrhea, insomnia, respiratory problems, and skin problems; 6% to 18% report accidents and injuries while abroad. 3. Psychosocial data are equally limited, but support the idea that IBTs may experience stress, anxiety, culture shock, and adjustment problems while overseas. 4. Multiple factors likely contribute to the physical and psychosocial health experiences of IBTs. The historical lack of data for this population of workers combined with the trend towards globalization confirm the need for further study from an occupational health perspective.

Tumor, normal tissue, and plasma pharmacokinetic studies of fluorouracil biomodulation with N-phosphonacetyl-L-aspartate, folinic acid, and interferon alfa.

PURPOSE: To evaluate the effect of N-phosphonacetyl-L-aspartate (PALA), folinic acid (FA), and interferon alfa (IFN-alpha) biomodulation on plasma fluorouracil (5FU) pharmacokinetics and tumor and liver radioactivity uptake and retention after [18F]-fluorouracil (5-[18F]-FU) administration. PATIENTS AND METHODS: Twenty-one paired pharmacokinetic studies were completed on patients with colorectal, gastric, and hepatocellular cancer, utilizing positron emission tomography (PET), which allowed the acquisition of tumor, normal tissue, and plasma pharmacokinetic data and tumor blood flow (TBF) measurements. The first PET study was completed when the patient was biomodulator-naive and was repeated on day 8 after the patient had been treated with either PALA, FA, or IFN-alpha in recognized schedules. RESULTS: TBF was an important determinant of tumor radioactivity uptake (r = .90; P < .001) and retention (r = .96; P < .001), for which radioactivity represents a composite signal of 5-[18F]-FU and [18F]-labeled metabolites and catabolites. After treatment with PALA, TBF decreased (four of four patients; P = .043), as did tumor radioactivity exposure (five of five patients; P = .0437), with no change in plasma 5FU clearance. With FA treatment, there were no differences observed in whole-body metabolism, plasma 5FU clearance, or tumor and liver pharmacokinetics. IFN-alpha had measurable effects on TBF and 5-[18F]-FU metabolism but had no apparent affect on liver blood flow. CONCLUSION: The administration of PALA and IFN-alpha produced measurable changes in plasma, tumor, and liver pharmacokinetics after 5-[18F]-FU administration. No changes were observed after FA administration. In vivo effects may negate the anticipated therapeutic advantage of 5FU biomodulation with some agents.

Oral-motor dysfunction in children who fail to thrive: organic or non-organic?

Forty-seven children with non-organic failure to thrive (NOFT) were identified from a whole-population survey of children's growth and development. A significant proportion (N=17) of these 47 children were found to have oral-motor dysfunction (OMD) identified using a previously validated assessment tool. NOFT children with OMD and those with normal oral-motor function (N=30) were compared in order to ascertain whether there were any neurodevelopmental differences which might explain this finding. We hypothesized that children with OMD might have a subtle neurodevelopmental disorder. Few psychosocial variables discriminated the two groups. However, cognitive stimulation within the home and cognitive-growth fostering during mealtimes was much poorer for children with OMD. Some evidence has suggested that NOFT children with OMD may be 'biologically' more vulnerable from birth. We suggest that the continued use of the term 'non-organic' to describe failure to thrive in such children is questionable and requires redefining.

Sprawling locomotion in the lizard Sceloporus clarkii: speed modulation of motor patterns in a walking trot.

Previous kinematic analyses in Sceloporus clarkii have shown that increased speed during trotting is attained by retracting the femur relatively faster (decreasing retraction time relative to stride duration) while all other aspects of axial and limb movements occur simply faster (scaling with stride duration). Thus, most of the limb muscles must be modulated to move the joints absolutely faster, while muscles effecting femoral retraction must be modulated differently to retract the femur relatively faster to increase speed. This prediction was examined by analyzing motor patterns in several key leg muscles in the spiny lizard running over a threefold increase in speed during a trot. The prediction is borne out in the limb muscles where the limb adductor (flexor tibialis), knee extender (femorotibialis), and plantar flexor of the ankle (gastrocnemius) have similar patterns of motor modulation that are different from that of the femoral retractor (caudofemoralis). To modulate a muscle to move simply faster (scaled with speed) the offset of the motor pattern is moved relatively earlier to decrease burst duration, while the intensity of electromyographical activation is ramped up. Increasing the relative speed of action is done by activating the muscle earlier, increasing the duration of the burst, and increasing the relative level of activation. Comparisons to other studies illustrate that the confounding effects that stance and swing duration have on stride duration with speed have important consequences for functional interpretations and that scaling locomotory data to stance duration is a more appropriate and useful convention because it relates information directly to the duty cycle when the propulsive effects of motor modulation are transmitted to the substrate. The iliocostalis in Sceloporus clarkii has a pattern of activity indicating that it functions to rotate the pelvis to aid the contralateral duty cycle. This is strikingly different from the function of the iliocostalis in the monitor lizard. Differences in axial function and differences among lizards in postures of the foot and crus during locomotion indicate that there are different ways that lizards run and that the functional and anatomical diversity of modes of locomotion in lizards is greater than is recognized at present.

Sources of error in tissue and tumor measurements of 5-[18F]fluorouracil.

UNLABELLED: Central to the assessment of variability of pharmacokinetic parameters is knowledge of bias and variability of the measurement technique, preventing observed differences from being ascribed inappropriate significance. This article presents an evaluation of sources of error in the measurement of normal tissue and tumor pharmacokinetics using 18F-labeled 5-fluorouracil (FU) and PET. METHODS: A standard approach to data acquisition, processing and analysis was developed using a PET scanner, filtered backprojection reconstruction and region of interest analysis. Fourteen tracer 5-[18F]FU patient studies and a phantom study were completed, with 4 of the patient studies repeated 1 wk later. These data allowed evaluation of the overall reproducibility of the technique and the components of measurement variability due to tissue sampling. The effect of reconstruction technique and sampling region size on quantification was assessed using phantom data. RESULTS: All measured radioactivity versus time curves were tissue specific. Week-to-week variability in the area under this curve (representing combined physiological and measurement difference) was -3% to +15% for liver and -9% to -16% for spleen and kidney. Metastasis variability was greatest at -20%. Visual and computer realignment of the second paired study produced similar results. Interobserver effects were small compared to differences between studies. CONCLUSION: These results confirm the feasibility of using PET as a pharmacokinetic tool for 5-[18F]FU studies. Although overall experimental error (i.e., random variation in data acquisition, processing and analysis) was low, constraints in data interpretation emerged.