External Perturbation of the Trunk in Standing Humans Differentially Activates Components of the Medial Back Muscles

During voluntary arm movements, the medial back muscles are differentially active. It is not known whether differential activity also occurs when the trunk is perturbed unpredictably, when the earliest responses are initiated by short-latency spinal mechanisms rather than voluntary commands. To assess this, in unpredictable and self-initiated conditions, a weight was dropped into a bucket that was held by the standing subject (   n = 7  ). EMG activity was recorded from the deep (Deep MF), superficial (Sup MF) and lateral (Lat MF) lumbar multifidus, the thoracic erector spinae (ES) and the biceps brachii. With unpredictable perturbations, EMG activity was first noted in the biceps brachii, then the thoracic ES, followed synchronously in the components of the multifidus. During self-initiated perturbations, background EMG in the Deep MF increased two- to threefold, and the latency of the loading response decreased in six out of the seven subjects. In Sup MF and Lat MF, this increase in background EMG was not observed, and the latency of the loading response was increased. Short-latency reflex mechanisms do not cause differential action of the medial back muscles when the trunk is loaded. However, during voluntary tasks the central nervous system exerts a 'tuned response', which involves discrete activity in the deep and superficial components of the medial lumbar muscles in a way that varies according to the biomechanical action of the muscle component.     

Reflex changes in muscle spindle discharge during a voluntary contraction

1. This study was undertaken to determine whether low-threshold cutaneous and muscle afferents from mechanoreceptors in the foot reflexly affect fusimotor neurons innervating the plantar and dorsiflexors of the ankle during voluntary contractions. 2. Recordings were made from 29 identified muscle spindle afferents innervating triceps surae and the pretibial flexors. Trains of electrical stimuli (5 stimuli, 300 impulses per second) were delivered to the sural nerve at the ankle (intensity: 2-4 times sensory threshold) and to the posterior tibial nerve at the ankle (intensity: 1.5-3 times motor threshold for the small muscles of the foot). The stimuli were delivered while the subject maintained an isometric voluntary contraction of the receptor-bearing muscle, sufficient to accelerate the discharge of each spindle ending. This ensured that the fusimotor neurons directed to the ending were active and influencing the spindle discharge. The effects of these stimuli on muscle spindle discharge were assessed using raster displays, frequencygrams, poststimulus time histograms (PSTHs) and cumulative sums ("CUSUMs") of the PSTHs. Reflex effects onto alpha-motoneurons were determined from poststimulus changes in the averaged rectified electromyogram (EMG). Reflex effects of these stimuli onto single-motor units were assessed in separate experiments using PSTHs and CUSUMs. 3. Electrical stimulation of the sural or posterior tibial nerves at nonnoxious levels had no significant effect on the discharge of the 14 spindle endings in the pretibial flexor muscles. The electrical stimuli also produced no significant change in discharge of 11 of 15 spindle endings in triceps surae. With the remaining four endings in triceps surae, the overall change in discharge appeared to be an increase for two endings (at latencies of 60 and 68 ms) and a decrease for two endings (at latencies of 110 and 150 ms). The difference in the incidence of the responses of spindle endings in tibialis anterior and in triceps surae was significant (P less than 0.05, chi 2 test). 4. For both triceps surae and pretibial flexor muscles the electrical stimuli to sural or posterior tibial nerves had clear effects on the alpha-motoneuron pool, whether assessed using surface EMG or the discharge of single-motor units. Based on EMG recordings using intramuscular wire electrodes, the reflex effects differed for the gastrocnemii and soleus. 5. In this study, reflex changes in the discharge of human spindle endings were more difficult to demonstrate than comparable changes in the discharge of alpha-motoneurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Touchdown General Primer (GP5+/GP6+) PCR and optimized sample DNA concentration support the sensitive detection of human papillomavirus

Background  

The GP5+/GP6+ PCR assay is a well-established HPV detection technique. This study has examined the effects of incorporating 'hot start' and 'touchdown' steps into the protocol. In addition, dTTP was substituted with dUTP to permit contamination control measures against carry-over PCR product.     

Genetic and physical mapping of the McKusick-Kaufman syndrome

McKusick-Kaufman syndrome is a human developmental anomaly syndrome comprising mesoaxial or postaxial polydactyly, congenital heart disease and hydrometrocolpos. This syndrome is diagnosed most frequently in the Old Order Amish population and is inherited in an autosomal recessive pattern with reduced penetrance and variable expressivity. Homozygosity mapping and linkage analyses were conducted using two pedigrees derived from a larger pedigree published in 1978. The PedHunter software query system was used on the Amish Genealogy Database to correct the previous pedigree, derive a minimal pedigree connecting those affected sibships that are in the database and determine the most recent common ancestors of the affected persons. Whole genome short tandem repeat polymorphism (STRP) screening showed homozygosity in 20p12, between D20S162 and D20S894 , an area that includes the Alagille syndrome critical region. The peak two-point LOD score was 3.33, and the peak three-point LOD score was 5.21. The physical map of this region has been defined, and additional polymorphic markers have been isolated. The region includes several genes and expressed sequence tags (ESTs), including the jagged1 gene that recently has been shown to be haploinsufficient in the Alagille syndrome. Sequencing of jagged1 in two unrelated individuals affected with McKusick-Kaufman syndrome has not revealed any disease- causing mutations.      

Saturation multipoint linkage mapping of chromosome 6q in type 1 diabetes

Linkage analysis of type 1 diabetes sib pair families (n = 334) has suggested two separate regions of human chromosome 6q are linked to disease (designated IDDM5 and IDDM8). To test if these are false positive results, all available sib pair families (n = 429) were typed using a 92% informative map of chromosome 6q and multipoint analysis. The two regions still showed positive evidence of linkage, most notably the proterminal region, 6q27, corresponding to IDDM8 (MLS = 2.57, p = 0.0006; lambda s = 1.17). In addition, some evidence of transmission disequilibrium was seen with marker a046xa9 (IDDM5).      

Induction of spermatogenesis in isolated hypogonadotrophic hypogonadism with gonadotrophins and early intervention with intracytoplasmic sperm injection

Idiopathic hypogonadotrophic hypogonadism (IHH) is a potentially correctable cause of male infertility. However hormonal treatment is usually a slow process and artificial reproductive techniques such as intracytoplasmic sperm injection (ICSI) might be resorted to before full testicular response has been achieved. We report here an unusual variant of IHH of post-pubertal onset in which early intervention with ICSI was attempted. Our patient was 37 years old and presented with male infertility due to azoospermia and undetectable serum gonadotrophin concentrations. He had an apparently normal pubertal development, a testicular volume of 8 ml, normal pituitary-thyroid and pituitary-adrenal function, as well as normal computerized tomographic appearance of the sella region. A combination of human chorionic gonadotrophin (HCG) and menopausal gonadotrophins (HMG) was administered. Spermatozoa were first detected in the semen after 3 months and reached a concentration of approximately 2x10(6)/ml after 9 months. ICSI was attempted at this point; the spermatozoa had good fertilizing ability and three embryos were obtained and replaced. Unfortunately no pregnancy resulted. Treatment with 5000 IU HCG and 150 IU HMG three times per week was continued and sperm counts rose rapidly thereafter to reach 28.3x10(6)/ml after 16 months of injections. His wife conceived naturally during this period and the pregnancy is now in the second trimester. This case illustrates the good prognosis of the rare patient with IHH of post-pubertal onset when treated with gonadotrophins, and suggests that ICSI procedures should be delayed until final testicular maturation is attained.      

Discharge patterns of human genioglossus motor units during sleep onset

STUDY OBJECTIVES: Multiunit electromyogram recordings of genioglossus have demonstrated an abrupt reduction in the muscle's activity at sleep onset. Recent evidence from single motor unit recordings indicates that the human genioglossus muscle consists of motor units with a variety of discharge patterns. The aim of the present study was to determine the effect of sleep onset on the activity of individual motor units as a function of their particular discharge pattern. DESIGN: Genioglossus activity was assessed using intramuscular fine-wire electrodes via a percutaneous approach. Sleep onsets (alpha-to-theta transitions) were identified and the genioglossus electromyogram recordings analyzed for single motor unit activity. SETTING: Sleep research laboratory. PARTICIPANTS: Sleep and respiratory data were collected in 8 healthy subjects (6 men). MEASUREMENTS AND RESULTS: One hundred twenty-seven motor units were identified: 23% inspiratory phasic, 45% inspiratory tonic, 4% expiratory phasic, 9% expiratory tonic, 16% tonic, and 3% other. Approximately 50% of inspiratory units (phasic and tonic) ceased activity entirely at sleep onset, whereas those inspiratory units that continued to be active showed a reduction in the proportion of each breath over which they were active. However, the rate of discharge of inspiratory units during the period they did fire was not altered. In contrast, tonic and expiratory units were unaffected by sleep onset, maintaining their discharge pattern over the alpha-to-theta transition. CONCLUSIONS: Central control of inspiratory motoneuron output differs from that of tonic and expiratory units during sleep onset, suggesting that the maintenance of airway patency during sleep may become more reliant on the stiffening properties of tonic and expiratory modulated motor units.     

Do we truly see what we think we see? The role of cognitive bias in pathological interpretation

In the histomorphological grading of prostate carcinoma, pathologists have regularly assigned comparable scores for the architectural Gleason and the now‐obsolete nuclear World Health Organization (WHO) grading systems. Although both systems demonstrate good correspondence between grade and survival, they are based on fundamentally different biological criteria. We tested the hypothesis that this apparent concurrence between the two grading systems originates from an interpretation bias in the minds of diagnostic pathologists, rather than reflecting a biological reality. Three pathologists graded 178 prostatectomy specimens, assigning Gleason and WHO scores on glass slides and on digital images of nuclei isolated out of their architectural context. The results were analysed with respect to interdependencies among the grading systems, to tumour recurrence (PSA relapse > 0.1 ng/ml at 48 months) and robust nuclear morphometry, as assessed by computer‐assisted image analysis. WHO and Gleason grades were strongly correlated (r = 0.82) and demonstrated identical prognostic power. However, WHO grades correlated poorly with nuclear morphology (r = 0.19). Grading of nuclei isolated out of their architectural context significantly improved accuracy for nuclear morphology (r = 0.55), but the prognostic power was virtually lost. In conclusion, the architectural organization of a tumour, which the pathologist cannot avoid noticing during initial slide viewing at low magnification, unwittingly influences the subsequent nuclear grade assignment. In our study, the prognostic power of the WHO grading system was dependent on visual assessment of tumour growth pattern. We demonstrate for the first time the influence a cognitive bias can have in the generation of an error in diagnostic pathology and highlight a considerable problem in histopathological tumour grading. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Long-interval intracortical inhibition in a human hand muscle

When two motor cortical stimuli are delivered with an interstimulus interval of 50–200 ms, the response (motor evoked potential; MEP) to the second stimulus is typically suppressed. This phenomenon is termed long-interval intracortical inhibition (LICI), although data from one subject suggest that facilitation is possible. Moreover, we recently showed that suppression can be mediated at a spinal level. We characterized LICI more fully by exploring a broad range of contraction strengths and test stimulus intensities. MEPs were evoked in first dorsal interosseous by transcranial magnetic stimulation over the motor cortex. Single test and paired (conditioning-test interval of 100 ms) stimuli at intensities of 100–160% resting motor threshold were delivered at rest or during brief contractions of 10, 25, or 100% maximal voluntary force. Inhibition or facilitation was quantified with the standard ratio in which conditioned MEPs were expressed as a percentage of unconditioned MEPs. Inhibition was greatest at weak–moderate contraction strengths and least at rest and during maximal efforts. Both at rest and during maximal efforts, MEPs evoked by strong stimuli were facilitated. In a subset of subjects, cervicomedullary stimulation was used to activate the corticospinal tract to identify possible spinal influences on changes to MEPs. Contraction strength and test stimulus intensity each had different effects on unconditioned and conditioned MEP size, and hence, LICI is highly dependent on both factors. Further, because motoneurons are facilitated during contraction but disfacilitated after a strong conditioning stimulus, the standard ratio of LICI is of questionable validity during voluntary contractions.     

Coupling between human muscle spindle endings and motor units assessed using spike-triggered averaging

The electromyographic activity (EMG) generated by voluntary contraction of a muscle was averaged using the potentials from 18 identified muscle spindle afferents as a trigger. In post-spike averages of 1000-10,000 sweeps, no evidence of reflex excitation of the homonymous motoneurone pool was detected. In pre-spike averages there was no evidence of a motor-unit EMG potential that was closely correlated to the trigger spike. A single spindle afferent has only a weak reflex effect on an active motoneurone pool and must be part of a synchronized volley to affect motoneurone discharge significantly. No evidence was found for spindle activation via beta-motoneurones in weak voluntary contractions.