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Purpose: Theta-burst stimulation (TBS) over the primary motor cortex modulates activity of the underlying neural tissue, but little is known about its consequence on neuromuscular fatigue (NMF) and its neural correlates. This study aimed to compare the effects of facilitatory versus inhibitory TBS on the NMF and excitability/inhibition of the corticospinal pathway in an unfatigued/fatigued muscle., Methods: The effects of three TBS protocols (facilitatory/intermittent: iTBS; inhibitory/continuous: cTBS, and sham: sTBS) were tested on exercise performance, neuromuscular function, corticospinal excitability and inhibition in twenty young healthy participants. Transcranial magnetic and peripheral electrical stimulations were used at baseline, following TBS (unfatigued state), and after a fatiguing sustained contraction (fatigued state) at 35% of the maximal voluntary isometric contraction (MVIC) of the elbow flexors., Results: Time-to-task failure was shorter for cTBS (142±51 s) and longer for iTBS (214±68 s) compared with sTBS (173±65 s) (P < .05). In an unfatigued state, cTBS reduced MVIC and voluntary activation (VA), increased motor-evoked potential (MEP), and silent period (SP) (P < 0.05), while iTBS did not cause any change. In a fatigued state, MVIC and VA decreased in all TBS sessions (P < 0.05). However, the reduction in VA was larger after cTBS (Δ-18±18%) compared with iTBS (Δ-3±5%), and sTBS (Δ-9±9%) (P < 0.001). Furthermore, the increase in MEP and SP were greater for cTBS (P < .05), compared to iTBS and sTBS (P < .05)., Conclusions: Facilitatory TBS augments exercise performance that is independent of central parameters and corticospinal mechanisms whilst inhibitory TBS attenuates exercise performance through an exacerbation in the development of central fatigue and possibly intracortical inhibition., Competing Interests: Conflict of Interest and Funding Source: The study was partially supported by the Italian Ministry of Research and University (MIUR) 5-year special funding to strengthen and enhance excellence in research and teaching (https://www.miur.gov.it/dipartimenti-di-eccellenza). The authors declare no conflict of interest, (Copyright © 2024 by the American College of Sports Medicine.)

Objective: Existing literature indicates that females generally demonstrate higher fatigue resistance than males during isometric contractions. However, when it comes to single-limb dynamic exercises, the intricate interplay between performance fatigability (PF), cardiovascular responses, and muscle metabolism in relation to sex differences remains underexplored., Purpose: This study investigates how sex affects the relationship between muscle oxidative characteristics and the development of PF during dynamic single-leg exercise., Methods: Twenty-four young healthy participants (12 males vs. 12 females) performed a constant-load single-leg knee extension task (85% peak power output; 60 rpm) to exhaustion (TTE). Neuromuscular assessments via transcranial magnetic and peripheral stimulations were conducted pre- and post-exercise to evaluate central and peripheral factors of PF. Vastus lateralis muscle biopsies were obtained for mitochondrial respiration and immunohistochemistry analyses., Results: Participants performed similar total work (28 ± 7 vs. 27 ± 14 kJ, p = 0.81) and TTE (371 ± 139 vs. 377 ± 158 sec, p = 0.98); after the TTE, females' maximal isometric voluntary contraction (MVIC: -36 ± 13 vs. -24 ± 9 %, p = 0.006) and resting twitch (RT: (-65 ± 9 vs. -40 ± 24 %, p = 0.004) force declined less. No differences were observed in supraspinal neuromuscular factors (p > 0.05). During exercise, the cardiovascular responses differed between sexes. Although fiber type composition was similar (type I: 47 ± 13 vs. 56 ± 14 %, p = 0.11), males had lower mitochondrial net oxidative capacity (61 ± 30 vs. 89 ± 37, p = 0.049) and higher Complex II contribution to maximal respiration (CII; 59 ± 8 vs. 48 ± 6%, p < 0.001), which correlated with the decline in MVIC (r = -0.74, p < 0.001) and RT (r = -0.60, p = 0.002)., Conclusions: Females display greater resistance to PF during dynamic contractions, likely due to their superior mitochondrial efficiency and lower dependence on mitochondrial CII activity., Competing Interests: Conflict of Interest and Funding Source: This research was funded by the Italian Ministry of Research and University (MIUR; Rome, Italy) 5-year special funding (https://www.miur.gov.it/dipartimenti-di-eccellenza) and the research grant “Fondo Gianesini Emma” in collaboration with UniCredit Foundation and University of Verona (Italy). The authors declare no competing interest., (Copyright © 2024 by the American College of Sports Medicine.)

The force drop after transcranial magnetic stimulation (TMS) delivered to the motor cortex during voluntary muscle contractions could inform about muscle relaxation properties. Because of the physiological relation between skeletal muscle fiber-type distribution and size and muscle relaxation, TMS could be a noninvasive index of muscle relaxation in humans. By combining a noninvasive technique to record muscle relaxation in vivo (TMS) with the gold standard technique for muscle tissue sampling (muscle biopsy), we investigated the relation between TMS-induced muscle relaxation in unfatigued and fatigued states, and muscle fiber-type distribution and size. Sixteen participants (7F/9M) volunteered to participate. Maximal knee-extensor voluntary isometric contractions were performed with TMS before and after a 2-min sustained maximal voluntary isometric contraction. Vastus lateralis muscle tissue was obtained separately from the participants' dominant limb. Fiber type I distribution and relative cross-sectional area of fiber type I correlated with TMS-induced muscle relaxation at baseline ( r = 0.67, adjusted P = 0.01; r = 0.74, adjusted P = 0.004, respectively) and normalized TMS-induced muscle relaxation as a percentage of baseline ( r = 0.50, adjusted P = 0.049; r = 0.56, adjusted P = 0.031, respectively). The variance in the normalized peak relaxation rate at baseline (59.8%, P < 0.001) and in the fatigue resistance (23.0%, P = 0.035) were explained by the relative cross-sectional area of fiber type I to total fiber area. Fiber type I proportional area influences TMS-induced muscle relaxation, suggesting TMS as an alternative method to noninvasively inform about skeletal muscle relaxation properties. NEW & NOTEWORTHY Transcranial magnetic stimulation (TMS)-induced muscle relaxation reflects intrinsic muscle contractile properties by interrupting the drive from the central nervous system during voluntary muscle contractions. We showed that fiber type I proportional area influences the TMS-induced muscle relaxation, suggesting that TMS could be used for the noninvasive estimation of muscle relaxation in unfatigued and fatigued human muscles when the feasibility of more direct method to study relaxation properties (i.e., muscle biopsy) is restricted.

Previous studies in animal models showed that exercise-induced metabolites accumulation may sensitize the mechanoreflex-induced response. The aim of this study was to assess whether the magnitude of the central hemodynamic and ventilatory adjustments evoked by isolated stimulation of the mechanoreceptors in humans are influenced by the prior accumulation of metabolic byproducts in the muscle. 10 males and 10 females performed two exercise bouts consisting of 5-min of intermittent isometric knee-extensions performed 10% above the previously determined critical force. Post-exercise, the subjects recovered for 5 min either with a suprasystolic circulatory occlusion applied to the exercised quadriceps (PECO) or under freely-perfused conditions (CON). Afterwards, 1-min of continuous passive leg movement was performed. Central hemodynamics, pulmonary data, and electromyography from exercising/passively-moved leg were recorded throughout the trial. Root mean square of successive differences (RMSSD, index of vagal tone) was also calculated. Δpeak responses of heart rate (ΔHR) and ventilation ([Formula: see text]) to passive leg movement were higher in PECO compared to CON (ΔHR: 6 ± 5 vs 2 ± 4 bpm, p = 0.01; 3.9 ± 3.4 vs 1.9 ± 1.7 L min -1 , p = 0.02). Δpeak of mean arterial pressure (ΔMAP) was significantly different between conditions (5 ± 3 vs  - 3 ± 3 mmHg, p < 0.01). Changes in RMSSD with passive leg movement were different between PECO and CON (p < 0.01), with a decrease only in the former (39 ± 18 to 32 ± 15 ms, p = 0.04). No difference was found in all the other measured variables between conditions (p > 0.05). These findings suggest that mechanoreflex-mediated increases in HR and [Formula: see text] are sensitized by metabolites accumulation. These responses were not influenced by biological sex., (© 2023. The Author(s).)

Purpose: Both muscle mass and physical activity are independent mechanisms that play a role in vascular remodeling, however, the direct impact of muscle mass on the structure and function of the vessels is not clear. The aim of the study was to determine the impact of muscle mass alteration on lower limbs arterial diameter, blood flow, shear rate and arterial stiffness., Methods: Nine (33 ± 13 yrs) male individuals with a single-leg amputation were recruited. Vascular size (femoral artery diameter), hemodynamics (femoral artery blood flow and shear rate were measured at the level of the common femoral artery in both amputated (AL) and whole limbs (WL). Muscle mass of both limbs, including thigh for AL and thigh and leg for WL, was measured with a DXA system., Results: AL muscle mass was reduced compared to the WL (3.2 ± 1.2 kg vs. 9.4 ± 2.1 kg; p = 0.001). Diameter of the femoral artery was reduced in the AL (0.5 ± 0.1 cm) in comparison to the WL (0.9 ± 0.2 cm, p = 0.001). However, femoral artery blood flow normalized for the muscle mass (AL = 81.5 ± 78.7ml min -1  kg -1 ,WL = 32.4 ± 18.3; p = 0.11), and blood shear rate (AL = 709.9 ± 371.4 s -1 , WL = 526,9 ± 295,6; p = 0.374) were non different between limbs. A correlation was found only between muscle mass and femoral artery diameter (p = 0.003, R = 0.6561)., Conclusion: The results of this study revealed that the massive muscle mass reduction caused by a leg amputation, but independent from the level of physical activity, is coupled by a dramatic arterial diameter decrease. Interestingly, hemodynamics and arterial stiffness do not seem to be impacted by these structural changes., (© 2022. The Author(s).)

Purpose: This study evaluated whether central motor drive during fatiguing exercise plays a role in determining performance and the development of neuromuscular fatigue during a subsequent endurance task., Methods: On separate days, 10 males completed three constant-load (80% peak power output), single-leg knee-extension trials to task failure in a randomized fashion. One trial was performed without preexisting quadriceps fatigue (CON), and two trials were performed with preexisting quadriceps fatigue induced either by voluntary (VOL; involving central motor drive) or electrically evoked (EVO; without central motor drive) quadriceps contractions (~20% maximal voluntary contraction (MVC)). Neuromuscular fatigue was assessed via pre-post changes in MVC, voluntary activation (VA), and quadriceps potentiated twitch force ( Qtw,pot ). Cardiorespiratory responses and rating of perceived exertion were also collected throughout the sessions. The two prefatiguing protocols were matched for peripheral fatigue and stopped when Qtw,pot declined by ~35%., Results: Time to exhaustion was shorter in EVO (4.3 ± 1.3 min) and VOL (4.7 ± 1.5 min) compared with CON (10.8 ± 3.6 min, P < 0.01) with no difference between EVO and VOL. ΔMVC (EVO: -47% ± 8%, VOL: -45% ± 8%, CON: -53% ± 8%), Δ Qtw,pot (EVO: -65% ± 7%, VOL: -59% ± 14%, CON: -64% ± 9%), and ΔVA (EVO: -9% ± 7%, VOL: -8% ± 5%, CON: -7% ± 5%) at the end of the dynamic task were not different between conditions (all P > 0.05). Compared with EVO (10.6 ± 1.7) and CON (6.8 ± 0.8), rating of perceived exertion was higher ( P = 0.05) at the beginning of VOL (12.2 ± 1.0)., Conclusions: These results suggest that central motor drive involvement during prior exercise plays a negligible role on the subsequent endurance performance. Therefore, our findings indicate that peripheral fatigue-mediated impairments are the primary determinants of high-intensity single-leg endurance performance., (Copyright © 2022 by the American College of Sports Medicine.)

Transcranial magnetic stimulation (TMS)-induced relaxation rate reflects intrinsic muscle contractile properties by interrupting the drive from the central nervous system during voluntary muscle contractions. To determine the appropriateness of knee-extensor muscle relaxation measurements induced by TMS, this study aimed to establish both the within- and between-session reliability before and after a fatiguing exercise bout. Eighteen participants (9 females, 9 males, age 25 ± 2 years, height 171 ± 9 cm, body mass 68.5 ± 13.5 kg) volunteered to participate in two identical sessions approximately 30 days apart. Maximal and submaximal neuromuscular evaluations were performed with TMS six times before (PRE) and at the end (POST) of a 2-min sustained maximal voluntary isometric contraction. Within- and between-session reliability of PRE values were assessed with intraclass correlation coefficient (ICC 2,1 , relative reliability), repeatability coefficient (absolute reliability), and coefficient of variation (variability). Test-retest reliability of post-exercise muscle relaxation rates was assessed with Bland-Altman plots. For both the absolute and normalized peak relaxation rates and time to peak relaxation, data demonstrated low variability (e.g. coefficient of variation ≤ 7.8%) and high reliability (e.g. ICC 2,1  ≥ 0.963). Bland-Altman plots showed low systematic errors. These findings establish the reliability of TMS-induced muscle relaxation rates in unfatigued and fatigued knee-extensor muscles, showing that TMS is a useful technique that researchers can use when investigating changes in muscle relaxation rates both in unfatigued and fatigued knee-extensor muscles., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Fatigue is one of the most disabling symptoms of multiple sclerosis (MS); it influences patients' quality of life. The etiology of fatigue is complex, and its pathogenesis is still unclear and debated. The objective of this review was to describe potential brain structural and functional dysfunctions underlying fatigue symptoms in patients with MS. To reach this purpose, a systematic review was conducted of published studies comparing functional brain activation and structural brain in MS patients with and without fatigue. Electronic databases were searched until 24 February 2021. The structural and functional outcomes were extracted from eligible studies and tabulated. Fifty studies were included: 32 reported structural brain differences between patients with and without fatigue; 14 studies described functional alterations in patients with fatigue compared to patients without it; and four studies showed structural and functional brain alterations in patients. The results revealed structural and functional abnormalities that could correlate to the symptom of fatigue in patients with MS. Several studies reported the differences between patients with fatigue and patients without fatigue in terms of conventional magnetic resonance imaging (MRI) outcomes and brain atrophy, specifically in the thalamus. Functional studies showed abnormal activation in the thalamus and in some regions of the sensorimotor network in patients with fatigue compared to patients without it. Patients with fatigue present more structural and functional alterations compared to patients without fatigue. Specifically, abnormal activation and atrophy of the thalamus and some regions of the sensorimotor network seem linked to fatigue.

Previous studies demonstrated that aging, neurodegeneration, and the level of physical activity are associated with vascular alterations. However, in Parkinson's disease (PD) only cerebral vascular function has been investigated; instead, the contribution of PD on systemic vascular function and skeletal muscle circulation remains a matter of debate. In this study, the hyperemic response during the single passive leg movement test (sPLM), largely nitric oxide dependent, was examined at the level of the common femoral artery with an ultrasound Doppler system to assess systemic vascular function in 10 subjects with PD (PDG), compared with 10 aged-sex and physically active matched healthy elderly (EHG), and 10 physically active young healthy individuals (YHG). Interestingly, femoral blood flow at rest, normalized for the thigh volume, was similar in PDG (64 ± 15 mL·min -1 ·L -1 ), EHG (44 ± 8 mL·min -1 ·L -1 ), and YHG (58 ± 11 mL·min -1 ·L -1 , all P values > 0.05). The sPLM-induced hyperemic response appeared markedly lower in PDG and EHG compared with YHG (8.3 ± 0.1 vs. 9.8 ± 0.8 vs. 17.3 ± 3.0 mL·min -1 ·L -1 ; P < 0.05) but the difference between PDG and EHG was negligible ( P > 0.05). The results of our study indicate that peripheral circulation and vascular function are not reduced in physically active patients with PD, suggesting that these vascular changes could resemble the physiological adjustments of aging, without any impact from the disease. NOTE & NOTEWORTHY Our study verified an intact peripheral circulation in patients with Parkinson's disease (PD). However, using the single passive leg movement, we observed a similar reduction of the vascular integrity in physically active patients and matched elderly, compared with young, likely induced by aging but independent on the pathology. This comparable effect confirmed that the disease, at early stage, with a dynamic lifestyle does not worsen the vascular system but reveals the cardinal symptoms of PD.

Purpose: Given the increased level of fatigue frequently reported by patients with Parkinson's disease (PD), this study investigated the interaction between central and peripheral components of neuromuscular fatigue (NF) in this population compared with healthy peers., Methods: Changes in maximal voluntary activation (ΔVA, central fatigue) and potentiated twitch force (ΔQtw,pot, peripheral fatigue) pre-post exercise were determined via the interpolated twitch technique in 10 patients with PD and 10 healthy controls (CTRL) matched for age, sex, and physical activity. Pulmonary gas exchange, femoral blood flow, and quadriceps EMG were measured during a fatiguing exercise (85% of peak power output [PPO]). For a specific comparison, on another day, CTRL repeat the fatiguing test matching the time to failure (TTF) and PPO of PD., Results: At 85% of PPO (PD, 21 ± 7 W; CTRL, 37 ± 22 W), both groups have similar TTF (~5.9 min), pulmonary gas exchange, femoral blood flow, and EMG. After this exercise, the maximal voluntary contraction (MVC) force and Qtwpot decreased equally in both groups (-16%, P = 0.483; -43%, P = 0.932), whereas VA decreased in PD compared with CTRL (-3.8% vs -1.1%, P = 0.040). At the same PPO and TTF of PD (21 W; 5.4 min), CTRL showed a constant drop in MVC, and Qtwpot (-14%, P = 0.854; -39%, P = 0.540), instead VA decreased more in PD than in CTRL (-3.8% vs -0.7%, P = 0.028)., Conclusions: In PD, central NF seems exacerbated by the fatiguing task which, however, does not alter peripheral fatigue. This, besides the TTF like CTRL, suggests that physical activity may limit NF and counterbalance PD-induced degeneration through peripheral adaptations., (Copyright © 2021 by the American College of Sports Medicine.)

Muscle fatigue induced by voluntary exercise, which requires central motor drive, causes central fatigue that impairs endurance performance of a different, nonfatigued muscle. This study investigated the impact of quadriceps fatigue induced by electrically induced (no central motor drive) contractions on single-leg knee-extension (KE) performance of the subsequently exercising ipsilateral quadriceps. On two separate occasions, eight males completed constant-load (85% of maximal power-output) KE exercise to exhaustion. In a counterbalanced manner, subjects performed the KE exercise with no pre-existing quadriceps fatigue in the contralateral leg on one day (No-PreF), whereas on the other day, the same KE exercise was repeated following electrically induced quadriceps fatigue in the contralateral leg (PreF). Quadriceps fatigue was assessed by evaluating pre- to postexercise changes in potentiated twitch force (ΔQ tw,pot ; peripheral fatigue), and voluntary muscle activation (ΔVA; central fatigue). As reflected by the 57 ± 11% reduction in electrically evoked pulse force, the electrically induced fatigue protocol caused significant knee-extensors fatigue. KE endurance time to exhaustion was shorter during PreF compared with No-PreF (4.6 ± 1.2 vs 7.7 ± 2.4 min; P < 0.01). Although ΔQ tw,pot was significantly larger in No-PreF compared with PreF (-60% vs -52%, P < 0.05), ΔVA was greater in PreF (-14% vs -10%, P < 0.05). Taken together, electrically induced quadriceps fatigue in the contralateral leg limits KE endurance performance and the development of peripheral fatigue in the ipsilateral leg. These findings support the hypothesis that the crossover effect of central fatigue is mainly mediated by group III/IV muscle afferent feedback and suggest that impairments associated with central motor drive may only play a minor role in this phenomenon.

Aim: Decreased muscle strength has been frequently observed in individuals with Parkinson's disease (PD). However, this condition is still poorly examined in physically active patients. This study compared quadriceps (Q) maximal force and the contribution of central and peripheral components of force production during a maximal isometric task between physically active PD and healthy individuals. In addition, the correlation between force determinants and energy expenditure indices were investigated., Methods: Maximal voluntary contraction (MVC), resting twitch (RT) force, pennation angle (θp), physiological cross-sectional area (PCSA) and Q volume were assessed in 10 physically active PD and 10 healthy control (CTRL) individuals matched for age, sex and daily energy expenditure (DEE) profile., Results: No significant differences were observed between PD and CTRL in MVC (142 ± 85; 142 ± 47 N m), Q volume (1469 ± 379; 1466 ± 522 cm 3 ), PCSA (206 ± 54; 205 ± 71 cm 2 ), θp (14 ± 7; 13 ± 3 rad) and voluntary muscle-specific torque (MVC/PCSA [67 ± 35; 66 ± 19 N m cm -2 ]). Daily calories and MVC correlated (r = 0.56, P = .0099). However, PD displayed lower maximal voluntary activation (MVA) (85 ± 7; 95 ± 5%), rate of torque development (RTD) in the 0-0.05 (110 ± 70; 447 ± 461 N m s -1 ) and the 0.05-0.1 s (156 ± 135; 437 ± 371 N m s -1 ) epochs of MVCs, whereas RT normalized for PCSA was higher (35 ± 14; 20 ± 6 N m cm -2 )., Conclusion: Physically active PDs show a preserved strength of the lower limb. This resulted by increasing skeletal muscle contractility, which counterbalances neuromuscular deterioration, likely due to their moderate level of physical activity., (© 2021 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Background: Exercise is highly recommended in patients with Parkinson's disease (PD). Exercise-induced amelioration of motor, non-motor, and drug-induced symptoms are widely known. However, specific guidelines on exercise testing and prescription in PD are lacking., Objective: This study reviews the literature on exercise-based approaches to the management of symptoms at each stage of the disease and evaluate: (1) the most suitable clinical exercise testing; (2) training programs based on testing outcomes and PD stage; (3) the effects of exercise on antiparkinsonian drugs and to suggest the most effective exercise-medication combination., Methods: A systematic search was conducted using the databases MEDLINE, Google Scholar and, Cochrane Library using "Parkinson's Disease AND Physical therapy", "Training AND Parkinson", "Exercise", "Exercise AND Drug" as key words. In addition, references list from the included articles were searched and cross-checked to identify any further potentially eligible studies., Results: Of a total of 115 records retrieved, 50 (43%) were included. From these, 23 were included under the rubric "exercise testing"; 20 focused on the effectiveness of different types of exercise in PD motor-functional symptoms and neuroprotective effects, throughout disease progression, were included under the rubric "training protocol prescription"; and 7 concern the rubric "interaction between exercise and medication", although none reported consistent results., Conclusions: Despite the lack of standardized parameters for exercise testing and prescription, all studies agree that PD patients should be encouraged to regularly train according to their severity-related limitations and their personalized treatment plan. In this manuscript, specific guidelines for tailored clinical testing and prescription are provided for each stage of PD.

Blood flow (BF) to exercising muscles is susceptible to variations of intensity, and duration of skeletal muscle contractions, cardiac cycle, blood velocity, and vessel dilation. During cyclic muscle activity, these elements may change proportionally with or without direct optimal temporal alignment, likely influencing BF to active muscle. Ideally, the pulsed delivery of blood to active muscle timed with the inactive phase of muscle duty-cycle would enhance the peak and average BF. To investigate the phenomenon of muscle contraction and pulse synchronicity, electrically evoked muscle contractions (trains of 20 Hz, 200-ms duration) were synchronized with each systolic phase of the anterograde blood velocity spectrum (aBVS). Specifically, unilateral quadriceps contractions matched in-phase (IP) with the aBVS were compared with contractions matched out-of-phase (OP) with the aBVS in 10 healthy participants (26 ± 3 yr). During each trial, femoral BF of the contracting limb and central hemodynamics were recorded for 5 min with an ultrasound Doppler, a plethysmograph, and a cardioimpedance device. At steady state (5th min) IP BF (454 ± 30 mL/min) and vascular conductance (4.3 ± 0.2 mL·min -1 ·mmHg -1 ), and OP MAP (108 ± 2 mmHg) were significantly lower ( P < 0.001) in comparison to OP BF (784 ± 25 mL/min) and vascular conductance (6.7 ± 0.2 mL·min -1 ·mmHg -1 ), and IP MAP (113 ± 3 mmHg). On the contrary, no significant difference (all, P > 0.05) was observed between IP and OP central hemodynamics (HR: 79 ± 10 vs. 76 ± 11 bpm, CO: 8.0 ± 1.6 vs. 7.3 ± 1.6 L/min), and ventilatory patterns (V̇e:14 ± 2 vs. 14 ± 1 L/min, V̇o 2 :421 ± 70 vs. 397 ± 34 mL/min). The results suggest that muscle contractions occurring during OP that do not interfere with aBVS elicit a maximization of muscle functional hyperemia. NEW & NOTEWORTHY When muscle contraction is synchronized with the pulsed delivery of blood flow to active muscle, muscle functional hyperemia can be either maximized or minimized. This suggests a possibility to couple different strategies to enhance the acute and chronic effects of exercise on the cardiovascular system.

Superficial adenocarcinoma of the oesophagus is defined as carcinoma limited to the mucosa or submucosa regardless of lymph node status. Columnar epithelium lined lower oesophagus, now generally referred to as Barrett's oesophagus, is probably the main cause of adenocarcinoma in the lower oesophagus. Twelve cases of superficial adenocarcinoma arising in Barrett's oesophagus are presented. They were observed over a 6 year period and taken from a series of 50 cases of patients with Barrett's oesophagus and adenocarcinoma, a prevalence of 24%. Endoscopic diagnosis of malignancy was made in six patients. The initial biopsies showed an adenocarcinoma in six patients and some degrees of dysplasia in the other six patients. Prior to surgery, a histological diagnosis of adenocarcinoma was made in all twelve patients. In four patients the adenocarcinoma was confined to the mucosa, and in eight it extended to the submucosa. One patient had a metastatic lymph node. Ten patients are alive without evidence of tumour spread after a mean follow-up of 30 months.

Case presentation : Multiple tumor nodules in both lungs, identified by biopsy and necropsy, in a 48 year old woman, 8 years after radiological discovery ; death due to respiratory failure after long tolerance ; peculiar angio-leiomyomatous type pulmonary tumors. This purely pulmonary tumor disease is difficult to understand ; the most probable hypothesis envisaged is that of hamartomatosis ; comparison with certain general dysplastic disease is possible, and in particular Bourneville's disease and lymphangio-myomatosis.

Two cancer-prone families are reported. In the first one four first-degree relatives over three generations presented a colonic carcinoma, three of them at a proximal anatomic site. For grandmother and father these occurred at ages of 43 and 54 years, respectively, for the son and the daughter at ages of 26 and 22. The grandmother underwent a palliative ileotransversostomy, surgery typically associated with a bad prognosis, but she survived for forty years that initial neoplasm and had an hysterectomy with oophorectomy at age of 63 for endometrial malignancy; she deceased at age of 83 a few days after surgical treatment of tumoral small bowel obstruction: pathological evaluation disclosed a fourth cancer on first duodenum. The second kindred shows over three generations 11 cancer-affected individuals, three of them with double primary cancer: breast and sigmoid, breast and endometrium, colon and Hodgkin disease. This pedigree includes 8 colorectal neoplasms occurring at 47 years of mean age. These findings are consistent with the cancer-family syndrome and hereditary non-polyposis colon cancer described by Henry Lynch upon four criteria: high frequency of adenocarcinoma, excess of multiple primary malignancies, synchronous or metachronous, early age of onset of cancer and autosomal dominant inheritance. Moreover the hereditary colon cancer is usually localised to the proximal colon, not associated to polyposis coli and allows a prolonged survival. Up to day such families are only identified by pedigree data. The identification of a cancer-prone family calls for an active follow-up of relatives putatively at risk starting at the age of 15 to 20.