Testosterone deficiency and quality of life in Australasian testicular cancer survivors: a prospective cohort study.

This is the first prospective study in a contemporary Australian/New Zealand population to determine the prevalence of testosterone deficiency in testicular cancer survivors at 12 months from treatment, and any association with poorer quality of life. Hormone assays from 54 evaluable patients in a prospective cohort study revealed biochemical hypogonadism in 18 patients (33%) and low-normal testosterone in 13 patients (24%). We found no association between testosterone levels and quality of life (all P > 0.05). Hypogonadal patients should be considered for testosterone replacement to prevent long-term morbidity.

Accelerated BEP for metastatic germ cell tumours: a multicenter phase II trial by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP).

BACKGROUND: This Australian single-arm, multicenter, phase II trial evaluated feasibility, tolerability and activity of accelerated bleomycin, etoposide and cisplatin (BEP) as first-line chemotherapy for metastatic germ cell tumours. PATIENTS AND METHODS: Patients were planned to receive cisplatin 20 mg/m(2) and etoposide 100 mg/m(2) days 1-5, and pegfilgrastim 6 mg day 6, all repeated every 2 weeks for four cycles (three cycles for good prognosis). Bleomycin was given at 30 000 IU weekly to a total of 12 doses (9 doses for good prognosis). Primary end point was feasibility, defined as the proportion of patients able to complete the etoposide and cisplatin components of BEP and be eligible to receive a fourth cycle of BEP by day 50. RESULTS: Twelve poor, 16 intermediate and 15 good prognosis (n = 43) eligible patients were enrolled. Two patients aged >40 years were ineligible and excluded from analyses. The regimen was feasible in 86%, not feasible in 7% and not assessable in 7% of patients. Most common grade 3/4 adverse events were non-neutropenic infection (16%) and febrile neutropenia (12%). Complete response (CR) to chemotherapy and surgery was achieved in 33% poor-prognosis, 81% intermediate-prognosis and 100% good-prognosis patients. At median follow-up of 27 months (range 6-42), the 2-year progression-free survival was 50% for poor-prognosis, 94% for intermediate-prognosis and 92% for good-prognosis patients. CONCLUSION: Accelerated BEP is feasible and tolerable. Efficacy data appear to be promising. This trial and a similar UK study provide the rationale for a randomised trial comparing accelerated versus standard BEP. Australian New Zealand Clinical Trials Registry Registration number. ACTRN 12607000294459.

Positron emission tomography and pathological evidence of response to neoadjuvant therapy in adenocarcinoma of the esophagus.

Our aim was to determine if fluorodeoxyglucose positron emission tomography (FDG-PET) could be correlated with a pathological response in patients with esophageal adenocarcinoma receiving neoadjuvant chemotherapy and/or chemoradiation therapy. Patients with resectable, histologically proven adenocarcinoma of the esophagus were entered in the study. Preoperative chemotherapy comprised two cycles of cisplatin and 5-fluorouracil. Radiation therapy commenced with the second cycle on day 22. FDG-PET images were obtained pre-treatment and on completion of intended neo-adjuvant treatment. Quantification was achieved by the calculation of both standardized uptake values (SUV) and tumor/liver ratios (TLR). Evidence of histopathological response was identified according to the Mandard tumor regression scoring system. There were 45 patients, 22 receiving neoadjuvant chemotherapy and 23 chemoradiation therapy. Forty patients underwent surgical resection. Seven patients (16%) had a histopathological response. The mean percentage change in SUV in the histological responders group was -56.8% (SD 29) and in the non-responders -27.8% (SD 32.1) (P = 0.035). The mean percentage change in TLR was -49.1% (SD 44.8) in the responders and in the non-responders -27.3% (SD 31.3) (P = 0.128). There was no difference between the two methods of assessment, however there was less variation with SUV. There was no correlation between the FDG-PET response and the histopathological response. Presently an FDG-PET scan performed 3-6 weeks after neoadjuvant therapy for adenocarcinoma of the esophagus should not be used as a marker of the potential result of the treatment. The optimal timing of a second FDG-PET remains unclear.

Outcomes from salvage esophagectomy post definitive chemoradiotherapy compared with resection following preoperative neoadjuvant chemoradiotherapy.

Chemoradiotherapy (CRT) as a definitive treatment for esophageal cancer, is being used with increasing frequency and as a result, surgeons will be required to assess more patients who have residual or recurrent local malignancy. This article aimed to assess outcomes after esophagectomy following definitive CRT (dCRT) and compare any difference between them and patients who had preoperative neoadjuvant CRT (nCRT) using a similar regimen of chemotherapy. From a prospective database the details of patients who had a resection following nCRT and dCRT were analyzed. The main therapeutic difference between the groups was the dose of radiotherapy (35 vs 60 Gy) and the timing of the resection following completion of the CRT (median 4 vs 28 weeks). Fourteen patients had an esophagectomy following a dCRT and 53 had one following a nCRT. Preoperatively, the dCRT group had worse respiratory function and more ECG abnormalities. Preoperative tumor length, pathological TNM staging and R0 resection rates were the same in both groups. Post resection, the dCRT group had greater morbidity than the nCRT group, spending longer in the intensive care unit (median 48 vs 24 h), more days in hospital (median 31 vs 13) and having more severe respiratory complications (37%vs 6%). The operative mortality was higher in the dCRT group (7%vs 0%). The three-year survival was 24% after dCRT. Patients selected for salvage esophagectomy following dCRT are a major challenge in postoperative care. However, some patients survive for a reasonable period of time, making resection a worthwhile option.

Chemoradiation therapy is effective for the palliative treatment of malignant dysphagia.

Between 1993 and 2001, 106 patients with esophageal cancer were reviewed at a multidisciplinary clinic and treated with palliative intent by chemoradiation therapy. This study assesses the palliative benefit on dysphagia and documents the toxicity of this treatment. The study population comprised 72 men and 34 women with a median age of 69 years. Patients were treated with a median radiation dose of 35 Gy in 15 fractions with a concurrent single course of 5 FU-based chemotherapy. Dysphagia was measured at the beginning and completion of treatment and at monthly intervals until death, using a modified DeMeester (4-point) score. Treatment was well tolerated, with only 5% of patients failing to complete therapy. The treatment-related mortality was 6%. The median survival for the study population was 7 months. The median baseline score at presentation was 2 (difficulty with soft food). Following treatment, 49% of patients were assessed as having a dysphagia score of 0 (no dysphagia). Seventy-eight per cent had an improvement of at least one grade in their dysphagia score after treatment. Only 14% of patients showed no improvement with treatment. Fifty-one per cent maintained improved swallowing until the time of last follow-up or death. This single-institution study shows that chemoradiation therapy administered for the palliation of malignant dysphagia is well tolerated and produces a sustainable normalization in swallowing for almost half of all patients.

Use of oesophagogastroscopy to assess the response of oesophageal carcinoma to neoadjuvant therapy.

BACKGROUND: Approximately 25 per cent of patients with oesophageal cancer who undergo neoadjuvant chemoradiotherapy have no evidence of tumour in the resected specimen (complete pathological response). Those who do not respond have a poor 5-year survival compared with complete responders, regardless of whether or not they undergo surgery. Selecting for surgery only those who have a response to neoadjuvant therapy has the potential to improve overall survival as well as to rationalize the management of non-responders. This study assessed the accuracy of oesophagogastroscopy in this setting. METHODS: A prospective database of 804 patients undergoing oesophageal resection for carcinoma was reviewed. Endoscopic assessment of the response to neoadjuvant therapy in 100 consecutive patients was compared with the pathological assessment of response. The survival for each level of response was compared. RESULTS: At endoscopy 30 patients were considered to have had a complete response. This was confirmed pathologically in 15 patients. Survival was improved in those with a pathologically confirmed complete response (3-year survival rate 62.4 (s.e. 12.9) per cent) compared with non-responders (16.3 (s.e. 6.6) per cent). Those with microscopic residual disease also had an improved 3-year survival rate (46.3 (s.e. 12.2) per cent); however, oesophagogastroscopy failed to identify this subset. CONCLUSION: Oesophagogastroscopy may be useful in the assessment of tumour response to neoadjuvant therapy. However, owing to its poor accuracy patients should not be excluded from further therapeutic intervention on the basis of this assessment alone.

Comparison of two standard chemotherapy regimens for good-prognosis germ-cell tumours: a randomised trial. Australian and New Zealand Germ Cell Trial Group.

BACKGROUND: Most patients with metastatic germ-cell tumours are cured with chemotherapy. However, the optimum chemotherapy regimen is uncertain, and there is variation in international practice. We did a multicentre randomised trial to compare two standard chemotherapy regimens for men with good-prognosis germ-cell tumours. METHODS: Good prognosis was defined by modified Memorial Sloan-Kettering criteria. The first regimen (regimen A) was based on treatment recommendations from Indiana University and comprised three cycles of 20 mg/m2 cisplatin on days 1-5, 100 mg/m2 etoposide on days 1-5, and 30 kU bleomycin on days 1, 8, and 15, repeated every 21 days. The second regimen (regimen B) was based on the control regimen of a published randomised clinical trial and comprised four cycles of 100 mg/m2 cisplatin on day 1, 120 mg/m2 etoposide on days 1-3, and 30 kU bleomycin on day 1, repeated every 21 days. The primary outcome measure was overall survival. Analysis was by intention to treat. FINDINGS: 166 patients were randomised, 83 to each regimen. The trial was stopped when the second planned interim analysis met predefined stopping rules. The median follow-up was 33 months. Overall survival was substantially better with regimen A (three vs 13 deaths, hazard ratio 0.22 [95% CI 0.06-0.77], p=0.008). This difference was due to deaths from cancer (one vs nine), and not deaths from treatment (two vs two) and remained significant after adjustment for other prognostic factors (0.25 [0.07-0.88], p=0.03). INTERPRETATION: In men with good-prognosis germ-cell tumours, the regimen developed at Indiana University is superior to the alternative regimen studied in this trial. The lower total dose and dose-intensity of bleomycin and the lower dose-intensity of etoposide in regimen B could be responsible for the worse outcome.

Cortical influences on the vestibular nuclei of the cat.

Our goal was to study potential substrates for cortical modulation of vestibular reflexes in the cat. In initial experiments, injections of wheat-germ-agglutinate-horseradish-peroxidase into Deiters' nucleus and the rostral descending nucleus revealed bilateral colonies of retrogradely filled neurons in cortical areas 6, 2, and 3a (about 60 cells per colony). In cats anesthetized with chloralose-urethane, we stimulated areas 2 and 3a with trains of pulses while recording from ipsilateral vestibular-nucleus neurons, which were characterized by their responses to sinusoidal tilts and tested for the presence of antidromic responses to stimulation of the upper cervical cord. A majority of the neurons was affected by cortical stimulation, showing either facilitation, inhibition, or a mixture of the two. Stimulation in area 2 was more effective than stimulation in area 3a. Despite the anatomic presence of direct cortico-vestibular projections, properties of facilitation and inhibition suggest that both were evoked by polysynaptic pathways. Cortical effects were broadly distributed to vestibular neurons without regard to responses of these neurons to sinusoidal tilts. There was no significant difference between effects on lateral and medial vestibulospinal tract neurons, but, as a group, vestibulospinal neurons were much more likely to be affected by cortical stimulation than neurons not antidromically activated from the C2 segment. We conclude that, by their influence on vestibulospinal neurons, neurons in cortical areas 2 and 3a should be able to modulate, in behaving animals, vestibular reflexes acting on the neck and limbs.

Morphometry, histochemistry, and innervation of cervical shoulder muscles in the cat.

Morphometric and histochemical methods were used to estimate the force-developing capabilities and fiber-type contents of four muscle complexes (rhomboideus, levator scapulae, trapezius, and sternomastoideus) that link the shoulder girdle to the skull and cervical vertebrae. Each complex contained at least two member muscles that were distinctive architecturally and often had specialized innervation patterns. Trapezius and sternocleidomastoideus were innervated by both cranial nerve XI and cervical spinal nerves. Glycogen depletion of trapezius suggested that the nerves derived from cervical roots might be entirely sensory. Muscles within each complex varied in physiological cross-sectional area from less than 0.1 cm2 to greater than 1 cm2. They showed differences in fiber-type composition that suggested specialized roles for different behaviors. The morphometric features of the cervical shoulder muscles suggest that they have considerable potential to produce head movements and should be incorporated into feline head-movement models.

Vestibulospinal effects on neurons in different regions of the gray matter of the cat upper cervical cord.

1. Previous studies of vestibular effects on the upper cervical cord have concentrated on the lateral and medial vestibulospinal tracts and on the actions that they exert on neck motoneurons and other neurons in the ventral horn. It is known, however, that both the rostral and the caudal areas of the vestibular nuclei (VN) give rise to axons that are located in the dorsal and dorsolateral funiculi and that terminate in the dorsal horn. A primary goal of our experiments was to investigate the effect of VN stimulation on neurons dorsal to lamina VII. 2. In decerebrate cats with the caudal cerebellar vermis removed, we stimulated different areas of the VN with an array of electrode. The area of stimulation extended from the caudal tip of the descending nucleus to Deiters' nucleus, and was divided into rostral and caudal halves with the use of the descending nucleus as a reference. For control purposes some stimulating points were placed in the external cuneate nucleus and restiform body. 3. We tested the effects of VN stimulation on spontaneously firing neurons in the ipsilateral C2 and C3 segments. For purposes of classification the gray matter was divided into four zones corresponding approximately to laminae 1-IV, V-VI, VII, and VIII of Rexed. Overall, the activity of 39 of 84 neurons was influenced from one or more stimulating sites. For six cells there was some possibility of current spread to the external cuneate nucleus or to the underlying reticular formation. 4. VN-evoked effects could consist of facilitation, or, less often, inhibition. In the majority of facilitated neurons conditioning stimuli evoked a synchronized, short-latency, increase in firing probability. When evoked by single stimuli this facilitation was considered monosynaptic. Facilitation that was diffuse, or that was only evoked by two or more stimuli, presumably involved more complex pathways. The latency of inhibition could not be measured, but was short. 5. Stimulation of either the rostral or caudal VN had no effect on neurons in laminae I-IV. Electrodes placed rostrally had little effect on neurons in laminae V-VI, but influenced more than half the neurons in laminae VII-VIII. Conversely, electrodes placed caudally were most effective on cells in laminae V-VII, although they also influenced some neurons in lamina VIII. 6. Stimulation of the dorsal rami influenced most neurons in laminae V-VI, and about a quarter of the neurons in laminae VII-VIII. When tested, there was often convergence between vestibulospinal and peripheral inputs. 7. Our results provide physiological evidence that vestibulospinal fibers influence neurons not only in laminae VII and VIII, but also as far dorsally as lamina V. Fibers that influence neurons in laminae V and VI originate primarily in the caudal areas of the VN. As suggested previously on anatomic grounds, the projection to the dorsal laminae, which is predominantly facilitatory, often converges with afferent input and can therefore modulate its influence on spinal neurons.

Responses of neurons of the cat central cervical nucleus to natural neck and vestibular stimulation.

1. The central cervical nucleus (CCN) is known to receive neck and vestibular input and to project to the contralateral cerebellum and vestibular nuclei. To investigate the processing of neck and vestibular input by cells in the CCN, we studied their responses to sinusoidal neck rotation and to whole-body tilt in vertical planes in decerebrate, paralyzed cats. CCN neurons were identified by antidromic stimulation with electrodes placed in or near the contralateral restiform body. 2. For every neuron, we first identified the preferred direction of neck rotation (response vector orientation), then studied the neuron's dynamics with rotations in a plane close to this direction at 0.05-1 Hz. 3. Responses of CCN neurons to neck rotation resembled those of previously studied neck spindle primary afferents in terms of their dynamics and nonlinear responses to stimuli of differing amplitudes. They also resembled the neck responses of Deiters' neurons studied in similar preparations. 4. The activity of two-thirds of CCN neurons also was modulated by natural vestibular stimulation. Orientation and dynamics of vestibular responses were characterized in the same way as neck responses. Labyrinthine input originated predominantly from the contralateral vertical canals, and there was no evidence of otolith input. Neck and vestibular inputs were always antagonistic, but the gain of the vestibular response was lower than that of the neck response at all frequencies studied. 5. The quantitative aspects of the interaction between neck and vestibular inputs can be expected to vary with the type of preparation and with stimulus parameters, and its functional significance remains to be investigated.

Effect of neck posture on patterns of activation of feline neck muscles during horizontal rotation.

The electromyographic (EMG) patterns of neck muscles were recorded during whole-body horizontal rotation in head-free, alert cats and head-restrained, decerebrate cats. In some trials the cervical column of the animal was oriented vertically, whereas in others it was oriented more horizontally. In alert cats making head movements that compensated for the motion of the platform, neck muscles with modulated patterns of activity could be divided into a subset whose individual EMG patterns changed significantly when the neck posture was altered (including longissimus capitis, obliquus capitis superior and scalenus anterior) and a subset whose individual EMG patterns were invariant regardless of neck posture (including obliquus capitis inferior, levator scapulae and complexus). In head-restrained, decerebrate cats, electromyograms from all implanted muscles were modulated similarly in phase with the platform position. Changing the orientation of the neck had little effect upon these EMG patterns evoked by the horizontal vestibulocollic reflex. One decerebrate cat with strong extensor tone was tested further under head-free conditions. There was very little compensatory head movement, but individual neck muscles displayed patterns of activity that were more similar to those observed in alert, head-free animals.

Tilt responses of neurons in the caudal descending nucleus of the decerebrate cat: influence of the caudal cerebellar vermis and of neck receptors.

1. In decerebrate cats with intact cerebellums, we studied the responses of neurons in the caudal areas of the vestibular nuclei to natural vestibular stimulation in vertical planes and to neck rotation. The activity of most neurons was recorded in the caudal half of the descending nucleus. 2. One goal of our experiments was to compare the dynamic and spatial properties of responses to sinusoidal vestibular stimulation with those seen in previous experiments in which the caudal cerebellar vermis, including the nodulus and uvula, was removed. This part of the cerebellum receives vestibular input and projects to the caudal areas of the vestibular nuclei, suggesting that it could influence responses to stimulation of the labyrinth. 3. As in our previous experiments, most neurons could be classified as receiving predominant input either from the otoliths or from one vertical semicircular canal. When mean gain and phase and response vector orientations were compared, there were no obvious differences between the behavior of neurons in the partially decerebellate preparation and the one with the cerebellum intact, demonstrating that in the decerebrate cat the nodulus and uvula have little or no influence on the processing of vertical vestibular input in this region of the vestibular nuclei. 4. Only 23 of 74 (31%) of neurons tested responded to neck rotation. This contrasts with the much larger fractions that respond to this stimulus in Deiters' nucleus and in the rostral descending nucleus. We also recorded from neurons near the vestibular nuclei, mainly in the external cuneate nucleus. All of them (9 of 9) responded to neck rotation. 5. Responses to neck rotation also differed in their dynamics from those found more rostrally in the vestibular nuclei. Dynamics of more rostral neurons resemble those of neck muscle spindles, as do those of external cuneate neurons. The dynamics of caudal vestibular neurons, on the other hand, have a steeper gain slope and more advanced phases than do those of neurons in the more rostral vestibular nuclei. This suggests the possibility of involvement of additional receptors in the production of these responses. 6. In the more rostral vestibular nuclei, responses to vestibular and neck rotation are most often antagonistic, so that head rotation results in little or no response. This is not the case in the caudal areas of the vestibular nuclei, where less than half the neurons tested displayed antagonistic behavior. Further experiments are required to put the neck projection to the caudal vestibular nuclei in a functional context.

Malignant sacrococcygeal germ cell tumour in an adult.

In adults, malignant sacrococcygeal germ cell tumour is a rare cause for a presacral tumour, with only 17 cases having been reported in the literature since 1907. We report the case of a 34 year old male who presented with a 6 month history of symptoms relating to a malignant presacral tumour which required en bloc excision including the lower sacrum and rectum. He died with lung and mediastinal metastasis 7 months following surgical excision and adjuvant chemotherapy using Cisplatin, Bleomycin and Etoposide. Prior to his death, he had a severe polyarthritis of his peripheral joints and evidence of hypertrophic osteo-arthropathy. The literature indicates that adults with these tumours have a poor prognosis, with only one reported long-term survivor. Surgical excision offers the only chance of cure, with the role of adjuvant therapy not having been defined because of the small numbers.

Effect of MLF transection on the vertical vestibulocollic reflex in decerebrate cats.

1. In the cat, motoneurons supplying biventer cervicis, complexus and rectus capitis posterior receive disynaptic input from the posterior semicircular canals and from the contralateral anterior canal via the medial vestibulospinal tract (MVST). Disynaptic excitation from the ipsilateral anterior canal reaches these motoneurons via the lateral vestibulospinal tract. 2. We hypothesized that if the MVST has a unique role in the production of the vertical vestibulocollic reflex (VCR) in these muscles then interruption of this tract by transection of the medial longitudinal fasciculus (MLF) would change the VCR responses. Specifically, response vector orientations would shift toward the plane of the ipsilateral anterior canal, and response gains would drop at high frequencies. 3. We lesioned the MLF bilaterally and observed no substantial effect on neck-muscle responses. Response vector orientations did not shift systematically toward a single plane, nor was there a consistent decrease in response gains at high frequencies. 4. As in the horizontal VCR, there is no unique contribution from MVST neurons; parallel pathways must play an important role in the vertical VCR.

Vertical vestibular input to and projections from the caudal parts of the vestibular nuclei of the decerebrate cat.

1. To investigate the type of vestibular signals that neurons in the caudal parts of the vestibular nuclei transmit to the cerebellum and spinal cord, we studied their responses to natural vestibular stimulation in vertical planes in decerebrate cats with the caudal cerebellum removed. Most neurons were in the caudal half of the descending vestibular nucleus, the remainder at corresponding levels of the medial nucleus or the medial-descending border. 2. Dynamics of the responses of spontaneously firing neurons were studied with sinusoidal tilts delivered at 0.05-1 Hz near the plane of body rotation that produced maximal modulation of the neuron's activity (response vector orientation). For most neurons the predominant vestibular input could be identified as coming from otolith organs (46%) or vertical semicircular canals (37%). Some neurons had otolith+canal convergence (9%) and others either had such converging input or some other form of central processing (8%). 3. Gain and phase of the responses of otolith neurons were comparable with values obtained in earlier studies on Deiters' nucleus and the rostral descending nucleus. Many canal neurons had a steeper gain slope and more advanced phase than observed previously for more rostral neurons. This may be due to more irregular afferent input to many neurons or to the absence of the vestibulocerebellum. 4. Response vector orientations of canal neurons were closely bunched near the planes of the ipsilateral vertical canals. The small number of contralaterally projecting vectors showed evidence of convergence between the two contralateral vertical canals. As is the case elsewhere in the vestibular nuclei, there was no evidence of convergence from bilateral vertical canals. Response vector orientations of otolith neurons were restricted to the roll quadrants; the majority pointed ipsilaterally. 5. Antidromic stimulation with an electrode in the restiform body or with several electrodes in the dorsal half of the white matter of the upper cervical cord was used to identify neurons projecting to the cerebellum and spinal cord, respectively. A substantial number of spontaneously firing neurons projected to the cerebellum, but there were few spontaneously active vestibulospinal neurons. The properties of the vestibular input to cerebellar-projecting neurons were the same as those of the population as a whole, but the effect of tilt on vestibulospinal neurons appeared weak or absent. 6. Many neurons were inhibited by stimulation of the restiform body. We suggest that this is mainly due to stimulation of the axons of vestibulocerebellar Purkinje cells. 7. Our results demonstrate a robust vertical vestibular input to the caudal parts of the vestibular nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of neck posture on the activation of feline neck muscles during voluntary head turns.

1. To determine whether neck posture affects the usage of neck muscles during a specific motor task, we recorded the electromyographic (EMG) patterns of neck muscles in four cats, which made horizontal, head-turning movements to fixate eccentrically placed targets. In some trials, the cervical column was oriented vertically whereas in other trials, the cervical column was oriented more horizontally. 2. During horizontal head movements, five muscles (obliquus capitis inferior, splenius, levator scapulae, complexus, and biventer cervicis) displayed activation patterns that were consistent from cat to cat and did not change when the cats adopted a different neck posture. Most of these muscles are large, superficial muscles that attach to the skull and span many cervical joints. 3. Posturally dependent patterns of activation were observed in five other neck muscles (semispinalis cervicis, longissimus capitis, levator scapulae ventralis, scalenus anterior, and obliquus capitis superior). Most of these muscles lie deeper and more laterally within the neck musculature and generally span fewer cervical joints than the muscles that displayed invariant patterns of activation. 4. These results suggest that the set of invariantly activated muscles may compose part of a basic motor program that is triggered during head movements in the horizontal plane. This motor program appears to be modified by the selective activation of ancillary muscles, which are recruited in a manner related to the neck posture. The deep positioning of the ancillary muscles may permit them to regulate the mobility of the cervical column and to adjust the net muscular force applied across the neck to the skull. Organizing the motor output in this manner might simplify the task of computing the appropriate patterns of neck-muscle activation.

Efficacy of seven retrograde tracers, compared in multiple-labelling studies of feline motoneurones.

The labelling efficacies of 7 retrograde tracers were evaluated following cut nerve exposure or intramuscular injection into the serially compartmentalized neck muscle, biventer cervicis. Tested tracers included Fast Blue (FB), Fluorogold (FG), dextran conjugated to fluorescein (FD), dextran conjugated to rhodamine (Fluororuby (FR), 3000 and 10,000 MW), fluorescent latex microspheres, horseradish peroxidase coupled to colloidal gold, and 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate (DiI). In 2 animals, horseradish peroxidase was also employed and spinal cords were processed for peroxidase activity to evaluate its effect on the appearance of cells labelled with fluorescent tracers. Four tracers, FB, FG, FD and FR, could be observed in motoneurones under the conditions of our study. FB and FG labelled comparable numbers of motoneurones following cut nerve exposure, but dissimilar numbers following intramuscular injection. FG diffused extensively following injection and was found in motoneurones not only in the appropriate ipsilateral segment but also adjacent ipsilateral and contralateral segments. Intramuscular injections of FB usually labelled fewer cells than cut nerve exposure, but evidence for spurious labelling following intramuscular injection could also be found. FD or FR labelled motoneurones following cut nerve exposure but not following intramuscular injection. The conjugated dextrans labelled more variable numbers of cells than FB or FG, but the labelled cells had similar patterns of distribution. The remaining tracers were ineffective as retrograde markers in our study, and the possible reasons for these failures are discussed.