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Notes: Abstract  Objective. To determine whether the load-bearing capacity of human proximal femora with metastatic defects can be predicted from the bone mineral content. Design. The bone mineral content (BMC) of the total proximal femur was measured by dual-energy X-ray absorptiometry (DXA). The femurs were loaded so as to simulate stair ascent or external rotation. Patients. Simulated lytic defects were created using specialized cutting tools in the intertrochanteric region of 32 human cadaveric femora. Bone density measurements were made before and after creating defects. Results. A linear relation could be used to predict failure load from BMC or bone mineral density. The slope of the linear relation was greater for loads representing external rotation than for loads representing stair ascent. The linear relations suggest that the BMC measurements account for both the density of the host bone and the amount of bone removed by the defect. Conclusions. The data suggest that between 70% and 80% of the variation in failure load of human femora with lytic metastatic defects can be predicted from the BMC and that relations between BMC and failure load are sensitive to the type of loading. Combined with information on the loads associated with the activities of daily living, these data may be used to help identify patients in whom prophylactic stabilization might prevent a pathologic fracture.

Notes: Abstract Advanced glycation endproducts have been implicated in the development of diabetic complications. In addition, these products could also mediate certain bone alterations such as diabetic osteopenia. Several receptors specific for advanced glycation endproduct-modified proteins have been characterized in different cell types, contributing to the recognition and degradation of senescent proteins. In the present report, we investigated the possible presence of advanced glycation endproduct-binding proteins on osteoblast-like cells. Both UMR106 and MC3T3E1 cell lines express specific advanced glycation endproduct-binding sites, with an affinity constant between 0.4 and 1.7 · 106 M−1, depending on the stage of osteoblastic differentiation; and with a receptor capacity of 1.5–2.0 · 107 sites/cell. Osteoblast-like cells were also found to participate both in the uptake and degradation of advanced glycation endproduct-modified bovine serum albumin at 37°C. Radiolabelled ligand blotting studies confirmed the presence of several membrane binding proteins, with apparent molecular masses of 50, 45–40, 30, 25 and 18 kDa; the major bands corresponded to 30 and 25 kDa proteins. This study provides evidence of the presence of advanced glycation endproduct-specific binding sites, and for their regulation with the stage of differentiation, in two osteoblast-like cells in culture.

Notes: Abstract  Pontine omnipause neurons (OPNs) have so far been considered as forming a homogeneous group of neurons whose tonic firing stops during the duration of saccades, when the head is immobilized. In cats, they pause for the total duration of gaze shifts, when the head is free to move. In the present study, carried out on alert cats with fixed heads, we present observations made during self-initiated saccades and during tracking of a moving target which show that the OPN population is not homogeneous. Of the 76 OPNs we identified, 39 were found to have characteristics similar to those of previously described neurons, ”saccade” (S-) OPNs: (1) the durations of their pauses were significantly correlated with the durations of saccades; (2) the discharge ceased shortly before saccade onset and resumed before saccade end; (3) visual responses to target motion were excitatory; and (4) during tracking, S-OPNs interrupted the discharge for the duration of saccades and resumed firing during perisaccadic ”drifts”. However, the characteristics of 37 neurons (”complex” (C-) OPNs) were different: (1) the pause duration was not correlated with the duration of self-initiated saccades; (2) time lead of pause onsets relative to saccades was, on average, longer than in the group of S-OPNs, and firing resumed after the saccade end; (3) visual target motion suppressed tonic discharges; and (4) during tracking, firing was interrupted for the total duration of gaze shifts, including not only saccades but also perisaccadic ”drifts”. We conclude that cat OPNs can be subdivided into two main groups. The first comprises neurons whose firing patterns are compatible with gating individual saccades (”saccade” OPNs). The second group consists of ”complex” OPNs whose firing characteristics are appropriate to gate total gaze displacements rather than individual saccades. The function of these neurons may be to disinhibit pontobulbar circuits participating in the generation of saccade sequences and associated perisaccadic drifts.

Notes: Summary Objective: Determination of the value of bone scanning in symptomatic total knee arthroplasties. Setting Academic Hospital Maastricht and Maasland Hospital Sittard. Design: Retrospective clinical investigation. Method: The clinical reports of 27 patients, who underwent a bone scintigraphic study, were investigated for complaints and analysis of diagnostic decision making. These patients had persistent symptoms after total knee arthroplasty. In addition, conventional radiographs and the isotope scans were studied without knowledge of the clinical records. Based on these data we evaluated in which cases isotope scanning of the knee had contributed decisively to the further treatment. Results: Isotope scanning did not contribute to the treatment planning if physical examination or conventional radiographs had not led to a clinical diagnosis. This comprised 37% of the patients in our series. If a clinical diagnosis was present, isotope scanning did influence decision making in 65% of the patients. However in the remaining patients with a clinical diagnosis (35%) this was not the case. Conclusion: Radionuclide imaging is of limited value in the diagnostic process of symptomatic total knee arthroplasty. It may support or reject a clinical diagnosis, but in the absence of abnormal findings at physical examinations or radiologic studies, it seldom will induce a change in treatment

Notes: Summary Biocompatible calcium phosphate ceramics has been used for several years in orthopeadic surgery. We have been using two new synthetic biphasic calcium phosphate ceramics (BCP) since September 1996 for bone defect filling in any orthopaedic or trauma operation where autograft use was not possible or even wanted. The first, Eurocer 400® has 300 to 500 micron wide macropores with a totally interconnected porosity. This salt seed like product can be used in bone defect filling, when solidity is not a major concern. The second, Eurocer 200® has not totally interconnected 200 micron large pores. Its main characteristic is a mechanical resistance up to 30 Mpa. We use it in any case of weight-bearing surgery. Different sizes and presentation forms are available and will be chosen according to the recipient site shape. We report one hundred and fifty cases with a six to thirty month follow-up. In one third of the patients hip revision surgery was addressed. Another third concerned recent trauma or sequelae cases,.whereas the last third involved cold orthopaedic procedures. General principles are the need of a living and non-infected site after thorough debridement if necessary. Osteocompatibility of calcium phosphate ceramic is confirmed by our results. We report no mechanical failure. In all cases X-rays show a progressive integration, with new bone formation. Our substitutes have been histologically studied in nine cases, four to fifteen months after implantation. New bone formation around and in the substitute is impressive. Indeed, their good mechanical properties without loss of biological quality is the most relevant feature of these BCPs, leading to a wider indication field; therefore we have now abandoned the use of any bony auto, allo or xenograft.

Notes: Abstract  Connections from the otolithic organs to sternocleidomastoid (SCM) motoneurons were studied in 20 decerebrate cats. The electrical stimulation was selective for the saccular or the utricular nerves. Postsynaptic potentials were recorded from antidromically identified SCM motoneurons; these muscles participate mainly in neck rotation and flexion. Partial transections of the brainstem at the level of the obex were performed to identify the possible pathway from the otolithic organs to the SCM motoneurons. Saccular or utricular nerve stimulation mainly evoked inhibitory postsynaptic potentials (IPSPs) in the ipsilateral SCM motoneurons. Some of the sacculus-induced IPSPs were preceded by small-amplitude excitatory PSPs (EPSPs). The latencies of the PSPs ranged from 1.8 to 3.1 ms after saccular nerve stimulation and from 1.7 to 2.8 ms after utricular nerve stimulation, indicating that most of the ipsilateral connections were disynaptic. In the contralateral SCM motoneurons, saccular nerve stimulation had no or faint effects, whereas utricular nerve stimulation evoked EPSPs in about two-thirds of neurons, and no visible PSPs in about one-third of neurons. The latencies of the EPSPs ranged from 1.5 to 2.0 ms, indicating the disynaptic connection. Thus, the results suggest a difference between the two otolithic innervating patterns of SCM motoneurons. After transection of the medial vestibulospinal tract (MVST), saccular nerve stimulation did not evoke IPSPs at all in ipsilateral SCM motoneurons, but some (11/40) neurons showed small-amplitude EPSPs. Most (24/33) of the utricular-activated IPSPs disappeared after transection, whereas the other 9 neurons still indicated IPSPs. In the contralateral SCM motoneurons, no utricular-activated EPSPs were recorded after transection. These MVST transection results suggest that most of the otolith-SCM pathways are located in the MVST at the obex level. However, the results also suggest the possibility that other otolith-SCM pathways exist at the obex level.

Notes: Abstract  Accurate performance by the vestibulo-ocular reflex (VOR) is necessary to stabilize visual fixation during head movements. VOR performance is severely affected by peripheral vestibular damage; after one horizontal semicircular canal is plugged, the horizontal VOR is asymmetric and its amplitude is reduced. The VOR recovers partially. We investigated the limits of recovery by measuring the VOR’s response to ipsilesional and contralesional rotation after unilateral peripheral damage in cats. We found that the VOR’s response to rotation at high frequencies remained asymmetric after recovery was complete. When the stimulus was a pulse of head velocity comprising a dynamic overshoot followed by a plateau, gain was partially restored and symmetry completely restored within 30 days after the plug, but only for the plateau response. The overshoot in eye velocity remained asymmetric. The asymmetry was independent of stimulus velocity throughout the known linear velocity range of primary vestibular afferents. Sinusoidal rotation at 0.05–8 Hz revealed that, within this range, the persistent asymmetry was significant only at frequencies above 2 Hz. Asymmetry was independent of the peak head acceleration over the range of 50–500°/s2. When both horizontal canals were plugged, a small residual VOR was observed, suggesting residual signal transduction by plugged semicircular canals. However, transduction by plugged canals could not explain the enhancement of the VOR gain, at high frequencies, for rotation away from the plugged side compared with rotation toward the plug. Also, the high-frequency asymmetry was present after recovery from a unilateral labyrinthectomy. These results suggest that high-frequency asymmetry after unilateral damage is not due to residual function in the plugged canal. The findings are discussed in the context of a bilateral model of the VOR that includes central filtering.

Notes: Abstract  Receptive-field properties of retinal ganglion cells (RGCs) that had regenerated their axons were studied by recording single-unit activity from strands teased from peripheral nerve (PN) grafts apposed to the cut optic nerve in adult cats. Of the 286 visually responsive units recorded from PN grafts in 20 cats, 49.7% were classified, according to their receptive-field properties, as Y-cells, 39.5% as X-cells, 6.6% as W-cells, and 4.2% were unclassified. The predominant representation of Y-cells is consistent with a corresponding morphological study (Watanabe et al. 1993a), which identified α-cells as the RGC type with the largest proportion of regenerating axons. Among the X-cells, we only found ON-center types, whereas both ON-center and OFF-center Y-cells were found. As in intact retinas, the receptive-field center sizes of Y-cells and W-cells were larger than those of X-cells at corresponding displacements from the area centralis. Within the 10° surrounding the area centralis, the receptive fields of X-cells with regenerated axons were larger than those in intact retinas, suggesting that some rearrangement of retinal circuitry occurred as a consequence of degeneration and regeneration. Receptive-field center responses of Y-, X-, and W-type units with regenerated axons were similar to those found in intact retinas, but the level of spontaneous activity of Y- and X-type units was, in general, less than that of intact RGCs. Receptive-field surrounds were weak or not detected in more than half of the visually responsive RGCs with regenerated axons.

Notes: Abstract  Functional connections of single reticulospinal neurons (RSNs) in the nucleus reticularis gigantocellularis (NRG) with ipsilateral dorsal neck motoneurons were examined with the spike-triggered averaging technique. Extracellular spikes of single NRG-RSNs activated antidromically from the C6, but not from the L1 segment (C-RSNs) were used as the trigger. These neurons were monosynaptically activated from the superior colliculus and the cerebral peduncle. Single-RSN PSPs were recorded in 43 dorsal neck motoneurons [biventer cervicis and complexus (BCC) and splenius (SPL)] for 21 NRG-RSNs and 135 motoneurons tested. All synaptic potentials were EPSPs, and most of their latencies, measured from the triggering spikes, were 0.8–1.5 ms, which is in a monosynaptic range. The amplitudes of single-RSN EPSPs were 10–360 µV. Spike-triggered averaging revealed single-RSN EPSPs in multiple motoneurons of the same species (SPL or BCC), their locations extending up to nearly 1 mm rostrocaudally. Synaptic connections of single RSNs with both SPL and BCC motoneurons were also found with some predominance for one of them. The results provide direct evidence that NRG-RSNs make monosynaptic excitatory connections with SPL and BCC motoneurons. It appears that some NRG-RSNs connect predominantly with SPL motoneurons and others with BCC motoneurons.

Notes: Abstract  Postsynaptic potentials (PSPs) evoked in motoneurons innervating the back and abdominal muscles in the lumbar part of the body by stimulating hindlimb cutaneous afferents were investigated in unanesthetized decerebate and spinal cats. Various types of PSP: pure excitatory postsynaptic potential (EPSP), pure inhibitory postsynaptic potential (IPSP), and mixed PSP (i.e., EPSP followed by IPSP, EPSP/IPSP; and IPSP followed by EPSP, IPSP/EPSP) were observed. The weak stimulation at 2 times threshold (2T) produced predominantly the EPSP, while at 5T the incidence of IPSP or EPSP followed by IPSP was increased. In about 20–50% of the various groups of motoneurons, PSPs evoked by ipsi- and contralateral nerves were qualitatively and quantitatively similar. For the other motoneurons, PSPs evoked by ipsi- and contralateral nerves were markedly different with respect to magnitude and/or polarity. These findings suggest that, within each motoneuron pool, some neurons act to increase stiffness of the trunk or to move vertically in response to an increased activity of cutaneous afferents, while the other motoneurons act to produce lateral bending of the trunk.

Notes: Abstract  The purpose of this review is to assess the role of short-latency pathways in the vestibulocollic reflex (VCR). First the current knowledge about the disynaptic and trisynaptic pathways linking semicircular canal and otolith afferents with cat neck motoneurons is summarized. We then discuss whether these pathways are sufficient or necessary to produce the responses observed in neck muscles by natural vestibular stimulation and conclude that they are neither. Finally, alternate pathways are considered, most likely involving reticulospinal fibers, which are an important part of the neural substrate of the VCR.

Notes: Abstract  Corticospinal (CS) axon terminations in several species are widespread early in development but are subsequently refined into a spatially more restricted distribution. We studied the role of neural activity in sensorimotor cortex in shaping postnatal development of CS terminations in cats. We continuously infused muscimol unilaterally into sensorimotor cortex to silence neurons during the postnatal CS refinement period (weeks 3–7). Using anterograde transport of WGA-HRP, we examined the laterality of terminations from the muscimol-infused (i.e., silenced) and active sides in the spinal cord, as well as in the cuneate nucleus and red nucleus. We found that CS terminations from the muscimol-infused cortex were very sparse and limited to the contralateral side, while those from the active cortex maintained an immature bilateral topography. Controls (saline infusion, noninfusion) had dense, predominantly contralateral, CS terminations. There was a substantial decrease in the spinal gray matter area occupied by terminations from the side receiving the blockade and a concomitant increase in the area occupied by ipsilateral terminations from the active cortex. Optical density measurements of HRP reaction product from the active cortex in muscimol-infused animals showed substantial increases over controls in the ratio of ipsilateral to contralateral CS terminations for all laminae examined (IV–V, VI, VII). Our findings suggest that ipsilateral dorsal horn terminations reflect new axon growth during the refinement period because they are not present there earlier in development. Those in the ventral horn are present earlier in development and thus could reflect maintenance of transient terminations. Increased ipsilateral terminations from active cortex were due to recrossing of CS axons in lamina X and not to an increase in labeled CS axons in the ipsilateral white matter. Examination of brain stem terminations suggested that, between postnatal weeks 3 and 7, development of corticocuneate terminations also is activity-dependent but that development of corticorubral terminations is not. Activity-dependent CS development is a plausible mechanism by which early motor experiences could shape the anatomical and functional organization of the motor systems during a critical postnatal period.

Notes: Abstract PURPOSE: This report presents a patient who developed severe buttock pain because of an ossified intramuscular metastasis from a sigmoid colon cancer. METHODS: This is a case report and review of the literature for intramuscular metastasis from colon cancer. RESULTS: Computed tomography and magnetic resonance imaging showed a soft-tissue mass with heavy calcification. Histologically, mature compact bone was observed with adenocarcinoma cells dispersed among the bony trabeculae. CONCLUSION: When an intramuscular mass is seen, even if it contains extensive calcification, metastasis from colon cancer should be included in differential diagnosis.

Notes: Abstract Embolism of bone marrow to the lungs is a quite frequent finding after trauma but transport and deposition of solid bone is rarely seen, which may simply be because pulmonary calcifications are not recognized as bone fragments. We report on three patients with embolism of bone spicules to small lung arteries of about 0.5 mm in diameter which were plentiful in two of the patients on postmortem examination. However, the true nature of the emboli was only recognizable after decalcification of lung tissues. It appears that trauma occurring in a septic bone lesion has the greatest chance to provoke bone embolism. The bone spicules do not usually occlude vessel lumina and thus do not severely disturb the blood circulation in the lungs. The bone fragments become covered by endothelium and can remain recognizable for months or even years.

Notes: Für die infizierte Osteoradionekrose (IORN) des Kiefers werden unterschiedliche pathogenetische Mechanismen initialer Strahlenfolgen im Knochen diskutiert: Wichtige Parameter sind dabei die direkte Zellschädigung der Osteozyten [28] und die Gefäßfibrosierung [21]. Bislang liegen wenige Kenntnisse zum Ausmaß der initialen, subklinischen Veränderungen vor. 4 Probengruppen wurden anhand verschiedener Patientenkollektive definiert: Gruppe 1: gesunde Unterkieferproben meist von orthodontischen Operationen (n = 10 Patienten); Gruppe 2: Unterkieferproben mit manifester IORN (n = 12 Patienten); Grruppe 3: Unterkieferproben nach 36 Gy präoperativer Radio(chemo)therapie (n = 9 Patienten); Gruppe 4: Unterkieferproben nach 60–70 Gy Bestrahlung ohne Hinweise auf IORN (n = 9 Patienten). Alle Proben wurden histotomographisch mit konfokaler Laser-Scanning-Mikroskopie (CLSM), durchlichtmikroskopisch (DL) und dunkelfeldmikroskopisch (DFM) nach Fluoreszenzmarkierung des intakten Zellkerns (Bisbenzimid H 33258) untersucht. Korrelierende Histologien identischer Probenareale erfolgten an Trenndünnschliffen [8]. Als Ergebnisse wurden gefunden: 1. Alle unterschiedlich bestrahlte Knochenproben zeigten Areale mit weitgehendem bis vollständigem Verlust vitaler Osteozyten. Diese Strahlenfolge trat auch schon nach 36 Gy und kurzem Intervall bis zur Operation (Gruppe 3) auf. 2. Im CLSM zeigten sich zusätzlich mikromorphologische Veränderungen der lamellären Struktur, die zwischen den Probengruppen progredient waren. Hieraus können folgende Schlußfolgerungen gezogen werden: 1. Der vorbeschriebene Vitalitätsverlust der Osteozyten [10, 23, 28] konnte als sehr frühe, initiale, radiogene Läsion bestätigt werden. 2. Zusätzlich zeigten sich Veränderungen der lamellären Mikroarchitektur des Knochens als frühe und im Gruppenvergleich progrediente Strahlenläsion. Die mikromechanisch funktionelle Bedeutung dieser Veränderung muß in weiterführenden Untersuchungen eruiert werden.

Notes: Abstract An in vivo model has been developed for chronic observation of the effects of ischemia on cortical bone remodeling and perfused vascularity. Diaphragm occluders were implanted around the right common iliac artery of four rabbits and inflated to produce 10 h of ischemia to the limb. Microcirculation was monitored with intravital microscopy of injected fluorescent microspheres and FITC-Dextran 70 through a bone window, the tibial bone chamber implant (BCI). Bone resorption and apposition in the BCI were indicated with mineralization dyes. Between 2 and 12 h following release of the occluder, secondary ischemia/no-reflow and other evidence of reperfusion injury were observed. Vessel damage was suggested by abnormally high leakage of FITC-D70 from the few vessels perfused during secondary ischemia. In the weeks following occluder release perfused vasculature increased beyond pre-occlusion levels. Net bone resorption reached a maximum when vascularity passed normal levels. In order to further validate the arterial occlusion model for osteonecrosis, techniques for (1) confirming bone death and (2) detecting increased leukocyte adherence to endothelial cells were added. The dead cell stain Ethidium homodimer-1 was used to tag dead osteocytes immediately after occlusion and produced a measure designated “osteonecrosis index.” To detect leukocytes adhering to vessel walls, carboxyfluorescein diacetate, succinimidyl ester was injected at occluder release. An increase in the number of adherent leukocytes was detected. © 1999 Biomedical Engineering Society. PAC99: 8764Rr, 8717-d, 8719Tt

Notes: Abstract The aim of this study was to describe the contrast-enhanced magnetic resonance imaging (MRI) appearance of bone tunnel enlargement detected on radiography after anterior cruciate ligament (ACL) reconstruction with semitendinosus and gracilis tendon endobutton (STG-endobutton) fixation technique. Fourteen patients with a STG-endobutton ACL reconstruction were examined 3 months (n = 1), 1 year (n = 1) and 2 years (n = 12) postoperatively. An age- and sex-matched group with a bone–patellar tendon–bone (BTB) autograft ACL reconstruction with similar follow-up was taken as control. Data on clinical examination, laxity and isokinetic muscle torque measurements, anteroposterior and lateral view radiography were obtained, and knee scores (Lysholm and Tegner) were collected. Contrast-enhanced MRI was performed in the STG-endobutton group with a 1.5-T imager. There were no statistical differences between the groups with respect to clinical findings, stability tests, or knee scores. In the STG-endobutton group the average femoral and tibial bone tunnel diameter detected on anteroposterior view radiography had increased at 2-year follow-up by 33% and 23%, respectively. On MRI the ligamentous graft itself was not enhanced by the contrast medium whereas periligamentous tissue within and around the STG graft bundles showed mild contrast enhancement. In conclusion, the MRI results suggest that enhancing periligamentous tissue accumulated in and around the STG graft associated with the tunnel expansion. In spite of the significant bone tunnel enlargement observed on the follow-up radiography the STG-endobutton knees were stable and the patients satisfied.

Notes: Zusammenfassung Die aneurysmatische Knochenzyste mit Lokalisation an der Hand, insbesondere an den Phalangen, ist ein extrem seltenes Krankheitsbild. Auch das Alter des Patienten und die ausgeprägte Aggressivität unseres Falles sind bemerkenswert. Anhand der Krankengeschichte eines 53jährigen Mannes mit Befall der Grundphalanx des fünften Fingers der rechten Hand werden die Problemstellung bzw. Differentialdiagnose verdeutlicht und die verschiedenen Therapiemöglichkeiten besprochen. In unserem Fall wurde zunächst eine Kürettage mit anschließender Spongiosaaufftüllung durchgeführt. Bereits nach fünf Monaten kam es zu einem aggressiven Rezidiv mit Zerstörung der gesamten Grundphalanx und des Grundgelenks, so daß wir uns schließlich unter Berücksichtigung der bestmöglichen Funktion der Hand für eine Amputation des Kleinfingers entschieden haben.

Notes: Abstract A 49-year-old man had three episodes of bacterial peritonitis in the 8 months after he started nocturnal intermittent peritoneal dialysis (NIPD) at home, using an automated cycler device. When peritonitis was first diagnosed, Enterobacter agglomerance was cultured in his peritoneal fluid. In the second and third episodes, Pasteurella multocida and alpha-Streptococcus were isolated, respectively. These bacteria are unusual pathogens in continuous ambulatory peritoneal dialysis (CAPD) peritonitis. Detailed questioning revealed that a domestic cat had bitten the dialysis tube before the patient experienced the second episode of peritonitis. Pasteurella multocida is part of the normal oral flora in cats and dogs. We isolated Pasteurella multocida from the teeth of the patient's cat. Enterobacter agglomerance is part of the common bacterial flora in animal's alimentary tract, and alpha-Streptococcus is commonly found in animal's respiratory tracts. Since the patient removed the cat from his bedroom, he has had no peritonitis. NIPD is a very convenient sysytem for patients in the final stage of renal failure; however, patients must be aware of the risks associated with keeping pets in their homes. This case is the first report of cat-associated peritonitis in Japan.

Notes: Zusammenfassung Fast jede Körperzelle ist estrogenrezeptiv. Es gibt allerdings Organe und Organsysteme, die besonders unter dem Einfluß von Estrogenen stehen und die sich bei Estrogenmangel krankhaft verändern können. Die vielfältigen Wirkungen von Estrogenen konnten nicht vollständig verstanden werden, solange die Existenz von nur einem Estrogenrezeptor quasi ein Dogma war. Erst die Klonierung eines zweiten (Estrogenrezeptor β = ERβ) sowie das bessere Verständnis von gewebespezifischen Enhancer- und Repressor-Genen konnten die vielfältigen und z. T. organspezifischen Wirkungen der Estrogene aufklären. Aus der Sicht der gynäkologischen Endokrinologie ist die Hormonersatztherapie mit Estrogenen für fast alle Organe des Körpers (Knochen, Herz-Kreislauf-System, Zentralnervensystem) segensreich. Eine nicht gestagenbegleitete Estrogentherapie kann allerdings verheerende Folgen am Endometrium mit Entwicklung eines Corpus-Karzinoms haben. Da der Uterus praktisch kein ERβ sondern nur den klassischen ERα exprimiert, hat eine intensive Suche nach ERβ-spezifischen Estrogenen begonnen. Ein erstes, halbwegs spezifisches nicht-steroidales Produkt scheint das kürzlich in die Klinik eingeführte Raloxifen zu sein, aber auch einige Phytoestrogene scheinen ERβ-spezifisch zu wirken.

Notes: Abstract  Two cases of osseous hemangiopericytoma are presented that were initially diagnosed as primary in origin, but later reclassified as metastases, after a history of resection for an intracranial tumor was discovered. An intracranial source should be excluded before an isolated osseous tumor is determined to be a primary hemangiopericytoma.

Notes: Abstract  Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon sarcomas that almost always arise in soft tissue. They can develop in pre-existing neurofibromas or schwannomas, de novo from peripheral nerves, or following radiation therapy. Primary intraosseous MPNST is rare and has been reported most frequently in the mandible. Of the reported cases involving the long bones, none has been associated with neurofibromatosis type 1 (NF-1). We report a case of MPNST arising in the femur in a patient with NF-1.

Notes: Abstract. The neonatal Bartter syndrome (NBS) is associated with a complex disorder of mineral metabolism in children, including hypercalciuria, nephrocalcinosis, and diminished bone mineral density. Although cyclooxygenase inhibition usually brings about improvement in these findings, there is a variable component which is resistant to such therapy in many children. The factor mediating this disorder has not been identified. Blood and urine from 12 children with NBS were examined. When compared with samples from normal children and adults, all (NBS) sera reduced bone calcium uptake in a bone disc bioassay. This effect persisted in the presence of parathyroid hormone (PTH) antibody and PTH receptor blockade, indicating that neither PTH nor PTH related peptide was responsible. It was eliminated by indomethacin, suggesting that prostanoid generation was essential. Protamine was also inhibitory, as was the addition of ecteola, an anion binder. Activity could be recovered from ecteola by elution with hypertonic buffer. Urine samples from children with NBS had the same calcitropic effect. The agent was removed by ecteola and recovered by hypertonic elution. Activity was eliminated by protamine and by heparinase, but not by trypsin digestion. Size exclusion centrifugation showed that the activity was associated with a material between 10 and 30 kilodaltons. Finally, urine ecteola eluates from NBS patients raised serum concentrations of calcium after intraperitoneal injection in rats. These data suggest that children with NBS have a calcitropic substance in their serum and urine which is not found in normal individuals. The substance is heparin like, and mediates its effects through prostanoid production. These studies provide additional evidence against a direct renal cause of the urinary calcium disturbance characteristic of the disorder.

Notes: Abstract  The retrograde axonal transport method was used to compare the topography and organization of the visual zone of the claustrum in rat, guinea pig, rabbit and cat. First, massive Fluoro-Gold injections were placed into the primary visual cortex and the secondary areas. Experiments showed differences in the location of the visual zone among the animals under study. In rat, the visual zone occupied the posteroventral part of the claustrum and spread to its anterior pole. In guinea pig, neurons projecting to the visual cortex were located dorsally in the posterior half of the claustrum. In rabbit, similarly to the rat, they were localized in the posteroventral part; however, they did not reach the anterior pole. In cat, neurons that project to the visual cortex were concentrated dorsally in the posterior fourth of the claustrum. In double-injection experiments, Fast Blue and Diamidino Yellow were placed into the primary and secondary visual areas in various combinations. The experiments showed that in the rat and the rabbit claustral neurons project to primary visual cortex (area 17) as well as to both secondary visual areas (areas 18a and b). Populations of neurons sending axons to the primary and secondary areas showed full overlap. The presence of double-labeled neurons indicates that some claustral neurons project both to the primary and secondary fields. In cat, neurons that project to the primary visual cortex appear to be clearly separated from those connected with the secondary visual area, as no double-labeled neurons were found. In all studied species, the double injections placed into the visual and primary somatosensory cortex did not result in any double-labeling neurons. Our results indicate that the location of the visual zone in the posterior part of the claustrum is a phylogenetically stable feature, whereas its dorsoventral shift as well as the extent toward the anterior pole is related to the particular species. The overlap of neurons projecting to the primary and secondary visual areas in the rat and rabbit as well as the separation of both projections in cat appear to reflect the higher degree of complexity of the visual system in the latter.

Notes: Abstract Muscular dystrophy has long been believed to be characterized by degeneration and abortive regeneration of muscle fibers (the muscle degeneration theory), but unfortunately its pathogenesis is still unclear and an effective treatment has yet to be developed. As a challenge to the theory, we have proposed an alternative muscle-defective-growth theory and a further bone muscle growth imbalance hypothesis supposing possible defects in bone-growth-dependent muscle growth based on our findings in hereditary dystrophic dy mice (C57BL/6Jdy/dy). This review presents some new insights into the pathogenesis of the disease along with our hypothesis, focusing on the physiological meaning of centronucleation, one of the major pathological changes commonly observed in dystrophic muscles of man and experimental animals.

Notes: Abstract The case of a 21/2-year-old boy with diffuse cystic angiomatosis of bone is presented. No evidence of visceral involvement was recorded. The clinical, radiographic and histologic findings during the course of the disease process are discussed. At the age of 15 years the patient died of neurologic alterations developed due to massive osteolysis and collapse of the cervical spine, and severe dyspnoea, secondary to persistent bilateral pleural effusions.

Notes: Abstract  The dendritic tree constitutes more than 93% of the receptive membrane area of a spinal motoneuron, yet little is known about its synaptic inputs. In this study we examined the distribution of glutamate-, GABA- and glycine-like immunoreactivity in boutons apposing dendrites in the L7 spinal cord motor nucleus, by use of postembedding immunohistochemistry on serial sections. We examined 799 boutons apposing 401 cross-sectioned dendrites of different calibre (range 0.2–15 µm), and 14 first-order (stem) dendrites. Thirty-five percent (35%) of the boutons were immunopositive for glutamate and 59% for GABA and/or glycine. Among the latter, 30% showed glycine immunoreactivity only and 24% were immunoreactive for both GABA and glycine. Very few were immunoreactive only for GABA (5%). As few as 6% of the boutons were judged as not enriched for any amino acid analysed. The fine structural characteristics of the boutons were in accordance with previous descriptions. The sample of dendrites was arranged in calibre bins in order to facilitate distribution analysis. Stem dendrites differed from the other bins, with a high total bouton covering (61%) and a high bouton density. Sixty-nine percent of the membrane covering was by glycine- and/or GABA-immunoreactive boutons, whereas 18% was covered by boutons enriched in glutamate. For non-stem dendrites, bouton covering fell from 33% to 12% with decreasing calibre. However, bouton apposition length decreased in parallel, yielding a fairly uniform bouton density among dendrites of different calibre. The lack of correlation between packing density and dendrite calibre was also evident when the sample of dendrites was broken down into subsamples based on content of amino acid immunoreactivity. The latter analysis also revealed that both the relative covering and density of boutons containing inhibitory amino acids (57%; glycine and/or GABA) and glutamate (38%), respectively, did not vary systematically with dendrite calibre. Combined, the data indicate that in non-stem dendrites the proportion of excitatory and inhibition inputs does not change systematically throughout the dendritic arborizations of spinal α-motoneurons. Thus, spinal motoneurons can, with respect to the general synaptic architecture, be divided into two main compartments, i.e. the proximal soma-juxtasomatic compartment (including stem dendrites) and the distal dendritc compartment. The proximal domain is under a powerful glycine and/or GABA influence. Finally, based on the data presented here and previously published data, it was calculated that spinal α-motoneurons receive in the range of 50–140×103 synaptic boutons.

Notes: Abstract  The robust behavior, the degree of response linearity, and the aspect of contrast gain control in visual cortical simple cells are (amongst others) the result of the interplay between excitatory and inhibitory afferent and intracortical connections. The goal of this study was to suggest a simple intracortical connection pattern, which could also play a role in other cortical substructures, in order to generically obtain these desired effects within large physiological parameter ranges. To this end we explored the degree of linearity of spatial summation in visual simple cells experimentally and in different models based on half-wave rectifying cells (’’push-pull models’’). Visual cortical push-pull connection schemes originated from antagonistic motor-control models. Thus, this model class is widely applicable but normally requires a rather specific design. On the other hand we showed that a more generic version of a push-pull model, the so-called cascaded inhibitory intracortical connection scheme, which we implemented in a biologically realistic simulation, naturally explains much of the experimental data. We investigated the influence of the afferent and intracortical connection structure on the measured linearity of spatial summation in simple cells. The analysis made use of the relative modulation measure, which is easy to apply but is limited to moving sinusoidal grating stimuli. We introduced two basic push-pull models, where the order of threshold nonlinearity and linear summation is reversed. Very little difference is observed with the relative modulation measure for these models. Alterative models, like half-wave squaring models, were also briefly discussed. Of all model parameters, the ratio of excitation to inhibition in the simple cell exerts the most crucial influence on the relative modulation. Linearity deteriorates as soon as excitatory and inhibitory inputs are imbalanced and the relative modulation drops. This prediction was tested experimentally by extracellular recordings from cat area 17 simple cells and we found that about 62% showed a significant deviation from linear behavior. The problem that individual basic push-pull models are hard to distinguish experimentally led us to suggest a different solution. In order to generically account for the observed behavior (e.g., imbalance of excitation versus inhibition), we suggested a rather generic version of a push-pull model where it no longer mattered about (the hard-to-distinguish) fine differences in connectivity. Thus, we introduced a new class of biophysically realistic models (’’cascaded inhibition’’). This model class requires very little connection specificity and is therefore highly robust against parameter variations. Up to 25 cells are connected to each target cell. Thereby a highly interconnected network is generated, which also leads to disinhibition at some parts of an individual receptive field. We showed that the performance of these models simulates the degree of linearity and its variability in recal simple cells with comparatively high accuracy. This behavior can be explained by the self-regulating properties of a cascaded inhibitory connection scheme by which the balance between excitation and inhibition at a given cell is improved by the joint network effects. The virtues and the generic design of this connection pattern, therefore, allow to speculate that it is used also in other parts of the cortex.

Notes: Abstract  The generation of locomotor-like spinal rhythms has been proposed to involve two neural centres with mutual reciprocal inhibition (Graham Brown’s ”half-centre” hypothesis). Much later a particular set of segmental flexor reflex pathways were described as being organized in accordance with this half-centre hypothesis. As these pathways became operative following injection of monoaminoxidase inhibitors and l-3,4-dihydroxyphenylalanine (l-dopa), i.e. under the same conditions under which a spontaneous locomotor activity may develop, it was assumed that these particular pathways and spinal rhythm generators involve the same neuronal networks. In order to give further evidence to this hypothesis, we investigated whether short trains to ”flexor reflex afferents” (FRA) reset the spinal locomotor rhythm, i.e. shorten or lengthen the stimulated cycle after which the regular rhythm is resumed with step cycles of the original duration. The experiments were performed in anaemically decapitated, high-spinal curarized cats. A steady locomotor rhythm was induced by injection of nialamide and l-dopa and the influence of electrical stimulation (trains of 50–1000 ms) of FRA (joint, cutaneous, and group II and III muscle afferents) onto this rhythm was tested. Stimulation of FRA induced a clear resetting of the locomotor rhythm, which was mainly characterized by a flexion reflex pattern: during the extension phase the extensor activity was interrupted and a flexion phase was initiated; during the late flexion phase mainly a prolongation of that phase with a variable change of the following extension phase was induced. In addition to this prevailing pattern, stimulation of some nerves (in particular nerves to more distal extensors and the sural nerve) could often prolong extension, when stimulated during the late extension, or terminate the flexor burst and initiate a new extension phase, when stimulated during the late flexion phase. This pattern is probably due to the concomitant stimulation of group I afferents in the case of the muscle nerves and to separate non-FRA pathways in the case of the sural nerve. The results demonstrate that the interneurones of the FRA pathways, which are operative during l-dopa-induced locomotion in spinal animals, can be considered as neuronal elements of the rhythm-generating network for locomotion.

Notes: Abstract  Micturition in the decerebrate cat is characterized by a coordinated bladder contraction and a simultaneous decrease in external urethral sphincter (EUS) efferent activity. Without the suppression of EUS activity, voiding is significantly impaired, resulting in a state sometimes referred to as bladder-sphincter dyssynergia. The aim of the present study was to determine whether glycinergic inhibition contributes to the suppression of EUS activity during micturition evoked by bladder distension or electrical stimulation of the pontine micturition center (PMC) in decerebrate cats. Using subconvulsive intravenous doses of strychnine (0.1–0.24 mg/kg), we examined changes in bladder and EUS electroneurographic (ENG) activity during micturition. Following subconvulsive doses of strychnine, tonic EUS ENG activity increased during bladder filling in five of six animals. In the presence of strychnine, it was possible to evoke reflex bladder contractions of similar duration and peak pressure to those observed before strychnine administration. However, there was an absence of suppression of EUS ENG activity during the bladder contractions in all the animals. To determine whether the changes in sphincter activity could be due to strychnine acting at glycine receptors on EUS motoneurons, sacral spinal tissue was processed for a structural protein (gephyrin) associated with the glycine receptor. Motoneurons in Onuf′s nucleus in S1 were identified using choline acetyltransferase immunohistochemistry and subsequently processed with a gephyrin monoclonal antibody. Abundant gephyrin labeling was evident throughout Onuf′s nucleus. Since Onuf′s nucleus is made up of EUS and other motoneuron populations, a sample of antidromically identified urethral and anal sphincter motoneurons were intracellularly labeled with tetramethylrhodamine dextran (TMR-D) and then processed with the gephyrin antibody. Using dual-beam confocal microscopy, gephyrin immunoreactivity was observed on the soma and proximal processes of individual EUS motoneurons in both male and female animals. It was concluded that a strychnine-sensitive mechanism contributes to the suppression of sphincter activity normally observed during voiding. Although glycinergic inhibition may affect several components of the circuitry responsible for micturition, it appears that the suppression of EUS motoneurons during micturition may be partly due to a direct glycinergic inhibition of the EUS motoneurons.

Notes: Abstract  This study examined the role of trunk extensor muscles in the thoracic and lumbar regions during postural adjustments in the freely standing cat. The epaxial extensor muscles participate in the rapid postural responses evoked by horizontal translation of the support surface. The muscles segregate into two regional groups separated by a short transition zone, according to the spatial pattern of the electromyographic (EMG) responses. The upper thoracic muscles (T5-9) respond best to posteriorly directed translations, whereas the lumbar muscles (T13 to L7) respond best to anterior translations. The transition group muscles (T10-12) respond to almost all translations. Muscles group according to vertebral level rather than muscle species. The upper thoracic muscles change little in their response with changes in stance distance (fore-hindpaw separation) and may act to stabilize the intervertebral angles of the thoracic curvature. Activity in the lumbar muscles increases along with upward rotation of the pelvis (iliac crest) as stance distance decreases. Lumbar muscles appear to stabilize the pelvis with respect to the lumbar vertebrae (L7-sacral joint). The transition zone muscles display a change in spatial tuning with stance distance, responding to many directions of translation at short distances and focusing to respond best to contralateral translations at the long stance distance.

Notes: Abstract  This study examined the configuration of the vertebral column of the cat during independent stance and in various flexed positions. The range of motion in the sagittal plane is similar across most thoracic and lumbar joints, with the exception of a lesser range at the transition region from thoracic-type to lumbar-type vertebrae. The upper thoracic column exhibits most of its range in dorsiflexion and the lower thoracic and lumbar in ventroflexion. Lateral flexion is limited to less than 5° at all segments. The range in torsion is almost 180° and occurs primarily in the midthoracic region, T4-T11. Contrary to the depiction in most atlases, the standing cat exhibits several curvatures, including a mild dorsiflexion in the lower lumbar segments, a marked ventroflexion in the lower thoracic and upper lumbar segments, and a profound dorsiflexion in the upper thoracic (above T9) and cervical segments. The curvatures are not significantly changed by altering stance distance but are affected by head posture. During stance, the top of the scapula lies well above the spines of the thoracic vertebrae, and the glenohumeral joint is just below the bodies of vertebrae T3-T5. Using a simple static model of the vertebral column in the sagittal plane, it was estimated that the bending moment due to gravity is bimodal with a dorsiflexion moment in the lower thoracic and lumbar region and a ventroflexion moment in the upper thoracic and cervical region. Given the bending moments and the position of the scapula during stance, it is proposed that two groups of scapular muscles provide the major antigravity support for the head and anterior trunk. Levator scapulae and serratus ventralis form the lateral group, inserting on the lateral processes of cervical vertebrae and on the ribs. The major and minor rhomboids form the medial group, inserting on the spinous tips of vertebrae from C4 to T4. It is also proposed that the hypaxial muscles, psoas major, minor, and quadratus lumborum could support the lumbar trunk during stance.

Notes: Abstract The aim of this electron-microscopic study was to analyze the distribution of synaptic contacts on the cell bodies and dendrites of permanently axotomized adult cat spinal α-motoneurons. Following transection and ligation of the medial gastrocnemius nerve, the synaptic covering of the cell bodies and three different dendritic compartments of homonymous α-motoneurons was analyzed quantitatively at 3, 6, and 12 weeks postoperatively. The synaptic boutons were classified according to their size and the shape of their synaptic vesicles. On the soma, a transient increase in the number of boutons was noted at 3 weeks and 6 weeks postoperatively, while after 12 weeks the bouton number had decreased to half of its normal value. The transient increase was mainly due to an increase in the number of F-type boutons. At 12 weeks postoperatively, the synaptic covering was reduced by 83% on the soma and by 57% on the proximal dendrites. In the distal dendritic regions, the values for synaptic covering remained largely unchanged. In summary, axotomized motoneurons exhibit a reduction in synaptic covering which is maximal on the cell body and becomes less pronounced centrifugally along the dendrites. However, if also taking into account the loss of distal dendritic branches that occurs in axotomized motoneurons, the total loss of boutons is several times larger in the dendrites than on the soma.

Notes: Abstract  In our previous report we found that subcutaneous (s.c.) formalin injection into the cutaneous receptive field (RF) of dorsal horn wide-dynamic-range (WDR) units and nociceptive primary afferent units resulted in a tonic, long-lasting increase in firing. However, s.c. formalin injection only resulted in a short-lasting increase in firing of non-nociceptive primary afferent units. In the present study, by using extracellular single-unit recording techniques we further studied effects of s.c. formalin on response properties of identified superficial-layer nociceptive-specific (NS) units and deeper-layer, low-threshold mechanoreceptive (LTM) units of L7 dorsal horn in urethane-chloralose-anesthetized cats. s.c. formalin injection into the RF of NS units resulted in a tonic, long-lasting increase in firing (7.08 ± 0.42 spikes/s, n = 5), for more than 1 h, compared with the spontaneous background (1.42 ± 0.03 spikes/s, n = 5). Formalin injection into the RF of LTM units also resulted in an increase in firing; however, the duration was short-lasting, for 25–520 s (152.92 ± 46.73 s, n = 12). The present study demonstrated that s.c. injection of dilute formalin solution resulted in activation of not only nociceptive but also non-nociceptive dorsal horn units, suggesting that tissue injury caused by s.c. formalin results in vigorous injury discharges of peripheral nerve terminals, which subsequently leads to activation of primary afferent neurons and secondary dorsal horn neurons.

Notes: Abstract  The purpose of this study was to investigate changes in neck muscle and eye movement responses during the early stages of vestibular compensation (first 3 weeks after unilateral vestibular neurectomy, UVN). Electromyographic (EMG) activity from antagonist neck extensor (splenius capitis) and flexor (longus capitis) muscles and eye movements were recorded during sinusoidal visual and/or otolith vertical linear stimulations in the 0.05–1 Hz frequency range (corresponding acceleration range 0.003–1.16 g) in the head-fixed alert cat. Preoperative EMG activity from the splenius and longus capitis muscles showed a pattern of alternate activation of the antagonist neck muscles in all the cats. After UVN, two motor strategies were observed. For three of the seven cats, the temporal activation of the individual neck muscles was the same as that recorded before UVN. For the other four cats, UVN resulted in a pattern of coactivation of the flexor and extensor neck muscles because of a phase change of the splenius capitis. In both subgroups, the response patterns of the antagonist neck muscles were consistent for each cat independently of the experimental conditions, throughout the 3 weeks of testing. Cats displaying alternate activation of antagonist neck muscles showed an enhanced gain of the visually induced neck responses, particularly in the high range of stimulus frequency, and a gain decrease in the otolith-induced neck responses at the lowest frequency (0.25 Hz) only. By contrast, for cats with neck muscle coactivation, the gain of the visually induced neck responses was basically unaffected relative to preoperative values, whereas otolith-induced neck responses were considerably decreased in the whole range of stimulation. As concerns oculomotor responses, results in the two subgroups of cats were similar. The optokinetic responses were not affected by the vestibular lesion. On the contrary, otolith-induced eye responses showed a gain reduction and a phase lead. Deficits and short-term changes after UVN of otolith- and semicircular canal-evoked collic and ocular responses are compared.

Notes: Abstract  Feline caudofemoralis (CF) is a promising preparation in which to study the properties of mammalian fast-twitch skeletal muscle, but little is known about its muscle fiber properties, architecture, and motor innervation. We used histochemical techniques to confirm that it contained predominantly type IIB fibers (95±2%, n=8, with six of eight muscles composed exclusively of type IIA and IIB fibers), but physiological experiments showed less fatiguability than for the type IIB component of medial gastrocnemius. This may be related to the surprisingly strong and regular recruitment of CF during repetitive tasks such as walking and trotting, which we demonstrated electromyographically. We measured muscle length over the anatomical range of motion for CF (∼0.6–1.2 L 0) and estimated working length during walking and trotting (∼0.95–1.15 L 0). The specific tension was similar to that of the exclusively slow-twitch soleus muscle (31.2±4.7 N/cm2 compared with 31.8±4.1 N/cm2; P〉0.8). Single fiber dissections of CF revealed a series-fibered architecture with a mean of 2.3 fibers, each 2.5 cm long, required to span the fascicle length. We identified two neuromuscular compartments in CF by cutting one of the two nerve branches innervating CF and depleting the glycogen stores in the intact motor units. These compartments were in parallel and extended the length of the muscle; their electromyographic activity was similar during various natural behaviors. CF and gluteus maximus motoneurons were labeled concurrently with a combination of fluorescent, retrograde tracers including Fluororuby, Fluorogold and Fast Blue. The CF motor nucleus was located in L7-S1, overlapping and intermingling extensively with the nucleus of the adjacent gluteus maximus muscle. Distributions of CF motoneuron diameter revealed one large peak around 50–55 µm, with relatively few small-diameter (less than 35 µm) cells. Using estimates of the total number of fibers in three muscles and the estimated number of α-motoneurons for those same muscles, we calculated a mean innervation ratio of ∼270, which is at the low end of the innervation ratios for type IIB motor units from other feline muscles and more similar to type IIA motor units. In general, CF appears to be a useful preparation in which to study the properties of fast-twitch muscle, but these properties may vary somewhat from type IIB fibers from different muscles.

Notes: Abstract  The possibility of collateral segmental actions of spinocervical tract (SCT) neurones upon interneurones with input from cutaneous and group II muscle afferents was investigated in deeply anaesthetized cats. To this end, intracellular and/or extracellular recordings were made from 35 dorsal horn and 15 intermediate zone interneurones in midlumbar segments of the spinal cord and effects of stimulation of the ipsilateral dorso-lateral funiculus (DLF) at C3 and C1 levels, i.e. below and above the lateral cervical nucleus where axons of SCT cells terminate, were compared. The stimuli applied at the C3 segment were within the range of stimuli (50–100 μA) required for antidromic activation of SCT neurones in the same experiment. Those applied at the C1 segment (200–500 μA) were at least 3 times stronger than C3 stimuli. Under the same experimental conditions, long ascending and descending tract neurones (dorsal spino-cerebellar and rubro-spinal tract neurones) with axons in the DLF were activated at similar thresholds from the C1 and C3 segments. Intracellular recordings were made from 29 interneurnoes of which 19 (65%) were dorsal horn and 10 (35%) were intermediate zone interneurones. Excitatory postsynaptic potentials (EPSPs) evoked by single stimuli applied at the C3 segment, but not the C1 segment, were found in 14 (48%) of those interneurones; their latencies (3.0–5.7 ms) and frequency following with only minimal temporal facilitation were as required for potentials being evoked monosynaptically by the fastest conducting SCT neurones. Extracellular recordings were made from 30 interneurones (24 dorsal horn and 6 intermediate zone interneurones), and in these neurones spike potentials induced from the C3, but not from the C1 segment, were evoked only by short trains of stimuli. However, their latencies from the first effective stimulus (4.3–5.4 ms) were compatible with mono- or oligosynaptically mediated collateral actions of SCT neurones. They were found in 10 (33%) of the 30 investigated interneurones. Similar effects of C3 stimuli were found in similar proportions of dorsal horn interneurones and intermediate zone interneurones. Indications were also found for synaptic actions evoked by C3 stimuli that could not be attributed to direct collateral actions of SCT neurones. In some intracellularly recorded dorsal horn interneurones, short-latency EPSPs were evoked from the C3 segment by the 2nd or 3rd stimulus in the train, but not by single stimuli. In other dorsal horn and intermediate zone interneurones, inhibitory postsynaptic potentials (IPSPs) were evoked from the C3 segment at minimal latencies (2.7–3.2 ms), which might be too short to allow their mediation via SCT neurones. We conclude that SCT neurones might be used to forward information from muscle group II and cutaneous afferents not only to neurones in the lateral cervical nucleus and via them to thalamus and cerebral cortex but also to interneurones in spinal reflex pathways. Thereby reflex actions evoked from group II and cutaneous afferents might be co-ordinated with responses mediated by supraspinal neurones. We conclude also that dorsal horn and intermediate zone mid-lumbar interneurones might contribute to the previously reported di-and poly-synaptic excitation or inhibition of postsynaptic dorsal column (PSDC), spinothalamic tract (STT) and spinomesencephalic tract (SMT) neurones by collateral actions of SCT cells. Thereby these interneurones might contribute to the co-ordination of responses mediated by various populations of supraspinal neurones.

Notes: Abstract  Cells in the superficial layers of the superior colliculus of the cat have mainly binocular receptive fields. The aim of the present experiment was to investigate the sensitivity of these cells to horizontal spatial disparity. Unit recordings were carried out in the superficial layers of the superior colliculus of paralyzed and anesthetized cats. Centrally located receptive fields were mapped, separated using prisms, and then stimulated simultaneously using two luminous bars optimally adjusted to the size of the excitatory region of the receptive fields. Only binocular cells were tested, and 65% of these units were found to be sensitive to spatial disparities. Some cells (20%) were clearly insensitive to spatial disparity and the remaining 15% showed complex, unclassifiable interactions. The sensitive cells could be divided into four classes based on their disparity-sensitivity profiles: 38% showed excitatory interactions, whereas 9% showed inhibitory interactions. Moreover, 11% and 7% of the cells responded, respectively, to crossed or uncrossed disparities, and were classified as near cells and far cells. Whereas the general shapes of the sensitivity profiles were similar to those of cells in areas 17–18, selectivity in the superior colliculus was significantly coarser. The superficial layers of the superior colliculus project topographically to the deep layers of the superior colliculus, which are known to contain circuits involved in the control of ocular movements. The results thus suggest that disparity-sensitive cells of the superior colliculus could feed information to these oculomotor neurons, allowing for the localization and fixation of objects on the appropriate plane of vision.

Notes: Abstract  The experiments reported here demonstrate that the mechanical sensitivity of peripheral nerve fibres typically seen after injury can be induced without overtly injuring the nerve, but by simply applying colchicine topically to the nerve. In cats anaesthetised with pentobarbitone sodium, the medial gastrocnemius nerve was exposed and 10 mM colchicine applied topically for 15 min. The animals recovered from the operation normally and showed no subsequent motor deficit. Six days later animals were re-anaesthetised, a laminectomy carried out and responses recorded in single afferents at the level of the dorsal root. It was found that many afferents, particularly those with conduction velocities in the group II–III range, had become sensitive to local mechanical stimulation of the nerve in the region treated with colchicine and showed slowly adapting responses to stretch of the nerve. Many of the smaller fibres exhibited spontaneous activity. Mechanically sensitive afferents exhibited impulse conduction blocks at the colchicine-treated site. Some afferents, which appeared to conduct impulses normally through the treated region, were associated with muscle receptors having normal response properties. However, other muscle receptors were clearly abnormal and were insensitive to muscle stretch or contraction or exhibited only phasic responses. When the nerve was cut proximal to the colchicine-treated site, some, but not all, spontaneous activity was abolished. It was subsequently shown using a collision technique that the activity in some axons had its origin in the cell body in the dorsal root ganglion. In one experiment, it was shown that after nerve section proximal to the colchicine-treated region three of five axons switched their activity from a peripheral to a central origin. It is postulated that colchicine disrupts fast axonal transport of mechanically sensitive or voltage-sensitive ion channels, from the cell body to the peripheral terminals of the axons, leading to an accumulation of these channels at the treated site. This induces mechanical sensitivity and spontaneous activity. It is postulated that interruption of a retrogradely transported signal induces the spontaneous activity in the cell body. These experiments suggest that an important influence is exerted by the cell body on the peripheral terminals of mechanoreceptors to confer on them their normal response properties.

Notes: Abstract  In cats the global (gCBF) as well as the regional cerebral blood flow (rCBF) and blood pressure were measured before, during, and after noxious inward and outward rotations of normal and inflamed elbow joints. The animals were anesthetized with halothane and immobilized by gallamine triethiodide. The gCBF as well as the rCBF were measured using positron emission tomography (PET) with a camera specifically designed for use in small animals. Slow intravenous bolus injections of 15O-labeled water were followed by 3-min acquisition of regional radioactivity starting at the time of injection. In all experiments the gCBF as well as the blood pressure were increased by noxious inward-outward rotations of the normal and of the inflamed joint, whereas the blood pressure and the rCBF remained unchanged during bolus injections under control conditions (without any joint movement). Movements of the inflamed joint evoked significantly greater increases in blood pressure and gCBF than corresponding ones of the normal joint. These increases in gCBF were paralleled by increases in rCBF along the complete anterior to posterior axis of the brain. Again, the increases in rCBF were larger, more extensive and more uniform following the stimulation of the inflamed joint relative to the results obtained with stimulation of the normal joint. No significant laterality was seen, but when an atlas-based region of interest (ROI) analysis was carried out and when the individual variations in rCBF were removed with two-way ANOVA, significant differences were disclosed in rCBF between the stimulated condition and the resting condition in a large number of brain regions. In particular, noxious rotation of the normal (right) elbow joint induced a significant increase in rCBF over the cerebral cortex and in the right thalamus and hippocampus. The same stimulation of the (left) inflamed joint induced a significant increase in rCBF throughout the brain; the biggest increase being over the right posterior cortex. It is concluded that under the conditions of the present experiments the generally accepted autoregulation of the cerebral blood flow is not fully functioning, and various factors that may be responsible for this failure (which obscures rCBF differences) are discussed. The more pronounced increases in rCBF when moving inflamed joints instead of normal ones is thought to be a direct consequence of the peripheral sensitization of the articular nociceptors and the consequent central hyperexcitability induced in the articular nociceptive pathways.

Notes: Abstract  This study examined (1) how changes in head position affect postural orientation variables during stance and (2) whether changes in head position affect the rapid postural response to linear translation of the support surface in the horizontal plane. Cats were trained to stand quietly on a moveable platform and to maintain five different head positions: center, left, right, up, and down. For each head position, stance was perturbed by translating the support surface linearly in 16 different directions in the horizontal plane. Postural equilibrium responses were quantified in terms of the ground reaction forces, kinematics, dynamics (net joint torques), body center of mass, and electromyographic (EMG) responses of selected limb and trunk muscles. A change in head position involved rotation of not only the neck but also the scapulae and anterior trunk. Tonic EMG levels were modulated in several forelimb and scapular muscles but not hindlimb muscles. Finally, large changes in head orientation in both horizontal and vertical planes did not hamper the ability of cats to maintain postural equilibrium during linear translation of the support surface. The trajectory of the body’s center of mass was the same, regardless of head position. The main change was observed in joint torques at the forelimbs evoked by the perturbation. Evoked EMG responses of forelimb and scapular muscles were modulated in terms of magnitude but not spatial tuning. Hindlimb responses were unchanged. Thus, the spatial and temporal pattern of the automatic postural response was unchanged and only amplitudes of evoked activity were modulated by head position.

Notes: Abstract  Visually evoked potentials (VEPs) measured under conditions of retinal image stabilization that minimized the influences of visual masking and smearing were averaged from electroencephalographic records measured from striate cortex of three cats. The amplitudes of the VEPs increased around saccade initiation. The grating-evoked potentials obtained at different times relative to the saccade exhibited changes in waveform shape that could be attributed to a saccade-evoked potential. The changes in the shape of the waveform were reasonably accounted for by the summation of the grating-evoked potential (produced when the cat did not make a saccade) and an appropriately timed saccade-evoked potential. The fundamental amplitudes of the residual potentials were computed and found to vary across the time course of the saccade. These observations suggest that there are other influences besides visual masking that are exerted early in the visual pathway to modulate visual processing during saccadic eye movements. A corollary discharge process is the most likely candidate to exert these influences.

Notes: Abstract  The neuronal responsiveness to three-dimensional (3D) motion in cat posteromedial lateral suprasylvian (PMLS) cortex was studied using a computer-controlled, stereoscopic 3D graphic display capable of reproducing the major visual cues for natural 3D motion, including motion disparity, size, texture, and shading changes. The animals were anesthetized with nitrous oxide supplemented with alphaxalone, and paralysis prevented eye movement. Systematic investigation of neuronal responsiveness to 3D motions in 26 different directions revealed that more than half of the PMLS cells were selectively responsive to approaching (AP cells, 112 of 271) or recessive motion (RC cells, 64 of 271). The remaining cells were selectively responsive to frontoparallel motion (FP cells, 49 of 271) or nonselectively responsive to motion in multiple directions (NS cells, 46 of 271). The dependency on these visual cues was investigated as a reduction in the response amplitude or the response selectivity for the removal of a single cue from the motion stimuli containing the full visual cues. The AP and RC cells showed a strong dependency on the motion disparity cue, moderate dependency on the size cue, and weak dependency on the texture and shading cues. The FP cells showed no dependency on those visual cues. The cue dependency analysis indicated the existence of nonlinear interactions between those visual cues. Comparison of the responses to a combination of the motion disparity and size cues with the summed responses to each of the individual cues revealed that the responses to the combined cues are roughly predicted as a linear sum between the preferred responses. This comparison also showed nonlinear summation between the nonpreferred responses, i.e., responses to the combined cues were smaller than the summed responses. A similar quasilinear summation of the preferred responses between the two eyes and a nonlinear summation of the nonpreferred responses were found in the AP and RC cells for the motion disparity stimulus. All of these observations indicate that quasilinear and nonlinear interactions of the responses to various stimulus elements underlie the 3D motion responsiveness of the PMLS cells.

Notes: Abstract  In pentobarbitone-anaesthetised spinal cats, a comparison was made of the effects of intravenous bicuculline hydrochloride, a GABAA-receptor antagonist, and several (-)-baclofen (GABAB-receptor) antagonists (CGP 35348, 46381, 56999A) on the prolonged inhibition of extensor-muscle monosynaptic reflexes, recorded from lumbar ventral roots, by brief or continuous tetanic stimulation of low-threshold afferent fibres of hindlimb flexor muscles. Two components of brief tetanus inhibition were detected. Whilst possibly of similar central latency, the inhibition associated with GABAB receptors had a longer time course than that reduced by bicuculline. Furthermore, whereas bicuculline reduced primary afferent depolarization, generated by the inhibitory volleys, and detected as dorsal-root potentials, such potentials were generally enhanced by intravenous baclofen antagonists. The inhibition of reflexes during and after continuous (333 Hz) tetanic flexor-nerve stimulation appeared to be predominantly associated with the activation of GABAB receptors. In the period following continuous tetanic flexor-nerve stimulation, during which monosynaptic extensor reflexes were reduced in amplitude, the action potentials of the intraspinal terminations of extensor-muscle group-Ia afferent fibres were reduced in duration, as detected by the time course of the recovery of the threshold to extracellular microstimulation following the arrival of an orthodromic impulse. A reduction in termination action-potential duration also accompanied the reduction by microelectrophoretic (-)-baclofen of the release of excitatory transmitter from group-Ia terminations, both presynaptic effects being blocked by microelectrophoretic baclofen antagonists. However, the reduction of the duration of the action potential of individual group-Ia terminations, which followed continuous flexor-nerve stimulation, was not sensitive to the baclofen antagonist CGP 55845A, but was diminished by bicuculline methochloride. Intravenously administered bicuculline hydrochloride, however, had little or no effect on the inhibition of reflexes following continuous flexor-nerve stimulation. These observations are discussed in the context of possible intraspinal pathways and pre- and postsynaptic mechanisms for GABAA and GABAB receptor-mediated inhibition of the monosynaptic excitation of spinal motoneurones and of the functional significance of central GABAB receptor-associated inhibitory processes, given the relatively minimal effects on motor activity and behaviour produced by baclofen antagonists that penetrate the mammalian blood-brain barrier.

Notes: Abstract The motile behaviour, growth and reactions of osteoblasts, chondrocytes, epitenal cells and endothelia to culture on extended concave surfaces inside tubes is reported. Time-lapse video observations show that these cells can be successfully grown in quartz tubes for up to 21days. The cells would attach to the concave surfaces even when the radius of curvature was as low as 25 μm. The cells attached to the walls were not oriented. As culturing progressed the chondrocytes, osteoblasts and epitenon cells tended to detach from the walls of the tubes, forming long cords of cells attached to the walls at a few points only. Endothelial cells did not detach. These cords showed extensive lamellipodial activity at their points of attachment to the tube wall. The cells in these cords do not show contact inhibition of movement.

Notes: Abstract Four transplantations of an allogeneic vascularized human knee joint were performed at the Trauma Center Murnau between April 1996 and July 1997. The indication for the procedure was the total loss of the knee joint including the extensor apparatus due to severe trauma. These were the first transplants of this type. Management of patients started with closure of soft-tissue defects. After successful completion, stabilization was achieved with femoral and tibial nails plus a temporary arthroplasty. AB0 compatibility and a negative cross-match were the main criteria for selecting patients for transplantation. Interlocking compression nails were used for osteosynthesis. Vascular anastomoses between graft and recipient vessels were established by the end-to-side technique. Immunosuppression was started as a quadruple induction therapy for 3 days, then reduced to a two-drug maintenance therapy with cyclosporine and azathioprine. Six months posttransplantation the osteotomies were bridged by callus and the patients became completely mobile. Radiographic and histological examinations revealed vital graft tissue.

Notes: Abstract Orofacial dyskinesia (OFD) is a disorder characterized by involuntary movements of the oral and facial muscles. OFD attacks can be elicited acutely in cats by local injections of dopaminergic agents into the anterodorsal part (r-CRM) of the caudate nucleus. Because the dopaminergic A8 cell group, being embedded in the retrorubral nucleus (RRN), gives rise to fibres which terminate in the r-CRM, two questions arose: (1) whether the A8 cell group forms part of the circuitry that directs and/or modulates OFD, and (2) whether GABA-ergic compounds in the RRN play a role in OFD, and if so, whether a pharmacological GABA-ergic intervention of the activity in the RRN modulates or mediates OFD. For this purpose, the activity of the RRN was manipulated with local injections of the GABAA agonist muscimol and antagonist bicuculline. These local injections into the RRN were subsequently combined with manipulations of dopamine transmission in the r-CRM with local injections of the selective DAi receptor agonist (3,4-dihydroxyphenylimino)-2-imidazoline. The present study shows that local injections of GABA-ergic compounds into the RRN do not elicit OFD attacks in cats, but can modulate oral behaviour elicited from the r-CRM. The latter effect is dose dependent and GABA-ergic specific.

Notes: Durch Fixierung (Formalin), Entkalkung (Schnitte) oder mechanische Bearbeitung (Schliffe) besteht bei der Hartgewebshistologie das Risiko physikalisch-chemischer oder mechanischer Artefakte. Da Studien zur Ätiopathogenese pathologischer Veränderungen meist auf subklinische Läsionen zielen, besteht die Gefahr, daß Artefakte frühe Veränderungen vortäuschen oder vorhandene überdecken. Es wird der Frage einer artefaktminimierten Histologie nachgegangen. Bei der konfokalen Laser-Scanning-Mikroskopie (CLSM) rastert ein monochromatischer Laserstrahl über die Probenoberfläche und dringt in das Gewebe ein. Die Intensität der remittierten Strahlung wird in einem Detektor gemessen. Durch eine konfokale Blende (pinhole) erreicht nur Laserlicht aus einer extrem dünnen In-Fokus-Ebene den Detektor, so daß schrittweises Bewegen des Objekttischs eine tomographische Serie von Einzelbildern visualisiert. Gesunde kortikale Knochenproben des Unterkiefers (n = 20) wurden durchlichtmikroskopisch und im CLSM untersucht: Dabei wurden identische Probenareale an Dünnschliffen nach HE-Färbung visualisiert. Außerdem wurden eingebettete und frische Gewebeblöcke derselben Knochenproben im CLSM histotomographiert. Als Ergebnisse wurden gefunden: 1. Lichtmikroskopische Mikromorphologie kortikalen Knochens ist im CLSM valide visualisierbar. 2. Viele lichtmikroskopisch erst nach Spezialfärbungen darstellbare Strukturen (z.B. Osteozytenfortsätze) können im CLSM an Probenblöcken ohne Vorbereitung mikroskopiert werden. Hieraus können folgende Schlußfolgerungen gezogen werden: 1. Die zerstörungsfreie Histotomographie des CLSM unter der Probenoberfläche vermeidet mechanische Artefakte völlig. 2. Physikalisch-chemische Artefakte werden kontrollierbar, da auch frische Proben mikroskopiert werden können. 3. Die pseudo-dreidimensionale Darstellung erlaubt eine histologische Gewebeinterpretation, die makroskopischen Schichtbildverfahren (CT, MRT) vergleichbar ist.

Notes: Zusammenfassung Ein neuer Kalziumphosphatzement besteht aus 73% Tetrakalziumphosphat und 27% Kalziumhydrogenphosphat. Er bindet bei Körpertemperaturen nach Zugabe von Wasser innerhalb von 20 min ab. Innerhalb von 4 h wird der Zement zu Hydroxylapatitkristallen umgesetzt und damit wasserunlöslich. Der Abbindeprozeß verläuft nahezu isotherm im pH-Bereich von 6,5–8,5 ohne Schrumpfung. Die Druckfestigkeit liegt im ausgehärteten Zustand oberhalb von 50 MPa, die Zugfestigkeit bei mehr als 8 Mpa. Der Zement ist für alle nicht lasttragenden Knochenaugmentationen und Knochenersatzanwendungen insbesondere am Gesichtsschädel geeignet. Bei 9 von 10 Patienten benutzten wir den Zement erfolgreich für Rekonstruktionen im kraniofazialen Bereich. Beim klinischen Einsatz muß besonders auf sorgfältige Trockenlegung des Operations- und Implantationsfelds geachtet werden. Weitere Anwendungsmöglichkeiten sind das Auffüllen von ausgeräumten und verblockten Schädelhöhlen, die Fixation von implantierten Hörelektroden in der Hals-Nasen-Ohren-Heilkunde sowie das Auffüllen von Zysten und Wurzelspitzenresektionsdefekten in der dentoalveolären Chirurgie. Besondere Perspektiven bietet der Hydroxylapatitzement wegen seiner isothermen Abbindereaktion und seiner intrinsischen osteokonduktiven Eigenschaften als Trägermaterial für osteogene Proteinkomplexe.

Notes: Abstract Studies were carried out on the organization of the internal connections of the striate cortex in cats in the projection zone of the center (0–5°) of the field of vision by microintophoretic application of horseradish peroxidase to electrophysiologically identified orientational columns. The area containing neurons showing retrograde labeling in most cases extended in the mediolateral direction. Labeled cells were located in the upper (II, III) and lower (V, VI) layers of the cortex, and the shapes and orientations of the areas containing labeled neurons in these layers coincided. Spatial asymmetry was detected in the distribution of labeled neurons relative to the orientational column studied. Labeled cells were located predominantly medial to the columns, regardless of the distance from the projection of the area centralis. Considering the visuotopical map of field 17, the asymmetry detected here provides evidence that neurons in orientational columns have more extensive connections with neurons of the peripheral part of the cortex. An asymmetrical distribution of “silent” zones around the receptive fields of neurons in orientational columns is suggested, and that these appear to receive influences from the periphery of the visual field.

Notes: Abstract The skull of a small child, which was largely devoid of soft tissue, was classified according to forensic/anthropological findings and could be identified on the basis of DNA typing by PCR using residual brain tissue, but not bone. This case illustrates the fact that careful forensic/anthropological investigation is an important basis for molecular biological identification from skeletal remains and that DNA typing by PCR may even be possible on brain tissue that has been exposed to damp conditions and is an advanced state of decomposition.

Notes: Abstract Stress fractures are being increasingly reported as a common cause of morbidity in both healthy populations and those withunderlying diseases involving abnormal bone. An insight into the types and pathogenesis of stress fractures is necessary to considering the diagnosis, management and prevention of such conditions. The classification, aetiology and aspects of management are discussed.

Notes: Abstract  Substance P (SP) is a neuropeptide that is released from axons of sensory neurons and causes signal transduction through the activation of the neurokinin-1 receptor (NK1-R). The present study demonstrates the distribution of SP-like-immunoreactive (SP-LI) axons and the localization of NK1-Rs in rat bone tissue using the avidin-biotin-peroxidase complex method. Axons with SP-LI were commonly found near the trabecular bone in the temporal bone marrow, but they were only sparsely distributed in the mandible, femur, and tibia. Immunoreactivity for NK1-Rs was found on the plasma membrane and in the cytoplasm of the osteoclasts. In the osteoblasts and osteocytes, a small number of weak, punctate immunoreactive products of NK1-Rs were distributed close to the plasma membrane. At the electron-microscopic level, immunoreactivity for NK1-R was distributed mainly in the whole cytoplasm, except for the clear zone of the osteoclasts, and in pit-like structures along the plasma membrane. The NK1-R-immunoreactive structures in the cytoplasm were divided into two types of organelles, consisting of vesicular and vacuolar structures (probably transport vesicles and early endosomes). In the osteoblasts and osteocytes, the number of NK1-R-positive vesicular structures was fewer than in the osteoclasts. These results thus suggest that SP secreted by the sensory axons could directly modulate bone metabolism via NK1-Rs.

Notes: Abstract  There is evidence that glycans carrying terminal galactose residues are differently expressed in the sarcoplasm of different muscle fiber types. In this study monoclonal antibodies directed against P blood group antigens Pk: Galα1–4Galβ1–4Glcβ- and P1: Galα1–4Galβ1–4GlcNAcβ- were used to detect terminal α-galactosylated glycoconjugates on muscle proteins. Electrotransfer of proteins, extracted from human masseter and biceps muscles, to nitrocellulose after polyacrylamide gel electrophoresis (PAGE) and incubation with anti-Pk (CD77) consistently showed two bands with apparent molecular weights of 66 kDa and 64 kDa. In fresh frozen muscle sections from some humans there was endothelial reaction with anti-CD77 in capillaries, venules and veins but not in arterioles and arteries. In muscle samples from other humans there was no staining of endothelial cells. Formalin-fixed human muscle displayed a CD77 reaction with highest accumulation of reaction product at the periphery of the fibers. This may be explained by the presence of Pk glycoconjugates on intermediate filaments in muscle fibers. In preparations of cat masseter muscle proteins the antibodies against P1Pk antigens reacted with a 170 kDa and a 55 kDa band while in preparations of cat biceps brachii only a 55 kDa band was reactive. The specificities of the antibodies were investigated by fluorescence-activated cell sorter (FACS), α- and β-galactosidase digestion and inhibitory sugars. This study indicates that glycans carrying Galα1–4Galβ1- epitopes are expressed on myofibrillar associated proteins.

Notes: Abstract  Glutaraldehyde-formaldehyde fixed undecalcified alveolar bone from 7-day-old rats was prepared for light and electron microscopy. Colloidal lanthanum was used as an ultrastructural tracer, and both random and semi-serial sections were examined. Lanthanum penetrated the infoldings of the ruffled border and some nearby vacuoles and vesicles. The majority of vacuoles and vesicles were lanthanum-free. Some osteoclast profiles contained a large vacuole with a cell enclosed in its interior. The enclosed cell exhibited an irregular nucleus containing condensed peripheral chromatin, intact cytoplasmic organelles, conspicuous rough endoplasmic reticulum and large blebs on the cell surface. These features are characteristic of osteoblasts or bone-lining cells or immature osteocytes which may be undergoing apoptosis or necrosis. The observation of remnants of cellular structures within internalized osteoclast vacuoles, together with the above results, suggests that osteoclasts engulf and probably degrade dying osteoblasts/bone-lining cells or immature osteocytes.

Notes: Abstract  Objective. The present study demonstrates the osseous and soft tissue manifestations of alveolar echinococcosis (AE). Patients. We report on eight patients with AE with bone or soft tissue involvement confirmed at biopsy or needle cytology. Results. All eight patients showed hepatic involvement. Four exhibited infiltration of the spine as a result of direct spread of the hepatic primary lesion; distant metastases were observed in only three of these patients. Calcifications, which are typical for hepatic manifestations of the disease, were observed in soft tissue in only two of eight cases (25%); we observed no instances of endovesicular daughter cysts. Conclusion. AE manifests itself in the vertebral column as a form of spondylitis and in soft tissue presents similar to an abscess. Since in most of these cases spread of the disease per continuitatem from the liver is present, the diagnosis is easily made from the characteristic hepatic findings.

Notes: Abstract Minimum onset latency (Lmin) of single- and multiple-unit responses were mapped in the primary auditory cortex (AI) of barbiturate-anesthetized cats. Contralateral Lmin for multiple units was non-homogeneously distributed along the dorso-ventral/isofrequency axis of the AI. Responses with shorter latencies were more often located in the central, more sharply tuned region while longer latencies were more frequently encountered in the dorsal and ventral portions of the AI. For single units, a large scatter of Lmin values was found throughout the extent of the AI including cortical depth. The relationship between Lmin and previously reported spectral, intensity and temporal parameters was analyzed and revealed statistically significant correlations between minimum onset latency and the following response properties in some but not all studied animals: sharpness of tuning of a frequency response area 10 dB above threshold, broadband transient response, strongest response level, monotonicity of rate/level functions, dynamic range, and preferred frequency modulation sweep direction. This analysis suggests that Lmin is determined by several independent factors and that the prediction of Lmin based on relationships with other spectral and temporal response properties is inherently weak. The spatial distribution and the functional relationship between these response parameters may provide an important aspect of the time-based cortical representation of specific features in the animal's natural environment.

Notes: Summary. Hydatid disease is caused by the parasitic tapeworm Echinococcus. The larval stage of this parasite can thrive in many parts of the body, most frequently in the liver. Primary bone location is very rare, accounting for less than 2 % of all hydatid lesions. We report on a case of left-sided extended pelvic infestation. The destruction of the hip joint, os pubis, large parts of the ileum and the femoral head made pelvic resection and prosthetic replacement necessary. Recurrence of a hydatid cyst 5 years later in the left groin originating from the proximal femur was treated with second femoral resection and new total hip replacement. Because of instability, the primarily inserted polyacetal pelvic replacement had to be exchanged for a custom-made device fabricated with the aid of computer-aided design (CAD) techniques. This surgical procedure was combined with chemotherapy (mebendazole). The necessity of radical resection in osseus hydatid disease is discussed.

Notes: Abstract The reinnervation pattern of crural pacinian corpuscles was examined by light and electron microscopy in eight adult cats of both sexes 3–18 months after sciatic nerve crush. Normal pacinian corpuscles are each supplied with a single myelinated axon and a single cylindrical axon terminal which may branch in the distal part of the inner core. Reinnervation of these vibroreceptors was very satisfactory after sciatic nerve crush: in a sample of 68 corpuscles examined 3–18 months after the operation, 92.6% were found reinnervated, while only 7.4% remained denervated. At the nerve entry, 84.2% of the reinnervated corpuscles were supplied with a single myelinated axon, while 15.8% received two myelinated axons; some of the axons branched before or after entering the inner core. Near the mid-level of the inner core, 60.3% of 63 reinnervated corpuscles were innervated with a single axon terminal, 22.2% were biterminal, while 17.5% had three or more terminals. Regenerated axon terminals induced the formation of thin lamellar layers in the axial region of the original core and, exceptionally, also at the outer aspect of the original core. In monoterminal corpuscles, the shape and ultrastructure of regenerated endings resembled those of normal controls, whereas in multiterminal corpuscles their shape and profiles were variable. In contrast to previous reports, reinnervated corpuscles did not ultimately become monoterminal. On the contrary, the mean number of 1.3 terminals found in reinnervated crural corpuscles at 3–5 months increased to 1.9 terminals per corpuscle 6–18 months after axotomy.

Notes: Abstract  This study was primarily aimed at investigating the selectivity of the cortico-spinal actions exerted on the pathways mediating primary afferent depolarization (PAD) of muscle spindle and tendon organ afferents ending within the intermediate nucleus at the L6–L7 segmental level. To this end we analyzed, in the anesthetized cat, the effects produced by electrical stimulation of sensory nerves and of the cerebral cortex on (a) the intraspinal threshold of pairs of single group I afferent fibers belonging to the same or to different hindlimb muscles and (b) the intraspinal threshold of two collaterals of the same muscle afferent fiber. Afferent fibers were classified in three categories, according to the effects produced by stimulation of segmental nerves and of the cerebral cortex. Twenty-five of 40 fibers (62.5%) were depolarized by stimulation of group I posterior biceps and semitendinosus (PBSt) or tibialis (Tib) fibers, but not by stimulation of the cerebral cortex or of cutaneous and joint nerves, which instead inhibited the PBSt- or Tib-induced PAD (type A PAD pattern, usually seen in Ia fibers). The remaining 15 fibers (37.5%) were all depolarized by stimulation of the PBSt or Tib nerves and the cerebral cortex. Stimulation of cutaneous and joint nerves produced PAD in 10 of those 15 fibers (type B PAD pattern) and inhibited the PBSt- or Tib-induced PAD in the 5 remaining fibers (type C PAD pattern). Fibers with a type B or C PAD pattern are likely to be Ib. Not all sites in the cerebral cortex inhibited with the same effectiveness the segmentally induced PAD of group I fibers with a type A PAD pattern. With the weakest stimulation of the cortical surface, the most effective sites that inhibited the PAD of individual fibers were surrounded by less effective sites, scattered all along the motor cortex (area 4γ and 6) and sensory cortex (areas 3, 2 and 1), far beyond the area of projection of group I fibers from the hindlimb. With higher strengths of cortical stimulation, the magnitude of the inhibition was also increased, and previously ineffective or weakly effective sites became more effective. Maps obtained when using the weakest cortical stimuli have indicated that the most effective regions that produced PAD of group I fibers with a type B or type C PAD pattern were also scattered throughout the sensory-motor cortex, in the same general area as those that inhibited the PAD of group I afferents with a type A PAD pattern. In eight fibers with a type A PAD pattern it was possible to examine the intraspinal threshold of two collaterals of the same single afferent fiber ending within the intermediate nucleus at the L7 segmental level. In six fibers, stimulation of the PBSt nerve with trains of pulses between 1.5 and 1.86 times threshold (×T) produced a larger PAD in one collateral than in the other. In seven fibers, stimulation of the sensory-motor cortex and of cutaneous nerves produced a larger inhibition of the PBSt-induced PAD in one collateral than in the other. The ratio of the cortically induced inhibition of the PAD elicited in the two collaterals could be modified by changing the strength of cortical and of PBSt stimulation. In three fibers it was possible to inhibit almost completely the background PAD elicited in one collateral while having little or no effect on the PAD in the other collateral. Changes in the intraspinal threshold of pairs of collaterals following electrical stimulation of segmental nerves and of the somato-sensory cortex were examined in three fibers with a type B and two fibers with a type C PAD pattern. In four fibers the PAD elicited by stimulation of cutaneous (4–20×T) and muscle nerves (1.54–3.7×T), or by stimulation of the sensory-motor cortex, was of different magnitude in the two collaterals. In two experiments it was possible to find cortical sites in which weak surface stimulation produced PAD in one collateral only. The magnitude of the PAD elicited in pairs of collaterals of group I afferents with a type B or C PAD pattern, or the inhibition of the PAD in pairs of collaterals of fibers with a type A PAD pattern, appeared not to be topographically related to the site of spinal projection of the cutaneous and cortico-spinal fibers used for conditioning stimulation. The present demonstration of a differential control of the PAD exerted on two collaterals of the same afferent fiber suggests that the profuse intraspinal branching of muscle spindle and tendon organs is a potentially rich substrate for information transmission. By means of presynaptic control mechanisms, the terminal arborizations of the afferent fibers could function either as a simple unit or in a fractionated manner, allowing funneling of information to selected groups of central neurons.

Notes: Abstract Results of previous studies have indicated that the rostral superior colliculus (SC) plays an important part in the control of accommodation. The present study was carried out to investigate retinal projections to the accommodation-related area in the rostral SC. We injected WGA-HRP into the accommodation-related area in the rostral SC of the cat, where accommodative responses were elicited by stimulation with weak currents of less than 20 μA. Following injection of WGA-HRP into the accommodation-related area in the rostral SC, retrogradely labeled ganglion cells were observed mainly in the area centralis. Projections from the contralateral eye were denser than those from the ipsilateral eye. Almost all retrogradely labeled cells were classified as γ-cells owing to their small cell-body diameters and thin dendrites, although a few were classified as α-cells. These findings suggest that the accommodation-related area in the rostral SC is located in the portion corresponding to the area of representation of the central visual field and receives mainly γ-cell projections

Notes: Abstract  In the ventral horn of the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium, microelectrophoretically administered (–)-baclofen, but not (+)-baclofen, reversibly reduced the duration of the orthodromic action potential of muscle group Ia afferent terminations, but not those of muscle group I afferent myelinated fibres. The presumably submicromolar concentrations are already known to reversibly reduce excitatory transmitter release from muscle group Ia afferent terminations. Action potential durations were estimated from threshold recovery curves after an orthodromic impulse using an extracellular microstimulation technique. Both of these presynaptic effects of (–)-baclofen were blocked by baclofen antagonists, and neither appeared to be reduced by the potassium channel blocking agents tetraethylammonium and 4-aminopyridine. Tetraethylammonium and 4-aminopyridine also did not significantly modify the reduction by (–)-baclofen of monosynaptic field potentials in the lumbar cord of rats anaesthetised with pentobarbitone sodium. In the cat the maximum reduction by (–)-baclofen of termination action potentials was considerably less than that produced by cadmium ions, which, unlike (–)-baclofen, also reduced the action potential duration of group I myelinated fibres. These findings are consistent with a reduction by (–)-baclofen of the influx of calcium through voltage-activated channels in the membrane of group Ia terminations, a proposal which also accounts for the reduction by (–)-baclofen of the release of GABA at axo-axonic depolarizing synapses on these terminations. The results are discussed in relation to the mode of action of (–)-baclofen and the different sensitivities of transmitter release at various central synapses.

Notes: Abstract  Axonal pathways, projection levels, conduction velocities, and locations of the cell bodies of saccular nerve-activated vestibulospinal neurons were studied in decerebrated cats and anesthetized cats, using a collision test of orthodromic and antidromic spikes. The saccular nerve was selectively stimulated by bipolar tungsten electrodes. Three monopolar electrodes were inserted into the left and right lateral vestibulospinal tract (LVST) and medial vestibulospinal tract (MVST) of the C1 segment, to determine the pathway of axons. Three pairs of similar electrodes were positioned bilaterally in the C3–4, T1, and L3 segments to examine projection levels. Another monopolar electrode was placed in the oculomotor nucleus to determine whether saccular nerve-activated vestibulospinal neurons have branches ascending to the oculomotor nucleus. Of 145 vestibular neurons orthodromically activated by stimulation of the saccular nerve, 46 were activated from the C1 segment antidromically. Forty-three were second-order vestibulospinal neurons and 3 were third-order vestibulospinal neurons. Four saccular nerve-activated vestibulospinal neurons were also antidromically activated from the oculomotor nucleus. Sixty-three percent of the saccular nerve-activated vestibulospinal neurons descended through the MVST; one-third of these terminated in the upper cervical segments, one-third reached the lower cervical segments and the remaining one-third reached the upper thoracic segments. Thirty percent of the saccular nerve-activated vestibulospinal neurons descended through the ipsilateral LVST; most of these reached the upper thoracic segments. Seven percent of the saccular nerve-activated vestibulospinal neurons descended through the contralateral vestibulospinal tracts terminating in the upper cervical segments. Most of the saccular nerve-activated vestibulospinal neurons originated in the caudal part of the lateral nucleus and rostral part of the descending nucleus.

Notes: Abstract The effects of human growth hormone (hGH) therapy on biochemical markers of bone metabolism were studied in 17 children (10 boys and 7girls, aged 3.7–13.1 years old) with idiopathic GH deficiency, before and 1 and 6 months after GH therapy (0.5–0.7 IU/kg weekly, SC). Serum levels of calcium, phosphate, alkaline phosphatase, osteocalcin, parathyroid hormone, 1,25 dihydroxyvitamin D, insulin-like growth factor I (IGF-I) and renal phosphate per 100 ml glomerular filtrate (TPO4/GFR) were assessed. During therapy with hGH, a significant decrease of serum calcium levels and increases of phosphate, osteocalcin, parathyroid hormone 1,25 dihydroxyvitamin D and IGF-I were observed. TPO4/GFR was also significantly increased. Growth response (increment in HV) was positively related with changes in alkaline phosphatase and IGF-I levels after 6 months of hGH therapy. There was also a significant positive correlation between increment in HV and increment in TPO4/GFR after 1 month of GH therapy, whereas no correlation between HV and changes in osteocalcin levels was found. Conclusion GH treatment significantly influences mineral metabolism and the measurement of TPO4/GFR after 1 month of GH therapy may serve as a useful predictor of growth response to hGH therapy in GH-deficient children.

Notes: Abstract  In decerebrate cats that had been acutely hemilabyrinthectomized (HL), the extracellular activities of vestibular nuclear neurons on the lesioned and labyrinth-intact sides were studied during constant-velocity off-vertical axis rotations (OVAR) in the clockwise (CW) and counterclockwise (CCW) directions (at 10° tilt). Over the range of 1.75–15°/s, two types of neuronal responses were identified on both sides. Some neurons showed symmetric and velocity-stable bidirectional response sensitivity (δ defined as the CW gain over the CCW gain) while other neurons exhibited asymmetric and velocity-variable δ. The mathematically derived gain tuning ratios of these two groups of neurons were within the range of one-dimensional and two-dimensional neurons respectively. The best response orientations in one-dimensional neurons and the orientations of the maximum response vector, S max, in two-dimensional neurons were found to point in all directions on the horizontal plane. On the labyrinth-intact side, both the one-dimensional and two-dimensional neurons showed asymmetry in the neuron numbers and/or the response gains between the two roll quadrants as well as between the two pitch quadrants. In addition, both the neuron number and gain were significantly higher for neurons in the head-down/ipsilateral-side-down half-circle than those in the head-up/contralateral-side-down half-circle. None of the aforementioned asymmetries was observed on the lesioned side. That a comparable pattern of distribution was observed in the one-dimensional and two-dimensional neurons suggests that these neurons maintain a common spatial reference frame in encoding head orientational signals arising from the ipsilateral and contralateral otoliths. Furthermore, a predominance of two-dimensional neurons that exhibited a greater gain with CW rotations was observed on both sides of HL cats. Of the response dynamics observed amongst neurons on the two sides of HL cats, no difference was found with regard to the response gain and the pattern of response lead. However, a difference in response lag was observed between neurons on the two sides of HL cats. These suggest that there is a segregation of otolithic signals to reach the ipsilateral and contralateral vestibular nuclei. Taken together, the present study demonstrates that one-dimensional and two-dimensional neuronal responses could be elicited with inputs arising solely from the ipsilateral or contralateral otoliths. The observed orientational tuning and the CW-CCW asymmetry to bidirectional rotation may provide the essential directional coding of head orientations. Further, the imbalance of spatial/dynamic response patterns between the bilateral vestibular nuclei following the restriction of otolith inputs by HL implies that converging otolithic inputs from the bilateral labyrinths are essential for producing the neuronal responses in control animals. The results are also discussed in terms of the possible contribution of the various neural asymmetries between neuronal subpopulations in the bilateral vestibular nuclei to the behavioral symptoms accompanying acute HL.

Notes: Abstract  Previous studies have reported that stimulation of group I afferents from extensor muscles prolongs stance duration during walking in decerebrate cats. The main objective of this investigation was to determine whether this phenomenon occurs during walking in conscious cats. In conscious cats without lesions of the central nervous system (CNS), stimulation of group I afferents in the lateral gastrocnemius/soleus (LGS) nerve during stance prolonged extensor burst duration and increased the cycle period in five of seven animals. The mean increases in cycle period were modest, ranging from 6 to 22%. In five of six animals that walked both quadrupedally and bipedally at the same rate, the effects on cycle period were stronger during bipedal stepping (18% mean increase in cycle period compared with 9%). The stimulated nerves were transected and the experimental procedure was usually delayed in the conscious animals for 2–3 days following implantation of the stimulating electrodes. To assess whether chronic axotomy of the LGS nerve was a factor in the decreased effectiveness, four of the cats with chronic nerve section were decerebrated and their LGS nerves were stimulated after the animals began to spontaneously walk on a motorized treadmill. In all four of these animals, the effects of stimulating the chronically cut LGS nerve on the step cycle period became stronger following decerebration. However, these effects were not as strong as those produced when an acutely sectioned LGS nerve was stimulated. During both quadrupedal and bipedal walking, stimulation of the LGS nerve increased the amplitude of the medial gastrocnemius (MG) electromyogram. The augmented activity of the MG muscle contributed to an increased extension of the ankle during stimulated steps. The conclusion from these experiments is that stimulation of the group I afferents in extensor nerves can prolong stance in the conscious cat, but this effect is weaker than in decerebrate animals. It is likely that transmission in the polysynaptic group I pathways controlling stance duration is regulated in a complex fashion by descending signals from the brain in the conscious animal.

Notes: Abstract  In the lumbar ventral horn of pentobarbitone-anaesthetised cats, (-)-baclofen reduces both the synaptic release of excitatory transmitter from muscle group Ia afferent terminations and the duration of the presynaptic action potentials of these terminations, presumably by interfering with the influx of calcium ions through voltage-activated channels. Baclofen, however, has little or no effect on cholinergic excitation at motor axon collateral synapses on spinal Renshaw cells and, in the present study, was found not to reduce the duration of the action potential of axon collateral terminations located in the vicinity of Renshaw cells in pentobarbitone-anaesthetised cats. Furthermore, in contrast to group Ia terminations, a 4-aminopyridine-sensitive potassium conductance could not be detected as contributing to axon collateral termination action potentials. These results suggest that there may be differences in presynaptic ion fluxes associated with transmitter release at the intraspinal terminations of group Ia afferent fibres and motor axon collaterals in the cat spinal cord.

Notes: Abstract  The purpose of this study was to determine (1) whether the nucleus retroambigualis (NRA) plays an essential role in periaqueductal gray (PAG)-induced vocalization and (2) which NRA neurons are involved in the projection from the PAG to laryngeal motoneurons. Bilateral injections of the neurotoxin kainic acid into the NRA in decerebrate cats abolished PAG-induced vocalization; PAG stimulation after the injections no longer modulated vocal fold adductor or tensor activity, and only tonically, but no longer phasically, activated the abdominal muscles. In contrast, PAG-induced inspiratory excitation remained even after the injections. These results suggest that the NRA is essential for the vocal activation of the laryngeal adductor and abdominal muscles, and that an additional pathway from the PAG to respiratory motoneurons other than through the NRA is important for mediating PAG-induced inspiratory activation. Secondly, axonal projections of NRA neurons to the contralateral nucleus ambiguus (NA) were studied electrophysiologically. Five expiratory neurons, which had decrementing (n=4) or constant (n=1) firing patterns, were identified as both having axonal projections to the NA and receiving inputs from the PAG. Furthermore, following NA stimulation many constant-latency action potentials of silent cells were recorded in the vicinity of the NRA, where many silent cells were also orthodromically activated by PAG stimulation. No NRA augmenting expiratory neurons could be antidromically activated from the NA. It is suggested that the NRA and adjacent reticular formation integrate inputs from the PAG and send outputs to laryngeal motoneurons for vocalization.

Notes: Abstract  The effect of exposure to repeated angular velocity steps about the earth-vertical axis on the vertical vestibulo-ocular reflex (VOR) during onside pitch rotation was investigated in normal cats. By contrast with the VOR in the horizontal plane, the amplitude and duration of the vertical VOR did not progressively decrease throughout the repetition of velocity steps alternated in both directions. Instead, the amplitude of VOR decreased by about 40% during the very first trials in naive cats and then stayed unchanged with repeated stimuli. Habituation of the amplitude of the vertical VOR was observed when the velocity steps were always directed in the same direction. However, the duration of the vertical VOR did not show any signs of habituation. The habituation of the amplitude of the vertical VOR during unidirectional training was due to the progressive development of an initial inhibition of the VOR. This initial inhibition appeared much earlier during the bidirectional protocol, and was presumably responsible for the larger reduction in VOR amplitude observed during the very first session. These results support the model of two distinct mechanisms for VOR habituation, one producing an increasing inhibition of nystagmus, and the other depressing the response duration, and suggest that only the first mechanism is generated during repeated stimulation in the vertical plane. The low-frequency information provided by the velocity storage mechanism during onside pitch rotation, when the otoliths are positioned so they do not signal head tilt relative to gravity, could prevent a decrease in the overall response by the second mechanism.

Notes: Abstract  The aim of this investigation was to understand the functions of long horizontal connections projecting from area 17 to area 18 in cats. The animals were anesthetized and prepared for recording single-cell responses to sine-wave gratings in area 18. Neuronal activity was analyzed under three conditions: prior to, during, and after inactivation of a circumscribed region of area 17. The latter was depressed with micro-injections of GABA. Cells in both areas were in close retinotopic correspondence. Cells were classified as simple and complex types. Globally, simple cells were less affected than complex units, and those which were affected shifted their optimal spatial frequency to higher values. Complex neurons were more often influenced by the interruption of area 17 input. Namely, the peaks of the tuning curves were displaced on the x-axis to a new optimal spatial frequency. This effect was obtained by a dual change: a decline in the discharge strength to the optimal spatial frequency and an enhancement to nonoptimal spatial frequency. Contrast sensitivity function disclosed similar shifts of optimal spatial frequencies. Likewise bandwith, spatial resolution, high cutoff, and low cutoff were modified to a greater extent in complex cells. It appears that there is no relationship between areas 17/18 orientation difference and the modifications observed in tuning curves to spatial frequencies. The results suggest that neurons of area 18 may carry multiple-frequency channels and that area 17 facilitates the emergence of one particular spatial frequency.

Notes: Abstract  In this study we examined connections between the moment-generating capacity of the neck muscles and their patterns of activation during voluntary head-tracking movements. Three cats lying prone were trained to produce sinusoidal (0.25 Hz) tracking movements of the head in the sagittal plane, and 22.5º and 45º away from the sagittal plane. Radio-opaque markers were placed in the cervical vertebrae, and intramuscular patch electrodes were implanted in five neck muscles, including biventer cervicis, complexus, splenius capitis, occipitoscapularis, and rectus capitis posterior major. Videofluoroscopic images of cervical vertebral motion and muscle electromyographic responses were simultaneously recorded. A three-dimensional biomechanical model was developed to estimate how muscle moment arms and force-generating capacities change during the head-tracking movement. Experimental results demonstrated that the head and vertebrae moved synchronously, but neither the muscle activation patterns nor vertebral movements were constant across trials. Analysis of the biomechanical model revealed that, in some cases, modification of muscle activation patterns was consistent with changes in muscle moment arms or force-generating potential. In other cases, however, changes in muscle activation patterns were observed without changes in muscle moment arms or force-generating potential. This suggests that the moment-generating potential of muscles is just one of the variables that influences which muscles the central nervous system will select to participate in a movement.

Notes: Abstract  For an understanding of how various degrees of altered use (training, disuse) affect the properties of skeletal muscles, it is important to know how much they are used normally. The main aim of the present project was to produce such background knowledge for hindlimb muscles of the cat. In four adult female cats, each one being studied in several experimental sessions, ankle muscles were chronically implanted with electrodes for electromyographic (EMG) recording. The muscles recorded from were: extensor digitorum longus (EDL), peroneus longus (PL), tibialis anterior (TA), lateral gastrocnemius (LG) and soleus (SOL). For PL, TA and LG, there were anterior as well as posterior recording sites. During 24-h experimental sessions, the studied animal stayed, together with another cat, in a box large enough for playing and walking around. Using telemetric techniques, samples of EMG signals were recorded on tape for 4 min every 30 min. In an off-line analysis, measurements were made of the total accumulated duration of activity from each one of the studied muscle regions. These ”duty times” were expressed as a percentage of total sampling duration. When averaged over the whole 24-h experimental period, the mean duty times per muscle region varied from 1.9% for EDL up to about 13.9% for SOL. Also, among predominantly fast muscles of mixed-fibre composition (i.e. all studied muscles except SOL), marked and statistically significant differences in duty time were found, mean values varying fivefold from 1.9% (EDL) to 9.5% (PL, posterior site). For all three muscles with simultaneous recordings from different sites, consistent and statistically significant differences in daily duty time were found between anterior and posterior regions (anterior less than posterior for TA and PL; anterior more than posterior for LG). We also measured the extent to which each 4-min sampling period was filled with activity (if any). As compared to muscles with a low mean 24-h duty time, those with high duty times were not active during more sampling periods per day, but, whenever being used, their activity lasted relatively longer. Such results were consistent with the view that differences in mean 24-h duty time might largely reflect differences in the extent to which the various muscles and muscle regions were used for long-lasting stabilizing contractions.

Notes: Abstract  A technique was developed to measure, in the anesthetized and paralyzed cat under artificial ventilation, changes of excitability to intraspinal stimulation simultaneously in two different afferent fibers or in two collaterals of the same afferent fiber. Intraspinal stimulation reduced the threshold of single muscle afferent fibers ending in the intermediate nucleus. This effect was seen with strengths below those required to activate the afferent fiber tested (1.5–12 μA), occurred at a short latency (1.5–2.0 ms), reached a maximum between 15 and 30 ms, and lasted up to 100 ms. The effects produced by graded stimulation applied at the shortest conditioning-testing stimulus time intervals increased by fixed steps, suggesting recruitment of discrete elements, most likely of last-order interneurons mediating primary afferent depolarization (PAD). The short-latency increases in excitability produced by the weakest effective intraspinal stimuli were usually detected only in the collateral closest to the stimulating micropipette, indicating that the stimulated interneurons mediating PAD have spatially restricted actions. The short-latency PAD produced by intraspinal stimuli, as well as the PAD produced by stimulation of the posterior biceps and semitendinosus (PBSt) nerve or by stimulation of the bulbar reticular formation (RF), was depressed 19–30 min after the i.v. injection of 0.5 mg/kg of picrotoxin, suggesting that all these effects were mediated by GABAergic mechanisms. The PAD elicited by stimulation of muscle and/or cutaneous nerves was depressed following the i.v. injection of (–)-baclofen, whereas the PAD elicited in the same collateral by stimulation of the RF was baclofen-resistant. The short-latency PAD produced by intraspinal stimulation was not always depressed by i.v. injections of (–)-baclofen. Baclofen-sensitive and baclofen-resistant monosynaptic PADs could be produced in different collaterals of the same afferent fiber. The results suggest that the intraspinal terminals of single muscle afferents receive synapses from more than one PAD-mediating GABAergic interneuron and that a single last-order interneuron has synaptic connections with a restricted number of intraspinal terminals and/or collaterals of the same afferent fiber. In addition, they support the existence of separate subsets of last-order baclofen-sensitive and baclofen-resistant interneurons that respond predominantly to segmental and to descending inputs. It is suggested that the restricted nature of the PAD plays an important role in the central control of the synaptic effectiveness of group I muscle afferents.

Notes: Abstract  The central cervical nucleus (CCN) of the cat receives input from upper cervical muscle afferents, particularly primary spindle afferents. Its axons cross in the spinal cord, and while in the contralateral restiform body give off collaterals to the vestibular nuclei. In order to study the connections between CCN axons and vestibular neurons, we stimulated the area of the CCN in decerebrate cats while recording intra- or extracellularly from neurons in the contralateral vestibular nuclei. CCN stimulation evoked excitatory postsynaptic potentials (EPSPs) or extracellularly recorded firing in the lateral, medial and descending vestibular nuclei. The latency of EPSPs (mean 1.6 ms) was on average 0.4 ms longer than the latency of antidromic spikes evoked in the CCN by stimulation of the contralateral vestibular nuclei (mean 1.2 ms), demonstrating that the excitation was typically monosynaptic. The results provide further evidence that the CCN is an important excitatory relay between upper cervical muscle afferents and neurons in the contralateral vestibular nuclei.

Notes: Abstract  The ventrolateral (VL) thalamus in mammals is a site well-situated to show vocalization-related neural activity if there is general or classical motor system involvement in vocal production. It receives input from both the basal ganglia and cerebellum, and forms reciprocal connections with motor cortical areas. The current study examined the activity in cat VL thalamus neurons during instrumentally conditioned vocalization. Units in our sample showed irregular spontaneous firing which could be modulated by slowly occurring fluctuations in intensity of vocalization task performance. Two main types of behavioral events were associated with changes in neural firing rate. The first of these was the ingestion of food reward. More than half of all recordings showed phasic bursting patterns during licking; a similar number had increases in firing preparatory to this phasic activity. The second behavioral event modulating unit responses was vocalization. Approximately 60% of recordings showed activity changes time-locked to vocalization. These responses were almost always excitatory, and often involved changes in firing that preceded vocalization onset. No spatial organization of differences in firing pattern between neurons could be distinguished. Our results suggest that VL thalamus may well be involved in mediating vocal behavior, although its functional role remains an object of speculation. Results are compared with previous studies of vocalization-related activity and of VL thalamus activity.

Notes: Abstract  Neurophysiological studies of the blink reflex to supraorbital nerve stimulation were conducted in eight alert, adult male cats. The cat, like other mammals, shows both short-latency (R1) and long-latency (R2) orbicularis oculi electromyographic (OOemg) components. Measures of OOemg latency, duration, integrated area, and maximum amplitude (MA) were obtained at a stimulus magnitude of 1.5×R2 threshold. The mean (±SE) minimal latencies for R1 and R2 were 8.26±0.85 and 22.97±1.53 ms, respectively. On average, R1 MA was larger than R2 MA. R1 and R2 area measures were similar. Three stimulus paradigms were tested. In a paired-stimulus paradigm, the interstimulus interval (ISI) was randomly varied from 100 to 1200 ms. Ratios were constructed for the OOemg area and MA by dividing the test response by the conditioning response. In this paradigm, although a significant linear relationship was observed only between ISI and R2 MA, conditioning effects were noted on both R1 and R2 area and MA test responses at several ISIs. In a habituation paradigm, both R2 and R1 showed habituation at stimulus frequencies from 0.5 to 2 Hz. In a stimulus-response paradigm, stimulus magnitude was randomly varied between threshold and 2×threshold. In this paradigm, OOemg area and MA of both R1 and R2 were linearly related to stimulus magnitude. Neither the systemically administered centrally acting α2-adrenergic antagonist yohimbine nor agonist clonidine had significant effects on blink reflex parameters, habituation, or the paired-stimulus paradigm. Overall, these results suggest that there are important similarities in the control and modulation of the R1 and R2 components of the blink reflex to supraorbital nerve stimulation in cats.

Notes: Abstract  Somaesthetic input to rubrospinal cells, bypassing the cerebellum and cerebral cortex, has been demonstrated in the cat. The detailed organization of this somatic afferent system was studied using electrophysiological methods on multiple-lesion, chloralose-anaesthetized preparations. Stimulation of the dorsal column (DC) at upper cervical cord segments induced significant responses in magnocellular red nucleus (RNm) cells in cats without a cerebellum and with ablation of the frontal cortex. As classic descriptions state that primary afferents fibres have ascending and descending branches in the DC, with many collaterals arborizing in the grey matter at the segmental level of the cord, this procedure is equivalent to stimulating the somatic fibres coming from a large portion of the body, leading to the simultaneous activation of most ascending spinal pathways. To show that the pathway responsible for the rubral responses ascends in the ventral spinal cord, and that the synaptic relays are located at the segmental level, the stimulation was applied to the DC, caudally to the sectioned dorsal spinal half. Various tests confirmed that the activation was conducted to rubral cells through antidromically activated primary afferents. Their multiple collaterals relay the messages to cells located caudal to the spinal lesion, with fibres ascending in the ventral cord. Any relay of the somatic rubral responses in the DC’s nuclei was excluded. When the DC was sectioned and its rostral end was dissected free and lifted onto two hook electrodes for stimulation, no response was obtained in the rubral cells. This dissection indeed sectioned all DC fibre collaterals entering the grey matter, thus excluding the possibility of segmental relay. Single shocks applied to the ventral quadrant of the cord or in the medial lemniscus (LM) in the medulla oblongata induced monosynaptic excitatory post-synaptic potentials (EPSPs) in most rubrospinal cells. The spinal EPSPs could be collided by stimulation in the LM, thus demonstrating the existence of direct connections from the cord to the RNm. This somaesthetic pathway to the RNm could be involved in on-line correction of movements and in learning new motor strategies.

Notes: Abstract  In a proportion of simple cells of the striate cortex, the weighting functions of the receptive fields (RFs) had more periods than could be established by mapping using responses to light bars and dark bars. In these multiperiodical cells, side subfields do not respond to single bars, as they have lower weights than central zones and the excitation is under the threshold of impulse response if a single bar is applied. This fact has been established by different methods: conditioning and testing stimuli, grating patches, and inverse Fourier transform of the amplitude-phase characteristic, combining them in one cell. We assume that this type of nonlinarity can be used in analyzing the image, as it acts as a spatial-frequency filter of the area overlapped by the RF. The responses to complex gratings composed by two sinusoidal gratings of different frequency, contrast, and phase shift were compared with the sum of the responses to the gratings when they were presented separately. The results show that the principle of superposition holds a reasonable approximation even if the response is evoked from the side subzones. Some simple cells have nonlinear properties beyond the classic zone of RF (2nd type of nonlinearity). Linear cells have a tendency to be localized in layer 4 of striate cortex, cells with a nonlinear surround in layers 2, 3, 5, and 6. The significance of both types of nonlinearities in simple cells is discussed.

Notes: Abstract  A region of the caudal ventrolateral medullary reticular formation (CVLM) participates in baroreceptor, vestibulosympathetic, and somatosympathetic reflexes; the adjacent retroambigual area is involved in generating respiratory-related activity and is essential for control of the upper airway during vocalization. However, little is known about the connections of the CVLM in the cat. In order to determine the locations of terminations of CVLM neurons, the anterograde tracers Phaseolus vulgaris leucoagglutinin and tetramethylrhodamine dextran amine were injected into this region. These injections produced a dense concentration of labeled axons throughout the lateral medullary reticular formation (lateral tegmental field), including the retrofacial nucleus and nucleus ambiguus, regions of the rostral ventrolateral medulla, the lateral and ventrolateral aspects of the hypoglossal nucleus, nucleus intercalatus, and the facial nucleus. A smaller number of labeled axons were located in the medial, lateral, and commissural subnuclei of nucleus tractus solitarius, the A5 region of the pontine reticular formation, the ventral and medial portions of the spinal and motor trigeminal nuclei, locus coeruleus, and the parabrachial nucleus. We confirmed the projection from the CVLM to both the rostral ventrolateral medulla and lateral tegmental field using retrograde tracing. Injections of biotinylated dextran amine or Fluorogold into these regions resulted in retrogradely labeled cell bodies in the CVLM. However, the neurons projecting to the lateral tegmental field were located mainly dorsal to those projecting to the rostral ventrolateral medulla, suggesting that these neurons form two groups, possibly with different inputs. Injections of retrograde tracers into the lateral tegmental field and rostral ventrolateral medulla also produced labeled cell bodies in other regions, including the medial and inferior vestibular nuclei and nucleus solitarius. These data are consistent with the view that the CVLM of the cat is a multifunctional area that regulates blood pressure, produces vocalization, affects the shape of the oral cavity, and elicits contraction of particular facial muscles.

Notes: Abstract Ultrasonic propagation in bone has been investigated using the Leeds Ultrasonic Bone Phantom Material. Phantoms were produced with different porosities in the range of 45−83% and pore sizes of 1.3 and 0.6 mm. The phase velocity at 600 kHz was found to follow a second-order polynomial as a function of porosity. Phase velocity values between 1545 and 2211 m s−1 were measured and found to be largely independent of pore size for a given porosity. The slope of the phase velocity as a function of frequency (dispersion) decreases with increasing porosity. The values obtained from samples having different pore sizes were also similiar. The attenuation coefficient and normalized broadband ultrasonic attenuation (nBUA) reached a maximum at about 50%. The normalized attenuation ranged from 6 to 25 dB cm−1 over the porosity range available and consistently showed higher values for the larger pore size. Similarly, the nBUA values were found to be between 14 and 53 dB MHz−1 cm−1, with the values for the larger pore size being roughly 10 dB MHz−1 cm−1 greater than those for the smaller pore size. These findings demonstrate that the Leeds phantom can be used to investigate the effect of structural changes in bone and to aid the understanding of quantitative ultrasound. The results support the assumption that the velocity in trabecular bone is not dependent on pore size but is influenced by the mechanical properties of the bone's constituents and the overall framework, whereas the attenuation and BUA are also influenced by structure.

Notes: Abstract To help resolve the uncertainty whether sodium fluoride (NaF) therapy should be given intermittently or continuously, we examined iliac crest bone biopsies (before and after treatment) and fragility fracture rates in 35 intermittently treated (group I) and 69 continuously treated (group C) patients; all received calcium. The following statistically significant results were obtained. Reduction in vertebral fracture rate was similar in the two groups. Trabecular thickness and the structurally more important mineralized thickness increased only in group I. Group I also accumulated less excess osteoid (surface, volume). Mean osteoid thickness did not change in either group because of a bimodal distribution of wide seams with osteoblasts and double tetracycline labels, and thin seams without osteoblasts or labels. Osteoid was lamellar. Osteoid in abnormal sites (within bone marrow or bone, or around osteocytes) was found less frequently in group I. Adjusted apposition rate declined and mineralization lag time increased in both groups because of extended unlabelled osteoid seams. Erosion surface increased only in group C. Hook and/or tunnel erosion was seen less frequently in group I; it was closely associated with osteoid in abnormal sites and correlated with osteoid surface. Extended osteoid surface may have forced osteoclasts to hollow out trabeculae, leaving the empty osteoid shell in marrow. Excess osteoid volume and eroded surface and osteoid and erosion in abnormal sites correlated with bone fragility in group C. We conclude that intermittent therapy is to be preferred because it (1) increased mineralized trabecular thickness, (2) did not cause excessive osteoid accumulation and erosion, (3) showed less osteoid and erosion in abnormal sites and (4) led to a similar reduction in the vertebral fracture rate as did continuous treatment. The question of whether intermittency of therapy has some other effect independent of the cumulative dose of fluoride administered cannot be answered by this study.

Notes: Summary Several calcium supplements are currently available and many of them are marketed without proper comparison of the bioavailability of the actual preparations. The aim of the present trial was to evaluate and compare the acute changes in serum calcium (Ca) and parathyroid hormone (PTH) levels following the oral administration of a vehicle and of five calcium salts currently prescribed in Western Europe. No significant changes in serum Ca or PTH levels were observed after administration of the vehicle. All calcium salts induced significant increases in serum Ca and decreases in serum PTH compared to baseline values. Comparison of the six response curves revealed a significantly greater increase in serum Ca and a greater decrease in serum PTH after each of the calcium salts than observed after the vehicle. However, no statistically significant differences were observed between the different calcium salts for serum Ca increments. The decrease in serum PTH observed after administration of an ossein-hydroxyapatite complex was significantly less important than after the four other calcium salts, even if statistically different than after vehicle. When assessing the area under the curve (AUC) of PTH values, we observed that calcium carbonate and citrate induce a significantly greater decrease in serum PTH than the other calcium salts which are, however, statistically more active than the vehicle. Serum PTH is decreased under the lower limit of the normal range (10 pg/ml), between t60 and t120 for calcium carbonate and citrate and between t60 and t90 for calcium gluconolactate while the mean PTH values remain within the normal range throughout the study with calcium pidolate, the ossein-hydroxyapatite complex and the vehicle. In conclusion, all calcium preparations significantly increase serum calcium and decrease serum parathormone, compared to what is observed after oral intake of a vehicle. However, significant differences in suppression of parathormone are observed between the different calcium preparations and might be of importance for their clinical use.

Notes: Abstract. We investigated the binding characteristics of two monoclonal antibodies, 4F3 and 3F8, which in the retina specifically stain Müller cells, both with protein blots and immunohistochemically in sections of various regions of the central nervous system of neonatal and adult cats and rats. Clear differences emerged between the two antibodies. In addition, some species-specific as well as developmental differences within the staining pattern of each individual antibody were evident. The epitopes recognized by 4F3 lay mainly in the 57–63 kDa range. Histologically, 4F3 labelled mainly glia cells: oligodendrocytes and astrocytes in optic nerve, astrocytes in neocortex and cerebellum, Bergmann glia in the cerebellum and radial glia in neonatal animals. This was confirmed by double-immunofluorescence with the astrocyte marker GFAP. By contrast, 3F8 epitopes lay mainly in the 47–49 kDa range. Histologically, 3F8 labelled oligodendrocytes in the optic nerve, but only neurons in cerebellum and neocortex as confirmed by double-labelling with neuronal markers. Neither 4F3 nor 3F8 recognized GFAP or vimentin. These results clearly indicate (1) that the two antibodies identify new epitopes/molecules, (2) that the antigens are not retina-specific, and (3) that Müller cells share epitopes with other glial cells as well as with neurons outside the retina.

Notes: Abstract  We report a case of MFH of the mandible in a 16-year-old girl. The mandible is a rare location of MFH of bone, with only 21 cases described in the literature. Clinical, pathologic, and radiologic features are discussed, with special emphasis on the unusual pathologic and radiographic features.

Notes: Abstract  Objective. Intra-arterial chemotherapy (IAC) is frequently used as an adjuvant treatment for musculoskeletal tumors. Past studies have noted that IAC not only induces favorable effects in tumor, but may also cause muscle edema and necrosis in previously normal tissue, reflected as increased signal on T2-weighted scans. In order to evaluate the prevalence of these effects, we reviewed all patients receiving IAC and MRI at our institution. Methods. Our study population consisted of 24 patients who underwent IAC. All subjects were studied with MRI both pre-and post-IAC. None of the subjects in this study underwent surgery or radiation therapy until after the post-IAC MRI examination. Any muscle group involved by the tumor or peritumoral edema on the initial scan was excluded from the study. Catheter position during IAC was recorded as central or peripheral. Scans were scored positive if muscle groups in regions remote from the tumor site demonstrated increased T2 signal following IAC. Results. Six out of these 24 patients (25%) were found to have positive results. A significant association was found between peripheral catheter position and a positive scan post-IAC (Fisher’s exact test, P=0.024). Conclusion. Because of our exclusion criteria, we are convinced that the finding of increased T2 signal in 25% of our patients was caused by IAC and represents muscle edema or necrosis. Knowledge of this post-chemotherapy MR finding should help prevent confusion during the interpretation of follow-up MR examinations.

Notes: Abstract  We report a case of a 12-year-old girl with idiopathic tumoral calcinosis of the neck. There are calcium deposits in the paraspinal soft tissue with bony involvement in the cervical spine. CT and MR images are presented along with clinical and pathological features. Bony involvement in this disease has not been recognized before.

Notes: Abstract  Objective. The objective of this study was to determine the value of MRI in the detection of degenerative bone marrow abnormalities in an animal osteoarthritis model. Design. In 10 dogs with experimentally induced unilateral osteoarthritis of the knee, MRI was performed using two-dimensional spin-echo (2D-SE) and three-dimensional gradient-echo (3D-GE) imaging. Contrast enhanced T1-weighted 2D-SE sequences were also obtained after injection of gadolinium-DTPA. The results were compared with the gross and histopathologic findings and with radiography. Results. Histopathologic specimens revealed 21 osteosclerotic lesions and 5 intraosseous cysts. On 2D-SE images, 24 of 26 lesions were detected, while 21 of 26 lesions were identified on 2D-GE sequences. Radiography, including conventional tomography, demonstrated 9 of 26 lesions. Regardless of the sequence weighting, all osteosclerotic lesions appeared hypointense on MRI. Signal loss in bone sclerosis resulted primarily from the reduction of intact fat marrow, the increased bone density being of secondary importance. Quantitative signal analysis allowed approximate estimation of the grade of sclerosis. On postcontrast images, sclerotic bone remained hypointense, although significant but non-specific enhancement relative to the normal fat marrow was observed. The extent of contrast enhancement did not correlate with the grade of osteosclerosis. All five cysts were readily diagnosed by MRI. Cysts displayed either central or marginal contrast enhancement within their cavities. Conclusions. MRI provides a sensitive method for the diagnosis of osteoarthritic bone abnormalities, allowing their differentiation from most non-degenerative subarticular lesions.

Notes: Abstract This study was designed to determine the in vitro and in situ diameter vs pressure relationship of 200- to 1,200-μm diameter pulmonary arteries in the cat. Diameter vs pressure relationships of these arteries were obtained using two methods, microscopic observation of in vitro cannulated and pressurized arteries and X-ray angiography of in situ arteries. Both in vitro and in situ arteries were studied first under normal conditions and then after reducing tone with Ca2+-free solution (in vitro) or papaverine (in situ). In vitro arteries commonly increased their tone in response to elevated transmural pressure, and in some cases, the diameter actually decreased as pressure increased. This behavior was not observed in the in situ arteries. The major difference between in vitro and in situ arteries was that when the in vitro arteries were relaxed, the slope of the diameter vs pressure curves increased, whereas the slope was not altered significantly by relaxation of the in situ arteries. This difference is emphasized by the increased distensibility with relaxation of the in vitro arteries but the decreased distensibility with relaxation of the in situ arteries. The results of this study suggest that, at least in the cat, small pulmonary arteries possess a mechanism that is dormant in the in situ environment within the normal lung. However, the potential for pressure-induced constriction may be unmasked by changing the vessel history and/or environment. Extrapolating results obtained from in vitro pulmonary arteries to the in situ situation should therefore be done with caution. Studies directed at what factors contribute to differences in the responses of in vitro and in situ arteries might help in understanding pulmonary vascular pathophysiology.

Notes: Abstract Extracellular recordings were made from the cat intact neocortex and guinea-pig neocortical slices during microiontophoretic application of amino acid neurotransmitters. Spike train autocorrelation analysis showed a high stability of firing patterns in the intact neocortex. When excitation of a cell was increased in a step-wise manner with glutamate iontophoresis only an enhancement of the rate of firing was observed. The rhythmic component, which was mainly due to periodic multiple discharges, remained up to the highest firing frequencies. In contrast to the in vivo observation, glutamate, aspartate or K+ iontophoresis in cortical slices resulted in firing pattern alternations (always from bursts or irregular activity to regular spike firing) as well as an increase in firing rate. In slices the periodic component was typically due to single-spike regularity and its frequency rose with an increase of firing rate. The comparison of autocorrelogram alternations in vivo and in vitro suggests that the temporal organization of spike trains in the intact cortex is under tight external control and is defined mainly by neuronal interactions, whereas virtually all the neurons in vitro are very sensitive to the same iontophoretic influences and their individual outputs easily change according to the excitation (depolarization) level. The coincidence of the lowest frequencies of single-spike regularity in the in vitro preparation (5–7 Hz and 8–10 Hz) with theta- and alpha-rhythms in the electroencephalogram (EEG), and with single unit firing rhythmicity in the whole brain, may represent the basis of a unit-circuit resonance and provide a high stability of these EEG-rhythms.

Notes: Abstract Bone mineral measurements with quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) were compared with chemical analysis (ChA) to determine (1) the accuracy and (2) the influence of bone marrow fat. Total bone mass of 19 human femoral necks in vitro was determined with QCT and DXA before and after defatting. ChA consisted of defatting and decalcification of the femoral neck samples for determination of bone mineral mass (BmM) and amount of fat. The mean BmM was 4.49 g. Mean fat percentage was 37.2% (23.3%–48.5%). QCT, DXA and ChA before and after defatting were all highly correlated (r〉0.96,p〈0.0001). Before defatting the QCT values were on average 0.35 g less than BmM and the DXA values were on average 0.65 g less than BmM. After defatting, all bone mass values increased; QCT values were on average 0.30 g more than BmM and DXA values were 0.29 g less than BmM. It is concluded that bone mineral measurements of the femoral neck with QCT and DXA are highly correlated with the chemically determined bone mineral mass and that both techniques are influenced by the femoral fat content.

Notes: Abstract High-density lipoproteins (HDL) are the predominant lipoproteins in plasma of dogs and cats and are the major cholesterol-carrying particles. Two HDL subfractions are identifiable in dog: small, dense particles (equivalent to human HDL3) and large, buoyant particles called HDL1, which overlap in hydrated density with low-density lipoproteins (LDL). The HDL1 are enriched in cholesterol and apolipoprotein (apo) E, and are prevalent in dogs fed high amounts of cholesterol and, or, saturated fat, when they are also referred to as HDLc. Lipoproteins similar to human HDL2 and HDL3 are identifiable in feline plasma, along with trace HDL1. Lipoprotein lipase (LPL), hepatic lipase (HL) and lecithin: cholesterol acyl transferase (LCAT) activities are present in dogs and cats. Both species lack significant cholesteryl ester transfer protein activity, and reverse cholesterol transport is probably accomplished by receptor-mediated hepatic uptake of HDL1. Methods for the measurement of canine and feline plasma lipoprotein-cholesterol concentrations, apolipoprotein concentrations, and the activities of LPL, HL and LCAT have been developed. Together with oral and intravenous fat tolerance tests, these methods provide the basis for studying lipoprotein metabolism in cats and dogs.

Notes: Abstract A technique to correlate the ultrastructural distribution of mineral with its organic material in identical sections of mineralized turkey leg tendon (MTLT) and human bone was developed. Osmium or ethanol fixed tissues were processed for transmission electron microscopy (TEM). The mineralized tissues were photographed at high, intermediate, and low magnifications, making note of section features such as fibril geometry, colloidal gold distribution, or section artifacts for subsequent specimen realignment after demineralization. The specimen holder was removed from the microscope, the tissue section demineralized in situ with a drop of 1 N HCl, then stained with 2% aqueous vanadyl sulfate. The specimen holder was reinserted into the microscope, realigned with the aid of the section features previously noted, and rephotographed at identical magnification used for the mineralized sections. A one to one correspondence was apparent between the mineral and its demineralized crystal “ghost” in both MTLT and bone. The fine structural periodic banding seen in unmineralized collagen was not observed in areas that were fully mineralized before demineralization, indicating that the axial arrangement of the collagen molecules is altered significantly during mineralization. Regions that had contained extrafibrillar crystallites stained more intensely than the intrafibrillar regions, indicating that the noncollagenous material surrounded the collagen fibrils. The methodology described here may have utility in determining the spatial distribution of the noncollagenous proteins in bone.

Notes: Abstract Bone soft tissue remodelling at the femoral and tibial insertions of the medial collateral ligament (MCL) of the rat knee was monitored at regular intervals from birth to 120 days of age in 40 Sprague Dawley rats. At birth the femoral insertion originated from the perichondrium of the epiphysis. By day 8 the perichondrium within the insertion had turned into fibrocartilage. Secondary ossification of the femoral epiphysis had progressed in the region near to the insertion site by day 15. The epiphyseal cartilage was entirely replaced by bone by day 40 except for the fibrocartilage within the insertion. After that stage, no qualitative change in zonal insertion characteristics was observed, but only increase in size and decrease in cellularity. At birth, the tibial ligament inserted onto the thin cortical bone of the metaphysis via periosteum. At day 8, osteoclasts started to resorb the thin cortical bone at the ligament insertion, thus forming a metaphyseal depression between days 10 and 20. From days 20 to 120, the insertion remained qualitatively unchanged, showing three zones, the ligament, periosteum, and metaphyseal trabecular bone. The deep periosteal layer showed osteoclastic activity in the proximal part and osteoblastic activity in the distal part. The migration mechanism of the ligament insertion during growth seems to be caused by this growth-related osteoclastic resorption of the proximal metaphyseal bone and by simultaneous osteogenic activity, which successively cements the distal part of the ligament to bone. The persistence of the periosteal layer and the metaphyseal depression for up to 120 days may be regarded as a sign of continuing growth in this animal model. This is the first investigation showing that the formation of the metaphyseal depression is a purely postnatal event, and suggests that this process might be initiated by the change in mode of growth and joint biomechanics after birth, enabling ligament development and migration in a growing and increasingly loaded weight-bearing joint. The mainly resorptive process, which takes place during development of the tibial MCL insertion, may account for the tensile failure of this ligament that commonly occurs at this site during growth. The pronounced morphological differences between the chondral femoral and the periosteal tibial attachment of the adult MCL are apparently caused by the different postnatal developmental processes at epiphyses and metaphyses.

Notes: Abstract Senile plaques were found in the cerebral cortices of three very aged cats (more than 18 years old). The plaques consisted of a coarse assembly of silver staining-positive materials, and was morphologically different from the well-known classical, primitive, and diffuse plaques. Congophilic amyloid angiopathy was observed in a few cortical arterioles of the oldest cat (20 years old). The senile plaques and a few cortical blood vessels were immunopositive for amyloid β-protein (Aβ). Aβ-positive materials were also sparsely distributed in the cortical neuropil but did not form senile plaques there. These findings should help to clarify the development of senile plaques and the early stage of Aβ deposition.

Notes: Abstract Interleukin-1 (IL-1) and tumor necrosis factor (TNF), two pleiotropic cytokines produced in inflammatory processes, inhibit bone matrix biosynthesis and stimulate prostanoid formation in osteoblasts. In the present study, the importance of prostaglandin formation in IL-1 and TNF-induced inhibition of osteocalcin and type I collagen formation has been examined. In the human osteoblastic cell line MG-63, IL-1α (10–1000 pg/ml), IL-1β (3–300 pg/ml) and TNF-α (1–30 ng/ml) stimulated prostaglandin E2 (PGE2) formation and inhibited, 1,25(OH)2-vitamin D3-induced osteocalcin biosynthesis as well as basal production of type I collagen. Addition of PGE2 or increasing the endogenous formation of PGE2 by treating the cells with arachidonic acid, bradykinin, Lys-bradykinin or des-Arg9-bradykinin, did not affect osteocalcin and type I collagen formation in unstimulated or 1,25(OH)2-vitamin D3-stimulated osteoblasts. Four non-steroidal anti-inflammatory drugs, indomethacin, flurbiprofen, naproxen and meclofenamic acid, inhibited basal, IL-1 β- and TNF-α-stimulated PGE2 formation in the MG-63 cells without affecting IL-1 β- or TNF-α-induced inhibition of osteocalcin and type I collagen formation. In isolated, non-transformed, human osteoblast-like cells, IL-1 β and TNF-α stimulated PGE2 formation and concomitantly inhibited 1,25(OH)2-vitamin D3-stimulated osteocalcin biosynthesis, without affecting type I collagen formation. In these cells, indomethacin and flurbiprofen abolished the effects of IL-1 β and TNF-α on prostaglandin formation without affecting the inhibitory effects of the cytokines on osteocalcin biosynthesis. These data show that IL-1 and TNF inhibit osteocalcin and type I collagen formation in osteoblasts independently of prostaglandin biosynthesis and that non-steroidal antiinflammatory drugs do not affect the effects of IL-1 and TNF on bone matrix biosynthesis.

Notes: Abstract Systemic and focal cerebral acidosis is considered deleterious to cell metabolism and neuronal recovery. We investigated the immediate effect of tris-(hyroxymethyl)-aminomethane (THAM), an alkalizing agent, on focal cerebral ischemia produced by occlusion of the left middle cerebral artery (MCA) in cats with systemic acidosis. Occlusion of MCA resulted in prompt decreases in local cerebral blood flow of the ipsilateral marginal and ectosylvian gyri from 47.7 ml/100 g per minute in control to 32.3 ml/100 g per minute and 8.3 ml/100 g per minute, respectively. In the control group, physiological saline was infused continuously and the treated group received 0.3 M THAM to normalize systemic and focal cerebral acidosis. There were no significant changes in the systemic arterial pressure, arterial PO2 and PCO2 throughout the experiments in the two groups. Arterial pH decreased from 7.42 to 7.30 in the control, while it remained normal during THAM treatment. Extracellular pH of the marginal gyrus (peri-infarct zone) decreased from 7.39 to 6.87 with 6 h ischemia in the control group. In THAM infusion, extracellular pH was kept between 7.26 and 7.29, which was significantly higher than the control group. THAM significantly decreased infarct volume and lactate and water contents of the gray matter in the marginal gyrus at 6 h after occlusion. It is concluded that THAM infusion immediately after ischemia onset is considered effective in improving acidosis at the site of ischemic penumbra and consequently reduces lactate production, brain edema, and infarct volume.

Notes: Abstract Head-fixed gaze shifts were evoked by electrical stimulation of the deeper layers of the cat superior colliculus (SC). After a short latency, saccades were triggered with kinematics similar to those of visually guided saccades. When electrical stimulation was maintained for more than 150–200 ms, postsaccadic smooth eye movements (SEMs) were observed. These movements were characterized by a period of approximately constant velocity following the evoked saccade. Depending on electrode position, a single saccade followed by a slow displacement or a “staircase” of saccades interspersed by SEMs were evoked. Mean velocity decreased with increasing deviation of the eye in the orbit in the direction of the movement. In the situation where a single evoked saccade was followed by a smooth movement, the duration of the latter depended on the duration of the stimulation train. In the situation where evoked saccades converged towards a restricted region of the visual field (“goal”-directed or craniocentric saccades), the SEMs were directed towards the centre of this region and their mean velocity decreased as the eye approached the goal. The direction of induced SEMs depended on the site of stimulation, as is the case for saccadic eye movements, and was not modified by stimulation parameters (“place” code). On the other hand, mean velocity of the movements depended on the site of stimulation and on the frequency and intensity of the current (“rate” code), as reported for saccades in the cat. The kinematics of these postsaccadic SEMs are similar to the kinematics of slow, postsaccadic correction observed during visually triggered gaze shifts of the alert cat. These results support the hypothesis that the SC is not exclusively implicated in the control of fast refixation of gaze but also in controlling postsaccadic conjugate slow eye movements in the cat.

Notes: Abstract Children with phenylketonuria (PKU) obtain a great deal of their protein and mineral intakes from synthetic elemental formulae devoid of phenylalanine. To assess the effect of such diets and/or the disease on bone mineralization, children with PKU were compared to normal children for many parameters of mineral homeostasis and bone mineralization. A total of 11 children with PKU of mean age 10.9 ± 4.2 years were compared to a large group of normal control children mean age 11.4 ± 4.2, and an age and sex matched subset (n = 11). Children with PKU had lower serum calcium (9.1 ± 0.9 vs 10.4 ± 1.9 mg/dl P 〈 0.01) amd magnesium (1.67 ± 1.4 vs 2.07 ± 0.16 mg/ dl, P 〈 0.001) but normal values for phosphorus, zinc, and copper. The percentage tubular reabsorption of phosphorus was increased in PKU (93 ± 3% vs 88 ± 6%, P 〈 0.05) suggesting a lower phosphorus intake and/or absorption. Serum 25-hydroxyvitamin D, parathyroid hormone and 1,25 dihydroxyvitamin D were similar in PKU and control children. Serum albumin and lean body mass by dual energy X-ray absorption were not different suggesting that protein intake was adequate. In the 11 pairs, a decreased bone mineral density was seen for the lumbar spine (0.61 ± 0.15 vs 0.72 ± 0.24 P 〈 0.05), and lower extremities (1.56 ± 0.30 vs 1.87 ± 0.56 P 〈 0.05) by paired t-test. Compared to the total controls and the paired controls, decreases were seen in markers of bone formation; bone alkaline phosphatase, (72 ± 30 vs 126 ± 43 P 〈 0.001), osteocalcin (10.7 ± 3.4 vs 13.1 ± 2.0 P 〈 0.05) and procollagen type I carboxyterminal propeptide. No differences were seen in the bone resorption markers tartrate resistant acid phosphatase and urine Ca/Cr. The changes noted could not be related after age correction to serum phenylalanine levels, protein intake, or mineral intakes. It is unclear whether deficits in bone mineralization relate to the disease process itself or its treatment.

Notes: Abstract The present investigation documents the patterns of primary afferent depolarization (PAD) of single, functionally identified muscle afferents from the medial gastrocnemius nerve in the intact, anesthetized cat. Classification of the impaled muscle afferents as from muscle spindles or from tendon organs was made according to several criteria, which comprised measurement of conduction velocity and electrical threshold of the peripheral axons, and the maximal frequency followed by the afferent fibers during vibration, as well as the changes in discharge frequency during longitudinal stretch, the projection of the afferent fiber to the motor pool, and, in unparalyzed preparations, the changes in afferent activity during a muscle twitch. In confirmation of a previous study, we found that most muscle spindle afferents (46.1–66.6%, depending on the combination of criteria utilized for receptor classification) had a type A PAD pattern. That is, they were depolarized by stimulation of group I fibers of the posterior biceps and semitendinosus (PBSt) nerve, but not by stimulation of cutaneous nerves (sural and superficial peroneus) or the bulbar reticular formation (RF), which in many cases inhibited the PBSt-induced PAD. In addition, we found a significant fraction of muscle spindle primaries that were depolarized by stimulation of group I PBSt fibers and also by stimulation of the bulbar RF. Stimulation of cutaneous nerves produced PAD in 9.1–31.2% of these fibers (type B PAD pattern) and no PAD in 8.2–15.4% (type C PAD pattern). In contrast to muscle spindle afferents, only the 7.7–15.4% of fibers from tendon organs had a type A PAD pattern, 23–46.1% had a type B and 50–61.5% a type C PAD pattern. These observations suggest that the neuronal circuitry involved in the control of the synaptic effectiveness of muscle spindles and tendon organs is subjected to excitatory as well as to inhibitory influences from cutaneous and reticulospinal fibers. As shown in the accompanying paper, the balance between excitation and inhibition is not fixed, but can be changed by crushing the afferent axons in the peripheral nerve and allowing subsequent reconnection of these afferent fibers with muscle receptors.

Notes: Abstract Membrane potential changes and/or discharges from 36 inspiratory neurons were recorded intracellularly in the dorsal respiratory group (DRG; i.e., the ventrolateral subdivision of the nucleus tractus solitarii) in decerebrate, paralyzed, and ventilated cats. Electrical activities were recorded from both somata (n=10) and axons (n=26). Activities during quiet breathing were compared with those observed during fictive coughing and swallowing evoked by repetitive electrical stimulation of afferent fibers of the superior laryngeal nerve (SLN). These nonrespiratory behaviors were evident in paralyzed animals as characteristic discharge patterns of the phrenic, abdominal, and hypoglossal nerves. Twenty-six neurons exhibiting antidromic action potentials in response to electrical stimuli applied to the cervical (C3–5) spinal cord were classified as inspiratory bulbospinal neurons (IBSNs). These neurons were considered as premotoneurons. The remaining 10 inspiratory neurons (INAA) were not antidromically activated by electrical stimuli applied to either cervical spinal cord or ipsilateral cervical vagus. These neurons are thought to be propriobulbar neurons. We recorded the activity of 31 DRG inspiratory neurons (24 IBSNs and 7 I-NAA) during coughing. All but one (a late-recruited IBSN) discharged a burst of action potentials during the coughing-related phrenic nerve activity. Typically, ramp-like membrane depolarization trajectories and discharge frequencies during coughing were similar to those observed during inspiration. We recorded the activity of 33 DRG inspiratory neurons (23 IBSNs and 10 I-NAA) during swallowing. Most (28/33) neurons were briefly activated, i.e., discharged a burst of action potentials during swallowing, but peak discharge frequency decreased compared with that measured during inspiration. The membrane potentials of nine somata exhibited a brief bell-shaped depolarization during swallowing, the amplitude of which was similar to that observed during inspiration. These results suggest that some inspiratory premotoneurons and propriobulbar neurons of the DRG might be involved in nonrespiratory motor activities, even if clearly antagonistic to breathing (e.g., swallowing). We postulate the existence in the medulla oblongata of adult mammals of neurons exhibiting a “functional flexibility”.