Autoantibodies against inosine-5'-monophosphate dehydrogenase 2--characteristics and prevalence in patients with HCV-infection.

BACKGROUND: Indirect immunofluorescence (IIFT) on in house HEp-2 cell preparations revealed a novel antibody giving a granular cytoplasmic pattern not described before, which on two commercial cell preparations revealed a "rings and rods" pattern. This pattern was also observed in four HCV-RNA carriers and prompted the identification of the reactive antigen and the evaluation of the antibody prevalence in HCV-RNA carriers and control groups. METHODS: The antigen's molecular weight was determined by radioimmunoprecipitation of 35S-methionine labeled cell proteins. Expression library screening and sequencing was performed by standard techniques using an oligo(dT)-primed human HeLa cell cDNA expression library. Antibodies against the novel antigen Inositol-5'-monophosphatdehydrogenase 2 (IMPDH2) were analyzed by IIFT, western blot, line blot, and radioimmunoprecipitation assay (RIPA). IIFT was performed on commercial HEp-2 cells and cells cultivated in house for 24 - 60 hours, with or without the IMPDH2 inhibitors mycophenolic acid (MPA) or ribavirin, and subjected to various fixation conditions. Western and line blots were performed with IMPDH2 synthesized in E. coli, RIPA with 35S-methionine-IMPDH2 from in vitro transcription/translation products. Sera screened were positive for HCV-RNA (108), HBV-DNA (100), anti-mitochondrial (31), anti-actin (42), and anti-nuclear antibodies (51) and negative for HCV-RNA (100) and blood donors (100). RESULTS: IMPDH2 is capable of considerable intracellular rearrangements (upon action of inhibitors like MPA and ribavirin), which explains the contrasting immunofluorescence patterns in cells from different sources. By RIPA, proven to be the sole assay suitable for screening of anti-IMPDH2 in human sera, autoantibodies were found in 35.2% of HCV-RNA carriers and in low concentrations in 31% of anti-actin positive patients suspicious of autoimmune hepatitis. Antibodies reacted preferentially with conformational epitopes. Compared to the low concentration of anti-IMPDH2 found in other disease groups, high antibody concentrations were observed in HCV-RNA carriers. CONCLUSIONS: The common occurrence of anti-IMPDH2 in HCV-RNA carriers may be related to ribavirin therapy, causing intracellular aggregation of IMPDH2 thereby altering its immunogenicity. In this study the "rods and rings" immunofluorescence pattern observed could be ascribed to anti-IMPDH2. Anti-IMPDH2 may cause difficulties in interpretation of immunofluorescence patterns in routine autoantibody testing.

Evaluation of patients with a painful total knee replacement.

Evaluation of patients with painful total knee replacement requires a thorough clinical examination and relevant investigations in order to reach a diagnosis. Awareness of the common and uncommon problems leading to painful total knee replacement is useful in the diagnostic approach. This review article aims to act as a guide to the evaluation of patients with painful total knee replacement.

Mid-term survivorship and clinical outcomes of the Avon patellofemoral joint replacement.

BACKGROUND: We present the largest series of Avon patellofemoral joint (PFJ) replacements outside of the design centre. There is discussion over its efficacy and usefulness. We report an independent opinion of its indications, survivorship and outcomes. METHODS: We prospectively collected demographic data and patient reported outcome measures (PROM's) on our cohort of Avon Patellofemoral replacements since its adoption in our unit in 2003 until 2014. We performed a retrospective review of radiographs. RESULTS: We performed 103 PFJ replacements in 85 patients, 36 were male (mean age 61 - range 34 to 78) and 67 female (mean age 60 - range 38 to 82), mean follow up time was 5.6years (range 2.9 to 14.2years) with 93 implants still in situ. Their mean post-operative Oxford Knee Score was 36 (range seven to 48). There were nine conversions to TKR for disease progression and one revision of a femoral component for trochlear malpositioning. Mean time to revision was 2.9years (1.0 to 6.0years). Radiographic evidence of progression on Kellgren and Lawrence score in the un-replaced compartments was demonstrated in 23% of cases with imaging available. The Avon PFJ replacement delivers reproducible and effective pain relief and function to patients with isolated patellofemoral osteoarthritis. We believe PFJ replacement has an important role to play, and we will continue to perform this procedure for a carefully selected group of patients. Conversion to TKR does not and should not be regarded as failure of the index operation.

The largest survivorship and clinical outcomes study of the fixed bearing Stryker Triathlon Partial Knee Replacement - A multi-surgeon, single centre cohort study with a minimum of two years of follow-up.

BACKGROUND: The surgical management of isolated medial compartment degenerative disease of the knee causes debate. Unicompartmental arthroplasty options include fixed and mobile bearing implant designs with fixed bearing becoming increasingly popular. We present the largest cohort of a fixed bearing single radius design, Stryker Triathlon Partial Knee Replacement (PKR). METHODS: We prospectively collected demographic data and patient reported outcome measures (PROMs) on our cohort of PKR implants since its adoption in our unit, 2009 until March 2015. RESULTS: A total of 129 implants in 115 patients with a mean follow-up of 5.5 years (2.5 to 8.5 years) were included. There were 11 revisions at an average of 1.7 years (0.6-4.1 years), two for infection, two for mal-alignment, five for progression of disease and two for loosening. The survivorship of the implants at five years is 90%. CONCLUSION: The PKR provides good survivorship at five years and PROM scores that are equal to the largest and most popular comparable implants. There is an associated learning curve with this implant, as there is with all systems and this is reflected in our results.

Molecular genetic analyses of a 376-kilodalton Golgi complex membrane protein (giantin)

Molecular genetic analyses of a 376-kDa Golgi complex (GC) membrane protein (giantin) are described. The immunoglobulin G fraction of a human serum containing antibodies against GC antigens as revealed by indirect immunofluorescence microscopy with Hep-2 cells was used to screen a HeLa cDNA expression library, yielding four overlapping cross-hybridizing clones. Additional cDNA clones were retrieved from a lambda gt11 human thyroid cDNA library or generated by reverse transcriptase-mediated PCR from HeLa cell mRNA. Alignment of the clones resulted in a consensus cDNA of 10,300 bp encoding a protein of 376 kDa. The corresponding mRNA with a size of about 10 kb was detected by Northern (RNA) blotting of HeLa, Hep-G2, and Jurkat cell RNA. Sequence analyses of the protein revealed an extraordinarily high content of heptad repeats with the probability of forming coiled coils similar to the proteins of the myosin family. Five overlapping recombinant proteins covering the entire sequence were synthesized and used for antibody production in rabbits and for affinity purification of human and rabbit antibodies. Indirect immunofluorescence experiments also done with brefeldin A-treated Hep-2 and Pt K1 cells revealed an identical GC staining of both the affinity-purified human and rabbit antibodies. Double labeling experiments with antibodies against the GC marker mannosidase II as well as immunoelectron microscopic studies confirmed the localization of the protein within the GC. A corresponding endogenous large-molecular-mass protein of about 390 kDa was found in [35S]methionine-labeled Hep-2 cell lysates as well as in GC-enriched subcellular fractions from rat liver. The protein as well as the recently described proteins golgin-95 and golgin-160 (M. J. Fritzler, J. C. Hamel, R. L. Ochs, and E. K. L. Chan, J. Exp. Med. 178:49-62, 1993) may belong to a new group of Golgi proteins with a high content of heptad repeats which may exert functions in scaffold formation or vesicle transport. As far as can be concluded from immunological and personally communicated partial cDNA sequence data, the protein seems to be identical with a 400-kDa Golgi protein (giantin) recently described (A. D. Linstedt and H. P. Hauri, Mol. Biol. Cell 4:679-693, 1993). Therefore, we agreed to adopt the name giantin.

Complications associated with opening wedge high tibial osteotomy--A review of the literature and of 15 years of experience.

BACKGROUND: Complication rates following opening wedge high tibial osteotomy (OWHTO) is an issue that has not been comprehensively addressed in current literature. METHODS: We performed a retrospective study of local patients who underwent OWHTO for isolated medial compartment knee osteoarthritis from 1997 to 2013. We analysed survivorship and complication rates and compared this to a literature review of previously reported data. RESULTS: One hundred and fifteen patients met the inclusion criteria. Mean follow-up=8.4 years. Mean age=47 (range 32 to 62). Mean Body Mass Index (BMI)=29.1 (range 20.3 to 40.2). Devices used consisted of Tomofix (72%), Puddu plate (21%) and Orthofix (seven percent) (no significant differences in age/sex/BMI). Wedge defects were filled with autologous graft (30%), Chronos (35%) or left empty (35%). Five years survival rate (without requiring conversion to arthroplasty)=80%. Overall complication rate=31%. Twenty five percent of patients suffered 36 complications including minor wound infections (9.6%), major wound infections (3.5%), metalwork irritation necessitating plate removal (seven percent), non-union requiring revision (4.3%), vascular injury (1.7%), compartment syndrome (0.9%), and other minor complications (four percent). No thromboembolic complications were observed. CONCLUSION: No significant differences existed in complication rates following OWHTO relative to BMI, implant type, type of bone graft used or patient age at surgery. When the complications from OWHTO were analysed closely they appear higher than previously reported in the literature; however serious complications appear rare. LEVEL OF EVIDENCE 3: Retrospective cohort study.

The chronic myelocytic cell line K 562 contains minor (m) as well as major (M) ber/abl fusion mRNAs.

By searching for additional chimeric bcr/abl transcripts in K 562 cells characterized by major (M) bcr/abl fusions, a new mRNA, a minor (m) bcr/abl transcript, was detected. A practical implication of this finding is that the K 562 cell line can be used as positive control for the detection by the polymerase chain reaction of both types of transcripts for the diagnosis of Philadelphia chromosome associated leukemias.

The risk of anterior cruciate ligament rupture with generalised joint laxity.

We assessed hyperextension of the knee and joint laxity in 169 consecutive patients who underwent an anterior cruciate ligament reconstruction between 2000 and 2002 and correlated this with a selected number of age- and gender-matched controls. In addition, the mechanism of injury in the majority of patients was documented. Joint laxity was present in 42.6% (72 of 169) of the patients and hyperextension of the knee in 78.7% (133 of 169). All patients with joint laxity had hyperextension of their knee. In the control group only 21.5% (14 of 65) had joint laxity and 37% (24 of 65) had hyperextension of the knee. Statistical analysis showed a significant correlation for these associations. We conclude that anterior cruciate ligament injury is more common in those with joint laxity and particularly so for those with hyperextension of the knee.

The Lateral Meniscus as a Guide to Anatomical Tibial Tunnel Placement During Anterior Cruciate Ligament Reconstruction.

PURPOSE: The aim of the study is to show, on an MRI scan, that the posterior border of the anterior horn of the lateral meniscus (AHLM) could guide tibial tunnel position in the sagittal plane and provide anatomical graft position. METHOD: One hundred MRI scans were analysed with normal cruciate ligaments and no evidence of meniscal injury. We measured the distance between the posterior border of the AHLM and the midpoint of the ACL by superimposing sagittal images. RESULTS: The mean distance between the posterior border of the AHLM and the ACL midpoint was -0.1mm (i.e. 0.1mm posterior to the ACL midpoint). The range was 5mm to -4.6mm. The median value was 0.0mm. 95% confidence interval was from -0.5 to 0.3mm. A normal, parametric distribution was observed and Intra- and inter-observer variability showed significant correlation (p<0.05) using Pearsons Correlation test (intra-observer) and Interclass correlation (inter-observer). CONCLUSION: Using the posterior border of the AHLM is a reproducible and anatomical marker for the midpoint of the ACL footprint in the majority of cases. It can be used intra-operatively as a guide for tibial tunnel insertion and graft placement allowing anatomical reconstruction. There will inevitably be some anatomical variation. Pre-operative MRI assessment of the relationship between AHLM and ACL footprint is advised to improve surgical planning. LEVEL OF EVIDENCE: Level 4.

Acute fractures of the scaphoid. Treatment by cast immobilisation with the wrist in flexion or extension?

Acute fractures of the scaphoid were randomly allocated for conservative treatment in a Colles'-type plaster cast with the wrist immobilised in either 20 degrees flexion or 20 degrees extension. The position of the wrist did not influence the rate of union of the fracture (89%) but when reviewed after six months the wrists which had been immobilised in flexion had a greater restriction of extension. We recommend that acute fractures of the scaphoid should be treated in a Colles'-type cast with the wrist in slight extension.

Arthroscopic anterior cruciate ligament reconstruction: An air-fluid medium to enhance visual clarity.

We describe a surgical technique that has been used successfully during arthroscopic anterior cruciate ligament reconstruction to enhance the visual clarity of the operating field specifically during tunnel placement. The precise siting of both tibial and femoral tunnels is critical to both the short- and long-term success of this procedure. Gentle insufflation of the knee joint with air prior to tunnel siting allows for an excellent view of the intercondylar notch. This visual clarity helps in the precise placement and measurement of the femoral tunnel.

Trans-radial styloid, trans-scaphoid, trans-triquetral perilunate dislocation.

A rare case of trans-radial styloid, trans-scaphoid, trans-triquetral perilunate dislocation is described. The injury was treated by reduction and internal fixation using a Herbert screw and Kirschner wire. A good functional result was achieved. A review of the literature illustrates that early surgery is recommended. Alternative surgical approaches are discussed.

Kapandjii's procedure in a former far eastern prisoner of war with poliomyelitis of the affected limb.

A case of traumatic radio-ulnar dislocation in a limb previously affected by poliomyelitis is presented. Treatment with Kapandjii's procedure is described and discussed.

The outcome of all-inside meniscal repair with relation to previous anterior cruciate ligament reconstruction.

BACKGROUND: Arthroscopically assisted all-inside meniscal repair has become a popular treatment for meniscal tears. Previous studies have suggested a beneficial effect of concomitant anterior cruciate ligament reconstruction on meniscal repair outcomes. The effect of prior cruciate ligament reconstruction (predating the meniscal injury) on meniscal repair success is unreported. The aim of this study was to assess the success of meniscal repair in our practice. Further aims were to analyze the effect of concomitant- and past-anterior cruciate ligament reconstruction on meniscal repair outcomes. METHODS: Retrospective review of all patients undergoing arthroscopic meniscal repair during a 53 month period was performed. Mean followup was 13.5 months (mean 6-50). The primary outcome measure was meniscal reoperation. RESULTS: Sixteen of 104 patients required reoperation, giving an overall meniscal repair success rate of 85%. Patients undergoing concomitant anterior cruciate ligament reconstruction enjoyed significantly improved outcomes (91%, p=0.049), while those with a past history of anterior cruciate ligament reconstruction had significantly worse meniscal repair success rates (63%, p=0.016). CONCLUSIONS: Arthroscopic meniscal repair in a selected patient group offers good success rates, especially when performed with concomitant anterior cruciate ligament reconstruction. We have identified a subgroup of patients, those with a past history of anterior cruciate ligament reconstruction predating the meniscal injury, who appear to have relatively poor outcomes from meniscal repair. Potential reasons for this finding are discussed. LEVEL OF EVIDENCE: Level IV, case series.

The measurement of patellar height: a review of the methods of imaging.

Many radiographic techniques have been described for measuring patellar height. They can be divided into two groups: those that relate the position of the patella to the femur (direct) and those that relate it to the tibia (indirect). This article looks at the methods that have been described, the logic behind their conception and the critical analyses that have been performed to test them.

Undisplaced fractures of the distal third of the radius in children: an innocent fracture?

A series of 107 undisplaced or minimally displaced distal third radial fractures in children were assessed to try to identify the incidence and the factors associated with displacement. Of 27 fractures showing a volar (pronation) pattern, there were no cases of progression of the deformity. Of the 80 fractures showing a dorsal (supination) pattern, 22.5 per cent progressed. Of the unicortical fractures, 13.6 per cent showed a progression of the deformity compared with 47.6 per cent of the bicortical fractures. Of the unicortical fractures, 7.1 per cent of those showing a dorsal buckle displaced compared with 29.4 per cent of those with a cortical breach.

The Kapandji procedure for post-traumatic problems.

The Kapandji procedure was performed on 14 patients who presented with chronic pain at the distal radioulnar joint, limited forearm rotation or poor grip after an injury involving the distal radioulnar joint. Ten patients were able to resume their original occupation and leisure activities. Some complained of mild aching after heavy use. Postoperatively, grip strength on the affected side was, on average, 84 per cent that of the opposite side. Forearm rotation in the affected arm averaged 129 degrees before operation and 170 degrees afterwards, compared with 171 degrees on the normal side, while wrist flexion-extension averaged 129 degrees preoperatively, 126 degrees postoperatively and 148 degrees on the normal side. Four patients had less satisfactory results because of pain and a feeling of insecurity due to an unstable proximal ulna. However, two of these had severe residual problems in relation to the initial forearm component of the injury, the symptoms from which were difficult to separate from the distal radioulnar injury. Although the Kapandji procedure can yield excellent results, it is difficult to predict which patients will suffer from an unstable ulna.

Nucleotide sequence of a new HLA-DQB1 allele, DQB1*03033.

HLA-genotyping by sequencing of the corresponding polymerase chain reaction (PCR) product allow the identification of a new HLA-DQB1 allele, DQB1*03033. To confirm the finding the entire exon 2 was sequenced.