Quantifying how location and dose of botulinum toxin injections affect muscle paralysis

Despite the widespread use of botulinum toxin to treat muscle dystonias, no method exists to quantify muscle paralysis in either human or nonhuman models. In this study we examined how the location, dose, and volume of botulinum injection affects paralysis in the rat tibialis anterior muscle. Paralysis was quantified by electrically stimulating the nerve to the tibialis anterior and then staining sections of the muscle for glycogen. The areas of glycogen-containing fibers represented regions of botulinum action. The results showed that the most important injection technique is to inject botulinum directly into the motor endplate region of a muscle. Injections only 0.5 cm from the motor endplate resulted in a 50% decrease in paralysis. Increases in dose increased paralysis, however, some of that increase was simply due to the increased volume of injection. Thus, delivering toxin in small volumes near the MEP band of a muscle should produce the most effectiveparalysis. © 1993 John Wiley & Sons, Inc.     

Nafarelin controlled release injectable: theoretical clinical plasma profiles from multiple dosing and from mixtures of microspheres containing 2 per cent, 4 per cent and 7 per cent nafarelin

Nafarelin controlled release injectable (CRI) releases a decapeptide drug for target one month therapy. Nafarelin, a luteinizing hormone releasing hormone agonistic analogue, is microencapsulated in biodegradable poly(lactide-co-glycolide) microspheres and given by intramuscular injection. Clinical data from a human single dose Phase I clinical study are modelled to develop theoretical multiple dose profiles and theoretical single dose profiles from mixtures of two or three formulations. Single dose injections of nafarelin CRI microspheres (4 mg nafarelin) containing 2, 4, or 7 per cent nafarelin all achieve useful plasma drug levels throughout the target 30 day interval. Therapeutic suppression of testosterone levels was observed in all subjects participating in the phase I clinical study. Highest plasma nafarelin levels are achieved in the 0-10 and 20-35 day post-injection intervals. Theoretical multiple dosing profiles generated from the single dose clinical results show significant oscillations in plasma nafarelin levels depending on the particular dosing interval selected. Thirty or forty day dosing intervals yield significant variability in plasma nafarelin levels at steady state; 15 day dosing intervals show less variability. Therapeutic testosterone suppression was observed in the single dose study, so the nafarelin dose per injection can be reduced in multiple dosing therapies. Theoretical plasma nafarelin profiles from certain mixtures of 2 and 4 per cent nafarelin microspheres or 2 and 7 per cent nafarelin microspheres indicate that a 60 day product could be achieved. In general, all three formulations yield their lowest plasma drug levels during the 10-20 day post-injection interval. Therefore any mixture of these formulations will likewise exhibit low plasma drug levels during this interval.     

Calcaneal fractures

Fractures of the calcaneus generally occur in the event of high-energy trauma, resulting in complex, three-dimensionally oriented fracture patterns. Surgical management is generally indicated for displaced intra-articular fractures, which allows restoration of calcaneal height, width and overall morphology, in addition to the posterior facet articular surface where possible, and allows for a late in situ arthrodesis as a means of salvage in the event of posttraumatic arthritis. What follows is a brief discussion of our preferred methods in the diagnosis and management of calcaneal fractures.     

Automatic analysis of the electromyographic interference pattern. Part II: Findings in control subjects and in some neuromuscular diseases

The electromyographic (EMG) interference pattern (IP) was measured in the biceps muscle of 16 normal male and 17 normal female subjects. The activity, upper centile amplitude (UCA), and the number of small segments (NSS) (defined in a companion paper) were measured from 500-msec epochs of the IP. The normal values of these features were defined separately for men and women by plotting the UCA and NSS values against activity for each epoch and defining an area on these plots, called a “cloud,” that contained more than 90% of the datum points from each study. The mean deviation of the individual datum points from the overall mean values was also calculated for each study. A study in one muscle is considered to be normal if more than 90% of the datum points from that muscle are within the normal clouds and the deviation values are within their normal range. In patients with neuropathy, the characteristic pattern was increased UCA with normal or decreased NSS. In patients with myopathy, NSS was increased and the UCA was normal or decreased. In all studies, the interpretations of the IP from the plots agreed with qualitative assessments of the IP made independently by an electromyographer. The use of these features to understand and quantitate the changes in the motor units produced by disease is demonstrated by serial studies performed in a patient with motor neuron disease.