The weekly 24 hour infusion of topotecan at 1.75 mg/m2 was ineffective in relapsed ovarian cancer. The daily-times-five schedule remains the schedule of choice. As the regimens were not equitoxic, one cannot differentiate between an ineffective schedule and an ineffective dose as the reason for the differing response rates. However, the degree of myelotoxicity that already occurs will preclude any substantially higher dosing with the weekly regimen.

No abstract

Six isolates originating from acute outbreaks of infectious bursal disease recently reported in broiler and pullet flocks in France were studied with respect to their pathogenicity and their antigenic relatedness to the Faragher 52/70 reference strain. Although the mortality experimentally induced in susceptible chickens by the field strains was sometimes four times higher than that which followed the inoculation of the reference strain (16 to 48 % versus 12 YO), neither mortality nor morbidity were observed in chickens previously vaccinated with a commercial live vaccine and then challenged under the same conditions. Agar gel precipitation tests demonstrated the existence of common antigens in the different strains, and high cross-neutralization indices measured in embryonated specific pathogen free eggs showed them all to belong to serotype I. These data are discussed with reference to previous European and North-American studies on the antigenic status of infectious bursal disease virus.

This study tested the hypothesis that a novel, gravity-induced blood flow restricted (BFR) aerobic exercise (AE) model will result in greater activation of the AMPK–PGC-1α pathway compared with work rate-matched non-BFR. Thirteen healthy males (age: 22.4 ± 3.0 years; peak oxygen uptake: 42.4 ± 7.3 mL/(kg·min)) completed two 30-min work rate-matched bouts of cycling performed with their legs below (CTL) and above their heart (BFR) at ∼2 weeks apart. Muscle biopsies were taken before, immediately, and 3 h after exercise. Blood was drawn before and immediately after exercise. Our novel gravity-induced BFR model led to less muscle oxygenation during BFR compared with CTL (O2Hb: p = 0.01; HHb: p < 0.01) and no difference in muscle activation (p = 0.53). Plasma epinephrine increased following both BFR and CTL (p < 0.01); however, only norepinephrine increased more following BFR (p < 0.01). PGC-1α messenger RNA (mRNA) increased more following BFR (∼6-fold) compared with CTL (∼4-fold; p = 0.036). VEGFA mRNA increased (p < 0.01) similarly following BFR and CTL (p = 0.21), and HIF-1α mRNA did not increase following either condition (p = 0.21). Phosphorylated acetyl-coenzyme A carboxylase (ACC) increased more following BFR (p < 0.035) whereas p-PKA substrates, p-p38 MAPK, and acetyl-p53 increased (p < 0.05) similarly following both conditions (p > 0.05). In conclusion, gravity-induced BFR is a viable BFR model that demonstrated an important role of AMPK signalling on augmenting PGC-1α mRNA. Novelty Gravity-induced BFR AE reduced muscle oxygenation without impacting muscle activation, advancing gravity-induced BFR as a simple, inexpensive BFR model. Gravity-induced BFR increased PGC-1α mRNA and ACC phosphorylation more than work rate-matched non-BFR AE. This is the first BFR AE study to concurrently measure blood catecholamines, muscle activation, and muscle oxygenation.

The oxygen-conforming response (OCR) of skeletal muscle refers to a downregulation of muscle force for a given muscle activation when oxygen delivery (O2D) is reduced, which is rapidly reversed when O2D is restored. We tested the hypothesis that the OCR exists in voluntary human exercise and results in compensatory changes in muscle activation to maintain force output, thereby altering perception of effort. In eight men and eight women, electromyography (EMG), oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb), forearm blood flow (FBF), and task effort awareness (TEA) were measured. Participants completed two nonfatiguing rhythmic handgrip tests consisting of 5-min steady state (SS) followed by two bouts of 2-min brachial artery compression to reduce FBF by ~50% of SS (C1 and C2), separated by 2 min of no compression (NC1) and ending with 2 min of no compression (NC2). When FBF was compromised during C1, EMG/Force (1.58 ± 0.39) increased compared with SS (1.31 ± 0.33, P = 0.001). However, EMG/Force was not restored upon FBF restoration at NC1 (1.48 ± 0.38, P = 0.479), consistent with C1 evoking skeletal muscle fatigue. When FBF was compromised during C2, EMG/Force increased (1.73 ± 0.50) compared with NC1 (1.48 ± 0.38, P = 0.013). EMG/Force returned to NC1 levels during NC2 (1.50 ± 0.39, P = 0.016), consistent with an OCR in C2. TEA (SS 2.2 ± 2.3, C1 3.9 ± 2.5, NC1 3.4 ± 2.7, C2 4.6 ± 2.7, NC2 3.9 ± 2.8) mirrored changes in EMG. It is noteworthy that during the second compromise and then restoration of muscle oxygenation EMG and TEA were rapidly restored to precompromise levels. We interpreted these findings to support the existence of an OCR and its ability to rapidly modify perception of effort during voluntary exercise. NEW & NOTEWORTHY In healthy individuals, when force output is maintained during rhythmic handgrip exercise, muscle activation and perception of effort rapidly increase with compromised muscle oxygen delivery (O2D) and then return to precompromised levels when muscle O2D is restored. These findings suggest that an oxygen-conforming response (OCR) exists and is able to modify perception of effort during voluntary exercise. Therefore, similar to fatigue, an OCR may have implications for exercise tolerance.

SUMMARYVirological 1 examination of a severe infectious bronchitis (IB)-like field case in laying hens, led to the isolation of a coronavirus antigenically different from Massachusetts, Connecticut and four Dutch IB variant strains. The virulence of the isolate for the fowl, and its dual tropism for the respiratory and genital tracts were demonstrated. In preliminary cross-protection studies Commercial vaccines did not protect against challenge with this isolate. These points and the possible economic significance of the virus are discussed.

This study tested the hypotheses that 1) skeletal muscle biopsies performed with the Bergström needle evoke larger perceptions of pain and greater hemodynamic reactivity compared to biopsies performed with the microbiopsy needle, and 2) both needles yield samples with similar fibre type compositions when samples are collected at similar skeletal muscle depths. Fourteen healthy (age: 21.6 ± 3.2 years; VO 2 peak: 41.5 ± 5.8 mL/kg/min) males (n = 7) and females (n = 7) provided two resting skeletal muscle biopsies, one with each needle type, following a randomized crossover design. Participants completed the short-form McGill Pain Questionnaire and the Brief Pain Inventory before, during, and after the skeletal muscle biopsies. Hemodynamic reactivity was assessed by measuring heart rate (HR) and mean arterial pressure (MAP) at rest and during the biopsy procedures. Immunofluorescence analysis was used to assess fibre type composition in vastus lateralis samples. Compared to the microbiopsy needle, the Bergström needle elicited a larger perception of pain but similar hemodynamic reactivity during the biopsy. Both needles yielded skeletal muscle samples with similar fibre type composition and resulted in similar perceptions of pain and pain-related interference during the post-biopsy recovery period. Collectively, these findings suggest that studies should consider using the microbiopsy needle rather than the Bergström needle unless large amounts of muscle tissue or certain muscle fibre lengths are required. However, future work should determine whether our findings are generalizable to biopsies performed with different procedures and/or types of Bergström/microbiopsy needles.

In electrically stimulated skeletal muscle, force production is downregulated when oxygen delivery is compromised and rapidly restored upon restoration of oxygen delivery in the absence of cellular disturbance. Whether this 'oxygen-conforming' response of force occurs and is exercise intensity dependent during stable voluntary muscle activation in humans is unknown. In 12 participants (six female), handgrip force, forearm muscle activation (EMG), muscle oxygenation and forearm blood flow (FBF)were measured during rhythmic handgrip exercise at forearm EMG achieving 50, 75 or 90% critical impulse (CI). Four minutes of brachial artery compression to reduce FBF by ∼60% (Hypoperfusion) or sham compression (adjacent to artery; Control) was performed during exercise. Sham compression had no effect. Hypoperfusion rapidly reduced muscle oxygenation at all exercise intensities, resulting in contraction force per muscle activation (force/EMG) progressively declining over 4 min by ∼16% at both 75 and 90% CI. No force/EMG decline occurred at 50% CI. Rapid restoration of muscle oxygenation after compression was closely followed by force/EMG such that it was not different from Control within 30 s for 90% CI and after 90 s for 75% CI. Our findings reveal that an oxygen-conforming response does occur in voluntary exercising muscle in humans. Within the exercise modality and magnitude of fluctuation of oxygenation in this study, the oxygen-conforming response appears to be exercise intensity dependent. Mechanisms responsible for this oxygen-conforming response have implications for exercise tolerance and warrant investigation.