Motor unit territories supplied by primary branches of the phrenic nerve

Recent studies have demonstrated that, under certain circumstances, the diaphragm does not contract as a homogeneous unit. These observations suggest that motor units may not be randomly distributed throughout the muscle but confined to localized subvolumes. In the present study, electromyographic (EMG) and glycogen depletion methods were combined to investigate the organization of motor units supplied by the primary branches of the phrenic nerve in the cat. Four primary branches are generally present, one branch to the crus and three branches to the sternocostal region. The gross motor-unit territory of each of the four phrenic primary branches was determined by stimulating each nerve separately, while recording from nine EMG electrodes distributed over the hemidiaphragm. Stimulation of the crural branch evoked activity in the ipsilateral crus, whereas stimulation of each of the remaining branches evoked activity in discrete but overlapping areas of the sternocostal diaphragm. A more precise analysis of the distribution and borders of the motor territories was obtained by mapping regions depleted of muscle glycogen due to stimulation of each primary branch for 90 min. Glycogen depletion results closely matched the EMG findings of a localized distribution of motor units served by single primary branches. Stimulation of the crural branch typically caused depletion of the ipsilateral crus, whereas the sternocostal branches each served a striplike compartment. In the majority of cases, the borders of the sternocostal compartments were relatively abrupt and consisted of a 1- to 2-mm transition zone of depleted and nondepleted fibers. These studies demonstrate that motor unit territories of the primary branches of the phrenic nerve are highly delineated. This compartmentalization provides the central nervous system with the potential for a more precise regional motor control of costal and crural diaphragm than previously suspected.     

Measurement of Phloem transport rates by an indicator-dilution technique

An indicator-dilution technique for the measurement of flow rates, commonly used by animal physiologists for circulation measurements, was adapted to the measurement of phloem translocation rates in the wheat (Triticum aestivum L.) peduncle. The approach is based on the observation that, during the transport of a given amount of solute, its mean concentration will be inversely proportional to flow rate. For phloem transport in the wheat peduncle, the necessary measurements are (a) the time course of tracer kinetics in the peduncle phloem, (b) the volume of sieve tubes and companion cells in the monitored segment of the peduncle, and (c) the amount of tracer transported past that point. The method was evaluated by in situ monitoring of ³²PO₄ transport in pulse-labeling experiments. Specific activities (i.e.³²P concentrations) of phloem exudate were in good agreement with those calculated from in situ count rates and measured phloem areas. Mass transport rates, calculated from volume flow rates and phloem exudate dry matter content, also agreed well with expected mass transport rates based on measurements of grain growth rate and net CO₂ exchange by the ear. The indicator-dilution technique appears to offer good precision and accuracy for short-term measurements of phloem transport rates in the wheast peduncle and should be useful for other systems as well. In contrast to velocities based on time-delay measurements, it is more precise, more accurate, and produces an estimate of mean, rather than maximum, velocity. Also, since only a single detector is required, it can be applied to very short transport paths.     

Cholinotoxicity induced by ethylcholine aziridinium ion after intracarotid and intracerebroventricular administration

The effect of ethylcholine aziridinium ion (AF64A) after an intracerebroventricular (icv) injection was compared to that obtained after an intravascular administration. Reductions in choline acetyltransferase (ChAT) and acetylcholinesterase activities in the hippocampus but not in the cerebral cortex or the corpus striatum were observed 10 days after bilateral injection of AF64A into the rat cerebroventricles (3 nmol/side). However, when AF64A was injected into the carotid artery (1 mumol/kg) following a unilateral opening of the blood-brain barrier by a hypertonic treatment, a significant decrease in ChAT activity was observed in the ipsilateral side of the cerebral cortex but not in hippocampus, corpus striatum, or cerebellum. High-affinity choline transport was reduced significantly 11 days after an icv injection of AF64A in all the above mentioned brain regions, and recovered 60 days post injection in the cerebral cortex and in the corpus striatum but not in the hippocampus. Our results suggest that in various brain regions, AF64A causes various degrees of damage to cholinergic neurons, depending on the quantity of the toxin that reaches the target tissue.     

Ventilatory control during exercise in calves with artificial hearts

To determine the role of cardiac reflexes in mediating exercise hyperpnea, we investigated ventilatory responses to treadmill exercise in seven calves with artificial hearts and seven controls. In both groups, the ventilatory responses were adequate for the metabolic demands of the exercise; this resulted in regulation of arterial PCO2 and pH despite the absence of cardiac output increase in the implanted group. In this group, there was a small but significant reduction of arterial PO2 by 4 +/- 3 Torr and a rise of blood lactate by 1.1 +/- 1 mmol/l. When cardiac output was experimentally increased in the implanted calves to a level commensurate with that spontaneously occurring in the control calves, ventilation was not affected. However, experimental reductions of cardiac output led to an immediate augmentation of exercise hyperpnea by 4.56 +/- 4.3 l/min and a further significant lactate increase of 1.2 +/- 1.22 mmol/l that was associated with a significant decrease in the exercise O2 consumption (0.32 +/- 0.13 l/min). These observations indicate that neither cardiac nor hemodynamic effects of increased cardiac output constitute an obligatory cause of exercise hyperpnea in the calf.     

The analysis of the NSW wheat variety database. I. Modelling trial error variance

The retrospective analysis of a large database on wheat variety testing in New South Wales (NSW) is considered. This analysis involved three key steps. Initially error variance heterogeneity is modelled, indicating significant differences in error variance due to trial location, year of trialling, sowing date and trial mean yield. The implication of this modelling for the estimaion of variance components is discussed.     

Design considerations for two-stage enrichment clinical trials

When there is a predictive biomarker, enrichment can focus the clinical trial on a benefiting subpopulation. We describe a two-stage enrichment design, in which the first stage is designed to efficiently estimate a threshold and the second stage is a “phase III-like” trial on the enriched population. The goal of this paper is to explore design issues: sample size in Stages 1 and 2, and re-estimation of the Stage 2 sample size following Stage 1. By treating these as separate trials, we can gain insight into how the predictive nature of the biomarker specifically impacts the sample size. We also show that failure to adequately estimate the threshold can have disastrous consequences in the second stage. While any bivariate model could be used, we assume a continuous outcome and continuous biomarker, described by a bivariate normal model. The correlation coefficient between the outcome and biomarker is the key to understanding the behavior of the design, both for predictive and prognostic biomarkers. Through a series of simulations we illustrate the impact of model misspecification, consequences of poor threshold estimation, and requisite sample sizes that depend on the predictive nature of the biomarker. Such insight should be helpful in understanding and designing enrichment trials.