In vitro activity of the aryl-fluoroquinolones A-56619 and A-56620 and evaluation of disk susceptibility tests

The activity of two new quinolones, A-56619 and A-56620, was compared in vitro to that of norfloxacin and ciprofloxacin against 6,699 bacterial isolates in four separate clinical laboratories. The overall percentage of strains susceptible to designated concentrations were as follows: 99.1% for norfloxacin (MIC4.0 g/ml), 96.1% for ciprofloxacin (MIC1.0 g/ml), 96.8% for A-56620 (MIC 2.0 g/ml) and 96.1% for A-56619 (MIC 4.0 g/ml). For disk diffusion susceptibility tests 10 g A-56619 disks are tentatively recommended with interpretive standards of 18mm for susceptibility and 13mm for resistance; 5 g A-56620 disks may be used with tentative standards of 19mm for susceptibility and 14mm for resistance.     

Effects of aerobic endurance training status and specificity on oxygen uptake kinetics during maximal exercise

The main purpose of this study was to analyze the effects of exercise mode, training status and specificity on the oxygen uptake (O₂) kinetics during maximal exercise performed in treadmill running and cycle ergometry. Seven runners (R), nine cyclists (C), nine triathletes (T) and eleven untrained subjects (U), performed the following tests on different days on a motorized treadmill and on a cycle ergometer: (1) incremental tests in order to determine the maximal oxygen uptake (O_2max) and the intensity associated with the achievement of O_2max (IO_2max); and (2) constant work-rate running and cycling exercises to exhaustion at IO_2max to determine the effective time constant of the O₂ response (O₂). Values for O_2max obtained on the treadmill and cycle ergometer [R=68.8 (6.3) and 62.0 (5.0); C=60.5 (8.0) and 67.6 (7.6); T=64.5 (4.8) and 61.0 (4.1); U=43.5 (7.0) and 36.7 (5.6); respectively] were higher for the group with specific training in the modality. The U group showed the lowest values for O_2max, regardless of exercise mode. Differences in O₂ (seconds) were found only for the U group in relation to the trained groups [R=31.6 (10.5) and 40.9 (13.6); C=28.5 (5.8) and 32.7 (5.7); T=32.5 (5.6) and 40.7 (7.5); U=52.7 (8.5) and 62.2 (15.3); for the treadmill and cycle ergometer, respectively]; no effects of exercise mode were found in any of the groups. It is concluded that O₂ during the exercise performed at IO_2max is dependent on the training status, but not dependent on the exercise mode and specificity of training. Moreover, the transfer of the training effects on O₂ between both exercise modes may be higher compared with O_2max.     

Dissemination in five French hospitals ofKlebsiella pneumoniae serotype K25 harbouring a new transferable enzymatic resistance to third generation cephalosporins and aztreonam

A strain ofKlebsiella pneumoniae K25 resistant to newer-lactam drugs was isolated in clusters in five hospitals in the Paris area. The MICs of ceftazidime and aztreonam (128 mg/l) were higher than that of cefotaxime (16 mg/l) for the strain but when measured in the presence of clavulanic acid, they were 1 mg/l. The donor strains and derivatives produced a-lactamase with a pI of 7.75–7.8 and hydrolysing activity against a wide spectrum of-lactams similar to that of SHV-2 and SHV-3, but with significant hydrolysis of ceftazidime. This new enzyme could be designated SHV-4.     

Thermoregulation during exercise in relation to sex and age

Summary The thermoregulatory responses to 1 h exercise of 14 male (age range 18–65 year) and 7 female (age range 18–46 year) athletes and 4 (3 and 1 ) non-athletic subjects have been investigated in a moderate environment (T _db=21 C, T _wb=15 C and rh<50%) and analysed in relation to age, sex, and maximum aerobic power output (VO₂ max).The maximal sweat loss (M _{sw max}) under the given conditions was closely related (r=+0.90) to VO_{2 max} and for a given relative work load (%VO_{2 max}), rectal (T _re) and mean skin (¯T _sk) temperatures was the same in all subjects.Sweat loss (004d _sw) was linearly related to total heat production (H) and to peripheral tissue heat conductance (K) and if expressed in relative terms (%M _{sw max}) was linearly related to T _re. For a given T _re relative sweat rate was identical in the groups studied. From these results it would seem that during exercise T _re rises to meet the requirements of heat dissipation by establishing a thermal gradient from core to skin and stimulating sweating in proportion to maximal capacity of the system. Thus provided the thermal responses to work were standardised using the appropriate physiological variables, there was no evidence to be found for differences in thermoregulatory function which could be ascribed to sex or age.     

Early adaptations in gas exchange,cardiac function and haematology to prolonged exercise training in man

Summary In order to determine the effect of shortterm training on central adaptations, gas exchange and cardiac function were measured during a prolonged submaximal exercise challenge prior to and following 10–12 consecutive days of exercise. In addition, vascular volumes and selected haematological properties were also examined. The subjects, healthy males between the ages of 19 and 30 years of age, cycled for 2 h per day at approximately 59% of pre-training peak oxygen consumption (VO₂) i.e., maximal oxygen consumption (VO_{2 max}). Following the training,VO_{2 max} (1·min^–1) increased (P<0.05) by 4.3% (3.94, 0.11 vs 4.11, 0.11; mean, SE) whereas maximal exercise ventilation (V _E,max) and maximal heart rate (_c,max) were unchanged. During submaximal exercise,VO₂ was unaltered by the training whereas carbon dioxide production (V _E) and respiratory exchange ratio were all reduced (P<0.05). The altered activity pattern failed to elicit adaptations in either submaximal exercise cardiac output or arteriovenous O₂ difference. _c was reduced (P<0.05). Plasma volume (PV) as measured by¹²⁵I human serum albumin increased by 365 ml or 11.8%, while red cell volume (RCV) as measured by⁵¹chromium-labelled red blood cells (RBC) was unaltered. The increase in PV was accompanied by reductions (P<0.05) in haematocrit, haemoglobin concentration (g. 100 ml^–1), and RBCs (10⁶ mm^–3). Collectively these changes suggest only minimal adaptations in maximal oxygen transport during the early period of prolonged exercise training. However, as evidenced by the changes during submaximal exercise, both the ventilatory and the cardiodynamic response were altered. Since RCV did not change, it is suggested that the elevated PV accompanying training is instrumental in eliciting the change in cardiac function.     

Einstellzeit der Pt-Elektrode bei Messungen nicht stationärer O2-Partialdrucke

Zusammenfassung Das Meßsignal bei sprunghaftenpO₂-Änderungen wird anhand des Diffusionsfeldes der Elektrode beschrieben. Es wird das zeitliche Verhalten des Meßsignals von blanken und membranbespannten Elektroden in gasförmigen und nicht gasförmigen Meßmedien betrachtet. Aus dem Verhalten des Meßsignals kann jeweils die Einstellzeit alssystematischer Meßfehler abgeleitet werden. In nicht gasförmigen Medien (z. B. biologisches Gewebe) übersteigt das Meßsignal nach einempO₂-Sprung zu höheren Werten das stationäre Endsignal. Daraus ergibt sich eine besondere Betrachtung der Einstellzeit in solchen Medien.Die Einstellzeit für Pt-Elektroden mit einfacher und doppelter Membran wird explizit angegeben. Schließlich wird für biologische Medien die Einstellzeit mit dem Diffusionsfehler [8] verglichen. Die Forderungen an eine Membran der Pt-Elektrode mit kleiner Einstellzeit und gleichzeitig kleinem Diffusionsfehler sind zusammengestellt.

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Erklärung der Symbole a Verhältnis der Diffusionskoeffizienten zweier Membranen - Bunsenscher Löslichkeitskoeffizient des Mediums - _m Bunsenscher Löslichkeitskoeffizient der Membran - b Verhältnis der Diffusionsleitfähigkeiten von Membran und Medium - C ₁,C ₂ Proportionalitätskonstanten zwischen Meßsignal und O₂-Partialdruck - D Diffusionskoeffizient des Mediums - D _m,D _m Diffusionskoeffizienten der Membranen - Diffusionskoeffizient der effektiven Membran - DF Diffusionsfehler - DGl Differentialgleichung - d _m,d _m Dicke der Membranen - Dicke der effektiven Membran - dimensionsloser Parameter des Diffusionsfehlers - erf Fehlerfunktion - exp Exponentialfunktion - F Faradaykonstante - grad Gradient - I stationäres Meßsignal vor dempO₂-Sprung - I stationäres Meßsignal nach dempO₂-Sprung - I(t), I(),I() instationäres Meßsignal als Funktion der Zeit bzw. zeitabhängiger dimensionsloser Parameter - K Diffusionsleitfähigkeit des Mediums - K _m Diffusionsleitfähigkeit der Membran - Diffusionsleitfähigkeit der effektiven Membran - dimensionsloser Parameter - n Summationsindex - pO₂ O₂-Partialdruck - pO₂ als Funktion von Ort und Zeit bzw. zeitabhängiger dimensionsloser Parameter; Diffusionsfeld der Elektrode - p _c konstanterpO₂ vor dempO₂-Sprung - p _c konstanterpO₂ nach dempO₂-Sprung - p(r ₀+d _m , ) pO₂ an der Grenze Membran/Medium in Abhängigkeit des Zeitparameters - p(r,o) Diffusionsfeld zum Zeitpunkt (t=0) despO₂-Sprunges - p(r₀+d_m, o) pO₂ an der Grenze Membran/Medium zum Zeitpunkt despO₂-Sprunges - R Radius der ebenen, kreisförmigen Elektrode - r ₀ Radius der Elektrode mit halbkugelförmiger Pt-Oberfläche - r Kugelkoordinate - ₁,₂ dimensionslose ortsabhängige Parameter - T ₉₀,T ₉₅ Zeit, bis 90% bzw. 95% des Signalunterschiedes nach dempO₂-Sprung ausgeglichen sind (Einstellzeit) - T ₉₀,T ₉₅ Einstellzeit der Elektrode mit Doppelmembran - T _90*,T _95* Zeit, bis sich das Signal nach Übersteigen des stationären Endwertes diesem auf 10% bzw. 5% angenähert hat - dimensionslose Parameter zu den vorangegangenen Einstellzeiten - t Zeitkoordinate - , dimensionslose zeitabhängige Parameter - t _max, _max Zeit maximaler Signalhöhe nachpO₂-Sprung und zugehöriger dimensionsloser Parameter - V(t) Diffusionsgesamtfluß zur Pt-Oberfläche - Stromdichtevektor der diffundierenden O₂-Moleküle - x, y, z Kartesische Koordinaten - Integrationsvariable - ² Laplace-Operator - partielle Ableitung nach der Zeit - Integral über eine Fläche - gerichtetes Flächenelement     

Effect of alteration of peripheral blood flow on the central circulation in man during supine cycling in different ambient temperatures

Summary Whether the alteration of peripheral circulation caused by changing ambient temperature (T_a) affects central circulatory changes in man during supine cycling was investigated in four well-trained men, who exercised at two levels (117.7 or 176.6 W). Exercise metabolic rate (VO₂) in cold (0 C or 10 C) was the same as it was at 20 C, whereas the cardiac output (CO; CO₂ rebreathing technique) and heart rate were significantly lower (e.g., 176.6 W at 0 C, both p<0.01). In heat (30 C or 40 C), the VO₂ reduced with falling CO and mean arterial blood pressure from those at 20 C (e.g., 176.6 W at 40 C, all cases p<0.01), whereas the peak post-exercise calf blood flow (CBF_p) increased (p<0.01). The VO₂ and stroke volume (SV) were inversely proportional to the ratio of CBF_p to CO/kg body weight (CBF_p/CO) (r>–0.78, p<0.001). Total peripheral resistance (TPR) was related to arteriovenous oxygen difference (A-VO₂ difference) (r>0.78, p<0.001). The TPR and A-VO₂ difference decreased as T_a rose, while CBF_p/CO was almost the same. As CBF_p/CO had exceeded 50 and further progressed, however, the two parameters elevated until the same level as that at 0 C. The present results suggest that during moderately prolonged (16–60 min) supine cycling in different T_a's the central circulatory changes are mainly affected by the altered peripheral blood flow in competing between skin and muscle for blood flow.     

Susceptibility to beta-lactam antibiotics in septicemia isolates from twenty-nine European laboratories

In 1984 the European Study Group on Antibiotic Resistance (ESGAR) consecutively collected gram-negative bacilli and staphylococci blood isolates and performed susceptibility testing with 11 antibiotics using the microdilution method. In all 2,578 isolates were collected: 68% gram-negative bacilli and 32% staphylococci. The MICs of ampicillin and cefazoline for the susceptible gram-negative bacilli were 1–8g/ml; of piperacillin0.5–4; of Sch 34343, cefotaxime, moxalactam, ceftazidime and aztreonam0.5–2g/ml; of cefoxitin, cefuroxime and cefamandole0.5–8g/ml. For susceptible staphylococci the MICs of cefazoline and cefuroxime were0.5–1g/ml, and of cefoxitin, moxalactam, ceftazidime and cefotaxime,0.5–32 g/ml. The resistance levels varied between laboratories and countries, being lower in Northern Europe. In clinical protocols on patients with gram-negative septicemia from whom cefazoline-resistant strains were isolated, cefotaxime was the beta-lactam most commonly used (12%). In protocols on patients with staphylococcal septicemia from whom gentamicin-resistant or cefazoline-resistant strains were isolated, the most commonly used beta-lactam was cloxacillin (6%).     

Contraluminal p-aminohippurate transport in the proximal tubule of the rat kidney

Using the stop-flow peritubular capillary microperfusion method contraluminal transport of corticosteroids was investigated (a) by determining the inhibitory potency (apparent K _i values) of these compounds against p-aminohippurate (PAH), dicarboxylate (succinate) and sulphate transport and (b) by measuring the transport rate of radiolabelled corticosteroids and its inhibition by probenecid. Progesterone did not inhibit contraluminal PAH influx but its 17- and 6-hydroxy derivatives inhibited with an app. K_i of 0.36 mmol/l. Introduction of an OH group in position 21 of progesterone, to yield 11-deoxycorticosterone, augments the inhibitory potency considerably (app. K _{i, PAH} of 0.07 mmol/l). Acetylation of the OH-group in position 21 of 11deoxycorticosterone, introduction of an additional hydroxy group in position 17 to yield 11-deoxycortisol or in position 11 to yield corticosterone brings the app. K _{i, PAH} back again into the range of 0.2–0.4 mmol/l. Acetylation of corticosterone or introduction of a third OH group to yield cortisol does not change the inhibitory potency, but, omission of the 21-OH group or addition of an OH group in the 6 position reduces or abolishes it. Cortisol and its derivatives prednisolone, dexamethasone and cortisone exert similar inhibitory potencies (app. K _{i, PAH} 0.12–0.27 mmol/l). But again, omission of the 21-OH group in cortisone or addition of a 6-OH group reduces or even abolishes the inhibitory potency against PAH transport. The interaction of corticosterone was not changed when 11, 18-epoxy ring (aldosterone) was formed. On the other hand, the interaction was considerably augmented if the 11-hydroxy group was changed to an oxo group in 11-dehydrocorticosterone (app. K _{i, PAH} 0.02 mmol/l). When the A ring of corticosterone is saturated and reduced to 3, 11-tetrahydrocorticosterone the inhibitory potency is not changed very much. But if more than four OH or oxo groups are on the pregnane skeleton or if the OH in position 21 is missing, the inhibitory potency decreases drastically (app. K_{i, PAH} 0.7–1.7 mmol/l). Introduction of a 21-ester sulphate into corticosterone, cortisol and cortisone does not change app. K _{i, PAH} very much. Glucuronidation, however, reduces it (app. K_{i, PAH} 1.2 mmol/l). None of the tested corticosteroids interacts, in concentrations applicable, with dicarboxylate transport and only the sulphate esters interact with sulphate transport.Radiolabelled cortisol, d-aldosterone, 11-dehydrocorticosterone, and corticosterone are rapidly transported into proximal tubular cells. With the latter three compounds no sign of saturation and no transport inhibition with probenecid could be seen. Only with cortisol was a shift toward saturation observed. In addition, cortisol transport could be inhibited by probenecid. The data indicate that corticosteroids interact with the contraluminal renal PAH transporter, whereby hydroxylation in position 21 augments, and hydroxylation in the 6 or 3, 17 position reduces interaction. However, as tested so far, simple diffusion seems to prevail when corticosteroids cross the cell membrane. Sulphation makes corticosteroids also a substrate for the sulphate transporter.     

Continuous recording of intrapulmonary “Compressed air” as a sensitive noninvasive method of measuring bronchial obstruction in guinea pigs

The method presented is based on whole-body plethysmography. The apparatus consisted of two chambers (a=respiratory, b-body chamber) separated by a tight water-filled rubber cuff which was fixed around the head of the animal. Experiments were performed under constant gas conditions: temperature 30°C, 100% relative humidity, the volumes of the two chamber being identical. Volume changes in the chamber (V _a, V _b) were recorded continuously by means of pressure transducers. Respiratory flow was calculated by differentiation of V _a with respect to time. The three parameters V _a, V _b and respiratory flow allowed the calculation of breathing frequency, inspiration/expiration ratio, (peak) expiratory flow and specific airway conductance. In addition we describe a new parameter indicating bronchial obstruction: a graphical plot of V _b against V _a produces a closed loop, the area of which reflects the degree of airway obstruction, and we read off the parameter we term compressed air from this graph. In our hands this parameter was more than ten times as sensitive as other measures of bronchial obstruction. Using this new technique we have carried out pharmacological studies with eicosatetraynoic acid (ETYA), 2-aminomethyl 4-t-butyl-6-iodophenol (MK 447=radical scavenger), the histamine₁ antagonist elemastine and the histamine₂ antagonist cimetidine. In allergen-tested animals we observed mild protective effects of ETYA when given as an aerosol (3 mg) and pronounced effects of MK 447 (4 mg i.p.). Combined H₁H₂-antagonism was much more effective in preventing allergen-induced bronchial obstruction than H₁-antagonism alone.Supported by Deutsche Forschungsgemeinschaft (Do 240/1)     

A new approach to rowing ergometry: establishing exercise intensity relative to maximum force output

Summary The present experiment evaluated a new approach to establish exercise intensity during hydraulic rowing ergometry. In contrast to the traditional approach where exercise intensity is augmented by systematically increasing workload, the new procedure increments the intensity of exercise while maintaining a constant percentage of maximum force output. Ten college females exercised on a hydraulic rower that allowed for control of rowing speed and resistance. The new method to establish work intensity was to row at a cadence of 30 c·min^–1 at a force output equal to 50% of maximum rowing force at each setting determined dynamically prior to testing. Two protocols were used for the maximum tests on the hydraulic rower. Row 1 was a 17-min, six-stage, incremental continuous row test performed at increasingly difficult settings from easy (setting 1; 603 N) to difficult (setting 6; 893 N). Row 2 was identical to row 1 until 15 min when resistance was reduced to setting 2 (658 N) for allout effort during the last 2 min. During this time, cadence declined from 30 c·min^–1 to 19.4 c·min^–1 at dial setting 6 and increased to 35.4 c·min^–1 at dial setting 2. Both rowing protocols were compared to maximal physiological responses during treadmill running (TM). Compared to TM, both rowing protocols elicited. significantly lower maximum oxygen uptake (VO_2max;P<0.05; row 1=29.0% and row 2=12.9%) and maximum heart rate (HR_max;P<0.05; row 1=12.9% and row 2=6.7%). Maximum ventilation (V _Emax) during row 1 was also lower by 30.4% than TM (P<0.05). In addition, row 1 was significantly lower (P<0.05) than row 2 forVO_2max (2.23 vs 2.60 l·min^–1), HR_max (165.5 vs 177.3 beats·min^–1), andV _Emax (62.7 vs 86.3 1·min^–1). These results demonstrate thatVO_2max, HR_max, andV _Emax are depressed when rowing exercise is performed at a high intensity relative to maximum strength. We conclude that the new approach to establish exercise intensity relative to maximum force production is more effective for eliciting near maximum values ofVO₂, HR, andV _E than the conventional method that increases the workload by set increments without consideration of maximal strength.     

Modeling the Dynamic Characteristics of Pneumatic Muscle

A pneumatic muscle (PM) system was studied to determine whether a three-element model could describe its dynamics. As far as the authors are aware, this model has not been used to describe the dynamics of PM. A new phenomenological model consists of a contractile (force-generating) element, spring element, and damping element in parallel. The PM system was investigated using an apparatus that allowed precise and accurate actuation pressure (P) control by a linear servovalve. Length change of the PM was measured by a linear potentiometer. Spring and damping element functions of P were determined by a static perturbation method at several constant P values. These results indicate that at constant P, PM behaves as a spring and damper in parallel. The contractile element function of P was determined by the response to a step input in P, using values of spring and damping elements from the perturbation study. The study showed that the resulting coefficient functions of the three-element model describe the dynamic response to the step input of P accurately, indicating that the static perturbation results can be applied to the dynamic case. This model is further validated by accurately predicting the contraction response to a triangular P waveform. All three elements have pressure-dependent coefficients for pressure P in the range 207 P 621 kPa (30 P 90 psi). Studies with a step decrease in P (relaxation of the PM) indicate that the damping element coefficient is smaller during relaxation than contraction.© 2003 Biomedical Engineering Society. PAC2003: 8719Rr, 8719Ff, 8710+e, 8768+z     

Effects of the reactive oxygen species hypochlorous acid and hydrogen peroxide on force production and calcium sensitivity of rat cardiac myofilaments

Neutrophil activation occurs after myocardial infarction/ischaemia. They produce the reactive oxygen species (ROS) hypochlorous acid (HOCl) and hydrogen peroxide (H₂O₂) which could contribute to contractile dysfunction upon reperfusion. The myofilaments of skinned rat cardiac muscle were exposed to ROS in various states of activation. Isometric force was measured at controlled degrees of activation. A single application of 10 M HOCl for 1 min increased log [Ca²⁺] for half-maximal activation (log K _1/2) from 5.23 to 5.32, initial maximum Ca-activated force (F _{Ca, max}) was reduced by 18.8±5.8% and resting tension increased to 15.4±8.0% of F _{Ca, max}. At 50 M, a 1-min exposure to HOCl produced a greater increase in Ca-sensitivity (log K _1/2 increased from 5.23 to 5.47), a greater reduction in F_{Ca, max} (falling by 42.3±23.2%) and a greater increase in resting tension (to 25±10.7% of F _{Ca, max}). The nature of the resting tension rise was examined by reducing pH before and during exposure to HOCl; the results are consistent with rigor-like cross-bridges being involved. H₂O₂ was without effect on the myofilaments at physiologically relevant (< 10 M) concentrations. These results suggest that ROS associated with inflammation could contribute to post-ischaemic myocardial dysfunction.     

Test–retest errors and the apparent heterogeneity of training response

Published reports have shown large apparent inter-individual differences of gains in maximal oxygen intake (O_2max) in response to a standard 20-week programme of aerobic conditioning that progressed to 75% of the individuals initial O_2max. The observed gains of O_2max ranged from 0 to 1,000 ml min^–1, with a coefficient of variation (CV) of 8.4%. The present analysis evaluates the potential contribution of test–retest errors to these apparent large inter-individual differences in training response. The 2-day test–retest CV for O_2max readings in 742 healthy adults was initially 5.0%, dropping to 4.1% after training. Published training responses were estimated from the mean of paired measurements obtained before and after training if readings agreed by <5%, but from the highest of paired values if these differed by >5%. Taking account of the relative proportions of single and paired observations, the weighted O_2max data for the entire sample had an effective 2-day CV of 4.3% before and 3.4% after training. Assumption 1: if the 20-week test–retest error remained similar to the 2-day figure, measurement error would contribute a CV of 5.5% to apparent training responses, or (for the stated initial mean O_2max of 2,409 ml min^–1) an SD of 132 ml min^–1. Assumption 2: if the 20-week CV was similar to that in other long-term studies (~5%), measurement error would contribute a CV of 6.1%, or a SD of 146 ml min^–1. The published data show a total SD of 202 ml min^–1 for apparent inter-individual differences in training response, with age, gender, race and baseline O_2max accounting for only 11% of this variance. After estimating the likely effect of test–retest measurement errors, the SD due to inter-individual differences would decrease to 138 ml minO_2max (assumption 1) or 123 ml min^–1 (assumption 2). We conclude that when estimating the extent of inter-individual differences in training response, allowance must be made not only for the minor effects of recognized covariates (age, gender, race and initial fitness), but also for the larger influence of test-retest measurement errors. Nevertheless, substantial inter-individual differences persist after making such adjustments. The most likely explanation of these differences is a familial aggregation of training responses.     

Phenotypic differences between induced and spontaneous 2μ-plasmid-free segregants of Saccharomyces cerevisiae

Summary The maximum specific growth rates (_max) of 2 -plasmid-free ([cir°]) segregants of three haploid and one diploid strain of Saccharomyces cerevisiae have been determined and compared with the _max of their 2 -plasmid-containing ([cir ⁺]) progenitors. Two classes of [cir°] strains have been examined: those induced by transformation with a 2 -based recombinant plasmid according to the method of Dobson et al. (1980) and those isolated as spontaneous [cir°] segregants from glucose-limited continuous cultures. The _max of the spontaneous [cir°] segregants was not found to differ significantly from that of their [cir ⁺] parents. In all cases, however, the induced [cir°] strains had a _max which was significantly less than that of their [cir ⁺] counterparts. This effect was particularly marked in the case of the diploid strain where a 34% reduction in _max was observed. The implications of these results are discussed in terms of the effect of the transformation process on host yeast cells.     

Responses in human pretibial muscles to sudden stretch and to nerve stimulation

Summary Electromyograms have been recorded from the human tibialis anterior muscle during voluntary contraction. The accessibility of the nerve to this muscle (common peroneal) has permitted a comparison of reflex responses to low threshold electrical stimulation of the nerve with those to stretch of the muscle itself. Nerve stimulation elicited a reflex at monosynaptic latency (V₁ at 28–29 ms) and a second response (V₂ at 50–52 ms). A tendon tap induced two responses (m₁ at 29 ms and M₂ at 50 ms). The responses to a ramp stretch were similar. The homology of V₁ with M₁, and of V₂ with M₂ is discussed. V₂ and M₂ probably correspond to the transcortical reflexes described from other muscles.Neither V₁ V₂, M₁ nor M₂ were influenced by anaesthesia of the foot. m₁ and M₂ were both reduced in amplitude by a selective -efferent block produced by local anaesthetic in the common peroneal nerve. It is concluded, that muscle spindles are the receptors predominantly responsible for M₂ (transcortical) responses.The amplitudes of M₁ and M₂, but not V₁ and V₂ were augmented by prior instruction to resist the stimulus. This is interpreted as evidence for voluntary modulation of -efferent activity at a constant force of contraction.Beit Memorial Research Fellow     

Velocity at V̇O2 max and peak treadmill velocity are not influenced within or across the phases of the menstrual cycle

Velocity at VO_{2 max} (vO_{2 max}) and peak treadmill velocity (PTV) are variables highly predictive of endurance performance. However, how these variables are affected by the menstrual cycle is unknown. The aim of this study was to assess the effect of the menstrual cycle on vO_{2 max} and PTV. Ten, female runners were studied across three menstrual cycles. Training, menstrual history and mood states were assessed for 2 months, with daily salivary samples taken to detect menstrual phases. During the third menstrual cycle, participants completed a maximal test to determine O_{2 max}, vO_{2 max} and PTV in the early follicular phase, late follicular phase, early luteal phase, late luteal phase and menses. Progesterone increased at the onset of the luteal phase [mean (SEM); 490 (73.6) pmol l^–1] compared to the follicular phase [344.6 (59.7) pmol l^–1). No significant differences in the psychological mood states between the phases of the menstrual cycle were found (P>0.05). No significant differences in vO_{2 max} (P=0.611), or PTV (P=0.472) were found between the phases of the menstrual cycle. Thus, vO_{2 max} and PTV are not affected by the monthly menstrual cycle in female endurance runners.     

Comparison of fat oxidation in arm cranking in spinal cord-injured people versus ergometry in cyclists

The aim of our study was to establish the exercise intensity with the highest fat oxidation rate in spinal cord-injured (SCI) people compared with able-bodied subjects on a stationary ergometer in order to provide recommendations for ergometer training. Ten endurance-trained wheelchair athletes [O_{2peak,armcranking} 35.9 (5.7) ml kg^–1 min^–1; mean (SE)] and ten endurance-trained cyclists [O_{2peak,cycling} 62.3 (4.6) ml kg^–1 min^–1] were studied over 20 min at 55%, 65% and 75% O_{2peak,armcranking} or O_{2peak,cycling} on a cycling ergometer, respectively, in order to find the intensity with the highest fat oxidation. Total energy expenditure, and highest oxidation rate for fat and carbohydrate were highest at 75% O_{2peak,armcranking} and O_{2peak,cycling}. Relative fat oxidation was highest at 55% O_{2peak,armcranking} and O_{2peak,cycling}. Wheelchair athletes showed a tendency for higher lactate concentrations at each intensity compared to cyclists. Well-trained wheelchair athletes and cyclists reach the highest fat oxidation in arm cranking, respectively, in cycling on a stationary ergometer at the same relative intensity of 75% O_{2peak,armcranking} and O_{2peak,cycling}. We presume that well-trained wheelchair athletes can perform ergometer training on a stationary ergometer at 75% O_{2peak,armcranking}. Results are presented as mean (SE).     

Limiting factors to oxygen transport on Mount Everest 30 years after: a critique of Paolo Cerretelli’s contribution to the study of altitude physiology

In 1976, Paolo Cerretelli published an article entitled Limiting factors to oxygen transport on Mount Everest in the Journal of Applied Physiology . The paper demonstrated the role of cardiovascular oxygen transport in limiting maximal oxygen consumption (O_2max). In agreement with the predominant view of O_2max limitation at that time, however, its results were taken to mean that cardiovascular oxygen transport does not limit O_2max at altitude. So it was argued that the limiting factor could be in the periphery, and muscle blood flow was proposed as a possible candidate. Despite this suggestion, the conclusion generated a series of papers on muscle structural characteristics. These experiments demonstrated a loss of muscle oxidative capacity in chronic hypoxia, and thus provided an unambiguous refutation of the then widespread hypothesis that an increased muscle oxidative capacity is needed at altitude to compensate for the lack of oxygen. This analysis is followed by a short account of Cerretellis more recent work, with a special attention to the subject of the so-called lactate paradox.     

Die optische Rotationsdispersion elektrophoretisch isolierter Paraproteine

Zusammenfassung Bei einer Gruppe von 6 elektrophoretisch isolierten _ss -Globulinen Gesunder und 9 ebenso präparierter _ss -Paraproteinen wurden die Konstanten der optischen Rotationsdispersion bestimmt. Die Mittelwerte der Dispersionskonstanten _c beider Gruppen waren nicht signifikant unterschiedlich. Die Bestimmung der Konstanteb ₀ nachMoffitt ergab keinen Hinweis auf das Vorhandensein von -Helixstruktur in dem untersuchten Material. Eine signifikante Differenz ergab sich dagegen bei der Konstantea ₀. Die Beziehung dieses Befundes zu der immunologischen Gruppenspezifität des _ss -Paraproteins und seine strukturellen Grundlagen werden diskutiert.

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Summary The Optical Rotatory Dispersion of electrophoretically isolated _ss -Globulins of 6 normal individuals and 9 patients suffering from myeloma was measured. The mean value of the dispersion constants _c of the normal and myeloma group showed no significant difference. The constanta ₀ however of the myeloma group was significantly different froma ₀ of the normal group. The relation of this observation to the immunologic group specifity of _ss -Paraproteins and her structural basis is discussed.