Exploring management and outcomes of elderly patients with glioblastoma using data from two randomised trials (GEINO1401/EX-TEM).

PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. RESULTS: Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0-1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. CONCLUSION: In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.

A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma.

PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.

Sonda uretral flexível como método alternativo para aferição invasiva da pressão intracraniana em trauma cranioencefálico induzido em coelhos / Flexible urethral catheter as alternative method to invasive measurement of intracranial pressure in induced head trauma in rabbits

O objetivo deste estudo foi utilizar a sonda uretral flexível como método alternativo para aferição da pressão intracraniana em coelhos com trauma cranioencefálico induzido pelo cateter de Fogarty 4 Fr (balão epidural) e comparar os dados obtidos com o método convencional de cateter de ventriculostomia. Foram utilizados 12 coelhos, machos, adultos, distribuídos aleatoriamente em dois grupos, denominados de G1: mensuração da PIC com cateter de ventriculostomia (n=6) e G2: mensuração com sonda uretral (n=6). Foram realizadas duas craniotomias na região parietal direita e esquerda para a implantação do cateter de ventriculostomia ou sonda uretral flexível e o balão epidural, respectivamente. A PAM, a PPC, a FC, a FR e a TR foram mensurados antes e após a craniotomia. A PIC foi avaliada após a craniotomia e a cada 10 minutos depois do preenchimento do balonete com 0,3mL de NaCl 0,9%, durante 40 minutos, e com 0,6mL, pelo mesmo período de tempo, totalizando 80 minutos. A PIC aumentou em ambos os grupos, sendo menores os valores registrados com a sonda uretral flexível. Foi possível reproduzir o aumento da PIC com o modelo experimental de TCE utilizando o cateter de Fogarty 4 Fr na região epidural e, embora haja a necessidade de outros estudos, a sonda uretral flexível demonstra ser um método alternativo de mensuração da PIC em coelhos com trauma cranioencefálico.(AU)

The aim of this study was to evaluate the use of flexible urethral catheter as an alternative method for measuring intracranial pressure in rabbits with head trauma induced by 4 F Fogarty catheter (epidural balloon) and compare the data obtained with the conventional method of ventriculostomy catheter. In this study, New Zealand rabbits were randomly distributed into two groups, G1: measuring the ICP with ventriculostomy catheter (n=6) and G2: measuring the ICP with urethral catheter (n=6). Two craniotomies were performed in the right and left parietal region for the implantation of a ventriculostomy catheter and/or flexible urethral catheter and epidural 4 Fr Fogarty arterial embolectomy catheter, respectively. MAP, CPP, HR, RF and RT values were measured before and after of the craniotomy. The ICP value was measured after craniotomy, every five minutes during 40 minutes after the balloon was inflated with 0.3 ml with NaCl and further 40 minutes after the balloon was inflated with 0.6 ml. The ICP value increased in both groups; however, the ICP values were lower in the flexible urethral catheter. The flexible urethral catheter can be used as an alternative method to measure ICP values in rabbits with head injury.(AU)

Gemcitabine plus sirolimus for relapsed and progressing osteosarcoma patients after standard chemotherapy: a multicenter, single-arm phase II trial of Spanish Group for Research on Sarcoma (GEIS).

BACKGROUND: Patients with relapsed unresectable osteosarcoma represents an unmet need, so active and safe systemic treatments are required. Fas cell surface death receptor and mammalian target of rapamycin pathways are implicated in progressing osteosarcoma, and we had preclinical and clinical experience with a scheme that targets both pathways. Therefore, we designed a phase II trial with gemcitabine plus rapamycin, to determine the efficacy and safety, in this subset of patients. PATIENTS AND METHODS: A multicenter, single-arm phase II trial was sponsored by the Spanish Group for Research on Sarcoma. Osteosarcoma patients, relapsed or progressing after standard chemotherapy and unsuitable for metastasectomy received gemcitabine and rapamycin p.o. 5 mg/day except for the same day of gemcitabine administration, and the day before. The main end point was 4-month progression-free survival rate (PFSR), with the assumption that rates higher than 40% would be considered as an active regimen. Translational research aimed to correlate biomarkers with the clinical outcome. RESULTS: Thirty-five patients were enrolled and received at least one cycle. PFSR at 4 months was 44%, and after central radiologic assessment, 2 partial responses and 14 stabilizations (48.5%) were reported from 33 assessable patients. The most frequent grade 3-4 adverse events were: neutropenia (37%), thrombocytopenia (20%), anemia (23%), and fatigue (15%); however, only three patients had febrile neutropenia. Positive protein expression of RRM1 significantly correlated with worse PFS and overall survival, while positivity of P-ERK1/2 was correlated with significant better overall survival. CONCLUSION: Gemcitabine plus sirolimus exhibits satisfactory antitumor activity and safety in this osteosarcoma population, exceeding the prespecified 40% of 4-month PFSR. The significant correlation of biomarkers with clinical outcome encourages further prospective investigation.

GEIS-21: a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for the treatment of Ewing sarcoma of children and adults: a report from the Spanish sarcoma group (GEIS).

BACKGROUND: First Spanish trial of Ewing sarcoma (ES) including adults and children with the aim to test the efficacy of Gemcitabine and Docetaxel (G/D) in newly diagnosed high-risk (HR) patients. METHODS: This was a prospective, multicentric, non-randomised, open study for patients ⩽40 years with newly diagnosed ES. HR patients (metastatic, axial-pelvic primaries or bone marrow micrometastasis) received 2 window cycles of G/D. Patients with an objective response (OR) to G/D received 12 monthly cycles of G/D after completion of mP6. The primary end point was the OR rate to the G/D window phase and the event-free survival (EFS) and overall survival (OS) for all patients. The study is registered at ClinicalTrials.gov (identifier: NCT00006734). RESULTS: Forty-three patients were enroled, median age 17 years (range, 3-40). After a median follow-up of 43.4 months, the 5-year OS rate is 55.0% (95% CI, 41-74%) with an EFS of 50.0% (95% CI, 36-68%). The 5-year OS and EFS rates for standard risk (SR) patients was 76.0% (95% CI, 57-100%) and 71.0% (CI, 54-94%); for HR 36.0% (CI, 20-65%) and 29.0% (CI, 15-56%). Twelve of 17 (70.6%) high-risk (HR) patients showed an OR (7 PR and 5 SD) to G/D window therapy. The 5-year OS rate for patients ⩽18 years of age was 74.0% (CI, 56-97%) and 31.0% for >18 years (95% CI, 15-66%), P<0.001. Grade 4 adverse events during mP6 occurred in 28/39 of patients (72%) and did not correlate with age. Multivariate survival analyses with <18 vs ⩾18 and risk groups significant differences, P<0.00001. Using a Cox model for OS, both age and risk group were statistically significant (P=0.0011 and P=0.0065, respectively). CONCLUSIONS: Age at diagnosis is an independent prognostic factor superior to the presence of metastases with 18 years as the strongest cut-off. The mP6 regimen provided survival curves that plateau at 3 years and G/D produced significant responses in HR-ES that is worth further exploring.

Assessment of urinary dipstick in patients admitted to an ED for blunt abdominal trauma.

INTRODUCTION: Clinicians still face significant challenge in predicting intra-abdominal injuries in patients admitted to an emergency department for blunt abdominal trauma. This study was thus designed to investigate the value of dipstick urinalysis in patients with blunt abdominal trauma. METHODS: We performed a retrospective, multicenter, cohort study involving patients admitted to the emergency department for abdominal traumas, examined by means of urinary dipstick and abdominal CT scan. The primary endpoint was the correlation between microscopic hematuria detected via dipstick urinalysis (defined by the presence of blood on the dipstick urinalysis but without gross hematuria) and abdominal injury, as evidenced on CT scan. RESULTS: Of the 100 included patients, 56 experienced microscopic hematuria, 17 gross hematuria, and 44 no hematuria. Patients with abdominal injury were more likely to present with hypovolemic shock (odds ratio [OR]: 8.4; 95% confidence interval [CI]: 2.7-26), abdominal wall hematoma (OR: 3.1; 95% CI: 1.2-7.9), abdominal defense (OR: 5.2; 95% CI: 1.8-14.5), or anemia (OR: 3.6; 95% CI: 1.2-10.3). Moreover, dipstick urinalysis was less likely to predict injury, with just 72.2% sensitivity (95% CI: 54.8-85.8), 53.1% specificity (95% CI: 40.2-65.7), and positive and negative predictive values of 46.4% (95% CI: 33.0-60.3) and 77.3% (95% CI: 62.2-88.5), respectively. CONCLUSION: Dipstick urinalysis was neither adequately specific nor sensitive for predicting abdominal injury and should thus not be used as a key assessment component in patients suffering from blunt abdominal trauma, with physical exam and vital sign assessment the preferred choice.

GEINOFOTE: efficacy and safety of fotemustine in patients with high-grade recurrent gliomas and poor performance status.

PURPOSE: The treatment of recurrent high-grade gliomas (HGG) is controversial. There are different therapeutic schedules but without a clear orientation about which of them should be used in each clinical situation. In addition, when patients suffer a second recurrence or they have poor performance status, they are excluded from clinical trials, although second recurrences and poor performance status are indeed more and more real and common situations in the clinical setting. In this study, we assessed the efficacy and safety of fotemustine (FTM) in HGG [fundamentally, glioblastomas (GB)], independent of time of recurrence or performance status. METHODS/PATIENTS: Retrospective study in HGG patients treated with FTM in second or further line according to standard, the Addeo or any other scheme, starting treatment prior to 30 November 2012. Included patients reflect the regular situation in which the drug is used in terms of comorbidities and analytic situation (hematologic, renal and hepatic functions). Response assessment was performed by MRI and according to the clinical protocols of each center (every 8-12 weeks). Clinical situation and supportive care drugs were evaluated in each medical consultation. Clinical end-points analyzed, among others, were: PFS-6, PFS, OS, response rates, toxicity, quality of life and neurocognitive impact. RESULTS: In terms of activity, an overall response rate of 8 % was observed: partial response 6 % (7 patients) and complete response 2 % (2 patients). The median time to achieve the greater response with FTM was 73 days (4-841 days). Patients treated according to the Addeo schedule had a shorter time to greater response in comparison with other schedules (85.9 vs 114 days), although without statistical significance. There were no significant differences in progression-free survival (PFS) when comparing different FTM schedules or using FTM in first or second recurrence. Median PFS: 3 months. PFS-6: 30.3 %. Overall survival (OS): although without significant differences, a tendency to better survival when using the Addeo schedule versus other schedules was observed (at 6 months, 44.6 vs 34.5 %; at 12 months, 25 vs 23.6 %; at 18 months, 11.5 vs 7.9 %), as well as if earlier use (second vs third line) concerning OS-12 (33.7 vs 18.2 %). Median OS: 5.2 months. Grades 3-4 toxicity was 28 % (31 patients), being neutropenia (4 %) and thrombocytopenia (17 %) the most frequent adverse reactions. From quality of life and neuro-cognitive function perspectives, 11 patients (10 %) and 16 (14 %) improved the Karnofsky Index and neurological impairment, respectively, after FTM treatment. CONCLUSION: This study has shown that FTM is safe and has a comparable activity with other available therapeutic options of use in the treatment of recurrent HGG.

Should we continue temozolomide beyond six cycles in the adjuvant treatment of glioblastoma without an evidence of clinical benefit? A cost analysis based on prescribing patterns in Spain.

PURPOSE: The standard adjuvant treatment for glioblastoma is temozolomide concomitant with radiotherapy, followed by a further six cycles of temozolomide. However, due to the lack of empirical evidence and international consensus regarding the optimal duration of temozolomide treatment, it is often extended to 12 or more cycles, even in the absence of residual disease. No clinical trial has shown clear evidence of clinical benefit of this extended treatment. We have explored the economic impact of this practice in Spain. MATERIALS AND METHODS: Spanish neuro-oncologists completed a questionnaire on the clinical management of glioblastomas in their centers. Based on their responses and on available clinical and demographic data, we estimated the number of patients who receive more than six cycles of temozolomide and calculated the cost of this extended treatment. RESULTS: Temozolomide treatment is continued for more than six cycles by 80.5 % of neuro-oncologists: 44.4 % only if there is residual disease; 27.8 % for 12 cycles even in the absence of residual disease; and 8.3 % until progression. Thus, 292 patients annually will continue treatment beyond six cycles in spite of a lack of clear evidence of clinical benefit. Temozolomide is covered by the National Health Insurance System, and the additional economic burden to society of this extended treatment is nearly 1.5 million euros a year. CONCLUSIONS: The optimal duration of adjuvant temozolomide treatment merits investigation in a clinical trial due to the economic consequences of prolonged treatment without evidence of greater patient benefit.

Effects of intra-session exercise sequence during water-based concurrent training.

The aim was to investigate the effects of the intra-session exercise order during water-based concurrent training on the neuromuscular adaptations in young women. 26 women (25.1±2.9 years) were placed into 2 groups: resistance prior to (RA) or after (AR) aerobic training. Subjects performed resistance (sets at maximal effort) and aerobic training (exercises at heart rate corresponding to the second ventilatory threshold) twice a week over 12 weeks, performing both exercise types in the same training session. Upper (elbow flexion) and lower-body (knee extension) one-repetition maximum test (1RM) and peak torque (PT) were evaluated. The muscle thickness (MT) of upper (sum of MT of biceps brachii and brachialis) and lower-body (sum of MT of vastus lateralis, vastus medialis, vastus intermedius, and rectus femoris) was determined by ultrasonography. Moreover, the maximal electromyographic activity (EMG) of upper (biceps brachii) and lower-body (sum of EMG of vastus lateralis and rectus femoris) was measured. Both RA and AR groups increased the upper and lower-body 1RM and PT, while the lower-body 1RM increases observed in the RA was greater than AR (43.58±14.00 vs. 27.01±18.05%). RA and AR showed MT increases in all muscles evaluated, while the lower-body MT increases observed in the RA were also greater than AR (10.24±3.11 vs. 5.76±1.88%). There were increases in the maximal EMG of upper and lower-body in both RA and AR, with no differences between groups. Performing resistance prior to aerobic exercise during water-based concurrent training seems to optimize the lower-body strength and hypertrophy.

Time course of neuromuscular adaptations to knee extensor eccentric training.

This study investigated the chronology of neural and morphological adaptations to knee extensor eccentric training and their contribution to strength gains in isometric, concentric and eccentric muscle actions. 20 male healthy subjects performed a 12-week eccentric training program on an isokinetic dynamometer, and neuromuscular evaluations of knee extensors were performed every 4 weeks. After 12 training weeks, significant increases were observed for: isometric (24%), concentric (15%) and eccentric (29%) torques; isometric (29%) and eccentric (33%) electromyographic activity; muscle thickness (10%) and anatomical cross-sectional area (19%). Eccentric and isometric torques increased progressively until the end of the program. Concentric torque and muscle mass parameters increased until the eighth training week, but did not change from this point to the twelfth training week. Eccentric and isometric activation increased at 4 and 8 training weeks, respectively, while no change was found in concentric activation. These results suggest that: 1) the relative increment in concentric strength was minor and does not relate to neural effects; 2) eccentric and isometric strength gains up to 8 training weeks are explained by the increased neural activation and muscle mass, whereas the increments in the last 4 training weeks seem to be associated with other mechanisms.

Altered cell metabolism in tissues of the knee joint in a rabbit model of Botulinum toxin A-induced quadriceps muscle weakness.

Quadriceps muscle weakness is frequently associated with knee injuries in sports. The influence of quadriceps weakness on knee joint homeostasis remains undefined. We hypothesized that quadriceps weakness will lead to tissue-specific alterations in the cell metabolism of tissues of the knee. Quadriceps weakness was induced with repetitive injections of Botulinum toxin A in six 1-year-old New Zealand White rabbits for 6 months. Five additional animals served as controls with injections of saline/dextrose. Muscle weakness was assessed by muscle wet mass, isometric knee extensor torque, and histological morphology analysis. Cell metabolism was assessed for patellar tendon, medial and lateral collateral ligament, and medial and lateral meniscus by measuring the total RNA levels and specific mRNA levels for collagen I, collagen III, MMP-1, MMP-3, MMP-13, TGF-ß, biglycan, IL-1, and bFGF by reverse transcription and polymerase chain reaction. While the total RNA levels did not change, tissue-specific mRNA levels were lower for relevant anabolic and catabolic molecules, indicating potential changes in tissue mechanical set points. Quadriceps weakness may lead to adaptations in knee joint tissue cell metabolism by altering a subset of anabolic and catabolic mRNA levels corresponding to a new functional and metabolic set point for the knee that may contribute to the high injury rate of athletes with muscle weakness.

Effects of altering pedal frequency on the slow component of pulmonary VO2 kinetics and EMG activity.

This study investigated the effects of pedal frequency on the slow component of pulmonary oxygen uptake ( V O(2)) kinetics during heavy exercise at the same relative intensity. We hypothesized that higher pedal frequency (expected to enhance fast-twitch muscle fiber recruitment) would be associated with greater slow component amplitude (A' (s)), surface electromyography (normalized root mean square; RMS) and blood lactate concentration ([lactate]). Eight subjects performed square-wave transitions to heavy exercise at 35 and 115 rpm. Furthermore, alternated cadences square-wave transitions (35-115 rpm) were performed to examine the potential effects of additional fast-twitch muscle fiber recruitment on the slow component. Significance was accepted when P<0.05. The A' (s) was greater at higher cadences (0.58+/-0.08 and 0.70+/-0.09 L.min (-1) at 115 and 35-115 rpm, respectively) than at 35 rpm (0.35+/-0.04 L.min (-1)). Greater EMG increase over time (DeltaRMS ((10-3 min))) and [lactate] were observed at 115 and 35-115 rpm compared with 35 rpm. There was a significant correlation between A' (s) and overall DeltaRMS ((10-3 min)) for all pedal frequencies combined (r=0.63; P=0.001). Pedal frequency had no effect on time constants or time delays. These findings are consistent with the concept that progressive recruitment of muscle fibers is associated with the V O(2) slow component.

Low-frequency fatigue at maximal and submaximal muscle contractions

Skeletal muscle force production following repetitive contractions is preferentially reduced when muscle is evaluated with low-frequency stimulation. This selective impairment in force generation is called low-frequency fatigue (LFF) and could be dependent on the contraction type. The purpose of this study was to compare LFF after concentric and eccentric maximal and submaximal contractions of knee extensor muscles. Ten healthy male subjects (age: 23.6 ± 4.2 years; weight: 73.8 ± 7.7 kg; height: 1.79 ± 0.05 m) executed maximal voluntary contractions that were measured before a fatigue test (pre-exercise), immediately after (after-exercise) and after 1 h of recovery (after-recovery). The fatigue test consisted of 60 maximal (100 percent) or submaximal (40 percent) dynamic concentric or eccentric knee extensions at an angular velocity of 60°/s. The isometric torque produced by low- (20 Hz) and high- (100 Hz) frequency stimulation was also measured at these times and the 20:100 Hz ratio was calculated to assess LFF. One-way ANOVA for repeated measures followed by the Newman-Keuls post hoc test was used to determine significant (P < 0.05) differences. LFF was evident after-recovery in all trials except following submaximal eccentric contractions. LFF was not evident after-exercise, regardless of exercise intensity or contraction type. Our results suggest that low-frequency fatigue was evident after submaximal concentric but not submaximal eccentric contractions and was more pronounced after 1-h of recovery.

Low-frequency fatigue at maximal and submaximal muscle contractions.

Skeletal muscle force production following repetitive contractions is preferentially reduced when muscle is evaluated with low-frequency stimulation. This selective impairment in force generation is called low-frequency fatigue (LFF) and could be dependent on the contraction type. The purpose of this study was to compare LFF after concentric and eccentric maximal and submaximal contractions of knee extensor muscles. Ten healthy male subjects (age: 23.6 +/- 4.2 years; weight: 73.8 +/- 7.7 kg; height: 1.79 +/- 0.05 m) executed maximal voluntary contractions that were measured before a fatigue test (pre-exercise), immediately after (after-exercise) and after 1 h of recovery (after-recovery). The fatigue test consisted of 60 maximal (100%) or submaximal (40%) dynamic concentric or eccentric knee extensions at an angular velocity of 60 degrees /s. The isometric torque produced by low- (20 Hz) and high- (100 Hz) frequency stimulation was also measured at these times and the 20:100 Hz ratio was calculated to assess LFF. One-way ANOVA for repeated measures followed by the Newman-Keuls post hoc test was used to determine significant (P < 0.05) differences. LFF was evident after-recovery in all trials except following submaximal eccentric contractions. LFF was not evident after-exercise, regardless of exercise intensity or contraction type. Our results suggest that low-frequency fatigue was evident after submaximal concentric but not submaximal eccentric contractions and was more pronounced after 1-h of recovery.

Temporomandibular joint dysfunction and trapezius muscle fatigability

INTRODUCTION: It has been suggested that pain increases trapezius muscle activation in patients with temporomandibular joint dysfunction (TMD). Changes in muscle activation might change muscle resistance to fatigue. The purpose of this study was to evaluate the fatigability of the trapezius muscle in patients with TMD. METHOD: Fourteen patients with TMD (clinically diagnosed and referred by a dentist) and eleven healthy subjects performed a fatigue test consisting of shoulder elevation performed at 70 percent of the maximal voluntary isometric contraction, which was maintained for 30 seconds. Electromyographic signals were obtained from the upper portion of the trapezius muscle (sampling frequency: 2000 Hz/channel). Consecutive segments of three seconds in duration each were extracted from the electromyographic signal and analyzed in the frequency domain using a Fast Fourier Transform algorithm. Linear regression analysis was applied to the consecutive median frequencies for each subject. The slope of the regression line was used to describe muscle fatigability. RESULTS: No changes were observed in fatigability between the right and left trapezius of either group or between the left trapezius of the healthy and TMD groups. The linear regression for median frequencies in the right trapezius of the TMD group showed a slope of -0.15 ± 0.33 (mean ± SD), which was smaller than the slope for the healthy group (-0.44 ± 0.46; p= 0.049). These results suggested that the fatigability of the right trapezius was lower in the TMD group than in the healthy group.

INTRODUÇÃO: Tem sido sugerido que a dor aumenta a ativação do músculo trapézio em pacientes com disfunção temporomandibular (TMD). Mudanças na ativação do músculo podem alterar a resistência à fadiga. O objetivo do estudo foi investigar a fatigabilidade do músculo trapézio em pacientes com TMJ. MÉTODOS: Quatorze indivíduos com TMD (diagnosticados clinicamente e encaminhados pelo especialista odontólogo) e onze indivíduos saudáveis realizaram um protocolo de fadiga que consistiu em uma contração isométrica submáxima de elevação do ombro, em um nível de 70 por cento da contração voluntária máxima, mantida por um período de 30 segundos. O sinal eletromiográfico (EMG) foi obtido da porção superior do músculo trapézio, (taxa de amostragem de 2000Hz/canal). Três segundos consecutivos do sinal EMG foram analisados no domínio da freqüência usando a Transformada Rápida de Fourier (FFT). Uma análise de regressão linear foi aplicada para valores consecutivos da freqüência mediana (MF) de cada sujeito, e a inclinação da regressão linear foi utilizada para descrever a fatigabilidade muscular. RESULTADOS: Nenhuma diferença foi observada na fatigabilidade do músculo trapézio direito e esquerdo para ambos os grupos e entre o trapézio esquerdo do grupo saudável e com TMD. A MF do músculo trapézio direito do grupo com disfunção apresentou valores de inclinação da reta de regressão linear de -0,15 ± 0,33 (média ± SD), os quais foram menores que os valores do grupo saudável (-0,44 ± 0,46; média ± SD; p= 0,049). Esses resultados sugerem que a fatigabilidade do trapézio direito é menor no grupo com TMD do que no grupo saudável.

Long-term outcome of a phase II study of weekly docetaxel with a short course of estramustine and enoxaparine in hormone-resistant prostate cancer patients.

OBJECTIVE: The objective was to define the toxicity and activity of weekly docetaxel administered with a short course of estramustine and enoxaparine in patients with hormone-resistant prostate cancer (HRPC). PATIENTS AND METHODS: Twenty-four patients were treated with the next regimen: weekly docetaxel 36 mg/m(2) iv for three consecutive weeks every 28 days, and estramustine 280 mg three times a day for three consecutive days beginning the day before docetaxel (days 1-3, 8-10 and 15-17). In order to prevent thromboembolic events, 40 mg of subcutaneous enoxaparine was administered daily sc on the same days as estramustine. Primary endpoints were: toxicity, especially the presence of thromboembolic events, PSA response rate and response in measurable disease. Secondary endpoints were: time to PSA progression and overall survival. RESULTS: Nineteen of 24 patients (79.1%, 95% CI 71-87%) had a PSA response = or >50%. Four of the eleven patients with measurable disease had a partial response. The median time to PSA progression was 7 months (CI 95%: 6.5-9) and the median survival was 19 months (IC 95%: 11-24). Toxicity was manageable with no treatment- related mortality. Only two patients had grade 4 neutropenia. Two patients had thrombotic events, one deep venous thrombosis and one stroke. The main grade 3 non-haematologic toxicity was diarrhoea and asthenia, both in 25% of patients. CONCLUSIONS: Weekly docetaxel with a short course of estramustine and enoxaparine is active and tolerable in HRPC patients. The observed incidence of thrombosis was lower than previously reported but the association of enoxaparine was not enough to completely prevent the thromboembolic events.

Sindrome do tunel do carpo / carpal tunnel syndrome

A sindrome do tunel do carpo (STC) e a neuropatia de maior incidencia no membro superior e consiste na compressao do nervo mediano no interior do tunel do carpo.Atualmente, essa alteracao neuromuscular tem atingido um numero de pessoas cada vez maior, principalmente trabalhadores que desempenham atividades de intensa movimentacao do punho. Uma serie de estudos tem procurado investigar a fisiopatologia, o diagnostico e o tratamento para a STC. No entanto, os mecanismos neuromusculares envolvidos em seu desenvolvimento ainda n'ao sao totalmente compreendidos, o que dificulta um diagnostico mais sensivel e capaz de detectar inclusive a presenca de dupla compressao (coluna cervical e tunel carpo), assim como o tratamento adequado...

The torque-velocity relation of elite soccer players.

AIM: The purpose of this study was to describe the torque-velocity (T-V) relationship during concentric and eccentric contractions of the lower limb muscles in professional soccer players. METHODS: Soccer players (n=10) that were training systematically for at least 5 years were compared with moderately active individuals (n=13), that were not engaged in any systematic physical activity program in the last 5 years. Peak torque, and angle-specific torque at knee angles of 0.52 rad and 1.04 rad were evaluated during maximal concentric and eccentric contractions at 0.52 rad x sec(-1), 1.04 rad x sec(-1), 1.57 rad x sec(-1), 2.09 rad x sec(-1), 3.14 rad x sec(-1), 4.19 rad x sec(-1) and 5.23 rad x sec(-1) angular velocities. RESULTS: During concentric contractions, inverse hyperbolic relationships were fitted for the two groups [T = T(max) + (a x b)/(b + V)], with values for a and b of 1.4 and 347.6 for the control group, respectively, and 1.9 and 605.4 for the soccer players, respectively. When torque was measured at 0.52 rad, the torque-velocity relationship presented a plateau at low velocities in the two groups investigated. When torque was measured at 1.04 rad, the torque-velocity relationship presented a plateau at low velocities in the control group, in which force did not increase significantly as velocity was decreased. The plateau was not observed in soccer players. Peak torque and torque measured at 1.04 rad were higher in the soccer players than in the control group in all velocities investigated. However, the biggest difference was found in lower velocities of contraction. CONCLUSION: Soccer players produced a higher muscle torque in the lower limb than moderately active individuals, and this difference was bigger when the velocities were low.

Low concentration silver nitrate pleurodesis in rabbits: optimal concentration for rapid and complete sclerosing effect.

Pleurodesis is a useful therapeutic tool when local treatment of a recurrent malignant pleural effusion or pneumothorax is needed. We have previously demonstrated that the intrapleural injection of 0.5% silver nitrate (SN) produces a significant pleurodesis, while 0.25% SN has no sclerosing effect in a rabbit model. The objective of this study was to determine the minimum concentration of SN needed to induce pleurodesis in our experimental model. One hundred twenty male New Zealand white rabbits received 0.3, 0.4, or 0.5% SN (40 animals per group) in a total volume of 2 mL instilled intrapleurally. These animals were sacrificed 3, 7, 14 or 28 days after the intrapleural injection (n = 10 animals per group), and the pleural spaces were then assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. By 28 days, all concentrations of SN had produced a pleurodesis. There was evidence of a gross pleurodesis 7 days post-injection in animals that received 0.5% SN (score of 2.8 +/- 0.2 on a scale of 0-4). After 14 days, significant pleural adhesions were evident in the groups that received 0.4 or 0.5% SN. We conclude that SN concentrations as low as 0.3% can effectively produce a pleurodesis within 28 days of intrapleural injection. However, the precocious pleurodesis development observed 7 days after the intrapleural injection of 0.5% SN suggests that this concentration may be optimal when a fast result is necessary.