Step training improves the speed of voluntary step initiation in aging

BACKGROUND: Falls related to balance dysfunction are among the major problems of older individuals. The timing characteristics of protective voluntary stepping are critically related to effective balance recovery and are often delayed and slowed with age. This study investigated the influence of step training on the timing characteristics of voluntary step initiation in younger and older adults. METHODS: Voluntary reaction time stepping was evaluated before and after training in 12 younger adults and 8 healthy community-dwelling older adults who performed a 3-week regimen of either twice weekly induced step training (destabilizing large waist pulls) or voluntary step practice to a somatosensory reaction stimulus cue (nondestabilizing small waist pulls). RESULTS: Overall, the first step initiation times were slower for the older than for the younger subjects for both the somatosensory reaction stimulus cue task and an auditory transfer cue task. Step completion time was completed earlier for the young posttraining subjects, and older subjects generally had a longer step length. Training resulted in significant reductions in step initiation timing for the old (17%) and young (15%) subjects. Across age groups, the induced training group showed greater reductions in step initiation time than the voluntary practice group for the auditory transfer cue task. CONCLUSIONS: A 3-week period of either voluntary or waist-pull-induced step training reduced step initiation time in older and younger adults. Moreover, compared with voluntary step practice, induced step training resulted in a significantly greater improvement in reaction time stepping for an auditory transfer cue task. At least in the short term, such step training has the potential to help older adults perform more like younger adults in their step initiation timing.     

A phase I study of SPI-077 (Stealth liposomal cisplatin) concurrent with radiation therapy for locally advanced head and neck cancer

Background: Liposomal cisplatinpreparations have two potential advantagesover the free drug when combined withradiation therapy (RT): 1) selective tumorlocalization, improving the therapeuticratio, and 2) prolonged half-life, allowingmore radiosensitization. We performed aPhase I study of Stealth® liposomalcisplatin (SPI-077) concurrent with RT forhead and neck squamous cell carcinoma(HNSCC). Methods: Patients with StageIVa/b HNSCC were treated with SPI-077,given intravenously twice two weeks apart,concurrent with RT (60–72 Gy in 6–7 weeks).The SPI-077 dose was escalated in standardphase I design. Results: Twenty patientsreceived 38 doses of SPI-077, escalatedfrom 20–200 mg/m² in six dose levels.Two of these patients received one dosebecause of reversible Grade 3 livertoxicity or rash. Three patients had aGrade 1, and one had a Grade 2 infusionreaction. Four patients had transientlyelevated transaminases: Grade 1 (n = 1),Grade 2 (n = 1), and Grade 3 (n = 2). Grade 3neutropenia occurred in one patient. Therewas no ototoxicity, neurotoxicity, ornephrotoxicity. In-field radiation skin andmucosal toxicities did not appear to beintensified. Ten of 17 patients (59%)finishing treatment achieved initialcomplete response. Conclusions: Systemic andin-field radiation toxicities of SPI-077were minimal. Infusion reactions wereminimized with a slower and more diluteinitial infusion. Further dose escalationwas stopped in the absence of dose-limitingtoxicity to address the reformulation ofthe liposomally bound cisplatin.Nonetheless, this study shows that highdoses of SPI-077 can be given safely. Thepotentially beneficial therapeutic ratiosuggests that liposomal radiosensitizerpreparations warrant furtherinvestigation.     

Low-molecular-weight heparin (nadroparin) and very low doses of warfarin in the prevention of upper extremity thrombosis in cancer patients with indwelling long-term central venous catheters: a pilot randomized trial

BACKGROUND AND OBJECTIVES: Upper extremity thrombosis is a major complication of central venous catheters implanted for chemotherapy in cancer patients. Vitamin K antagonists and low-molecular-weight heparins have been recommended in this setting, but their relative benefit-to-risk ratios have never been compared. DESIGN AND METHODS: A prospective, randomized, open, parallel-group, multicenter trial was performed comparing the antithrombotic efficacy and safety of warfarin and the low-molecular-weight heparin, nadroparin, in cancer patients who had undergone central venous catheter implantation. Warfarin was given orally at a fixed daily dose of 1 mg and nadroparin was injected subcutaneously at a fixed daily dose of 2,850 IU for 90 days, or until venographically-confirmed thrombosis occurred. The primary efficacy outcome was the occurrence of upper extremity thrombosis confirmed by venography performed 90 days after insertion of the catheter, or earlier if symptoms of thrombosis had appeared. Safety end-points were bleeding and thrombocytopenia. RESULTS: Fifty-nine patients were included in the study. A total of 21 and 24 patients in the nadroparin and warfarin groups, respectively, were evaluable for primary efficacy. Six out of the 21 patients in the nadroparin group (28.6%) and 4 out of the 24 patients in the warfarin group (16.7%) had venographically-documented upper extremity thrombosis at day 90 (p=0.48). Safety was satisfactory and similar with both treatments. INTERPRETATION AND CONCLUSIONS: Warfarin at a fixed, very low dose and nadroparin at a fixed, prophylactic dose had comparable benefit-to-risk ratios in the prevention of thrombosis associated with central venous catheters in cancer patients.     

Estimation of the risk for nutritional state degradation in patients with cancer: development of a screening tool based on results from a cross-sectional survey.

BACKGROUND: In routine practice, the evaluation of the nutritional status of patients with cancer is not always performed although there is frequent modification as disease progresses. The validated screening and evaluation tools currently available are time-consuming and costly. In this study we analysed factors that could be used to identify patients likely to need nutritional surveillance or intervention. PATIENTS AND METHODS: A cross-sectional survey was carried out for 2 weeks in June 2006 on 477 patients with cancer. RESULTS: 30.2% of the patients had lost more than 10% of their body weight since the start of the illness. After adjustment, the factors significantly associated with weight loss were: depressive state (OR = 3.49; P = 0.002), digestive or ENT tumours (OR = 3.20; P = <0.001), chemotherapy (OR = 2.66; P = 0.011), male gender (OR = 2.30; P = 0.001) and professional status (OR = 2.08; P = 0.02). Using a logistic model, we calculated the risk of weight loss as a function of the presence of the identified predictive factors. CONCLUSION: We report a simple screening tool, which will not replace the available evaluation methods but will enable targeting of the patients most likely, after a specific evaluation, to benefit from nutritional intervention. This remains to be validated in further prospective studies.     

Endogenous competition against binding of [18F]DMFP and [18F]fallypride to dopamine D2/3 receptors in brain of living mouse

Aim . Molecular imaging studies with benzamide radioligands can reveal competition from endogenous binding at D_2/3‐receptors in living brain. However, single photon emission computed tomography (SPECT) methods suffer from limited spatial resolution, and [¹¹C]‐labeled ligands are only available at positron emission tomography (PET) research sites with cyclotron‐radiochemistry facilities, whereas [¹⁸F] can be transported, due to its longer physical half‐life. Therefore, we endeavored to characterize the vulnerabilities of the benzamide antagonist [¹⁸F]desmethoxyfallypride (DMFP) and its high‐affinity congener [¹⁸F]fallypride (FP) to competition from endogenous dopamine in living mouse brain. Methods . Groups of awake mice were pretreated with saline, amphetamine (10 mg/kg), or reserpine (5 mg/kg), followed by i.v. tracer injections. Mice were killed at 2.5–90 min (DMFP) or 2.5–180 min (FP) circulation times. Brains were dissected and regional radioactivity concentration measured by gamma counting. Other groups of mice were anesthetized for dynamic microPET recordings with DMFP or FP. Binding potentials (BP_ND) were calculated using cerebellum as reference region. Results . With 90‐min circulation, DMFP BP_ND in striatum was 2.4 by dissection and 2.2 by microPET, which showed a 62% decrease in response to amphetamine‐evoked dopamine release and a 33% increase after reserpine‐evoked dopamine depletion. With 120‐min circulation, FP BP_ND in striatum was 24.1 by dissection and 9.2 by microPET, which showed a 31% decrease in the amphetamine group, but no effect of reserpine. Dissection showed similar sensitivities for FP binding, but only a 29% amphetamine‐evoked reduction for DMFP. Conclusions . Relative to gold standard ex vivo results, microPET estimates of DMFP BP_ND were unbiased, whereas FP BP_ND in striatum was substantially underestimated. Both tracers proved suitable for revealing pharmacologically evoked changes in competition at D_2/3‐receptors in striatum of living mice. Synapse 64:313–322, 2010. © 2009 Wiley‐Liss, Inc.