THE CONTROL OF HUMAN MOTOR UNITS

1. The motor unit, consisting of a single motor neuron and the skeletal muscle fibres that it innervates, is the final output pathway of the motor system. 2. Much is now known about the way that human motor neurons are recruited and controlled during voluntary and reflex movements. This review briefly summarizes some of the recent experimental data that has contributed to our present understanding. The review is largely limited to data obtained in human experiments. While much of what we know about the organization of the nervous system has come from studies of the anatomy and physiology of experimental animals, there are some questions that cannot be addressed in reduced animal preparations. The development of new techniques has made it possible to investigate the human nervous system at a level of detail that has not hitherto been possible.     

Single- vs Multiple-Dose Pharmacokinetics of Clozapine in Psychiatric Patients

Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose-multiple dose-single dose). Each patient received a single 75-mg dose (3 x 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days. After the last dose, serial plasma samples were again obtained over 72 hr. Drug was then withheld for at least 7 days, a final single 75-mg dose was given, and plasma sampling was repeated. A subset of the patient population (N = 7) was used to test for a food effect during the single-dose treatments. The pharmacokinetic parameters between the initial and the final single dose periods were not significantly different. Similarly, there were no differences within patients when given the dose after fasting (fed 1 hr after dose) or with a meal. In contrast, the terminal elimination rate differed between the single-dose and the multiple-dose treatments (t1/2 m3 = 7.9 hr single dose and 14.2 hr multiple dose) (P less than 0.05) and the dose-normalized area under the plasma concentration/time curves increased 27% with multiple dosing. Since a previous study in patients (Choc et al., Pharm. Res. 4:402-405, 1987) showed dose proportionality of clozapine plasma concentrations during multiple-dose regimens, the present results cannot be described by Michaelis-Menten kinetics.     

Practical procedures for a radon etched track dosimetry service.

Etched track detectors are widely used for the detection of radon and its decay products. They have many desirable attributes: they are small, cheap, simple, non-toxic and non-hazardous. Etched track detectors provide adequate accuracy for most radiological protection purposes provided stringent quality assurance is maintained. The UK validation scheme provides an important component of QA but continuous monitoring of conditions and results is also needed. If these conditions are observed, these detectors provide an entirely adequate tool for large-scale use in assessing levels of radon in houses. Accurate estimates of long-term average radon levels require a measurement over several months because of the short-term fluctuations in radon concentrations.     

Long-term outcome of vocal cord dysfunction.

BACKGROUND: Vocal cord dysfunction (VCD) is an involuntary functional disorder commonly misdiagnosed as asthma. Previous reports describe the disorder and treatment but not the long-term outcome. OBJECTIVE: To determine the long-term outcome of VCD. METHODS: A retrospective medical record review identified 49 patients, ages 8 to 25 years, diagnosed as having VCD from 1989 to 2002. Telephone contact was attempted in all. RESULTS: Of the 49 patients, 41 had previously been treated for asthma; that diagnosis was confirmed by us as a comorbidity in only 12 patients. Two distinct phenotypes of VCD were observed. Symptoms were limited to exercise-induced VCD (EIVCD) in 29 and spontaneously occurring VCD (SVCD) in 20, only 4 of whom additionally had EIVCD. Twenty-eight of the 49 were successfully contacted by telephone. Eight of the 11 contacted patients with SVCD followed the recommendation to see our speech therapist, all of whom learned to control symptoms. However, 2 who also had EIVCD continued with that problem. Pretreatment with an anticholinergic inhaler prevented EIVCD in 6 patients in whom this was tried. Complete absence of symptoms, at times ranging from 1 week to 5 years (median, 5 months), was reported in 26 of the 28 contacted patients. CONCLUSIONS: VCD continues to be frequently misdiagnosed as asthma. Two phenotypes of VCD are apparent: EIVCD and SVCD. Speech therapy provides relief of symptoms for SVCD. Prevention of EIVCD with an anticholinergic inhaler in 6 patients suggests that a controlled clinical trial is warranted. Regardless of treatment, eventual spontaneous resolution was common.     

Simultaneous assessment of cardiac perfusion and function using 5-dimensional imaging with Tc-99m teboroxime

BACKGROUND: Dynamic single photon emission computed tomography (SPECT) acquisition and reconstruction of early poststress technetium 99m teboroxime washout images has been shown to be useful in the detection of coronary disease. Assessment of poststress regional wall motion may offer additional use in assessing coronary disease. Our goal was to investigate the feasibility of simultaneously imaging myocardial ischemia and transient poststress akinesis using gated-dynamic SPECT. METHODS AND RESULTS: A gated-dynamic mathematical cardiac torso (MCAT) phantom was developed to model both teboroxime kinetics and cardiac regional wall motion. A lesion was simulated as having delayed poststress teboroxime washout together with a transient poststress wall motion abnormality. Gated projection data were created to represent a 3-headed SPECT system undergoing a total rotation of 480 degrees . The dynamic expectation-maximization reconstruction algorithm with postsmoothing across gating intervals by Wiener filtering, and the ordered-subset expectation maximization reconstruction algorithm with 3-point smoothing across gating intervals were compared. Compared with the ordered-subset expectation maximization with 3-point smoothing, the dynamic expectation-maximization algorithm with Wiener filtering was able to produce visually higher-quality images and more accurate left ventricular ejection fraction estimates. CONCLUSION: From simulations, we conclude that changing cardiac function and tracer localization possibly can be assessed by using a gated-dynamic acquisition protocol combined with a 5-dimensional reconstruction strategy.     

Intracortical inhibition in the human trigeminal motor system.

OBJECTIVE: To investigate the presence and features of short-interval intracortical inhibition (SICI) in the human trigeminal motor system. METHODS: Surface electromyogram (EMG) was recorded from left and right digastric muscles in 7 subjects, along with additional experiments with intramuscular EMG in 2 subjects. Focal transcranial magnetic stimulation (TMS) was used to activate the motor cortex of one hemisphere and elicit motor evoked potentials (MEPs) in digastric muscles on each side, at rest and while subjects activated the muscles at 10% maximal EMG. Paired or single TMS pulses were delivered in blocks of trials, while conditioning TMS intensity and interstimulus interval (ISI) were varied. RESULTS: At rest, paired TMS (3-ms ISI) with conditioning intensities 0.8-0.9x active motor threshold (TA) reduced the digastric MEP amplitude to a similar extent bilaterally. Conditioning at 0.5-0.7TA did not significantly reduce the MEP. MEP amplitude was reduced to a similar extent in both digastric muscles by ISIs between 1 and 4 ms (0.8TA). Voluntary bilateral activation of digastric muscles reduced the effectiveness of conditioning TMS compared to the resting state, with no differences between sides. The similarity of the responses in both digastric muscles was not due to EMG cross-talk (estimated to be approximately 10% in surface records and approximately 2% in intramuscular records), as the intramuscular records showed the same pattern as the surface records. CONCLUSIONS: The effects of paired-pulse TMS on digastric are similar to those reported for contralateral hand muscles, and are consistent with activation of SICI circuits in M1 by conditioning TMS. Our evidence further suggests that the corticomotor representations of left and right digastric muscles in M1 of a single hemisphere receive analogous inhibitory modulation from SICI circuits. SIGNIFICANCE: SICI has been demonstrated in the face area of motor cortex controlling the trigeminal motor system in normal subjects. This method can be used to investigate abnormalities of SICI in movement disorders affecting the masticatory muscles in humans.     

Early detection of myocardial contusion and its complications in patients with blunt trauma

Myocardial contusion remains an elusive clinical entity, which consumes a disproportionate amount of scarce and expensive critical care resources for the purpose of cardiac monitoring. This study attempts to define a group of patients at high risk who can be identified from the available data present at the time of admission. All patients admitted with the suspicion of a myocardial contusion over a 3-year period were retrospectively studied. The records were examined for history, physical findings, electrocardiographic (ECG) results, creatine kinase levels, Injury Severity Score (ISS), and echocardiographic findings. A diagnosis of a myocardial contusion was made if patients had an ECG consistent with acute injury, increased creatine kinase-MB, or an abnormal echocardiogram consistent with acute injury. Patients were stratified into two groups: Group 1 patients satisfied the criteria for a myocardial contusion and Group 2 patients lacked sufficient evidence to substantiate this diagnosis. The records were then examined for the presence of factors available in the emergency room that might be predictive of a myocardial contusion or its complications. A total of 88 patients were evaluated; 27 of these were found to have a myocardial contusion (Group 1) with 61 patients placed in Group 2 (no myocardial contusion). Group 1 patients had an abnormal admission ECG (p less than 0.05), and an ISS greater than or equal to 10 (p less than 0.05). Multivariate analysis identified two factors predictive of a myocardial contusion: an abnormal ECG and an ISS greater than 10. When these two predictors were absent, the probability of a myocardial contusion was 1%. No predictors of a complication of a myocardial contusion were identified. These data suggest that a combination of easily obtained variables in the emergency department can be used to select a patient population at high risk for myocardial contusion. Prospective evaluation of these variables is necessary.     

Insulin-like growth factor I promotes leiomyoma cell growth in vitro

Objective: Our purpose was to determine whether insulin-like growth factors I and II preferentially stimulate uterine leiomyoma cells versus myometrial cells in monolayer culture.Study design: Leiomyomas and normal myometrium were obtained at hysterectomy from five premenopausal women. Specimens were enzymatically digested for use in primary monolayer cell cultures. By use of serum-free media, insulin-like growth factor I or II was added in 1, 10, and 100 ng/ml concentrations to both cell types with the patient serving as her own control. Cell number, prolactin production, and proliferative index values were measured on day 15 of cell culture.Results: Significant increases in cell number were found in the leiomyoma cultures (p < 0.05) treated with 10 and 100 ng/ml insulin-like growth factors I but not with insulin-like growth factos II. Neither factor exerted a stimulatory effect on myometrial cells.Conclusion: Insulin-like growth factor sI preferentially stimulates leiomyoma cells in monolayer culture. These results suggest an autocrine-paracine role in vivo for this factor in conjuction with gonadal steroids in promoting leiomyoma growth.