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Low concentrations of tetrodotoxin (TTX) and R-56865 block the slowly inactivating Na+ current in Langendorff perfused guinea pigs hearts subjected to normothermic global ischemia and reperfusion and thus decrease the increase in end-diastolic pressure in the left ventricle and the release of lactase dehydrogenase and creatine phosphokinase. In the papillary muscles TTX reduces the action potential duration and the maximum upstroke velocity but R-56865 only reduces the action potential duration. Systolic dysfunction caused by reperfusion is removed by high concentrations of TTX and R-56865.

Background: Several works have shown the benefits of foot orthosis intervention on postural stability in healthy individuals and patients with foot malalignment. However, the effects of foot orthoses on the daily ambulatory activities explored by the Six-Minute Walk Test (6MWT) were never examined. We hypothesized that foot orthoses could increase the gait distance and attenuate the post-6MWT posture alterations already reported in healthy individuals., Methods: In ten normal-weight (NW) and ten obese patients with foot malalignment and/or abnormal foot arch, we examined the benefits of 4 weeks of custom-molded orthosis intervention (D30) on 6MWT gait distance, fatigue sensation scores, ankle plantarflexion force, and post-6MWT sway of the center of pressure (COP) measured by a pedobarographic platform. Data were compared with those measured in two control-matched groups of ten NW and ten obese individuals, explored at study inclusion and at D30., Results: At study inclusion, the post-6MWT changes in COP surface and the medial and lateral COP deviations were significantly higher in obese participants who needed to wear the foot orthoses compared with obese control subjects. The foot orthosis intervention significantly improved the ambulatory performances of NW and obese individuals during the 6MWT, attenuated the bodily fatigue sensation after the 6MWT, and reduced the post-6MWT COP deviations, with the benefits of insoles being significantly accentuated in obese participants., Conclusions: Four weeks of foot orthosis intervention significantly increases gait distance and is an effective means to reduce postural sway after walking.

The six-minute walk test (6MWT) is used to evaluate the ambulatory capacity of patients suffering from respiratory disorders, obesity or neuromuscular diseases. Our primary aim was to evaluate the effects of the 6MWT on the postural sway and the ankle plantar flexion forces in healthy subjects. We measured the ankle plantar flexion forces and the plantar contact area before and after a 6MWT in normal weight and overweight subjects with no history of respiratory, cardiac, and neuromuscular disorders. A post-6MWT sensation of bodily fatigue was evaluated by Multidimensional Fatigue Inventory (MFI) and Pichot fatigue scales. A computerized pedobarographic platform was used to collect the mean plantar contact area, the changes of the center of pressure (CoP) surface and its medial and lateral deviations. In a limited number of subjects, the reproducibility of all the measurements was explored. In both groups, the 6MWT elicited a sensation of bodily fatigue. It also significantly reduced the ankle plantar flexion forces, and increased both the mean plantar contact area and the CoP surface, the changes being not apparent after 10min. The post-6MWT lateral CoP deviations were accentuated in normal weight subjects, while an increase in medial CoP deviations occurred in overweight ones. The 6MWT-induced changes in the plantar flexion force and pedobarographic variables were reproducible. Because this study clearly showed some post-6MWT alterations of the subjects' posture sway of our subjects, we questioned the possible mechanisms occurring that could explain the altered muscle force and the transient destabilization of posture after the 6MWT., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Podiatric physicians are increasingly using pedobarographs to measure plantar pressure. However, normal values of static pedobarographic variables for healthy men and women are lacking, which makes it difficult to evaluate abnormal foot positioning in standing patients with low- or high-arched feet or painful feet., Methods: During upright standing, a computerized pedobarograph measured the maximal (Pmax) and mean (Pmean) plantar pressures, total foot area, and forefoot and rearfoot areas in 84 healthy women and 84 healthy men, aged 18 to 83 years. After calibration of the pedobarograph, a correction factor was applied to area measurements, and data repeatability was assessed., Results: The Pmax and Pmean values were not correlated with age but with weight, body mass index, and shoe size. Total foot area was significantly higher in male participants and correlated with body weight, body mass index, and shoe size but not with age. In both sexes, forefoot area was significantly lower than rearfoot area. Significant positive correlations were observed between forefoot and rearfoot areas and weight and shoe size. The forefoot-rearfoot area ratio did not vary with sex, weight, shoe size, and age., Conclusions: These data provide relationships between Pmax, Pmean, and foot areas and weight and shoe size and clearly indicate no age dependence of pedobarographic data. They also provide stable values of the forefoot-rearfoot area ratio. These data should help clinicians evaluate abnormal foot placement in standing patients.

Objective: Vibration detection threshold of the foot sole was compared to the psychophysical estimate of vibration in a wide range of amplitudes in young (20-34 years old) and elderly subjects (53-67 years old)., Methods: The vibration detection threshold was determined on the hallux, 5th metatarsal head, and heel at frequencies of 25, 50 and 150 Hz. For vibrations of higher amplitude (reaching 360 μm), the Stevens power function ( Ψ  =  k  *  Φ n ) allowed to obtain regression equations between the vibration estimate ( Ψ ) and its physical magnitude ( Φ ), the n coefficient giving the subjective intensity in vibration perception. We searched for age-related changes in the vibration perception by the foot sole., Results: In all participants, higher n values were measured at vibration frequencies of 150 Hz and, compared to the young adults the elderly had lower n values measured at this frequency. Only in the young participants, the vibration detection threshold was lowered at 150 Hz., Conclusion: The psychophysical estimate brings further information than the vibration detection threshold which is less affected by age., Significance: The clinical interest of psychophysical vibration estimate was assessed in a patient with a unilateral alteration of foot sensitivity.

Insoles are known to alter plantar loads and thus plantar sensory input. We therefore hypothesised that plantar somatosensory sensation could be modified over time by use of hard metatarsal pads. A sample of 12 healthy female participants was randomly allocated to either soft metatarsal pads (n=6, latex foam, Shore A11) or hard metatarsal pads groups (n = 6, thermoplastic, ShoreA65). All wore the same shoe type and pedometers measured daily activities. Using a bespoke actuated device, multiple mechanical stimuli were applied to the forefoot and rearfoot before and after 8 and 30 days of wearing the pads. A control test comprised estimation of multiple auditory sensations at day 0, 8 and 30. Changes in detection of the mechanical and sound stimuli were estimated using the Stevens power function, Ψ = k × Φ(n) (estimate = Ψ; stimulus = Φ). The k coefficient measured the sensitivity, i.e. the lowest detectable load/sound, and the n coefficient the gain in perception over time. After 30 days, hard metatarsal pads group had increased plantar sensitivity in the forefoot but not the rearfoot. The soft metatarsal pads group showed no changes in plantar sensitivity and the detection of auditory sensation remained stable over the 30 days.Metatarsal pads with relatively high hardness increased the perception of the lowest mechanical stimulus in the forefoot compared to soft metatarsal pads. This provides initial evidence of the potential for changes in plantar somatosensory sensation due to choice of orthotic designs in patients with foot-related problems., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: We hypothesized that the repetitive use of a toenail clipper by podiatric physicians could induce fatigue of the flexor digitorum superficialis (FDS) muscle, reducing the accuracy of toenail cutting., Methods: We examined the consequences of cutting a plastic sheet, reproducing the resistance of thick toenails, with a podiatric medical clipper on the maximal handgrip force (Fmax) developed by the FDS muscle and an isometric handgrip sustained at 50% of Fmax, during which endurance to fatigue and changes in the power spectra of the surface FDS muscle electromyogram (root mean square and median frequency) were measured. The same participants randomly performed one or five runs of 30 successive cuttings, each on different days., Results: After the first and fifth cutting runs, Fmax increased, suggesting a post-tetanic potentiation. During the handgrip sustained at 50% of Fmax, we measured a significant reduction in the tension-time index after the first cutting run. Moreover, after the fifth cutting run, the tension-time index decrease was significantly accentuated, and the decrease in FDS muscle median frequency was enhanced. No median frequency decline was measured during the cutting runs., Conclusions: These results suggest that the efficacy of occupational podiatric medical tasks progressively declines with the repetition of toenail cutting. We propose solutions to remedy this situation.

We searched for the consequences of a maximal static foot inversion sustained until exhaustion on the post-exercise stationary upright standing and the proprioceptive control of the foot muscles. Twelve healthy subjects executed an unilateral maximal static foot inversion during which continuous power spectrum analyses of surface electromyograms of the tibialis anterior (TA), peroneus longus (PL), and gastrocnemius medialis (GM) muscles were performed. Superimposed pulse trains (twitch interpolation) were delivered to the TA muscle to identify "central" or "peripheral" fatigue. Before and after the fatiguing task, we measured (1) the repartition of the plantar and barycentre surfaces with a computerized stationary platform, (2) the peak contractile TA response to electrical stimulation (TA twitch), (3) the tonic vibratory response (TVR) of TA and GM muscles, and (4) the Hoffman reflex. During static exercise, "central" fatigue was diagnosed in 5/12 subjects whereas in the 7 others "peripheral" TA fatigue was deduced from the absence of response to twitch interpolation and the post-exercise decrease in twitch amplitude. The sustained foot inversion was associated with reduced median frequency in TA but not in PL and GM muscles. After static exercise, in all subjects both the mean plantar and rearfoot surfaces increased, indicating a foot eversion, the TVR amplitude decreased in TA but did not vary in GM, and the Hoffman reflex remained unchanged. Whatever was the mechanism of fatigue during the maximal foot inversion task, the facilitating myotatic reflex was constantly altered in foot invertor muscles. This could explain the prevailing action of the antagonistic evertor muscles., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Formulating the hypothesis that a maximal running exercise could induce fatigue of some foot muscles, we searched for electromyographic (EMG) signs of fatigue in the tibialis anterior (TA), peroneus longus (PL), and gastrocnemius medialis (GM) muscles. We also searched for post-exercise alterations of the stationary upright standing in normal-arched feet subjects. Healthy subjects performed a maximal running exercise. Surface EMGs of the TA, PL, and GM muscles were analysed during maximal dynamic efforts. Before and after the running bout, we measured the evoked compound muscle potential (M-wave) in TA, the maximal force into inversion (MIF), and the repartition of the plantar and barycentre surfaces with a computerised stationary platform. During maximal running exercise, the median frequency of the EMG spectra declined in TA while it remained stable in the PL and GM muscles. After the exercise, MIF decreased, and both the rearfoot plantar surface and the barycentre surface increased. We concluded that a maximal running bout elicits EMG signs of fatigue, though only in the TA muscle. It also elicits post-exercise changes in the foot position during stationary upright standing which indicates a foot eversion. These data solely concern a maximal running test and they can not be extrapolated to walking or running at a low speed., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective(s): To assess efficacy and tolerability of preoperative capecitabine chemoradiation in rectal cancer., Methods: Patients received radiotherapy 45 Gy in 25 fractions over 5 weeks and capecitabine 825 mg/m(2) twice daily throughout radiotherapy. Surgery was performed 5-7 weeks after radiotherapy. The primary endpoint was pathological complete response, secondary endpoints were downstaging and tolerability., Results: Fifty-one patients were enrolled in a phase II study, median age 62 years (range 35-78). Sixty-three percent of tumours involved the lower third of the rectum, 45% were fixed. The median delivered radiotherapy dose was 44.8 Gy (range 39.6-45.0 Gy) over 33-49 days. The treatment-related grade 3 adverse events were diarrhoea (12%), skin reactions (8%) and asthenia (8%), with no grade 4 toxicity. Fifty patients underwent surgery (29 conservative) and 1 patient refused. The pathological complete response rate was 20% and a further 10% of patients had minimal residual disease. Additional tumour downstaging was seen in 28% of patients and the sphincter preservation rate was 58%., Conclusions: Preoperative capecitabine chemoradiation is well tolerated and its efficacy supports further exploration, both as a single agent and as part of new therapeutic strategies., ((c) 2008 S. Karger AG, Basel)

Purpose: Between December 1998 and October 2001, patients <19 years old were treated for standard-risk medulloblastoma according to the Medulloblastome-Société Française d'Oncologie Pédiatrique 1998 (M-SFOP 98) protocol. Patients received hyperfractionated radiotherapy (36 Gy in 36 fractions) to the craniospinal axis, a boost with conformal therapy restricted to the tumor bed (to a total dose of 68 Gy in 68 fractions), and no chemotherapy. Records of craniospinal irradiation were reviewed before treatment start., Results: A total of 48 patients were considered assessable. With a median follow-up of 45.7 months, the overall survival and progression-free survival rate at 3 years was 89% and 81%, respectively. Fourteen major deviations were detected and eight were corrected. No relapses occurred in the frontal region and none occurred in the posterior fossa outside the boost volume. Nine patients were available for volume calculation without reduction of the volume irradiated. We observed a reduction in the subtentorial volume irradiated to >60 Gy, but a slight increase in the volume irradiated to 40 Gy. No decrease in intelligence was observed in the 22 children tested during the first 2 years., Conclusion: This hyperfractionated radiotherapy protocol with a reduced boost volume and without chemotherapy was not associated with early relapses in children. Moreover, intellectual function seemed to be preserved. These results are promising.

Background and Purpose: A retrospective study comparing chemotherapy and radiation, esophagectomy alone versus preoperative radiochemotherapy and surgery in localized squamous-cell esophageal carcinoma., Materials and Methods: Between 1989 and 1995, 139 patients (40 stage I, 77 stage IIA and 22 stage IIB according to the UICC 78 TNM classification) were treated in two different institutions. They were divided into three groups according to the treatment proposed: E group (treatment by esophagectomy; n = 30), RCT+E group (treatment by preoperative radiochemotherapy and esophagectomy; n = 46), RCT group (treatment by radiochemotherapy; n = 63). Factors like age, tumor localization and stage were similar in all groups. An intention to treat analysis was made., Results: The E group showed no postoperative mortality, while in the RCT+E group, the surgery mortality was 12.8%. The mortality after RCT was 1.7%. After preoperative radiochemotherapy, a pathological complete response was observed in 25% of cases and the curative resection rate was higher (82% after RCT + E versus 60% after E). The 5-year survival difference between the three groups was not relevant (E group, 12.6%; RCT group, 25.8%; RCT + E group, 38.7%). The median survival was 29, 24 and 28.5 months, respectively. The event-free survival was identical for the E group and the RCT group. For patients treated by radiochemotherapy, local and/or distant relapses were significantly reduced by esophagectomy (relapses occurred in 51% of patients in the RCT + E group versus 75% in the RCT group, P = 0.017). Palliative care (dilatations, prosthesis, gastrostomy or jejunostomy) to improve dysphagia was necessary for 38% of patients treated by exclusive radiochemotherapy versus 11% of patients treated by surgery (P = 0.001)., Conclusions: Treatments by esophagectomy or radiochemotherapy were not significantly different. Preoperative radiochemotherapy and surgery lead to a higher survival rate than exclusive radiochemotherapy, however, with a high postoperative mortality rate. This study suggests the relevance of a prospective randomized trial to compare RCT+E and RCT alone.

Ductal carcinoma in situ (DCIS), a non metastazing lesion of the breast is more frequently observed due to the improvement of mammography and widespread use of screening. The most important risk of this disease is local recurrence. In about half of cases, it occurs as an infiltrating carcinoma. In a series of 166 DCIS treated by lumpectomy plus radiotherapy, we have studied clinico-pathological factors for the prognosis of local recurrences and particularly the Van Nuys Index criteria (nuclear grade, necrosis, size, margin width). After median follow up of 75 months, 21 recurrences were observed with 10 corresponding to an infiltrating carcinoma and one of them died. The size of DCIS evaluated on pathological documents (histological slides and shames), the Van Nuys Prognostic Index (VNPI) and the mitotic index were the main prognostic factors of local recurrence. We discuss these results and confront them to a review of the literature focalised on the delicate problem of the decision of conservative treatment. A multidisciplinary approach (Breast : Surgeon, Radiologist, Pathologist and Radiotherapist), a standardisation of pathological criteria (size, margin width) and the continuation of randomised trials are necessary to fine the best attitude of conservative therapy.

We describe a new and original therapy with total body irradiation in two separate 4 gy single courses (double hemibody irradiation) combined with GM-CSF support, 5ug/day on days 1-15 after each hemibody irradiation, for refractory patients with B-chronic lymphocytic leukemia (CLL). A complete response was observed in a patient with a B-CLL resistant to CAP and FAMP therapy. Overall tolerance was good. The major points of interest in this technique are the combination of the antitumor effect of irradiation, limited bone marrow toxicity and a potential specific anti-leukemia effect of GM-CSF.

Purpose: To assess the influence of instantaneous total-body irradiation dose rate in hematological malignancies, we randomized 157 patients according to different instantaneous dose rates., Methods and Materials: Between December 10, 1986 and December 31, 1989 157 patients have undergone a total-body irradiation before bone-marrow transplantation according to two different techniques: either in one fraction (1000 cGy given to the midplane at the level of L4, and 800 cGy to the lungs) or in six fractions (1200 cGy over 3 consecutive days to the midplane at the level of L4, and 900 cGy to the lungs). Patients were randomized according to two instantaneous dose rates, called LOW and HIGH, in single-dose (6 vs. 15 cGy/min) and fractionated (3 vs. 6 cGy/min) TBI groups; there were 77 cases for the LOW and 80 for the HIGH groups, with 57 patients receiving single-dose (28 LOW, 29 HIGH) and 100 patients receiving fractionated total-body irradiation (49 LOW, 51 HIGH)., Results: As of July 1992, 16 (10%) of 157 patients developed cataracts after 17 to 46 months, with an estimated incidence of 23% at 5 years. Four (5%) of 77 patients in the LOW group, 12 (15%) of 80 patients in the HIGH group developed cataracts, with 5-year estimated incidences of 12% and 34%, respectively (p = 0.03). Ten (18%) of 57 patients in the single-dose group, and 6 (6%) of 100 patients in the fractionated group developed cataracts, with 5-year estimated incidences of 39% and 13%, respectively (p = 0.02). When the subgroups were considered, in the single-dose group, 3 (11%) of 28 LOW patients, and 7 (24%) of 29 HIGH patients developed cataracts, with 5-year estimated incidences of 24% and 53%, respectively; in the fractionated group, 1 (2%) of 49 LOW patients, and 5 (10%) of 51 HIGH patients developed cataracts, with 5-year estimated incidences of 4% and 22%, respectively (single-dose LOW vs. single-dose HIGH vs. fractionated LOW vs. fractionated HIGH, p = 0.006). There was no statistically significant difference in terms of 5-year estimated cataract incidence between the patients receiving steroids and those not (30% vs. 25%, p = 0.22). Multivariate analyses revealed that the instantaneous dose rate was the only independent factor influencing the cataractogenesis (p = 0.04)., Conclusion: We conclude that the total-body irradiation regimen (instantaneous dose rate and/or fractionation) may have an influence on the development of cataracts following bone-marrow transplantation.

Unlabelled: From 1972 to 1985, 260 cases of anal canal epidermoid carcinoma were irradiated. Eighteen cases treated for palliation were excluded from the study; 242 (93%) were treated with curative intent. The sex ratio was 1/5.5; mean age was 66 years., Histology: 60.3% were well differentiated epidermoid carcinoma; 31.0% moderately differentiated and 8.7%, cloacogenic cases. Staging: T1: 11.5%; T2: 16.1%; T3a: 17%; T3b: 33.5%; and T4: 21.9%. Abnormal inguinal nodes were present in 15.3% of cases. Crude overall survival (Kaplan-Meier) for the 242 cases is 86.4% at 1 year, 63.9% at 3 years, 51.2% at 5 years, and 30.8% at 10 years. Radiation therapy was the sole treatment for 193 cases. No chemotherapy was given. Patients were irradiated by external beam. They received a first course of X rays (mostly 18 MV, some 6 MV) 40 to 45 Gy (box technique) over 4 to 5 weeks in the pelvis. Age and size of tumor were considered when deciding on the target volume. After a rest period of 4 to 6 weeks, a second course of 15 to 20 Gy in 2 weeks was given through a perineal field by electron-beam of suitable energy. The mean total dose was 60.56 Gy and median was 62.5 Gy; the mean overall treatment duration was 85.3 days (median 82 days) and the mean Time Dose Factor including decay factor was 98.96. In this group, 5-year determinate survival was: T1-T2, 84.5%; T3a, 74.8%; T3b, 64.9%; T4, 58.9%. In 147/193 patients (76.2%) local control was achieved. The overall anal conservation rate was 62.6%. In 106 cases (55%), the anus had maintained normal function. The 5-year survival rate by N was 73.3% in the absence of inguinal nodes (169 cases) and 36.1% if such nodes were present. There was no significant difference in survival rate according to histological type. In the second group, receiving radiation therapy plus surgery, 33/49 cases (T3b-T4) were irradiated before surgery (median dose 40.5 Gy). Post operative radiation therapy was administered in 16 cases (T3b-T4) (median dose 49.6 Gy). The 5-year determinate survival is 53.2% for T3b and 79% for T4. According to the log-rank test, there was no significant difference between survival with radiation therapy alone and radiation therapy plus surgery. Multivariate analysis of the whole group indicated that T stage is the only predictive variable.(ABSTRACT TRUNCATED AT 400 WORDS)