Acetylcholine receptors do not mediate isoflurane's actions on spinal cord in vitro

Extensive studies on anesthetic mechanisms have focused on the nicotinic acetylcholine receptor, and to a lesser extent on the muscarinic receptor. We designed the present study to test the hypothesis that cholinergic receptors mediate some of the depressant actions of a volatile anesthetic in rat spinal cord. The cord was removed from 2- to 7-day-old rats and superfused in vitro; ventral root potentials were evoked by stimulating a lumbar dorsal root and recording from the corresponding ipsilateral ventral root. Both nicotine and muscarine depressed the nociceptive-related slow ventral root potential (sVRP). The nicotinic antagonists mecamylamine, methyllycaconitine, dihydro-beta-erythroidine, and the muscarinic antagonist atropine blocked the depressant effects of the respective agonists. Isoflurane 0.3 mini- mum alveolar anesthetic concentration depressed the sVRP area to approximately 40% of control. None of the antagonists changed the extent of isoflurane depression of the sVRP. The depressant actions of cholinergic agonists suggest that cholinergic receptors are important in spinal neurotransmission, but the lack of interaction between antagonists and isoflurane suggests that cholinergic receptors have little part in mediating the actions of this anesthetic in spinal cord. Because minimum alveolar anesthetic concentration is determined primarily in spinal cord, cholinergic receptors may be eliminated as molecular targets for this anesthetic end-point. IMPLICATIONS: Neither nicotinic nor muscarinic acetylcholine receptor antagonists altered spinal cord actions of isoflurane, suggesting that these receptors have little role in isoflurane actions in spinal cord. Cholinergic receptors thus may be eliminated as molecular targets in determining the anesthetic end-point of immobility in response to a noxious stimulus (minimum alveolar anesthetic concentration).     

Alendronate treatment in the revision setting, with and without controlled implant motion: an experimental study in dogs

Introduction Bisphosphonates have been proposed to delay or prevent loosening of joint replacement implants by reducing bone resorption. It is known, however, that implant motion prevents the bone anchorage necessary to maintain secure implant fixation.

Methods We used our experimental implant model with controlled motion to evaluate the relative effects of implant motion and bisphosphonate. We implemented our established 8-week experimental revision protocol to obtain a bony and soft tissue setting of revision joint replacement in 16 dogs. At 8 weeks, we had stabilized half of the implants. The other half of the implants continued pistoning. Half of the dogs were exposed to alendronate (oral).

Results Stabilization of the revision implant was more effective at improving fixation (higher shear strength) than administering alendronate. As expected, the fibrous membrane remained under unstable conditions, even with alendronate. With alendronate and stabilized implants, increased bone was observed near the sclerotic shell of the revision cavity, but it was reduced with alendronate when the implant was unstable.

Interpretation Our findings suggest that it may be difficult for alendronate administration alone to rescue implants that are already loose. In implants that have not progressed to loosening, alendronate may increase bone density at the border with the sclerotic shell, but the effect of this bone in delaying eventual loosening is not known.     

Relationship of family environment and parental psychiatric diagnosis to impairment in ADHD

OBJECTIVE: Family environmental factors as well as parental attention-deficit/hyperactivity disorder (ADHD) status have shown associations with variability in ADHD. The purpose of the present study was to examine the links among family environment, parental psychiatric diagnosis, and child impairment within a sample of ADHD-affected sibling pairs (ASPs) ages 5 to 18 years. METHOD: Parents in 220 ASP families completed a measure of family functioning, the Family Environment Scale. Children's impairment was measured by clinical ratings of global functioning and by maternal ratings of behavior. RESULTS: Parents of children with ADHD rate their families as higher in conflict and lower in achievement and organization than normative samples. High family conflict is significantly associated with impairment in ADHD ASPs accounting for approximately 40% of the sibling similarity in impairment. Parental psychiatric diagnosis revealed no significant direct link to sibling impairment, but rather a significant indirect link to impairment mediated by family conflict. Direct associations with parental diagnosis depend on birth order of the ASP members despite the comparable mean impairment scores for older and younger ADHD siblings. CONCLUSIONS: There are strong links between impairment in children with ADHD and family environment. Different processes and mechanisms may contribute to impairment in different children in the same family.     

Do Bone Graft and Cracking of the Sclerotic Cavity Improve Fixation of Titanium and Hydroxyapatite-coated Revision Implants in an Animal Model?

Background

We previously introduced a manual surgical technique that makes small perforations (cracks) through the sclerotic bone shell that typically forms during the process of aseptic loosening (“crack” revision technique). Perforating just the shell (without violating the proximal cortex) can maintain overall bone continuity while allowing marrow and vascular elements to access the implant surface. Because many revisions require bone graft to fill defects, we wanted to determine if bone graft could further increase implant fixation beyond what we have experimentally shown with the crack technique alone. Also, because both titanium (Ti6Al4V) and hydroxyapatite (HA) implant surfaces are used in revisions, we also wanted to determine their relative effectiveness in this model.

Questions/purposes

We hypothesized that both (1) allografted plasma-sprayed Ti6Al4V; and (2) allografted plasma-sprayed HA-coated implants inserted with a crack revision technique have better fixation compared with a noncrack revision technique in each case.

Methods

Under approval from our Institutional Animal Care and Use Committee, a female canine animal model was used to evaluate the uncemented revision technique (crack, noncrack) using paired contralateral implants while implant surface (Ti6Al4V, HA) was qualitatively compared between the two (unpaired) series. All groups received bone allograft tightly packed around the implant. This revision model includes a cylindrical implant pistoning 500 μm in a 0.75-mm gap, with polyethylene particles, for 8 weeks. This engenders a bone and tissue response representative of the metaphyseal cancellous region of an aseptically loosened component. At 8 weeks, the original implants were revised and followed for an additional 4 weeks. Mechanical fixation was assessed by load, stiffness, and energy to failure when loaded in axial pushout. Histomorphometry was used to determine the amount and location of bone and fibrous tissue in the grafted gap.

Results

The grafted crack revision improved mechanical shear strength, stiffness, and energy to failure (for Ti6Al4V 27- to 69-fold increase and HA twofold increases). The histomorphometric analysis demonstrated primarily fibrous membrane ongrowth and in the gap for the allografted Ti6Al4V noncrack revisions. For allografted HA noncrack revisions, bone ongrowth at the implant surface was observed, but fibrous tissue also was present in the inner gap. Although both Ti6Al4V and HA surfaces showed improved fixation with grafted crack revision, and Ti6Al4V achieved the highest percent gain, HA demonstrated the strongest overall fixation.

Conclusions

The results of this study suggest that novel osteoconductive or osteoinductive coatings and bone graft substitutes or tissue-engineered constructs may further improve bone-implant fixation with the crack revision technique but require evaluation in a rigorous model such as presented here.

Clinical Relevance

This experimental study provides data on which to base clinical trials aimed to improve fixation of revision implants. Given the multifactorial nature of complex human revisions, such a protocoled clinical study is required to determine the clinical applicability of this approach.

     

Cross-sectional area of cervical multifidus muscle in females with chronic bilateral neck pain compared to controls

DESIGN: Case-control study. OBJECTIVE: To analyze the differences in muscle size and shape of cervical multifidus between patients with bilateral chronic neck pain and healthy subjects. BACKGROUND: Researchers have demonstrated atrophy of lumbar multifidus in patients presenting with low back pain; however, there are only few published reports on cervical multifidus muscle size in individuals with chronic neck pain. METHODS AND MEASURES: Bilateral ultrasound images of multifidus muscle from the third to sixth cervical vertebrae (C3 to C6) were taken in 20 women with bilateral chronic neck pain and 20 healthy women. Cross-sectional area (CSA [cm2]) and muscle shape ratio (ratio between lateral [Lat] and anterior-posterior [AP] dimensions, [Lat/AP]) were measured without knowledge of group assignment. Two separate 3-way (4 x 2 x 2) mixed-model analyses of variance (ANOVAs) with cervical level (C3 to C6) and side (right, left) as within-subject factors and group (patient, control) as the between-subject factor, were used to evaluate differences in CSA and muscle shape ratio between groups, sides, and cervical levels. RESULTS: The ANOVA for CSA indicated a significant effect for cervical level (F = 6.81, P<.001) and group (F = 20.27, P<.001), but not for side (F = 1.26, P = .36). There were no significant interactions among the variables (P>.5). Post hoc analysis showed that the CSA of the C3 multifidus was smaller than the CSA of the C4 (P = .025), C5 (P<.001) or C6 (P<.01) multifidus. There was no significant difference between C4, C5, and C6 multifidus CSA (P>.05). The patients with neck pain had a smaller CSA of the cervical multifidus at all levels compared to controls (P<.001). The ANOVA for muscle shape ratio indicated a significant effect for level (F = 7.84, P<.001) and group (F = 12.501, P<.001), but not for side (F = 0.654, P = .58). There was a significant interaction between level and group (F = 3.651, P = .01). Patients had a wider ovoid shape (greater values in muscle shape ratio) of the C3 (P<.001) and C6 (P<.01) cervical multifidus compared to controls. Further, the C4 multifidus had a smaller shape ratio compared to C6 (P<.001), but was not significantly different than the shape ratio of the C3 and C5 (P>.05) multifidus. CONCLUSIONS: Females with bilateral chronic neck pain had generalized smaller CSA of the cervical multifidus muscles compared to healthy females.     

Comparison of anterolateral thigh and radial forearm free flap donor site morbidity

This study evaluated patient-reported outcome of the donor site in patients following head and neck cancer reconstruction. Patients who had undergone cancer reconstruction using either an anterolateral thigh or a radial forearm free flap and who were at least 6 months postsurgery were included and contacted by telephone. There were 37 patients (mean age 61 years, standard deviation 16 years) with 18 anterolateral thigh flaps and 19 radial forearm flaps. The majority of patients were not bothered by scar appearance, light touch, numbness or pain. Significantly more females (P = 0.038) and more patients with radial forearm flaps (P = 0.045) were bothered by the cold at the donor site and more females reported that the shape of the operated extremity was different (P = 0.009). Donor site morbidity is not significant following a radial forearm or anterolateral thigh free flap and the reconstruction should be based upon individual patient factors and surgeon expertise.     

Extended endoscopic endonasal transclival approach to the ventrolateral brainstem and related cisternal spaces: anatomical study

Advances in endoscopic endonasal skull base surgery have led to the development of new routes to areas beyond the midline skull base. Recently, feasible surgical corridors to the lateral skull base have been described. The aim of this study was to describe the anatomical exposure of the ventrolateral brainstem and posterior fossa through an extended endoscopic endonasal transclival transpetrosal and transcondylar approach. Six human heads were used for the dissection process. The arterial and venous systems were injected with red- and blue-colored latex, respectively. A pre- and postoperative computed tomography (CT) scan was carried out on every head. The endoscopic endonasal transclival approach was extended through an anterior petrosectomy and a medial condylectomy. A three-dimensional model of the approach was reconstructed, using a dedicated software, from the overlapping of the pre- and post-dissection CT imaging of the specimen. An extended endoscopic transclival approach allows to gain access through an extradural anterior petrosectomy and medial condylectomy to the anterolateral surface of the brainstem and the posterior fossa. Two main intradural anatomical corridors can be described: first, between the V cranial nerve in the prepontine cistern and the VII–VIII cranial nerves in the cerebellopontine and cerebellomedullary cistern; second, between the VII–VIII cranial nerves and the IX cranial nerve, in the premedullary cistern. Extending the transclival endoscopic approach by performing an extradural anterior petrosectomy and a medial condylectomy provides a safe and wide exposure of the anterolateral brainstem with feasible surgical corridors around the main neurovascular structures.     

Rinsing of allograft bone does not improve implant fixation

Background and purpose Impacted morselized allograft bone is a well-established method for reconstructing bone defects at revision surgery. However, the incorporation of bone graft is not always complete, and a substantial volume of fibrous tissue has been found around grafted implants. We hypothesized that rinsing the bone graft may improve graft incorporation by removing the majority of immunogenic factors present in blood, marrow, and fat.

Methods We implanted a cylindrical (10- × 6-mm) porous-coated Ti implant into each proximal tibia of 12 dogs. The implants were surrounded by a 2.5-mm gap into which morselized fresh frozen allograft bone was impacted. The bone graft was either (1) untreated or (2) rinsed in 37°C saline for 3 × 1 min. After 4 weeks, the animals were killed and implant fixation was evaluated by mechanical push-out and histomorphometry.

Results The groups (rinsed vs. control) were similar regarding mechanical implant fixation (mean (SD)): shear strength (MPa) 2.7 (1.0) vs. 2.9 (1.2), stiffness (MPa/mm) 15 (6.7) vs. 15 (5.6), and energy absorption (kJ/m²) 0.5 (0.2) vs. 0.6 (0.4), The same was evident for the new bone formation on the implant surface and around the implant: ongrowth (%) 6 vs. 7 and ingrowth (%) 9 vs. 9. Although not statistically significant, a 61% reduction in fibrous tissue ongrowth and 50% reduction in ingrowth were found in the rinsed group.

Interpretation Within the limits of this experimental model, we did not detect any benefits of rinsing morselized allograft bone prior to impaction grafting.