Reliability of the sourcil method of acetabular index measurement in developmental dysplasia of the hip.

PURPOSE: The ability to monitor and study developmental dysplasia of the hip (DDH) requires validated radiographic outcome measures. The sourcil method of acetabular index measurement (AI-S) has not yet been shown to be a reliable measure of acetabular dysplasia in a DDH population, despite its widespread use. The aims of this study were to test the reliability of the AI-S method in a DDH population, and to compare the reliability of the AI-S method with that of the classic lateral edge method (AI-L). METHODS: From an institutional database, standardized anteroposterior hip radiographs were obtained from a cohort of 35 female patients (70 hips) at two and five years of age who had been treated nonoperatively for DDH. Three observers independently measured the acetabular index using the AI-L and AI-S methods on all 70 hips at two time points, four weeks apart. RESULTS: The inter-rater reliability intraclass correlation coefficient (ICC) for the AI-L and AI-S methods was between good and excellent at 0.94 (confidence interval (CI) 0.89 to 0.96) and 0.91 (CI 0.87 to 0.94), respectively. The ICCs for intra-rater reliability for the AI-L method were excellent at 0.93 (CI 0.90 to 0.95), 0.95 (CI 0.93 to 0.97) and 0.95 (CI 0.94 to 0.97) for raters 1, 2 and 3, respectively. The ICCs for intra-rater reliability for the AI-S method were between good and excellent at 0.91 (CI 0.87 to 0.93), 0.93 (CI 0.90 to 0.95) and 0.90 (CI 0.86 to 0.93) for raters 1, 2 and 3 respectively. CONCLUSION: Both AI-S and AI-L methods are equally reliable radiographic measures of DDH. LEVEL OF EVIDENCE: Level III (diagnostic).

Expert-Based Consensus on the Principles of Pavlik Harness Management of Developmental Dysplasia of the Hip.

Developmental dysplasia of the hip (DDH) is the most common orthopaedic disorder in newborns. While the Pavlik harness is one of the most frequently used treatments for DDH, there is immense variability in treatment parameters reported in the literature and in clinical practice, leading to difficulties in standardizing teaching and comparing outcomes. In the absence of definitive quantitative evidence for the optimal Pavlik harness management strategy for DDH, we addressed this problem by obtaining international expert-based consensus on the subject. METHODS: An initial list of items relevant to Pavlik harness treatment was derived by a review of the literature. Delphi methodology was used to guide serial rounds of surveying and obtaining feedback from content matter experts from the International Hip Dysplasia Institute (IHDI), which continued in the same manner until consensus based on standard statistical analysis was reached. This was followed by a corroboration of face validity to derive the final set of management principles. RESULTS: Four rounds of structured surveying were required to reach consensus. Following 2 rounds of peer review, and from an initial list of 66 items in 8 categories, we were able to derive 2 simplified, yet comprehensive, print-friendly tables consisting of 28 items in 8 categories to assist clinicians in managing DDH with a Pavlik harness. The tables contain principles of treatment initiation, application and follow-up of the harness, complications, weaning, and end-of-treatment decision-making as well as specific criteria based on the severity of the DDH. Furthermore, highly contentious items were identified as important areas of future study. CONCLUSIONS: We developed a comprehensive set of principles based on expert consensus to assist clinicians in the management of DDH using the Pavlik harness. This study also generated a list of the most controversial areas in the nonoperative management of DDH, which should be considered high priority for future study to further refine and optimize outcomes. LEVEL OF EVIDENCE: Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.

The incidence of avascular necrosis and the radiographic outcome following medial open reduction in children with developmental dysplasia of the hip: a systematic review.

The incidence of clinically significant avascular necrosis (AVN) following medial open reduction of the dislocated hip in children with developmental dysplasia of the hip (DDH) remains unknown. We performed a systematic review of the literature to identify all clinical studies reporting the results of medial open reduction surgery. A total of 14 papers reporting 734 hips met the inclusion criteria. The mean follow-up was 10.9 years (2 to 28). The rate of clinically significant AVN (types 2 to 4) was 20% (149/734). From these papers 221 hips in 174 children had sufficient information to permit more detailed analysis. The rate of AVN increased with the length of follow-up to 24% at skeletal maturity, with type 2 AVN predominating in hips after five years' follow-up. The presence of AVN resulted in a higher incidence of an unsatisfactory outcome at skeletal maturity (55% vs 20% in hips with no AVN; p < 0.001). A higher rate of AVN was identified when surgery was performed in children aged < 12 months, and when hips were immobilised in ≥ 60° of abduction post-operatively. Multivariate analysis showed that younger age at operation, need for further surgery and post-operative hip abduction of ≥ 60° increased the risk of the development of clinically significant AVN.

Limb reconstruction using circular frames in children and adolescents with spina bifida.

We report the outcome of 28 patients with spina bifida who between 1989 and 2006 underwent 43 lower extremity deformity corrections using the Ilizarov technique. The indications were a flexion deformity of the knee in 13 limbs, tibial rotational deformity in 11 and foot deformity in 19. The mean age at operation was 12.3 years (5.2 to 20.6). Patients had a mean of 1.6 previous operations (0 to 5) on the affected limb. The mean duration of treatment with a frame was 9.4 weeks (3 to 26) and the mean follow-up was 4.4 years (1 to 9). There were 12 problems (27.9%), five obstacles (11.6%) and 13 complications (30.2%) in the 43 procedures. Further operations were needed in seven patients. Three knees had significant recurrence of deformity. Two tibiae required further surgery for recurrence. All feet were plantigrade and braceable. We conclude that the Ilizarov technique offers a refreshing approach to the complex lower-limb deformity in spina bifida.

Deletion of the 5-HT(3A)-receptor subunit blunts the induction of cocaine sensitization.

Serotonin (5-HT) receptors are classified into seven groups (5-HT(1-7)), comprising at least 14 structurally and pharmacologically distinct receptor subtypes. Pharmacological antagonism of ionotropic 5-HT(3) receptors has been shown to modulate both behavioral and neurochemical aspects of the induction of sensitization to cocaine. It is not known, however, if specific molecular subunits of the 5-HT(3) receptor influence the development of cocaine sensitization. To address this question, we studied the effects of acute and chronic intermittent cocaine administration in mice with a targeted deletion of the gene for the 5-HT(3A)-receptor subunit (5-HT(3A)-/-). 5-HT(3A) (-/-) mice showed blunted induction of cocaine-induced locomotor sensitization as compared with wild-type littermate controls. 5-HT(3A) (-/-) mice did not differ from wild-type littermate controls on measures of basal motor activity or response to acute cocaine treatment. Enhanced locomotor response to saline injection following cocaine sensitization was observed equally in 5-HT(3A) (-/-) and wild-type mice suggesting similar conditioned effects associated with chronic cocaine treatment. These data show a role for the 5-HT(3A)-receptor subunit in the induction of behavioral sensitization to cocaine and suggest that the 5-HT(3A) molecular subunit modulates neurobehavioral adaptations to cocaine, which may underlie aspects of addiction.

Combined mitochondrial and nuclear sequences support the monophyly of forcipulatacean sea stars.

Previous molecular phylogenetic analyses of forcipulatacean sea stars (Echinodermata: Asteroidea) have reconstructed a non-monophyletic order Forcipulatida, provided that two or more forcipulate families are included. This result could mean that one or more assumptions of the reconstruction method was violated, or else the traditional classification could be erroneous. The present molecular phylogenetic analysis included 12 non-forcipulatacean and 39 forcipulatacean sea stars, with multiple representatives of all but one of the forcipulate families and/or subfamilies. Bayesian analysis of approximately 4.2kb of sequence data representing seven partitions (nuclear 18S rRNA and 28S rRNA, mitochondrial 12S rRNA, 16S rRNA, 5 tRNAs and cytochrome oxidase I with first and second codon positions analyzed separately from third codon positions) recovered a consensus tree with three well-supported clades (78%-100% bootstrap support) that corresponded at least approximately to traditional taxonomic ranks: the superorder Forcipulatacea (Forcipulatida + Brisingida) + Pteraster, the Brisingida/Brisingidae and Asteriidae + Rathbunaster + Pycnopodia. When a molecular clock was enforced, the partitioned Bayesian analysis recovered the traditional Forcipulatacea. Five of six genera represented by two or more species were monophyletic with 100% bootstrap support. Most of the traditional subfamilial and familial groupings within the Forcipulatida were either unresolved or non-monophyletic. The separate partitions differed considerably in estimates of model parameters, mainly between nuclear sequences (with high GC content, low rates of sequence substitution and high transition/transversion rate ratios) and mitochondrial sequences.

Blood ordering protocol based on proposed surgical implant in fractured neck of femur patients.

INTRODUCTION: Fractured neck of femur patients frequently require blood transfusion. To improve the efficiency of blood ordering, we present a protocol which orders blood specific for the proposed surgical implant. PATIENTS AND METHODS: A retrospective audit over a 1-year period was performed. Patients were divided into six groups dependent on proposed surgical implant. The mean postoperative drop in haemoglobin concentration, the cross-match to transfusion ratio and transfusion indexes were calculated. RESULTS: Statistically significant differences in blood loss were found dependent on implant used. Using guidelines created by the British Committee for Standards in Haematology on the implementation of a maximum surgical blood ordering schedule, a new protocol for blood ordering based on proposed surgical implant was created. CONCLUSIONS: In fractured neck of femur patients awaiting operation, the type of implant can be used to anticipate blood loss and as a guide to blood ordering.

Orthopaedic surgeons in Yorkshire--are we ATLS positive?

INTRODUCTION: In 1993, the Major Trauma Working Group of Yorkshire proposed that hospitals should be accredited as Trauma Reception Hospitals with a policy for the response to the arrival of a trauma patient. These requirements include specific criteria for orthopaedics. METHODS: To evaluate if these criteria are being fulfilled, we carried out an audit comparing the response in the hospitals within the Yorkshire deanery to the arrival of major trauma. All consultant and middle-grade orthopaedic surgeons on call for trauma were contacted and questioned as to their ATLS provider status and involvement in the "trauma call". RESULTS: 16 hospitals were included of which 13 have a "trauma team". 191 surgeons (96% response) were included. 175 have completed an ATLS course. Of these, 72 (41%) had out-of-date qualifications. Only 9 (13%) were waiting to revalidate. Variation was seen in the frequency of accident and emergency department attendance by different grades of surgeon for major trauma. DISCUSSION: All hospitals have a response for major trauma although variations occur. The vast majority of orthopaedic surgeons in Yorkshire have been adequately trained in ATLS management (more so than any study has previously shown), particularly the middle grades, who are usually first to attend. The level of revalidation is low and reasons for this are discussed with recommendations for revalidation in the future.

Axillary artery transection following anterior shoulder dislocation: classical presentation and current concepts.

Injury to the axillary artery following anterior shoulder dislocation is a very rare occurrence. This review serves to illustrate the now classical case of an elderly gentleman with a recurrent dislocation, transection of the axillary artery and its invariable association with a severe brachial plexus lesion, which is the most important determinant of long-term disability. It also highlights the pathognomic triad of anterior shoulder dislocation, expanding axillary haematoma and diminished peripheral pulse, to highlight awareness of this important injury. The literature on this injury has been reviewed and recommendations for the immediate and early post-operative investigation and management have been brought up to date in line with current thinking.

Spontaneous recurrent haemarthrosis following unicompartmental knee arthroplasty and its successful treatment by coil embolisation.

A case of spontaneous recurrent haemarthrosis of the knee presenting 3 months after the unicondylar knee replacement is described. Femoral arteriography demonstrated hypertrophy of the saphenous branch of descending genicular artery with a prominent vascular blush in the region of posteromedial aspect of the popliteal fossa thought to represent a hypertrophic vascular mass of synovium. Therapeutic embolisation of the saphenous branch of descending genicular artery was performed using three fibred platinum coils with satisfactory clinical results. Since the embolisation, the haemarthrosis has not recurred. To our knowledge, this therapeutic procedure used to treat recurrent haemarthrosis following unicondylar knee arthroplasty has not been previously described in the literature.

The 5-hydroxytryptamine type 3 (5-HT3) receptor reveals a novel determinant of single-channel conductance.

5-HT3 (5-hydroxytryptamine type 3) receptors are cation-selective ion channels of the Cys-loop transmitter-gated ion channel superfamily. Two 5-HT3 receptor subunits, 5-HT3A and 5-HT3B, have been characterized in detail, although additional putative 5-HT3 subunit genes (HTR3C, HTR3D and HTR3E) have recently been reported. 5-HT3 receptors function as homopentameric assemblies of the 5-HT3 subunit, or heteropentamers of 5-HT3A and 5-HT3B subunits of unknown stoichiometry. The single-channel conductances of human recombinant homomeric and heteromeric 5-HT3 receptors are markedly different, being <1 and approx. 16 pS respectively. Paradoxically, from the results of studies performed on the closely related nicotinic acetylcholine receptor, the channel-lining M2 domain of the 5-HT3A subunit is predicted to enhance cation conduction, whereas that of the 5-HT3B subunit would not. The present study describes a novel determinant of single-channel conductance, out with the M2 domain, which accounts for this anomaly. Utilizing a panel of chimaeric 5-HT3A and 5-HT3B subunits, a profound determinant of single-channel conductance was traced to a putative amphipathic helix (the 'HA stretch') within the large cytoplasmic loop of the receptor. Replacement of three arginine residues (R432, R436 and R440) unique to the HA stretch of the 5-HT3A subunit with the aligned residues (Q395, D399 and A403) of the 5-HT3B subunit increased the single-channel conductance 28-fold. Significantly, from ultrastructural studies of the Torpedo nicotinic acetylcholine receptor, the key residues may be components of narrow openings within the inner vestibule of the channel, located in the cytoplasm, which contribute to the permeation pathway. Our findings indicate an important and hitherto unappreciated function for the HA stretch in the Cys-loop family of transmitter-gated ion channels.

The 'zero charge' partitioning behaviour of noble gases during mantle melting.

Noble-gas geochemistry is an important tool for understanding planetary processes from accretion to mantle dynamics and atmospheric formation. Central to much of the modelling of such processes is the crystal-melt partitioning of noble gases during mantle melting, magma ascent and near-surface degassing. Geochemists have traditionally considered the 'inert' noble gases to be extremely incompatible elements, with almost 100 per cent extraction efficiency from the solid phase during melting processes. Previously published experimental data on partitioning between crystalline silicates and melts has, however, suggested that noble gases approach compatible behaviour, and a significant proportion should therefore remain in the mantle during melt extraction. Here we present experimental data to show that noble gases are more incompatible than previously demonstrated, but not necessarily to the extent assumed or required by geochemical models. Independent atomistic computer simulations indicate that noble gases can be considered as species of 'zero charge' incorporated at crystal lattice sites. Together with the lattice strain model, this provides a theoretical framework with which to model noble-gas geochemistry as a function of residual mantle mineralogy.

Free hand-to-toe transfer: a method to minimise donor-site morbidity in free joint transfers.

Reconstruction of a congenital hand anomaly in a child using single free vascularised transfer of the proximal interphalangeal joint of a second toe with the simultaneous microvascular reconstruction of the donor toe using the stiff joint and its dorsal skin paddle from the hand is described. This is not the first reported case of a toe-finger switch, but it is the first in a free joint transfer, for which it is especially indicated.

A possible tektite strewn field in the Argentinian Pampa.

Impact glass associated with 11 elongate depressions in the Pampean Plain of Argentina, north of the city of Rio Cuarto, was suggested to be proximal ejecta related to a highly oblique impact event. We have identified about 400 additional elongate features in the area that indicate an aeolian, rather than an impact, origin. We have also dated fragments of glass found at the Rio Cuarto depressions; the age is similar to that of glass recovered 800 kilometers to the southeast. This material may be tektite glass from an impact event around 0.48 million years ago, representing a new tektite strewn field.

Allopregnanolone and pentobarbital infused into the nucleus accumbens substitute for the discriminative stimulus effects of ethanol.

BACKGROUND: The discriminative stimulus effects of ethanol are mediated in part by the gamma-aminobutyric acid type A (GABA(A)) receptor system. We have previously shown that microinjections of the competitive GABA(A) agonist muscimol in the nucleus accumbens and amygdala fully substitute for the discriminative stimulus effects of systemic ethanol. However, it is not known whether allosteric binding sites on GABA(A) receptors located within specific limbic brain regions contribute to the discriminative stimulus effects of ethanol. METHODS: Male Long-Evans rats were trained to discriminate between intraperitoneal injections of ethanol (1 g/kg) and saline under a fixed-ratio 10 schedule of sucrose (10% w/v) reinforcement. Injector guide cannulae, aimed at both the nucleus accumbens core and the hippocampus area CA1, were then implanted to allow site-specific infusion of GABA(A)-positive modulators. RESULTS: Infusion of the neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone, or 3alpha-5alpha-P) in the nucleus accumbens resulted in dose-dependent full substitution for intraperitoneal ethanol (50% effective dose = 0.38 ng/microl per side). Likewise, injection of the barbiturate pentobarbital into the nucleus accumbens also substituted dose-dependently for ethanol (50% effective dose = 1.55 microg/microl per side). However, infusions of either 3alpha-5alpha-P or pentobarbital in the hippocampus failed to substitute for ethanol and produced inverted U-shaped dose-response curves. CONCLUSIONS: These results demonstrate that allosteric positive modulation of GABA(A) receptors in the nucleus accumbens produces full substitution for the stimulus effects of ethanol. This suggests that GABA(A) receptors in the nucleus accumbens may play a more influential role in the discriminative stimulus effects of ethanol than those in the hippocampus.

Alcohol actions on GABA(A) receptors: from protein structure to mouse behavior.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were R. Adron Harris and Susumu Ueno. The presentations were (1) Protein kinase Cepsilon-regulated sensitivity of gamma-aminobutyric acid type A (GABAA) receptors to allosteric agonists, by Robert O. Messing, A. M. Sanchez-Perez, C. W. Hodge, T. McMahon, D. Wang, K. K. Mehmert, S. P. Kelley, A. Haywood, and M. F. Olive; (2) Genetic and functional analysis of a GABAA receptor gamma2 subunit variant: A candidate for quantitative trait loci involved in alcohol sensitivity and withdrawal, by Kari J. Buck and Heather M. Hood; (3) Tryptophan-scanning mutagenesis in GABAA receptor subunits: Channel gating and alcohol actions, by Susumu Ueno; and (4) Can a single binding site account for actions of alcohols on GABAA and glycine receptors? by R. Adron Harris, Yuri Blednov, Geoffrey Findlay, and Maria Paola Mascia.

Neuropeptide-Y in the paraventricular nucleus increases ethanol self-administration.

The paraventricular nucleus (PVN) of the hypothalamus is known to modulate feeding, obesity, and ethanol intake. Neuropeptide-Y (NPY), which is released endogenously by neurons projecting from the arcuate nucleus to the PVN, is one of the most potent stimulants of feeding behavior known. The role of NPY in the PVN on ethanol self-administration is unknown. To address this issue, rats were trained to self-administer ethanol via a sucrose fading procedure and injector guide cannulae aimed at the PVN were surgically implanted. Microinjections of NPY and NPY antagonists in the PVN were conducted prior to ethanol self-administration sessions. All doses of NPY significantly increased ethanol self-administration and preference, and decreased water intake. The NPY antagonist D-NPY partially reduced ethanol self-administration and completely blocked the effects of an intermediate dose of NPY (10 fmol) on ethanol intake, preference, and water intake. The competitive non-peptide Y1 receptor antagonist BIBP 3226 did not significantly alter ethanol self-administration or water intake when administered alone in the PVN but it completely blocked the effect of NPY (10 fmol) on ethanol intake. NPY infused in the PVN had no effect on ethanol self-administration when tested in rats that did not have a long history of ethanol self-administration. The doses of NPY tested produced no effect on food intake or body weight measured during the 24-h period after infusion in either ethanol-experienced or ethanol-inexperienced rats. These results indicate that elevation of NPY levels in the PVN potently increases ethanol self-administration and that this effect is mediated through NPY Y1 receptors.

The discriminative stimulus properties of self-administered ethanol are mediated by GABA(A) and NMDA receptors in rats.

RATIONALE: The neurobiological systems that mediate the discriminative stimulus effects of self-administered drugs are largely unknown. The present study examined the discriminative stimulus effects of self-administered ethanol. METHODS: Rats were trained to discriminate ethanol (1 g/kg, IP) from saline on a two-lever drug discrimination task with sucrose (10% w/v) reinforcement. Test sessions were conducted with ethanol (0 or 10% v/v) added to the sucrose reinforcement to determine if self-administered ethanol would interact with the discriminative stimulus effects of investigator-administered ethanol, or with the ethanol-like discriminative stimulus effects of the GABAA-positive modulator pentobarbital or the non-competitive NMDA antagonist MK-801. RESULTS: During a saline test session, ethanol (10% v/v) was added to the sucrose reinforcement. Responding by all animals began accurately on the saline-appropriate lever and then switched to the ethanol-appropriate lever after rats self-administered a mean dose of 1.2 +/- 0.14 g/kg ethanol. During cumulative self-administration trials, responding initially occurred on the saline lever and then switched to the ethanol-appropriate lever after ethanol (0.68 +/- 0.13 g/kg) was self-administered. Investigator-administered MK-801 (0.01-1.0 mg/kg, cumulative IP) and pentobarbital (0.3-10.0 mg/kg, cumulative IP) dose-dependently substituted for ethanol. When ethanol (10% v/v) was added to the sucrose reinforcer, MK-801 and pentobarbital dose-response curves were shifted significantly to the left. CONCLUSIONS: Self-administered ethanol substituted for and potentiated the stimulus effects of investigator-administered ethanol, suggesting that the discriminative stimulus effects of self-administered ethanol are similar to those produced by investigator-administered ethanol. Self-administered ethanol enhanced the ethanol-like discriminative stimulus effects of MK-801 and pentobarbital, which suggests that the discriminative stimulus effects of self-administered ethanol are mediated by NMDA and GABAA receptors.

Long term modulation of the HPA axis by the hippocampus. Behavioral, biochemical and immunological endpoints in rats exposed to chronic mild stress.

Mature rats were given lesions of the hippocampus (HIPPO), subiculum (SUBIC) or fimbria-fornix (FIFO) and then received the mild chronic stressors of food deprivation and isolation housing for ten months prior to testing. Group differences in circadian activity were investigated along with locomotion elicited by amphetamine (AMP 1.0-2.0 mg/kg i.p.) alone, and following the corticosterone (CORT) synthesis inhibitor, metyrapone (MET 10.0-25.0 mg/kg i.p.). Basal levels of plasma CORT, (ng/ml), plasma glucose (GLUC, mmol/l), thymic and splenic wet weights were subsequently determined along with complete blood counts (CBC). In comparison to age matched, unoperated controls, selective SUBIC lesions altered the circadian periodicity of locomotion, while rats with FIFO lesions were spontaneously hyperactive. Both HIPPO and FIFO animals showed significantly higher levels of amphetamine-induced locomotion. In all groups metyrapone significantly enhanced locomotion elicited by amphetamine, probably due to a pharmacokinetic interaction between these drugs. In comparison to controls, animals in the HIPPO group showed significant reductions in plasma glucose levels, decreased thymic wet weights and reductions in lymphocyte numbers, indicating lesion-related immuno-suppression. These findings highlight a functional difference among the effects of these specific hippocampal lesions on neural regulation of the HPA axis, under conditions of chronic mild stress, suggesting that the modulatory influence of the hippocampus on the stress axis is dependent on the neuroanatomical location and total extent of cell loss within this structure. They further suggest that the heightened response to amphetamine occurs independently of any lesion-induced changes in modulation of the HPA axis.