Equal suppression of cerebellar Purkinje cell activity by amphetamine stereoisomers

The two amphetamine isomers were compared for their ability to reduce spontaneous activity of noradrenoceptive Purkinje cells in the rat cerebellum. The drugs were applied iontophoretically to eliminate peripheral and remote central effects. Responses of Purkinje neurons were summed over several cycles of alternating (+)- and (?)-amphetamine, and poststimulus time histograms were compared. Inhibitions of Purkinje cell discharge by the two isomers were not statistically different over a wide range of pipette resistances. These data, taken together with studies showing equal effects of the two isomers on noradrenergic release and reuptake blockade and on locus coeruleus neuronal firing, indicate equipotency of the two isomers in their actions on noradrenergic mechanisms.     

Antibodies to low-incidence antigens and elimination of the antihuman globulin phase of the crossmatch-case report: anti-Wra

An antibody to a low-incidence antigen was identified in the serum of a nontransfused male patient. The antibody was subsequently identified as anti-Wra and was only detectable at the antihuman globulin (AHG) phase of the crossmatch. Instances of severe hemolytic transfusion reactions have been reported following the transfusion of red blood cells containing low-incidence antigens in patients with antibodies directed toward these antigens (e.g., anti- Wra, -Cob, -Jsa, etc.). Elimination of the AHG phase of the crossmatch can result in either risks or benefits. Since patients seen at this facility primarily have been multitransfused or are multiparous females, the AHG phase of the crossmatch has been maintained.     

Somatotopic organization of corticospinal and corticotrigeminal neurons in the rat

The method of retrograde axonal transport of horseradish peroxidase was employed to examine the topographic organization of corticospinal and corticotrigeminal neurons in the rat. In both the first somatic sensory (SI) area and the motor (MI) area of the cortex these labeled corticofugal neurons, all of which are found in layer V, are grouped in a well organized, somatotopic pattern. Corticospinal projections which extend to lumbar levels of the spinal cord originate only from neuronal somata located in the hindlimb representation of SI and MI. Those neurons projecting to the cervical enlargement have somata mainly in the forelimb representation of SI and MI and the ventrolateral part of the trunk representation within SI. Cortical projections to the rostral cervical spinal segments appear to originate mainly from the neck and posterior head representations of SI and MI, though this conclusion is clearest for SI. Finally, neurons located exclusively within the head, muzzle, and vibrissal representation of SI project to the spinal trigeminal complex. Corticofugal neurons near the frontal pole and in an area of cortex ventrolateral to SI also project to the spinal cord. The areas involved are probably homologous to the supplementary motor (MII) and second somatic sensory (SII) areas respectively. The corticospinal and corticotrigeminal projections from these areas also appear to be organized in a somatotopic manner.It is concluded that in the rat, as in other species, the corticospinal and corticotrigeminal neurons in the sensorimotor cortex are arranged somatotopically. The somatotopic pattern found correlates remarkably well with that determined by single unit, evoked potential and cortical stimulation techniques.     

Healing of osteochondral osteotomies after fixation with a hydroxyapatite-buffered polylactide. A histomorphometric and radiographic study in rabbits

The tissue response of subchondral bone to a biodegradable fixation device manufactured in the shape of a screw and made of polylactide with a hydroxyapatite buffer were implanted through the articular surface of the intercondylar portion of the distal rabbit femur. One screw was implanted per animal. The screws had a core diameter of 3.2 mm and an outer diameter of 4.5 mm. At insertion, the implants were cut flush with the articular surface. After follow-up times of 8 and 16 weeks, the specimens were examined radiographically and histomorphometrically. The intact contralateral femur served as a control for comparison. Only minimal signs of degradation of the polymer could be seen in the histologic specimens. These implant degradation sites were commonly areas of new bone formation adjacent to the screw implant. A brim of repair tissue was formed at the entrance and exit of the implant channel. The width of the repair tissue from the tissue-implant boundary towards the center of the entrance hole varied greatly between the specimens, from 80 to 750 microm. In most specimens this bridging tissue consisted of newly formed bone and undifferentiated mesenchymal tissue. Degenerative chondrocyte clustering occurred in the pre-existing cartilage within a 400 microm wide zone from the tissue-implant interface into the recipient tissues. Some new-bone formation was seen to envelop the implant in all specimens, but the fractional osteoid formation surface of the trabeculae was only significantly higher in the screw-implanted 16-week specimens, when compared to the non-operated contralateral controls. Although the bony osteotomy was invariably healed in all specimens with good implant integration, the quality and quantity of the reparative tissue of the articular cartilage near the screw hole was variable. This study showed that large polylactide implants, which are buffered with hydroxyapatite show benign tissue responses and good implant osteointegration when implanted in bone. They may be suitable for fixation of small bone fractures. However, insertion through intra-articular surfaces may require further improvement of the implant material to avoid the degenerative repair processes seen in this study.     

In vivo expression of classic PKC isoforms in the rat dental follicle as related to tooth eruption

Activation of protein kinase C (PKC) can upregulate tooth eruption molecules such as osteoprotegerin (OPG) and vascular endothelial growth factor (VEGF). In this study, we examined the in vivo gene expression of classic isoforms of PKC in the dental follicle of postnatal rats. The expression level of PKC-alpha was significantly reduced at day 3 followed by a gradual return to day 1 level, a profile similar to OPG expression. The expression of PKC-beta was the lowest at day 1 followed by elevated levels from day 3 to day 11. Expression of PKC-beta is positively correlated with the expression of overall VEGF and VEGF120. The expression level of PKC-gamma was relatively steady in the postnatal days. Injection of a PKC activator, phorbol 12-myristate 13-acetate (PMA), at late postnatal days, slightly accelerated first mandibular molar eruption. This study suggests that PKC isoforms may be involved in the regulation of tooth eruption.     

Influence of glial growth factor and Schwann cells in a bioresorbable guidance channel on peripheral nerve regeneration

Using an established rat peripheral nerve regeneration model, we investigated the role of glial growth factor (GGF) in nerve regeneration in combination with a novel bioresorbable poly(lactic-co-glycolic) acid (PLGA) guide in vivo. Schwann cells, established from a 1-cm segment of excised rat sciatic nerve, were isolated and seeded onto nerve guides with or without GGF (n = 24/group). Living nerve guides were re-established in these animals, and nerve regeneration was assessed over a period of 12 weeks. Histological studies revealed a reduction in the total axon count and the number of myelinated axons in the presence of exogenously added Schwann cells compared to saline controls. In contrast, the addition of GGF alone enhanced the total number of axons and significantly increased the number of blood vessels. Although combining GGF with Schwann cells negated the enhanced numbers of axons and blood vessels seen with GGF alone, this combination resulted in the highest myelination index and the fastest conduction velocities recorded. The PLGA guide material did not trigger any histologically detectable host response and was permissive for nerve regeneration in this animal model. The results from this study demonstrate the potential utility of this guide in vivo and establish a promotional role for GGF in nerve regeneration.     

Maturation of pyramidal cell form in relation to developing afferent and efferent connections of rat somatic sensory cortex.

Golgi and axonal labeling methods were used to examine the maturation of pyramidal cells in layers III and V of the rat somatic sensory cortex. The material came from animals late in the gestation period, postnatal, ranging from 0 to 43 days of age and at maturity. Special attention was paid to the period (0–7 days of age) during which it is known that thalamic and callosal fibers grow into the cortex. It is shown that the basic features of the pyramidal cell form are established before the long afferent fibers arrive in layers III and V and before the large number of synapses are established in these layers. Nevertheless, considerable dendritic growth and spine formation occurs after the afferent fibers establish an adult-like pattern of distribution. It is also shown that even at 1 day of age, the axons of pyramidal cells in all layers have reached the vicinity of targets such as the striatum, thalamus, brainstem, spinal cord and contralateral cortex.At 0–1 day the immature pyramidal cells are essentially bipolar in the upper cortical plate, but in the developing infragranular layers they have a few short, almost spine-free, basal dendrites and, rarely, a few oblique branches of the apical dendrite. The apical dendrite extends to the pial surface and the dendritic branches end in growth cones. The dendrites of cells in all layers increase in size and complexity of branching over the first postnatal week; the maturation of dendrites in layer V leads that of dendrites in the supragranular layers by about 2–3 days. As maturation proceeds, basal dendrites acquire secondary and tertiary branches and more oblique branches appear on the apical dendrite. Dendritic spines appear after 4 days of age but remain sparse up to 7–8 days. At 14 days of age, the spine density is much higher than in 7-day-old animals but remains at a much lower density than in 4-week-old, 6-week-old, or adult animals. By 7–14 days, the difference in maturity between superficial (layer III) and deep (layer V) pyramidal cells is difficult to discern qualitatively. All the pyramidal cells now have relatively complex, highly branched dendritic trees when compared to younger cells, but the dendritic tree is still immature in terms of the number, length and complexity of branching of the apical and basal dendritic systems.It can be concluded that the growth of the long axon of cortical pyramidal neurons precedes the acquisition of afferent connections and when these afferent fibers arrive in the cortex the dendritic tree of the pyramidal cell is still highly immature. Thus it remains possible that the finer modeling of the dendritic tree and the formation of spines may be affected by extrinsic influences such as the afferent fibers.     

Surgonomics: the cost dynamics of craniotomy

Prospective payment systems using the diagnostic related group (DRG) mechanism are being phased in for Medicare inpatient hospital care. The purpose of this study was to examine a common neurosurgical procedure (001), craniotomy without trauma, and characterize the cost dynamics of this DRG. All patients (n = 50) treated in this DRG at the Long Island Jewish Medical Center during 1983 had their financial charges exclusive of physician fees examined. The findings were: (a) each hospital service category had wide charge variances around the mean; (b) emergency (ER) admissions were 200% more expensive than nonemergency (non-ER) admissions; (c) ER admissions seemed to have no greater severity of illness than non-ER admissions, but had a significantly different referral pattern (i.e., admission from the ER to a nonneurosurgical service with a subsequent neurosurgical referral); (d) this DRG when grouped into clinical "subproducts" (i.e., craniotomy for tumor, hematoma, hydrocephalus, aneurysm, benign cyst, and other) showed marked charge differences; and (e) the most expensive 25% of patients had five times higher charges than the least expensive 25% for both ER and non-ER admissions. This type of financial analysis may give surgeons a methodology with which to address the problems of cost containment in a more serious manner.