Are there clinically relevant anatomical differences of the proximal femur in patients with mild dysplastic and primary hip osteoarthritis? A CT-based matched-pairs cohort study.

AIM: To investigate the three-dimensional anatomy and shape of the proximal femur, comparing patients with secondary osteoarthritis (OA) due to mild developmental dysplasia of the hip (DDH) and primary hip OA. MATERIALS AND METHODS: This retrospective radiographic computed tomography (CT)-based study investigated proximal femoral anatomy in a consecutive series of 84 patients with secondary hip OA due to mild DDH (Crowe type I&II/Hartofilakidis A) compared to 84 patients with primary hip OA, matched for gender, age at surgery, and body mass index. RESULTS: Men with DDH showed higher neck shaft angles (127±5° vs. 123±4°; p<0.001), whereas women with DDH had a larger femoral head diameter (46±4 vs. 44±3 mm; p=0.002), smaller femoral offset (36±5 vs. 40±4 mm; p<0.001), decreased leg torsion (25±13° vs. 31±16°; p=0.037), and a higher neck shaft angle (128±7° vs. 123±4°; p<0.001) compared to primary OA patients. Similar patterns of the three-dimensional endosteal canal shape of the proximal femur, but a high inter-individual variability for femoral canal torsion at the meta-diaphyseal level were found for DDH and primary OA patients. CONCLUSION: Standard cementless stem designs are suitable to treat patients with secondary hip OA due to mild DDH; however, high patient variability and subtle anatomical differences in the proximal femur should be respected.

An Overlapping Case of Miller Fisher Syndrome, Bickerstaff's Encephalitis, and the ASMAN Variant of Guillain-Barre Syndrome.

A 56-year-old man presented with a 3-day history of progressive tingling of the hands, unsteadiness, and diplopia. He was initially diagnosed clinically with Miller Fisher Syndrome (MFS) but later developed limb weakness consistent with Guillain-Barre Syndrome (GBS) and subsequently reduced consciousness consistent with Bickerstaff's brainstem encephalitis (BBE). Neurophysiology revealed an axonal motor and sensory neuropathy, in keeping with the Acute Motor and Sensory Axonal Neuropathy (AMSAN) variant of GBS. We believe that our patient had an MFS-AMSAN-BBE overlap syndrome. This is supported by his glycolipid antibody profile with high titres of anti-GQ1b IgG antibody and anti-GD1a IgG antibody. Anti-GQ1b antibodies are frequently found in both MFS and BBE and the anti-GD1a antibody is associated with axonal forms of GBS. Overlapping cases of MFS and BBE are well described, and because the same antibody is often found in both conditions, it is thought that they share a common autoimmune mechanism. BBE has also been previously reported in association with GBS lending support that it also lies on the same spectrum. This overlapping case of ASMAN variant of GBS, MFS, and BBE provides further support that these conditions are part of the same spectrum.

Influence of consciousness, muscle action and activity on medial condyle translation after Oxford unicompartmental knee replacement.

BACKGROUND: Quantification of the in vivo position of the medial condyle throughout flexion is important for knee replacement design, and understanding knee pathology. The influence of consciousness, muscle action, and activity type on condyle translation was examined in patients who had undergone medial unicompartmental knee replacement (UKR) using lateral video fluoroscopy. METHODS: The position of the centre of the femoral component relative to the tibial component was measured for nine patients under different conditions. The following activities were assessed; passive flexion and extension when anaesthetised, passive flexion and extension when conscious, and active flexion, extension and step-up. RESULTS: The position of the centre of the femoral component relative to the tibial component was highly patient dependent. The greatest average translation range (14.9 mm) was observed in anaesthetised patients, and the condyle was significantly more anterior near to extension. Furthermore, when conscious but being moved passively, the femoral condyle translated a greater range (8.9 mm) than when moving actively (5.2mm). When ascending stairs, the femoral condyle was more posterior at 20-30° of flexion than during flexion/extension. CONCLUSIONS: The similarity between these results and published data suggest that knee kinematics following mobile-bearing UKR is relatively normal. The results show that in the normal knee and after UKR, knee kinematics is variable and is influenced by the patient, consciousness, muscle action, and activity type. CLINICAL RELEVANCE: It is therefore essential that all these factors are considered during knee replacement design, if the aim is to achieve more normal knee kinematics.

A semi-automated measurement technique for the assessment of radiolucency.

The assessment of radiolucency around an implant is qualitative, poorly defined and has low agreement between clinicians. Accurate and repeatable assessment of radiolucency is essential to prevent misdiagnosis, minimize cases of unnecessary revision, and to correctly monitor and treat patients at risk of loosening and implant failure. The purpose of this study was to examine whether a semi-automated imaging algorithm could improve repeatability and enable quantitative assessment of radiolucency. Six surgeons assessed 38 radiographs of knees after unicompartmental knee arthroplasty for radiolucency, and results were compared with assessments made by the semi-automated program. Large variation was found between the surgeon results, with total agreement in only 9.4% of zones and a kappa value of 0.602; whereas the automated program had total agreement in 81.6% of zones and a kappa value of 0.802. The software had a 'fair to excellent' prediction of the presence or the absence of radiolucency, where the area under the curve of the receiver operating characteristic curves was 0.82 on average. The software predicted radiolucency equally well for cemented and cementless implants (p = 0.996). The identification of radiolucency using an automated method is feasible and these results indicate that it could aid the definition and quantification of radiolucency.

Prediction of three-dimensional femoral offset from AP pelvis radiographs in primary hip osteoarthritis.

BACKGROUND: In pre-operative planning for total hip arthroplasty (THA), femoral offset (FO) is frequently underestimated on AP pelvis radiographs as a result of inaccurate patient positioning, imprecise magnification, and radiographic beam divergence. The aim of the present study was to evaluate the accuracy and reliability of predicting three-dimensional (3-D) FO from standardised AP pelvis radiographs. METHODS: In a retrospective cohort study, pre-operative AP pelvis radiographs, AP hip radiographs and CT scans of a consecutive series of 345 patients (345 hips, 146 males, 199 females, mean age 60 (range: 40-79) years, mean body-mass-index 27 (range: 19-57)kg/m(2)) with primary end-stage hip OA were reviewed. Patients were positioned according to a standardised protocol and all images were calibrated. Using validated custom programmes, FO was measured on corresponding radiographs and CT scans. Measurement reliability was evaluated using intra-class-correlation-coefficients. To predict 3-D FO from AP pelvis measurements and to assess the accuracy compared to CT, the entire cohort was randomly split into subgroups A and B. Gender specific regression equations were derived from group A (245 patients) and the accuracy of prediction was evaluated in group B (100 patients) using Bland-Altman plots. RESULTS: In the entire cohort, mean FO was 39.2mm (95%CI: 38.5-40.0mm) on AP pelvis radiographs, 44.1mm (95%CI: 43.4-44.9mm) on AP hip radiographs and 44.6mm (95%CI: 44.0-45.2mm) on CT scans. In group B, we observed no significant difference between gender specific predicted FO (males: 48.0mm, 95%CI: 47.1-48.8mm; females: 42.0mm, 95%CI: 41.1-42.8mm) and FO as measured on CT (males: 47.7mm, 95%CI: 46.1-49.4mm, p=0.689; females: 41.6mm, 95%CI: 40.3-43.0mm, p=0.607). CONCLUSIONS: The present study suggests that FO can be accurately and reliably predicted from AP pelvis radiographs in patients with primary end-stage hip osteoarthritis. Our findings support the surgeon in pre-operative templating on AP-pelvis radiographs and may improve offset and limb length restoration in THA without the routine performance of additional radiographs or CT.

Femoral offset is underestimated on anteroposterior radiographs of the pelvis but accurately assessed on anteroposterior radiographs of the hip.

The aim of this retrospective cohort study was to identify any difference in femoral offset as measured on pre-operative anteroposterior (AP) radiographs of the pelvis, AP radiographs of the hip and corresponding CT scans in a consecutive series of 100 patients with primary end-stage osteoarthritis of the hip (43 men and 57 women with a mean age of 61 years (45 to 74) and a mean body mass index of 28 kg/m(2) (20 to 45)). Patients were positioned according to a standardised protocol to achieve reproducible projection and all images were calibrated. Inter- and intra-observer reliability was evaluated and agreement between methods was assessed using Bland-Altman plots. In the entire cohort, the mean femoral offset was 39.0 mm (95% confidence interval (CI) 37.4 to 40.6) on radiographs of the pelvis, 44.0 mm (95% CI 42.4 to 45.6) on radiographs of the hip and 44.7 mm (95% CI 43.5 to 45.9) on CT scans. AP radiographs of the pelvis underestimated femoral offset by 13% when compared with CT (p < 0.001). No difference in mean femoral offset was seen between AP radiographs of the hip and CT (p = 0.191). Our results suggest that femoral offset is significantly underestimated on AP radiographs of the pelvis but can be reliably and accurately assessed on AP radiographs of the hip in patients with primary end-stage hip osteoarthritis. We, therefore, recommend that additional AP radiographs of the hip are obtained routinely for the pre-operative assessment of femoral offset when templating before total hip replacement.

Improved radiograph measurement inter-observer reliability by use of statistical shape models.

Pre- and post-operative radiographs of patients undergoing joint arthroplasty are often examined for a variety of purposes including preoperative planning and patient assessment. This work examines the feasibility of using active shape models (ASM) to semi-automate measurements from post-operative radiographs for the specific case of the Oxford™ Unicompartmental Knee. Measurements of the proximal tibia and the position of the tibial tray were made using the ASM model and manually. Data were obtained by four observers and one observer took four sets of measurements to allow assessment of the inter- and intra-observer reliability, respectively. The parameters measured were the tibial tray angle, the tray overhang, the tray size, the sagittal cut position, the resection level and the tibial width. Results demonstrated improved reliability (average of 27% and 11.2% increase for intra- and inter-reliability, respectively) and equivalent accuracy (p>0.05 for compared data values) for all of the measurements using the ASM model, with the exception of the tray overhang (p=0.0001). Less time (15s) was required to take measurements using the ASM model compared with manual measurements, which was significant. These encouraging results indicate that semi-automated measurement techniques could improve the reliability of radiographic measurements.

Examination of ten fractured Oxford unicompartmental knee bearings.

Since the Oxford knee was first used unicompartmentally in 1982, a small number of bearings have fractured. Of 14 retrieved bearings, we examined ten samples with known durations in situ (four Phase 1, four Phase 2 and two Phase 3). Evidence of impingement and associated abnormally high wear (> 0.05 mm per year) as well as oxidation was observed in all bearings. In four samples the fracture was associated with the posterior radio-opaque wire. Fracture surfaces indicated fatigue failure, and scanning electron microscopy suggested that the crack initiated in the thinnest region. The estimated incidence of fracture was 3.20% for Phase 1, 0.74% for Phase 2, 0.35% for Phase 3, and 0% for Phase 3 without the posterior marker wire. The important aetiological factors for bearing fracture are impingement leading to high wear, oxidation, and the posterior marker wire. With improved surgical technique, impingement and high wear should be prevented and modern polyethylene may reduce the oxidation risk. A posterior marker wire is no longer used in the polyethylene meniscus. Therefore, the rate of fracture, which is now very low, should be reduced to a negligible level.

Encapsulation of the topoisomerase I inhibitor GL147211C in pegylated (STEALTH) liposomes: pharmacokinetics and antitumor activity in HT29 colon tumor xenografts.

The topoisomerase I inhibitor GL147211C [7-[(4-methylpiperazino)methyl]-10,11-(ethylenedioxy)-(20S)-campto thecin trifluoroacetate], a camptothecin analogue, has significant activity in tumor cell cytotoxicity assays in vitro and antitumor activity in both animal tumor models and human patients. Its toxicity is significant, however, effectively limiting the amount of drug that can be administered and its clinical utility. To determine whether the therapeutic index of GL147211C could be improved, the drug was encapsulated in long-circulating, pegylated (STEALTH) liposomes (SPI-355). The pharmacokinetics and antitumor activity of SPI-355 were compared to those of nonliposomal GL147211C. The plasma pharmacokinetics of SPI-355 in rats were typical of those of other pegylated liposomal formulations, with significantly increased blood circulation time; the dose-corrected area under the curve and Cmax of SPI-355 (10 mg/kg) were 1250- and 35-fold higher, respectively, than those of nonliposomal GL14711C (8.72 mg/kg). The comparative antitumor activity of SPI-355 and nonliposomal GL1472211C was evaluated in nude mice implanted with HT29 colon carcinoma xenografts. SPI-355 was 20-fold more effective than GL147211C in inhibiting tumor growth (1 mg/kg SPI-355 and 20 mg/kg GL147211C) and produced durable complete remissions of tumors at well-tolerated dose levels that were >5-fold lower than the maximally tolerated dose of GL147211C, which induced no durable complete responses. Signs of toxicity were similar between the two drugs, but liposome encapsulation increased the toxicity of drug approximately 4-fold, with increased weight loss and several deaths with SPI-355 (5 mg/kg SPI-355 versus 20 mg/kg GL147211C). Despite the increased toxicity seen with SPI-355, the therapeutic index of the liposomal formulation was increased approximately 5-fold over that of nonliposomal GL147211C, suggesting that such a pegylated liposomal formulation could demonstrate increased therapeutic index in human patients.

Buspirone therapy for Type A behavior, hostility, and perceived stress in cardiac patients.

Hostility is considered to be a risk factor for coronary artery disease. Despite the findings of reduced serotonergic function and effectiveness of treatment with serotonergic agents in similar symptom complexes, there have been no attempts at using serotonergic psychopharmacologic agents to treat this population. We conducted an 8-week open trial of 10 type A, irritable men with coronary artery disease and no diagnosable psychiatric (axis I) condition to examine the effects of buspirone on these subjects. Buspirone appears to significantly reduce type A behavior, hostility, anxiety, impatience, and perceived stress.

A survey of patent nematode infestations in dogs.

A survey of faecal samples taken from 1000 suburban dogs revealed an infestation of 7-2 per cent Toxocara canis, 2-7 per cent Toxascaris leonina, 1-3 per cent Trichuris vulpis and 1-3 per cent Uncinaria stenocephala. The faecal material examined was obtained per rectum from well cared-for pet dogs resident in an area of north-west suburban London. The age of the dogs examined, both male and female, ranged from three weeks to 18 years. The clinical picture of the dogs affected by ascariasis and in particular Toxocara canis is described and some advice on treatment is included.

Transcription and translation of cloned Drosophila DNA fragments in Escherichia coli.

The expression of three unique DNA fragments from Drosophila melanogaster which have been inserted into Escherichia coli (E. coli) via the plasmid, pSC 101, was studied. The hybrid plasmid DNA molecules containing Drosophila DNA were transformed into the minicell producing strain of E. coli, X1411. Drosophila DNA-directed RNA synthesis was studied by hybridizing newly synthesized RNA isolated from the minicells with various DNA fragments which were immobilized on nitrocellulose filters. RNA was synthesized as readily from the inserted Drosophila DNA as from the original bacterial plasmid, pSC 101. In one case, transcription appeared to be initiated preferentially on one of the two strands of a Drosophila DNA fragment regardless of the orientation of that Drosophila DNA fragment with respect to the pSC 101 sequences. Two of the three Drosophila DNA fragments did not induce the synthesis of new polypeptides in minicells as detected by autoradiography of [35S]methionine-labeled polypeptides on polyacrylamide gels. The third Drosophila DNA fragment caused the synthesis of one additional polypeptide of 29 000 daltons. When an 8200 base pair portion of the third inserted Drosophila DNA (63% OF THE TOTAL Drosophila insertion) was removed by digestion with the restriction enzyme, Eco R1, this new polypeptide was no longer synthesized by minicells containing the remaining Drosophila DNA. When the 8200 base pair fragment was placed back into its parent plasmid as an inversion, the new polypeptide did not reappear. In addition, the presence of some, but not all, of the Drosophila DNA insertions affected the relative synthesis of the six polypeptides coded for by the parent plasmid, pSC 101.