Does the thigh circumference affect the positioning of the acetabular component when using the direct anterior approach in total hip arthroplasty?

AIMS: The hypothesis of this study was that thigh circumference, distinct from body mass index (BMI), may be associated with the positioning of components when undertaking total hip arthroplasty (THA) using the direct anterior approach (DAA), and that an increased circumference might increase the technical difficulty. PATIENTS AND METHODS: We performed a retrospective review of prospectively collected data involving 155 consecutive THAs among 148 patients undertaken using the DAA at an academic medical centre by a single fellowship-trained surgeon. Preoperatively, thigh circumference was measured at 10 cm, 20 cm, and 30 cm distal to the anterior superior iliac spine, in quartiles. Two blinded reviewers assessed the inclination and anteversion of the acetabular component, radiological leg-length discrepancy, and femoral offset. The radiological outcomes were considered as continuous and binary outcome variables based on Lewinnek's 'safe zone'. RESULTS: Similar trends were seen in all three thigh circumference groups. In multivariable analyses, patients in the largest 20 cm thigh circumference quartile (59 cm to 78 cm) had inclination angles that were a mean of 5.96° larger (95% confidence interval (CI) 2.99° to 8.93°; p < 0.001) and anteversion angles that were a mean of 2.92° larger (95% CI 0.47° to 5.37°; p = 0.020) than the smallest quartile. No significant differences were noted in leg-length discrepancy or offset. CONCLUSION: There was an associated increase in inclination and anteversion as thigh circumference increased, with no change in the risk of malpositioning the components. THA can be performed using the DAA in patients with large thigh circumference without the risk of malpositioning the acetabular component. Cite this article: Bone Joint J 2019;101-B:529-535.

Assessment of knee laxity using a robotic testing device: a comparison to the manual clinical knee examination.

PURPOSE: The purpose of this study was to collect knee laxity data using a robotic testing device. The data collected were then compared to the results obtained from manual clinical examination. METHODS: Two human cadavers were studied. A medial collateral ligament (MCL) tear was simulated in the left knee of cadaver 1, and a posterolateral corner (PLC) injury was simulated in the right knee of cadaver 2. Contralateral knees were left intact. Five blinded examiners carried out manual clinical examination on the knees. Laxity grades and a diagnosis were recorded. Using a robotic knee device which can measure knee laxity in three planes of motion: anterior-posterior, internal-external tibia rotation, and varus-valgus, quantitative data were obtained to document tibial motion relative to the femur. RESULTS: One of the five examiners correctly diagnosed the MCL injury. Robotic testing showed a 1.7° larger valgus angle, 3° greater tibial internal rotation, and lower endpoint stiffness (11.1 vs. 24.6 Nm/°) in the MCL-injured knee during varus-valgus testing when compared to the intact knee and 4.9 mm greater medial tibial translation during rotational testing. Two of the five examiners correctly diagnosed the PLC injury, while the other examiners diagnosed an MCL tear. The PLC-injured knee demonstrated 4.1 mm more lateral tibial translation and 2.2 mm more posterior tibial translation during varus-valgus testing when compared to the intact knee. CONCLUSIONS: The robotic testing device was able to provide objective numerical data that reflected differences between the injured knees and the uninjured knees in both cadavers. The examiners that performed the manual clinical examination on the cadaver knees proved to be poor at diagnosing the injuries. Robotic testing could act as an adjunct to the manual clinical examination by supplying numbers that could improve diagnosis of knee injury. LEVEL OF EVIDENCE: Level II.

Plasticity of glomeruli and olfactory-mediated behavior in zebrafish following detergent lesioning of the olfactory epithelium.

The zebrafish olfactory system is a valuable model for examining neural regeneration after damage due to the remarkable plasticity of this sensory system and of fish species. We applied detergent to the olfactory organ and examined the effects on both morphology and function of the olfactory system in adult zebrafish. Olfactory organs were treated once with Triton X-100 unilaterally to study glomerular innervation patterns or bilaterally to study odor detection. Fish were allowed to recover for 4-10 days and were compared to untreated control fish. Axonal projections were analyzed using whole mount immunocytochemistry with anti-keyhole limpet hemocyanin, a marker of olfactory axons in teleosts. Chemical lesioning of the olfactory organ with a single dose of Triton X-100 had profound effects on glomerular distribution in the olfactory bulb at 4 days after treatment, with the most significant effects in the medial region of the bulb. Glomeruli had returned by 7 days post-treatment. Analysis of the ability of the fish to detect cocktails of amino acids or bile salts consisted of counting the number of turns the fish made before and after odorant delivery. Control fish turned more after exposure to both odorants. Fish tested 4 and 7 days after chemical lesioning made more turns in response to amino acids but did not respond to bile salts. At 10 days post-lesion, these fish had regained the ability to detect bile salts. Thus, the changes seen in bulbar innervation patterns correlated to odorant-mediated behavior. We show that the adult zebrafish brain has the capacity to recover rapidly from detergent damage of the olfactory epithelium, with both glomerular distribution and odorant-mediated behavior returning in 10 days.

Olfactory bulb recovery following reversible deafferentation with repeated detergent application in the adult zebrafish.

The neuroplasticity and regenerative properties of the olfactory system make it a useful model for studying the ability of the nervous system to recover from damage. We have developed a novel method for examining the effects of long-term deafferentation and regeneration of the olfactory organ and resulting influence on the olfactory bulb in adult zebrafish. To test the hypothesis that repeated damage to the olfactory epithelium causes reduced olfactory bulb afferent input and cessation of treatment allows recovery, we chronically ablated the olfactory organ every 2-3 days for 3 weeks with the detergent Triton X-100 while another group was allowed 3 weeks of recovery following treatment. Animals receiving chronic treatment showed severe morphological disruption of the olfactory organ, although small pockets of epithelium remained. These pockets were labeled by anti-calretinin, indicating the presence of mature olfactory sensory neurons (OSNs). Following a recovery period, the epithelium was more extensive and neuronal labeling increased, with three different morphologies of sensory neurons observed. Repeated peripheral exposure to Triton X-100 also affected the olfactory bulb. Bulb volumes and anti-tyrosine hydroxylase-like immunoreactivity, which is an indicator of afferent activity, were diminished in the olfactory bulb of the chronically treated group compared to the control side. In the recovery group, there was little difference in bulb volume or antibody staining. These results suggest that repeated, long-term nasal irrigation with Triton X-100 eliminates a substantial number of mature OSNs and reduces afferent input to the olfactory bulb. It also appears that these effects are reversible and regeneration will occur in both the peripheral olfactory organ and the olfactory bulb when given time to recover following cessation of treatment. We report here a new method that allows observation not only of the effects of deafferentation on the olfactory bulb but also the effects of reinnervation.

A matched pairs comparison of single- versus double-bundle anterior cruciate ligament reconstructions, clinical results and manual laxity testing.

PURPOSE: To compare the subjective clinical results as well as manual anterior and rotational stability in patients treated with either single- (SB) or double-bundle (DB) anterior cruciate ligament (ACL) reconstructions. METHODS: Sixty-four patients who had undergone SB or DB hamstring ACL reconstruction with hamstrings were included in a retrospective matched pair analysis. At follow-up IKDC subjective, CKS, KOOS, CKS and a visual analogue satisfaction scale was assessed. A blinded surgeon examined the joint laxity and completed the objective IKDC. The KT-1000 was used to bilaterally test anterior tibial translation. Patients with confounding variables, which statistically influenced the clinical outcome (passive flexion and extension deficits, persistent quadriceps deficit, tibiofemoral osteoarthritis and non-repairable medial meniscus injury), were identified and excluded from the statistical analysis (n = 10). RESULTS: For all subjective scores, DB patients reported increased scores compared with SB patients. While consistently higher scores were demonstrated, statistical significance was only achieved for the IKDC subjective (P = 0.04) and VAS satisfaction (P = 0.02). Graded stability results of the Lachman, anterior drawer and pivot-shift tests were significantly higher in the DB group and KT-1000 side-to-side difference was significantly better for DB (P = 0.01). CONCLUSION: DB ACL reconstruction appeared to more consistently result in significantly higher subjective outcome scores and manual tests of joint stability than SB ACL reconstruction. Besides the surgical technique, normal extension and quadriceps strength after surgery were identified to be an essential component in order to provide the patient with a successful outcome.

Double-bundle ACL reconstruction demonstrated superior clinical stability to single-bundle ACL reconstruction: a matched-pairs analysis of instrumented tests of tibial anterior translation and internal rotation laxity.

PURPOSE: To compare objective measures of in vivo joint laxity between patients treated with single-bundle (SB) or double-bundle (DB) anterior cruciate ligament (ACL) reconstructions. METHODS: Sixty-four patients matched by age, height, weight, and that had undergone unilateral SB or DB hamstring ACL reconstruction participated in this study. Bilateral anterior tibial translation (ATT) was recorded using the KT1000 arthrometer, and a robotic testing system was used to assess side-to-side differences in rotational characteristics. Each reconstruction was evaluated to determine how well it mimicked the anteroposterior (AP) and rotational biomechanics of the normal knee. A reconstruction was defined as mimicking the normal knee if ATT and internal rotation (IR) were within 3 mm and 3.5°, respectively. RESULTS: Side-to-side differences in ATT were significantly higher for the SB group (2.2 ± 1.4 mm) than the DB group (1.1 ± 1.0 mm, P = 0.001). While relative side-to-side differences in IR did not differ between the SB (1.3°) and DB groups (1.1°, P = 0.82), absolute IR differences were significantly less with the DB reconstruction (2.1° vs. 4.7°, P = 0.001). A significantly greater percentage of DB patients (81%, P = 0.0003) had both ATT and IR similar to the normal knee, compared to 34% of the SB patients; however, IKDC subjective scores did not differ between groups. Regardless of technique, patients with the greatest rotational laxity of their non-operative knee demonstrated significantly worse IKDC scores. CONCLUSION: DB reconstruction resulted in reduced side-to-side differences in both ATT and IR. The DB technique more consistently reproduced the biomechanical profile of the uninjured limb than did the SB technique without increasing the risk of over-constraining the knee.

In vivo biological effects of recombinant soluble interleukin-4 receptor.

We investigated the role of soluble interleukin-4 receptor (sIL-4R) as a regulator of IL-4 mediated activities in vivo. Administration of recombinant sIL-4R to mice resulted in (i) prolonged survival of heterotopic cardiac allografts; (ii) decreased popliteal lymph node enlargement in response to allogeneic cells; and (iii) inhibition of IgE secretion in response to anti-IgD treatment. Transgenic mice constitutively expressing elevated levels of biologically active sIL-4R displayed prolonged cardiac allograft survival compared with control animals. However the sIL-4R transgenic mice were capable of mounting normal antigen-specific IgE responses despite the presence in serum of up to 3 micrograms/ml sIL-4R. Surprisingly, coadministration of IL-4/sIL-4R or IL-4/anti-IL-4 mAb complexes caused a superinduction of IgE secretion in anti-IgD-treated normal mice and subsequently in other IL-4-dependent biological activities. Thus, recombinant sIL-4R can not only antagonize functions mediated by endogenous IL-4, but also potentiate the biological activity of exogenously administered IL-4. These dual roles may have possible clinical implications for the recombinant molecule, as well as for natural sIL-4R immunoregulation.

Human cutaneous allergic late-phase response is inhibited by soluble IL-1 receptor.

The late-phase allergic reaction (LPR) occurs 4 to 8 h after allergen exposure and probably causes the symptoms of chronic allergic disease. To determine the effects of soluble IL-1 receptor on the cutaneous LPR, we performed a prospective, randomized, double-blind, placebo-controlled study on 15 allergic subjects. Intradermal injections of allergen were placed on subjects' forearms, followed by immediate subcutaneous injections at the same site of either 1, 10, 25, 50, or 100 micrograms of rhu IL-1R to three subjects in each dosage group. Placebo was given to matched allergen-injected sites on the contralateral arm. Erythema, induration, and itching were recorded for each site. Sites were biopsied at 8 h for immunohistologic evaluations. Rhu IL-1R significantly reduced the clinical reaction at all concentrations. At 1 and 10 micrograms, measurements of LPR were significantly less (p < 0.05) than at placebo sites at several time points from 2 to 8 h. At higher concentrations, LPR was suppressed at rhu IL-1R and placebo sites, suggesting a systemic effect of rhu IL-1R. Histologic evaluation and indirect immunofluorescence for eosinophil granule major basic protein, neutrophil elastase, and mast cell tryptase showed no statistical differences between rhu IL-1R and placebo sites or among doses. IL-1 plays an important role in the generation of allergic LPR. While microgram quantities of rhu IL-1R inhibited the clinical signs and symptoms of LPR, its effects on the allergic inflammatory infiltrate are yet to be defined. In this short term trial, rhu IL-1R was neither immunogenic nor toxic.

Prevention of runting and cachexia by a chimeric TNF receptor-Fc protein.

Tumor necrosis factor alpha (TNF) is an important mediator of septic shock and cachexia. A soluble form of the human type 2 TNF receptor, constructed by joining the Fc region of human IgG1 to the TNF receptor, prevents weight loss in nude mice bearing a TNF-secreting tumor. This soluble receptor was also used to treat TNF transgenic mice which were runting and died before reaching reproductive age. After continuous treatment with soluble TNF receptor, the TNF transgenic mice grew to normal size and reproduced. Thus, soluble TNF may be useful in counteracting the detrimental systemic effects of TNF in a clinical setting.

Recombinant soluble murine IL-4 receptor can inhibit or enhance IgE responses in vivo.

This study examines the effects of soluble IL-4R (sIL-4R) administration on IgE production in vivo by using an anti-IgD injection model. Anti-IgD-treated mice were given various doses of sIL-4R or anti-IL-4 mAb over a 3-day period and serum IgE levels were determined by ELISA on day 9. The sIL-4R inhibited IgE production by up to 85%. Anti-IL-4 mAb administration resulted in comparable levels of inhibition at considerably lower doses. The disparity in efficacy between sIL-4R and anti-IL-4 mAb was likely the result of differences in the biodistribution and in vivo half-life of the two IL-4-binding proteins. The specificity of the sIL-4R inhibitory effect was assessed by mixing sIL-4R with various concentrations of IL-4 before injection. Exogenous IL-4 partially overcame the inhibitory effect of high-dose sIL-4R or anti-IL-4 mAb. Unexpectedly, coadministration of suboptimal concentrations of anti-IL-4 mAb or sIL-4R with IL-4 resulted in superinduction of the IgE response. This stimulatory effect was dose dependent for both IL-4 and the IL-4 cognates and was not seen in the absence of exogenous IL-4 over the entire concentration range tested for either sIL-4R or anti-IL mAb. The results indicate that sIL-4R can block IgE secretion by neutralizing endogenous IL-4. Furthermore, sIL-4R can enhance, in a dose-dependent manner, the biologic effects of exogenously administered IL-4, presumably by altering the biodistribution of the cytokine. These findings suggest two alternative applications for cytokine-binding proteins, i.e., 1) as antagonists of biologic activities of endogenously produced cytokines and, 2) as vehicles for cytokine delivery.

Pharmacokinetic parameters and biodistribution of soluble cytokine receptors.

The potential use of soluble cytokine receptors as therapeutics in disease states when excessive or prolonged cytokine expression leads to pathogenesis is just beginning (Van Brunt, 1989). The inhibitory effects of soluble receptors have been found to be highly potent and specific for their respective cytokines (Maliszewski and Fanslow, 1990; Maliszewski et al., 1990). Recent in vivo data have shown that exogenously administered soluble receptors can function as cytokine antagonists and suppress autoimmune inflammatory responses (Jacobs et al., 1991a), allograft rejection, and alloreactivity (Fanslow et al., 1990b). The proposed frequency of administration and dosage of a therapeutic agent is dependent on the half-life of the agent and the route of administration. The elimination or half-life of a drug usually depends on its physiochemical properties (molecular size, glycosylation, isoelectric point, and hydrophobic/hydrophilic properties) (DiPalma and DiGregorio, 1990; Katzung, 1984). The half-life will also depend on the mechanism of clearance for that specific receptor. Once pharmacokinetic data are available for soluble receptors, the therapeutic potential of these molecules can be better evaluated. Only limited pharmacokinetic data are currently available for soluble cytokine receptors (Jacobs et al., 1991b). For sIL-1R, the majority of an intravenously administered dose was cleared in the second elimination phase, with a reasonably long half-life (6.3 hr), such that the entire dose was not eliminated until 35 hr. If administration is by subcutaneous injection, the half-life was even more prolonged. One explanation for the prolonged half-life is the minimal distribution to liver and kidneys and thus low levels of clearance by these organs. In contrast, elimination of intravenously administered sIL-4R was relatively rapid, with a short half-life (2.3 hr). This appeared mainly due to liver distribution and clearance, which has been the highest observed for any soluble cytokine receptor. Administering sIL-4R by subcutaneous injection significantly prolonged the half-life. This was most likely due to delaying the rate of liver distribution by slowing the rate of sIL-4R absorption into the circulation. Thus, subcutaneous injection would be the recommended route of administration for this receptor. Construction of a larger dimeric sIL-4R fusion protein did not prolong the i.v. half-life compared to that of the monomer, as the sIL-4R fusion protein was distributed to, and was cleared by, the liver to a greater degree.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibition by human interleukin-1 alpha of parathyroid hormone-related peptide effects on renal calcium and phosphorus metabolism in the rat.

Humoral hypercalcemia of malignancy (HHM) is at least partly caused by tumor secretion of PTH-related peptide (PTHrP), but there is growing evidence for cosecretion with PTHrP of other bone-resorbing peptides, such as the cytokine interleukin-1 alpha (IL-1 alpha). Administration of PTHrP in vivo and in vitro generally mimics the actions of PTH itself, with increases in both resorption and formation of bone. However, bone in HHM is characterized by uncoupling of bone turnover, with increased resorption and decreased formation. We performed experiments to determine whether IL-1 alpha might alter the effects of PTHrP and produce uncoupling. Thus, we administered to 100-g male rats by sc osmotic minipumps synthetic PTHrP-(1-34) alone (2 micrograms/100 g/day), recombinant IL-1 alpha alone (1.5 micrograms/100 g/day), both peptides together at the previous doses, or vehicle only. We infused 5 groups of 12 rats each (PTHrP, IL-1 alpha, PTHrP plus IL-1 alpha, ad libitum fed control, and controls pair-fed to the PTHrP plus IL-1 alpha group) for 14 days. At the end of the study, blood and urine were taken for chemical measurements, and tibias and femurs were harvested for histomorphometry and extraction of RNA from periosteal cells. As expected, PTHrP induced hypercalcemia, relative hypophosphatemia, phosphaturia, and reduced bone mass. Osteoblast number was increased, but osteoclast number was not. Indices of bone formation were unchanged or reduced. The dose of IL-1 alpha chosen had no statistically significant effect, except for reduced longitudinal bone growth, but when combined with PTHrP, IL-1 alpha reduced hypercalcemia, hypophosphatemia, and phosphaturia. In contrast to the blood and urine effects, IL-1 alpha did not interact significantly with PTHrP's effect on bone measurements. Northern analysis of periosteal cell mRNA showed that PTHrP reduced expression of osteocalcin, but not glyceraldehyde-3-phosphate dehydrogenase; IL-1 alpha had no additional effect. These data suggest that 1) continuously administered PTHrP alone may induce uncoupled bone turnover with decreased cortical bone formation; 2) IL-1 alpha appears to inhibit strongly the renal effects of PTHrP and weakly (if at all) its actions on bone and, thus, to decrease its hypercalcemic, phosphaturic, and hypophosphatemic actions; and 3) cosecretion of IL-1 alpha, and possibly other peptide cytokines, with PTHrP may modify the clinical expression of HHM.

Characterization and pharmacokinetic parameters of recombinant soluble interleukin-4 receptor.

The interleukin-4 receptor (IL-4R) is expressed as a 140-Kd membrane glycoprotein that binds IL-4 with high affinity. Recently, cDNA clones for the murine IL-4R have been isolated. One clone encodes an integral membrane protein, while another encodes a protein in which translation is terminated before the transmembrane region, thus producing a soluble form of the IL-4R (sIL-4R). HeLa cell clones overexpressing sIL-4R were isolated using a novel filter-overlay and 125I-IL-4 ligand binding technique. Quantitative analysis demonstrated that the kinetics and affinity of IL-4 binding to the recombinant sIL-4R were similar to the native membrane-bound IL-4R. As low doses of sIL-4R specifically inhibited IL-4-induced proliferative responses in vitro, sIL-4R biodistribution and elimination parameters were evaluated to assess the pharmacokinetic potential of sIL-4R as a therapeutic agent. Pharmacokinetic studies demonstrated that radiolabeled sIL-4R had a distribution half-life of 9 minutes and an elimination half-life of 2.3 hours following intravenous (IV) administration. When administered by intraperitoneal or subcutaneous (SC) injection, the elimination half-lives were prolonged to 4.2 hours and 6.2 hours, respectively. Although the initial blood level of sIL-4R was reduced if administered by SC injection, the bioavailability was comparable with IV administration. The main sites of sIL-4R elimination were the liver and kidney.

Experimental autoimmune encephalomyelitis is exacerbated by IL-1 alpha and suppressed by soluble IL-1 receptor.

To assess the role of IL-1 in the development of experimental autoimmune encephalomyelitis (EAE), the effects of in vivo treatment with IL-1 alpha or an IL-1 antagonist on the clinical course of EAE were evaluated. First, Lewis rats were immunized with guinea pig myelin in CFA and treated for 19 consecutive days with i.p. injections of recombinant human IL-1 alpha. Clinical signs of paralysis in the IL-1 alpha-treated groups were of longer duration and of greater severity compared to placebo injected controls. In addition, more weight loss was observed in the IL-1 alpha-treated groups compared to controls. This enhanced weight loss was not due to IL-1 alpha injections alone as CFA-treated rats injected with IL-1 alpha did not lose weight when compared to placebo injected, CFA-treated controls. Second, soluble mouse rIL-1R (sIL-1R), which binds both IL-1 alpha and IL-1 beta, was given as an IL-1 antagonist. Treatment of guinea pig myelin/CFA immunized rats with sIL-1R for 13 consecutive days significantly delayed the onset of EAE, reduced the severity of paralysis and weight loss, and shortened the duration of disease. Treatment with sIL-1R was most effective in reducing EAE if administered for 15 consecutive days immediately after immunization. Shortened 5-day treatment regimens spanning days 1 to 5, days 6 to 10, or days 11 to 15 after immunization were less effective in reducing EAE. These data suggest that IL-1 may initiate or promote inflammation within the central nervous system. In addition, specifically blocking the biological activity of IL-1 in vivo by soluble receptors may prove beneficial for the treatment of autoimmune or inflammatory diseases.

Augmentation of lymphocyte and macrophage proliferation by caprine arthritis-encephalitis virus contributes to the development of progressive arthritis.

Infection by the lentivirus, caprine arthritis-encephalitis virus (CAEV), may lead to an intermittent arthritis due to the presence of lymphocytes and macrophages in synovial membranes. We have observed that the presence of CAEV increases the division of lymphocytes and macrophages. In association, antigen-induced arthritis is more severe in goats concurrently infected by CAEV than in noninfected goats. From these observations we propose that infection by this lentivirus increases reactivity of lymphocytes and macrophages to immune and nonimmune stimuli, leading to the increased likelihood of progressive arthritis in infected animals.

Lentivirus infection augments concurrent antigen-induced arthritis.

Experimental antigen-induced arthritis was compared in normal goats and goats infected with caprine arthritis-encephalitis virus. Although acute arthritis was the same in infected and uninfected animals, the disease lasted 16 weeks longer in the caprine arthritis-encephalitis virus-infected goats. Our findings suggest that the arthritis caused by this virus is due to events other than, or in addition to, the immune reaction to viral antigens.

Reliability of Estimates With Alternative Cluster Sizes in the Health InterviewSurvey.

The practice of grouping the elements of the universe of study into clusters and sampling the clusters is a common feature of sample designs. Dealing with clusters of elements ahnost invariably increases the sampling error of the statistics estimated from the sample. However, clustering usually reduces the per-unit costs of the sampling and data collection. As the cluster size is increased, the costs of conducting a survey are usually reduced but the sampling errors of the statistics generally increase for a given sample size. The increase in variance due to clustering may be considered as a "loss" in the reliability of a statistic. The purpose of this study is to obtain measurements of the loss in reliability due to clustering of households using various cluster sizes for data collected by the Health Interview Survey (HIS).