Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up.

BACKGROUND: Novel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045. PATIENTS AND METHODS: Adult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab [200 mg every 3 weeks (Q3W)] or investigator's choice of paclitaxel (175 mg/m2 Q3W), docetaxel (75 mg/m2 Q3W), or vinflunine (320 mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR. RESULTS: A total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n = 272). Median follow-up as of 26 October 2017 was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4 months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy. CONCLUSIONS: Long-term results (>2 years' follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02256436.

Desempenho produtivo de frangos de corte e utilização de energia e nutrientes de dietas iniciais com milho classificado ou não e suplementadas com complexo enzimático / Broiler performance and energy and nutrient utilization of starter diets with classified corn or not and supplemented with enzymatic complexes

Dois experimentos foram conduzidos com o objetivo de avaliar o efeito da adição de um complexo enzimático em dietas iniciais elaboradas com milho classificado ou não por mesa densimétrica sobre o desempenho produtivo e a digestibilidade de nutrientes. Foram utilizados 1080 frangos de corte, machos, distribuídos em um delineamento inteiramente ao acaso, em esquema fatorial 2 x 3 (milho classificado ou não vs. dieta controle, dieta controle acrescida de complexo enzimático e dieta controle acrescida de enzimas e com redução de 150kcal de EM), totalizando seis repetições e 36 unidades experimentais. No ensaio de metabolismo, foram utilizadas 96 aves de 21 dias de idade, alojadas em baterias metálicas e distribuídas aos seis tratamentos, com oito repetições e 48 unidades experimentais. Dietas suplementadas com enzima, independentemente da classificação do milho, resultaram em maior (P<0,05) ganho de peso das aves aos 21 dias de idade. A adição de enzimas em dietas com milho classificado melhorou (P<0,05) a conversão alimentar. O CDPB foi maior (P<0,05) para dietas elaboradas com milho classificado, independentemente da suplementação do complexo enzimático, enquanto o CDEE de dietas à base de milho não classificado aumentou (P<0,05) quando as enzimas foram incluídas na deita. Dietas elaboradas à base de milho classificado e acrescidas de complexo enzimático comercial melhoraram (P<0,05) a EMA e a EMAn. As enzimas exógenas podem ser empregadas como ferramenta para melhorar a digestibilidade de nutrientes e de energia dos grãos de milho com variação nutricional.(AU)

Two experiments were performed with the aim of evaluating the effect of inclusion of enzymatic complexes in starter diets containing classified corn or not on the productive performance of poultry and nutrient digestibility. In the performance test 1080 broilers were used, distribuited in a completely randomized design in a factorial 2 x 3 (classified corn or not and corn control diet, control diet plus enzyme complex, and control diet plus enzymes and reduction of 150kcal of ME) and consisting of six replicates and 36 experimental units. In the metabolism trial 96 21-day-old birds were used, housed in metal cages, distributed to six treatments with eight replicates of 48 experimental units. Diets supplemented with enzyme, regardless of the corn classification, resulted in higher (P<0.05) weight gain of birds at 21 days of age. The addition of enzymes in diets with classified corn improved (P<0.05) feed conversion ratio. The CDPB was higher (P<0.05) for diets formulated with classified corn, regardless of the supplementation of the enzyme complex, while the CDEE of not classified corn-based diets increased (P<0.05) when the enzymes were included. Diets formulated with classified corn plus commercial enzymatic complex, improved (P 0.05) the AME and AMEn. Exogenous enzymes may be employed as a tool to improve the digestibility of nutrients and energy of corn with nutritional variation.(AU)

Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996-2003).

BACKGROUND: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. METHODS: In 1996 an IBD register of disease onset was established on a national scale. RESULTS: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohn's disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996-2003 an increase of IBD incidence from 0.89 to 1.39/10(5) inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. CONCLUSIONS: The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD.

Maternal cardiovascular function in pregnancies complicated by intrauterine growth restriction.

OBJECTIVE: To investigate maternal cardiovascular function in pregnancies complicated by intrauterine growth restriction (IUGR). METHODS: Maternal echocardiography and ambulatory blood pressure monitoring were performed in pregnancies complicated by IUGR (n = 12) and controls (n = 12), all of whom were normotensive at enrollment. RESULTS: Compared to controls, maternal blood pressure (P = 0.016) and total vascular resistance (P = 0.008) were higher in IUGR pregnancies. Heart rate was lower (P = 0.003), as was systolic function expressed by midwall fractional shortening (P = 0.04). No significant differences between the two groups were observed for left atrial or left ventricular dimensions, nor for left ventricular geometry. Assessment of diastolic function by means of transmitral Doppler flow measurements revealed a significantly longer isovolumetric relaxation time in pregnancies with IUGR (P = 0.006). CONCLUSIONS: In normotensive pregnancies complicated by IUGR, as compared to controls, there is decreased diastolic and systolic maternal cardiac function, and a higher blood pressure.

[Role of Doppler velocimetry of uterine arteries and ambulatory blood pressure monitoring in detecting pregnancies at risk for preeclampsia]. / Ruolo della Doppler flussimetria delle arterie uterine e del monitoraggio in continuo della pressione arteriosa nell'individuazione di soggetti a rischio per lo sviluppo di preeclampsia.

AIM: The aim of this study is to evaluate the performance of ambulatory blood pressure monitoring (ABPM) in association with Doppler velocimetry of uterine arteries in the detection of preeclampsia (PE). METHODS: In a prospective study, 22 patients at risk for the development of PE have been en-rolled: 17 were nulliparous women with increased resistances in uterine arteries at 24 weeks and 5 had an obstetric history of PE. All patients were tested with ABPM and uterine arteries Doppler velocimetry. A resistance index (RI) higher than 0.62 for the Doppler velocimetry and a diastolic midline estimating statistic of rhythm (MESOR) higher than 68 for the ABPM were considered abnormal. Patients were followed longitudinally until delivery. The occurrence of PE and low birth weight were considered as gestational outcomes endpoints. RESULTS: Overall, the mean gestational age at delivery was 36.3+/-3.4 weeks (range 29.4-41). Six out of 22 (27.2%) patients developed PE; 4 out of 22 (18%) newborns were small for gestational age (SGA) <5 degrees percentile. In the prediction of PE, ABPM in association with Doppler velocimetry showed a positive predictive value (PPV) of 42% and a negative predictive value (NPV) of 90%, for the development of low birth weight the PPV was 33% and the NPV 100%. CONCLUSION: This study shows that ABPM in association with Doppler velocimetry evaluation is a useful test to detect patients at high risk for the development of PE.

The self selected speed of running in recreational long distance runners.

The aim of this study was to test the hypothesis that the self selected speed in running (vss) is dependent upon the same factors that determine maximal speed in endurance events (e. g. the anaerobic threshold). Experiments were carried out on 8 recreational long distance runners (42.1 +/- 8.6 years of age, 70.1 +/- 10.6 kg of body mass, 1.74 +/- 0.06 m of body height) while they were participating in a 14 day relay race. During the "race" the subjects were not requested to perform maximally but only to cover their running turn (1 hour per day) at their preferred pace. The relationships between heart rate (HR), perceived exertion (RPE), blood lactate concentration ([La]b) and speed (v) were determined in each subject, before the race, during an incremental running test. From these relationships the speed corresponding to a 4 mM concentration of lactate in blood (v4mM) was calculated and found to be 14.3 +/- 1.8 km x h(-1) (n = 8). At this speed the RPE and HR values were 13.6 +/- 1.4 and 156.4 +/- 12.8 bpm, respectively. The average values of speed (vss, 13.4 +/- 0.6 km x h(-1)), RPE (13.5 +/- 1.4) and HR (154.4 +/- 7.6 bpm) measured during the race (n = 47) were not significantly different from those measured at the lactate threshold (v4mM, RPE4mM and v4mM). However, vss and the average HR during the race showed significantly lower variances than v4mM and HR4mM suggesting that, besides the need of avoiding lactate accumulation in blood, other factors must be involved in the choice of speed in running.

High prevalence of stress hyperglycaemia in children with febrile seizures and traumatic injuries.

UNLABELLED: Although hyperglycaemia is relatively frequent in the course of severe illnesses and may be looked upon as the possible result of an uncoordinated insulin response to the increased glucose that the body may need during periods of stress, it is generally agreed that it does not constitute a prediabetic condition. Numerous studies have aimed to explain the pathophysiology of this occurrence but none has looked at which conditions are more prone to develop stress hyperglycaemia (SH). Therefore, the aim of this study was to evaluate the main clinical conditions that may be associated with SH in children. A total of 1199 children was studied: 833 children (439 M, 394 F, mean age 5.2 +/- 4.5 y) admitted for an acute illness or injury constituted the stress-exposed group, while 366 children (222 M, 144 F, mean age 6.2 +/- 4.6 y) admitted for elective minor surgery represented the stress-unexposed group and were considered as the control group. SH was defined as plasma glucose concentrations > or = 8.3 mmol l(-1) during an acute illness. Stress-exposed patients had significantly higher glycaemic levels than controls (5.6 +/- 1.4 vs 4.7 +/- 0.7 mmol l(-1); p < 0.0001). SH was found in 41 (4.9%) stress-exposed patients and in none of the controls. SH was significantly more prevalent in children affected by febrile seizures (12.9%) or traumatic injuries (11.7%; p < 0.008 and p < 0.02, respectively, vs other diagnoses). A significant correlation was found between glycaemia and systolic pressure (r = 0.1; p < 0.01), white cell count (r = 0.12; p < 0.0003) and body temperature (r = 0.16; p < 0.0001). SH was more frequent in patients with body temperature > 39 degrees C (14%) than in those with a temperature < or = 39 degrees C (4%; p < 0.0008). SH was more prevalent in clinical conditions of fever associated with seizures or pain (12.9% and 12.5%, respectively) than fever alone (4.4%). After a mean period of 3.5 +/- 0.6 y of follow-up none of the hyperglycaemic patients had developed diabetes mellitus. CONCLUSION: Traumatic injuries, febrile seizures or conditions in which an elevated body temperature may be found are frequently associated with SH in children. In the presence of these conditions specific studies directed towards unmasking a prediabetic state may be unnecessary.

Heart rate variability during dynamic exercise in elderly males and females.

It has been proposed that cardiac control is altered in the elderly. Power spectral analysis of heart rate variability (HRV) was performed on 12 male and 11 female elderly subjects (mean age 74 years) while at rest in supine and sitting positions, and at steady states during 5 min of exercise (35-95% peak oxygen consumption, VO2peak). There were no differences in power, measured as a percentage of the total of the high frequency peak (HF, centred at about 0.25 Hz; 13% in males vs 12% in females), low frequency peak (LF, centred at 0.09 Hz; 25% in males and 22% in females), and very low frequency component (VLF, at 0.03 Hz; 66% in males and 69% in females) between body positions at rest. There was no difference in spectral power between male and female subjects. Total power decreased as a function of oxygen consumption during exercise, LF% did not change up to about 14 ml x kg(-1) x min(-1) (40% and 80% VO2peak in males and females, respectively), then decreased towards minimal values in both genders. HF% power and central frequency increased linearly with metabolic demand, reaching higher values in male subjects than in female subjects at VO2peak, while VLF% remained unchanged. Thus, the power spectra components of HRV did not reflect the changes in autonomic activity that occur at increasing exercise intensities, confirming previous findings in young subjects, and indicated similar responses in both genders.

Bacterial infection in cirrhotic patients and its relationship with alcohol.

OBJECTIVE: Infections are regarded as a major complication and an important cause of death in cirrhotics. Alcohol is a predisposing factor to infections in such patients. This study was undertaken to compare the frequency and evolution of bacterial infection among alcoholic and nonalcoholic cirrhotics. METHODS: To observe this relationship, we retrospectively studied a cohort of 382 cirrhotic inpatients, 201 of whom were alcoholic (alcohol intake > or =80 g/day for > or =10 yr) and 181 of whom were nonalcoholic. RESULTS: A total of 128 (33.5%) patients presented with infection upon hospitalization, 78 of whom were alcoholic and 50 of whom were nonalcoholic (p = 0.02). A total of 157 cases of infection were diagnosed, with spontaneous bacterial peritonitis as the most prevalent one (54.1%), followed by pneumonia (18.5%), infection of the soft parts (10.8%), and urinary tract infection (7.0%). Infection and deaths were more frequent in patients with Child-Pugh C than in those with Child-Pugh A/B (p = 0.003, p = 0.0002 respectively). Alcoholic patients with Child-Pugh A/B were more susceptible to infection compared to nonalcoholic patients (p = 0.02), although no difference was noted as to the number of deaths (p = 0.1). With regard to patients with Child-Pugh C, no statistical difference was found in the infections or deaths among alcoholics and nonalcoholics (p = 0.8, p = 0.8). CONCLUSIONS: Our findings suggest that, despite the fact that bacterial infections are more common in cirrhotic alcoholics, its seems that the mortality rate is associated more with the severity than with the etiology of the hepatic disease.

Metabolic and cardiorespiratory responses to maximal intermittent knee isokinetic exercise in young healthy humans.

There have been many studies on the effects of isokinetic exercise on muscle performance in training and rehabilitative programmes. On the other hand, the cardiovascular and metabolic responses elicited by this type of exercise have been poorly investigated. This study was specifically designed to describe the relationships, if any, between metabolic and cardiorespiratory responses and power output during maximal intermittent knee isokinetic exercise when a steady state is reached. A group of 18 healthy subjects (10 men and 8 women, age range 25-30 years) were requested to perform at maximal concentric isokinetic knee extensions/flexions 60 degrees. s(-1) and 180 degrees. s(-1) for 5 min, with a 5-s pause interposed between consecutive repetitions. The power output (W) was calculated; before and during the tasks heart rate (f(c)) and arterial blood pressure (AP(a)) were continuously monitored. Pulmonary ventilation (V(E)) and oxygen uptake (VO(2)) were measured at the 4th and at the 5th min of exercise and blood lactate concentration at rest and at the 3rd min of recovery. From the 4th to the 5th min only a slight decrease in W was observed, both at 60 degrees. s(-1) and 180 degrees. s(-1). The VO(2), V(E), f(c) and AP(a) showed similar values in the last 2 min of exercise, suggesting that a steady state had been reached. The VO(2) increased linearly as a function of +W, showing a significantly steeper slope at 60 degrees. s(-1) than at 180 degrees. s(-1). The f(c), in spite of a large interindividual variation, was linearly related to metabolic demand, and was not affected by angular velocity. Systolic and diastolic AP(a) were not related either to VO(2) or to angular velocity. In conclusion it would appear that the metabolic response to maximal intermittent knee isokinetic exercise resembles that of dynamic exercise. Conversely, the cardiocirculatory responses would seem to reflect a relevant role of the isometric postural component, the importance of which should be carefully evaluated in each subject.

Heart rate variability in exercising humans: effect of water immersion.

Power spectrum analysis of heart-rate variability was made in seven men [mean age 22 (SEM 1) years] in head-out water immersion (W) and in air (A, control) at rest and during steady-state cycling to maximal intensity (maximum oxygen uptake, VO2max). At rest W resulted in a trebled increase in the total power (P < 0.05), coupled with minimal changes in the power (as a percentage of the total) of the high frequency peak (HF, centred at 0.26 Hz; 18% vs 28%) and of the low frequency peak (LF, 0.1 Hz; 24% vs 32%). A third peak at about 0.03 Hz (very low frequency, VLF) represented the remaining power both in W and A. These changes as a whole indicated that immersion caused a vagal dominance in cardiac autonomic interaction, due to the central pooling of blood and/or the pressure of water on the trunk. Exercise caused a decrease in the total power in W and A. The LF% did not change up to about 50% V02max, thereafter decreasing towards nil in both conditions. The HF% decreased in similar ways in W and A to about half at 55%-60% VO2max and then increased to reach 1.5 times the resting values at VO2max. The central frequency of HF increased linearly with oxygen uptake, showing a tendency to be higher in W than in A at medium to high intensities. The VLF% remained unchanged. The lack of differences in the LF peak between W and A during exercise would suggest that blood distribution had no effect on the readjustments in control mechanisms of arterial pressure. On the other hand, the findings of similar HF powers and the very similar values for ventilation in W and A confirmed the direct effect of the respiratory activity in heart rate modulation during exercise.

c-myc antisense oligodeoxynucleotides enhance the efficacy of cisplatin in melanoma chemotherapy in vitro and in nude mice.

This study was designed to assess the efficacy of a new antimelanoma therapeutic strategy that relies on the use of a c-myc antisense 15-mer phosphorothioate oligodeoxynucleotide ([S]ODN), in combination with cisplatin (cis-diamminedichloroplatinum; DDP), which is currently used in the clinical management of melanoma patients. Proliferation and colony formation of melanoma cells were both inhibited by the DDP/c-myc antisense [S]ODN combination to a greater extent than that observed with either agent alone. Inhibition was most effective when DDP was followed by c-myc antisense [S]ODNs. Cell cycle flow cytometric analysis of cells exposed to the two agents either alone or in combination demonstrated that (a) c-myc antisense [S]ODNs induced an accumulation of cells in S phase and apoptosis in a fraction of the cells, detectable at day 5 after the beginning of treatment; (b) DDP induced a block in G2-M phase detectable at day 1, which was partially recovered, and apoptosis similar in extent to that induced by c-myc antisense [S]ODNs; and (c) DDP and c-myc antisense [S]ODNs together induced arrest in G2-M phase, which was maximum at day 3, i.e., delayed as compared to the block induced by DDP. The combination induced a higher percentage of apoptosis, evident at day 3 from the start of treatment, that correlated with a marked reduction in Bcl-2 expression. Mice bearing human melanoma xenografts and treated sequentially with DDP and c-myc antisense [S]ODNs showed a higher inhibition of tumor growth, reduction in the number of lung metastases, and increase in life span compared with those treated with either agent alone. Together, these data lend support to the development of anticancer therapies involving oncogene-targeted antisense ODNs and conventional antineoplastic drugs.

Effects of high altitude acclimatization on heart rate variability in resting humans.

The sympatho-vagal nerve interaction at the heart was studied by means of power spectrum analysis of heart rate variability in seven Caucasians (aged 27-35 years) in resting supine and sitting positions before and during 35 days of a sojourn at 5050 m above sea level (asl) and in six Sherpas (aged 22-30 years) at high altitude only. A high frequency peak (HF)-central frequency between 0.20 and 0.33 Hz, a low frequency peak (LF)-central frequency between 0.08 and 0.14 Hz, and a very low frequency component (< 0.05 Hz), no peak observed, were found in the power spectrum in both positions and independent of altitude. The peak powers, as a percentage of the total power, were affected by both body position and altitude. At sea level the change from a supine to a sitting position yielded a decrease in percentage HF from 25 (SEM 1.9)% to 6.2 (SEM 1.5)% (P < 0.05) and a significant increase in the ratio between LF and HF powers (LF:HF) from 1.7 (SEM 0.4) to 6.9 (SEM 1.6). At altitude compared to sea level in the supine position, percentage HF decreased from 25% to 10.9 (SEM 1.0)% (P < 0.05) and the LF:HF ratio increased from 1.7 to 4.8 (SEM 0.7) (P < 0.05). No changes occurred at altitude in the sitting position either in the peak powers or in the LF:HF ratio, but the central frequency of HF peak increased significantly from 0.25 (SEM 0.02) Hz to 0.32 (SEM 0.01) Hz. In the Sherpas comparable results to the Caucasians were found in both body positions. The high LF:HF ratios observed at altitude in both body positions and groups would suggest that hypoxia caused a shift of sympatho-vagal nerve interaction at rest toward a dominance of the sympathetic system, which was found at sea level only in the sitting position. An acclimatization period of 10 days higher than 2850 m asl and 1 month at 5050 m asl did not modify the interactions of the autonomic systems.

Multiple elements and auto-repression regulate Rox1, a repressor of hypoxic genes in Saccharomyces cerevisiae.

The ROX1 gene encodes a heme-induced repressor of hypoxic genes in yeast. Using RNA blot analysis and a ROX1/lacZ fusion construct that included the ROX1 upstream region and only the first codon, we discovered that Rox1 represses its own expression. Gel-retardation experiments indicated that Rox1 was capable of binding to its own upstream region. Overexpression of Rox1 from the inducible GAL1 promoter was found to be inhibitory to cell growth. Also, we found that, as reported previously, Hap1 is partially responsible for heme-induction of ROX1, but, in addition, it also may play a role in ROX1 repression in the absence of heme. There is a second repressor of anaerobic ROX1 expression that requires the general repressor Tup1/Ssn6 for its function.

DNA tridimensional context affects the reactivity of eukaryotic DNA topoisomerase I.

Cleavage sites of eukaryotic DNA topoisomerase I on curved linear DNAs are clustered, map on the same side of the curve (the external one) and their distribution has the same period as the helical repeat, as observed on curved DNA tracts of Crithidia fasciculata, of Saccharomyces cerevisiae ARS1, of pT7CAT and on synthetic DNAs. The effects of the tridimensional context on both the cleavage and the topoisomerization reactions of DNA topoisomerase I were determined using serial DNA constructs made with inserts in which synthetic curves lie in a plane and in which the orientation of the planes of curvature is shifted by 72 degrees, 144 degrees, 216 degrees, 288 degrees and 360 degrees. The insertion of a curve markedly changes the reaction properties of the surrounding sequences.

Kinetics of heart rate and catecholamines during exercise in humans. The effect of heart denervation.

To elucidate the role of factors other than the nervous system in heart rate (fc) control during exercise, the kinetics of fc and plasma catecholamine concentrations were studied in ten heart transplant recipients during and after 10-min cycle ergometer exercise at 50 W. The fc did not increase at the beginning of the exercise for about 60 s. Then in the eight subjects who completed the exercise it increased following an exponential kinetic with a mean time constant of 210 (SEM 22) s. The two other subjects were exhausted after 5 and 8 min of exercise during which fc increased linearly. At the cessation of the exercise, fc remained unchanged for about 50 s and then decreased exponentially with a time constant which was unchanged from that at the beginning of exercise. In the group of eight subjects plasma noradrenaline concentration ([NA]) increased after 30 s to a mean value above resting of 547 (SEM 124) pg.ml-1, showing a tendency to a plateau, while adrenaline concentration ([A]) did not increase significantly. In the two subjects who became exhausted an almost linear increase in [NA] occurred up to about 1,300 pg.ml-1 coupled with a significant increase in [A]. During recovery an immediate decrease in [NA] was observed towards resting values. The values of the fc increase above resting levels determined at the time of blood collection were linearly related with [NA] increments both at the beginning and end of exercise with a similar slope, i.e. about 2.5 beats.min-1 per 100 pg.ml-1 of [NA] change.(ABSTRACT TRUNCATED AT 250 WORDS)

Body position affects the power spectrum of heart rate variability during dynamic exercise.

The power spectrum analysis of R-R interval variability (RRV) has been estimated by means of an autoregressive method in six men in supine (S) and sitting (C) postures at rest and during steady-state cycle exercise at about 14%, 28%, 45%, 67% of the maximal oxygen consumption (% VO2max). The total power of RRV decreased exponentially as a function of exercise intensity in a similar way in both postures. Three components were recognized in the power spectra: firstly, a high frequency peak (HF), an expression of respiratory arrhythmia, the central frequency (fcentral) of which increased in both S and C from a resting value of about 0.26 Hz to 0.42 Hz at 67% VO2max; secondly, a low frequency peak (LF) related to arterial pressure control, the fcentral of which remained constant at 0.1 Hz in C, whereas in S above 28% VO2max decreased to 0.07 Hz; and thirdly, a very low frequency component (VLF; less than 0.05 Hz, no fcentral). The power of the three components (as a percentage of the total power) depended on the body posture and the metabolic demand. HF% at rest was 30.3 (SEM 6.6) % in S and 5.0 (SEM 0.8) % in C. During exercise HF% decreased by about 30% in S and increased to 19.7 (SEM 5.5) % at 28% VO2max in C. LF% was lower in S than in C at rest [31.6 (SEM 5.7) % vs 44.9 (SEM 6.4) %; P < 0.05], remaining constant up to 28% VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscle sound and electromyogram spectrum analysis during exhausting contractions in man.

The changes in the soundmyogram (SMG) and electromyogram (EMG) frequency content during exhausting contractions at 20%, 40%, 60% and 80% of the maximal voluntary contraction (MVC) were investigated by the spectral analysis of the SMG and EMG detected from the biceps brachii muscles of 13 healthy men. The root mean squares (rms) of the two signals were also calculated. Throughout contraction the EMG rms always increased while this was true only at 20% MVC for the SMG. A marked decrease was detected at 60% and 80% MVC. With fatigue the EMG spectra presented a compression towards the lower frequencies at all exercise intensities. The SMG showed a more complex behaviour with a transient increase in its frequency content, followed by a continuous compression of the spectra, at 60% and 80% MVC, and a nearly stable frequency content at lower contraction intensities. This study suggested that different aspects of the changes in the motor unit's activation strategy at different levels of exhausting contractions can be monitored by SMG and EMG signals.

The energy cost of walking or running on sand.

Oxygen uptake (VO2) at steady state, heart rate and perceived exertion were determined on nine subjects (six men and three women) while walking (3-7 km.h-1) or running (7-14 km.h-1) on sand or on a firm surface. The women performed the walking tests only. The energy cost of locomotion per unit of distance (C) was then calculated from the ratio of VO2 to speed and expressed in J.kg-1.m-1 assuming an energy equivalent of 20.9 J.ml O2-1. At the highest speeds C was adjusted for the measured lactate contribution (which ranged from approximately 2% to approximately 11% of the total). It was found that, when walking on sand, C increased linearly with speed from 3.1 J.kg-1.m-1 at 3 km.h-1 to 5.5 J.kg-1.m-1 at 7 km.h-1, whereas on a firm surface C attained a minimum of 2.3 J.kg-1.m-1 at 4.5 km.h-1 being greater at lower or higher speeds. On average, when walking at speeds greater than 3 km.h-1, C was about 1.8 times greater on sand than on compact terrain. When running on sand C was approximately independent of the speed, amounting to 5.3 J.kg-1.m-1, i.e. about 1.2 times greater than on compact terrain. These findings could be attributed to a reduced recovery of potential and kinetic energy at each stride when walking on sand (approximately 45% to be compared to approximately 65% on a firm surface) and to a reduced recovery of elastic energy when running on sand.