Survival of cementless dual mobility socket with a mean 17 years follow-up.

PURPOSE OF THE STUDY: As part of the 2006 symposium of the French Hip and Knee Society devoted to the dual mobility socket, we report a retrospective multicentric series of 438 first-intention total hip prostheses with a dual mobility socket at a mean 17 years follow-up. The purpose of our report was to ascertain the 15-year survival of this socket and analyze failures. MATERIAL AND METHODS: The series included 438 primary replacements. This was a homogeneous multicentric series. The cementless sockets were 80 Novae-1 titanium Serf cups and 358 Novae-1 stainless steel Serf cups. All stems were inserted without cement: 185 Pf((R)) stainless steel screwed Serf stems, 228 PRO titanium screwed Serf stems, and 25 Corail stems. The mobile polyethylene insert was retaining. All of the heads were 22.2-mm chromium-cobalt heads. Degenerative hip disease was the main etiology and mean follow-up was 17 years (range, 12-20). Mean age at implantation was 54.8 years (range, 23-87). The actuarial method with a 95% confidence interval was used to determine the 15-year cup survival rate. RESULTS: At the last follow-up, none of the patients had presented an episode of early or late instability. Analysis of the socket at last follow-up showed 13 aseptic loosenings, 23 intraprosthetic dislocations, and seven replacements of the polyethylene insert for wear. The overall 15-year prosthesis survival rate was 89.2+/-8.7%. The overall 15-year socket survival rate was 96.3+/-3.7%. DISCUSSION: The fact that, at last follow-up, none of the implants had shown instability confirms the long-term stability of the dual mobility socket. The results in terms of 15-year survival confirm earlier reports. The main cause of failure was cup fixation, which is the weak point of this technique with the initial Novae cup design, which did not have hydroxyapatite coating. The second leading cause was intraprosthetic dislocation, which can be divided into three main categories. The first is intraprosthetic dislocation in a context of pure wear with normal function of the dual mobility socket; the retaining feature of the insert loses its efficacy due to wear. The second category is intraprosthetic dislocation in a context of cup loosening with a third-body effect and increased retention wear, in which case we consider that cup loosening is the primary event leading to rapid secondary wear and subsequent intraprosthetic dislocation. The third category is intraprosthetic dislocation caused by a blockage in a context of fibrosis or impingement involving severe heterotopic ossifications. We had only two femoral failures related to aseptic loosening, most certainly related to use of noncemented implants, which limits the extension of granulomas to the polyethylene. Studying the three series from Saint-Etienne more specifically, where three different configurations were used, it would appear that the titanium cup has a better survival rate and that the titanium used for the thinner necks may be an unfavorable factor for intraprosthetic dislocation.

[Survival of dual mobility socket with a mean 17 years follow-up]. / Etude d'une série de 438 cupules non cimentées à double mobilité

PURPOSE OF THE STUDY: Within the framework of the 2007 symposium of the French Hip and Knee Society devoted to the dual mobility socket, we report a retrospective multicentric series of 438 first-intention total hip prostheses with a dual mobile socket at 17 years mean follow-up. The purpose of our report was to ascertain the 15-year survival and analyze failures. MATERIAL AND METHODS: The series included 438 first-intention prostheses. This was a homogeneous multicentric series. Sockets were: 80 Novae-1 titanium Serf cups and 358 Novae-1 stainless steel Serf cups. All stems were inserted without cement: 185 Pf) stainless steel screwed Serf stems, 228 PRO titanium screwed Serf stems, 25 Corail stems. The mobile polyethylene insert was retaining. All of the heads were 22.2mm chromium-cobalt heads. Degenerative hip disease was the main etiology and mean follow-up was 17.18 years (range: 12-20). Mean age at implantation was 54.8 years (range: 23-87). The actuarial method with 95% interval of confidence was used to determine the 15-year cup survival. RESULTS: At last follow-up, none of the patients had presented an episode of early or late instability. Analysis of the socket at last follow-up showed: 13 aseptic loosenings, 23 intraprosthetic dislocations, and seven replacements of the polyethylene insert for wear. The overall 15-year prosthesis survival was 89.2+/-8.7%. The overall 15-year socket survival was 96.3+/-3.7%. DISCUSSION: The fact that at last follow-up none of the implants had exhibited instability confirms the long-term stability of the dual mobility socket. The results in terms of 15-year survival confirm earlier reports. The main cause of failure was cup fixation, which is the weak point of this technique with the initial Novae cup, which did not have hydroxyapatite coating. The second leading cause was intraprosthetic dislocation, which can be divided into three main categories. The first is intraprosthetic dislocation in a context of pure wear with normal function of the dual mobility; the retaining feature of the insert looses its efficacy due to wear. The second category is intraprosthetic dislocation in a context of cup loosening with a third-body effect and increased retention wear, in which case we consider that the cup loosening is the primary event leading to secondary rapid wear and subsequent intraprosthetic dislocation. The third category is intraprosthetic dislocation cause by a cam effect in a context of fibrosis or impingement involving a large calcification. We have had only two femoral failures by aseptic loosening, most certainly related to use of noncemented implants, which limits the extension of granulomas to the polyethylene. Studying more specifically the three series from Saint-Etienne where three different configurations were used, it would appear that the titanium cup has a better survival and that the titanium used for the thinner necks would be an unfavorable factor for intraprosthetic dislocation.

[Mac Farland fractures: a retrospective study of 26 cases]. / Les fractures de Mac Farland: étude rétrospective d'une série de 26 cas.

PURPOSE OF THE STUDY: MacFarland fractures are known to have poor prognosis. There is a major risk of misalignment due to the formation of an epiphysiodesis bridge. The purpose of this study was to evaluate the functional and radiological outcome of these fractures in a retrospective series of patients. MATERIAL AND METHODS: We analyzed retrospectively the cases of 26 patients (14 boys and 12 girls), mean age 11 years 6 months (range 7-15) with MacFarland fractures. The Salter and Harris classification was Salter III (n = 17) and Salter IV (n = 9). Surgery was used for 21 patients and cast immobilization for five. Mean follow-up was 28.4 months (19-63 months). None of the children were lost to follow-up. Outcome was noted good (no stiffness, no pain, no limp, no misalignment, no surgical complication, no healing problem), fair (stiffness and/or pain and/or limp and/or healing problem without misalignment, no surgical complication), or poor (misalignment or surgical complication). RESULTS: The three-months postoperative assessment showed three patients with ankle pain, five with stiff ankles, one with a medial problem (snapping) and two with wound healing complications. The long-term outcome was considered good for 24 patients and fair in two (one wound adherence and one hypertrophic scar tissue). There were no poor outcomes. DISCUSSION: We used surgery more than is generally reported by other teams, opting for surgery when the displacement was 1 mm rather than the 2 mm used by others. Surgical treatment was arthrotomy in all cases to achieve anatomic reduction under direct view, followed by osteosynthesis. For some, this therapeutic scheme may be considered too surgical. In order to achieve anatomic reduction, we use an epiphyseal lag screw for cancellous bone to achieve better compression of the fracture line. A washer is also used to improve compression and maintain perfect reduction. Theoretically, the washer could raise the risk of perichondral virola and consequently an iatrogenic epiphysiodesis bridge, but we have not had any problems in our experience. Arthrotomy did not lead to ankle stiffness, which is feared by some, in any of our patients.

What factors influence functional ability in patients with rheumatoid arthritis. Do they alter over time?

OBJECTIVES: To describe the changes in functional ability (FA) taking place over 5 yr in patients with rheumatoid arthritis (RA) starting disease-modifying anti-rheumatic drug (DMARD) therapy, to investigate the factors having most influence upon FA and to compare these factors at baseline and after 5 yr of treatment. METHODS: Three hundred and sixty-six patients with active RA were studied as part of a 5-yr randomized controlled study of DMARD therapy. FA was assessed by Health Assessment Questionnaire (HAQ) score every 6 months. Multiple linear regression was used to identify factors affecting FA at baseline and at 5 yr. The independent variables used were age, sex, visual analogue scale (VAS) pain, Ritchie articular index, C-reactive protein (CRP), Larsen score and log-transformed morning stiffness (EMS). RESULTS: Mean HAQ score was 1.64 at baseline, improved by 21% at 1 yr and gradually returned towards baseline levels by 5 yr. At baseline only 34% of variance in HAQ score could be explained; the most significant explanatory variables were the Ritchie articular index and CRP. At 5 yr the variance explained was 60%. The Ritchie articular index remained the strongest factor followed by VAS pain, log(10) EMS and Larsen score. CONCLUSIONS: Improvement in function did occur after commencement of the first DMARD therapy but was not maintained to 5 yr. The most consistent factor affecting function was joint tenderness. Global pain and duration of EMS were of lesser importance. Disease activity measures such as the CRP exerted an influence in the earlier, more active stages of disease: radiographic damage assumed greater importance as the arthritis progressed.

A comparative study to assess the clinical use of Fluorescein Meniscus Time (FMT) with Tear Break up Time (TBUT) and Schirmer's tests (ST) in the diagnosis of dry eyes.

INTRODUCTION: The clinical diagnosis of dry-eye is confirmed by a suitable test of tear production and the technique commonly used today to diagnose dry eye is the Schirmer's test (ST). Although the ST is easy to perform it gives variable results, poor reproducibility and low sensitivity for detecting dry eyes. Another test, the tear break up time (TBUT) is used to assess the stability of tears which if abnormal may also cause symptomatic dry-eye. We present the results of both these tests and a new test, which shows greater sensitivity than the ST in detecting aqueous tear deficiency. The fluorescein meniscus time (FMT) is a new test developed in conjunction with one of the authors (CL) and the Department of Ophthalmology at the University Hospital of Wales. The FMT is a measure of the rate at which a fluorescent tear meniscus is formed using 2% sodium fluorescein, a stopwatch and suitable illumination with a slit lamp. METHOD: An open controlled study in 62 patients and 51 controls was conducted to compare the ability of ST, FMT and TBUT to detect dry-eye in a group of patients diagnosed with rheumatoid arthritis and symptomatic dry eyes for a minimum period of 6 months. A separate control group of 15 subjects was tested on three separate occasions to assess the reproducibility of the FMT test. RESULTS: All three tests showed a statistically significant difference between the patient and control populations; Mann-Whitney P < 0.001. There was a correlation between the right and left eye for all three tests in the control group (ST r(2) = 0.77, FMT r(2) = 0.98, TBUT r(2) = 0.94). This correlation was markedly reduced for FMT and TBUT in the patient population and was in keeping with the symptoms reported as being worse on one side in a proportion of the patients (FMT r(2) = 0.52, TBUT r(2) = 0.54, ST r(2) = 0.75). A correlation with age was also observed for all the three tests in the control group (ST r(2) = 0.74, FMT r(2)= 0.92, TBUT r(2) = 0.51), but not in the patient population (ST r(2) = 0.06, FMT r(2) = 0.18, TBUT r(2) = 0.03). A significant correlation was observed between the ST and FMT in both the control (ST vs FMT r(2) = 0.65) and patient population (ST vs FMT r(2) = 0.44). There was no value greater than 200 seconds for FMT recorded in the control group. Using this value to define an abnormal FMT, 85% of the patients (72% of the eyes tested) had an abnormal result. This was in contrast to 35% of patients (26% of the eyes tested) with abnormal results detected by ST. Using ANOVA and Student's paired t-test, there were no significant differences between the three sets of values recorded serially over 3 months to assess the reproducibility of the FMT. The average standard error of the mean was 2.72% and the average co-efficient of variation 4.07%. CONCLUSION: Our study suggests that the FMT is a more sensitive test with good reproducibility compared to the Schirmer's test. The FMT correlates with the ST and suggests that both tests measure aqueous tear deficiency. The FMT therefore is a better alternative to ST currently being used to test aqueous tear deficiency.

Serum soluble interleukin 2 receptor levels and radiological progression in early rheumatoid arthritis.

OBJECTIVE: To investigate the association between serum soluble interleukin 2 receptor (sIL-2R) levels and radiological changes in patients with early rheumatoid arthritis (RA). METHODS: sIL-2R levels from 155 patients with active RA were measured by immunoassay over a 2 year period and the associations with radiological change and other measures of disease activity were analyzed. RESULTS: The area under the curve for sIL-2R is weakly associated with the change in the modified Larsen score over a 2 year period; this is weaker than the association of radiological change with serum C-reactive protein. CONCLUSION: We found no significant association of sIL-2R levels with erosive change in early RA.

A long-term five-year randomized controlled trial of hydroxychloroquine, sodium aurothiomalate, auranofin and penicillamine in the treatment of patients with rheumatoid arthritis.

OBJECTIVE: To compare the efficacy of hydroxychloroquine, penicillamine, sodium aurothiomalate and auranofin in the treatment of active rheumatoid arthritis over a period of 5 yr. METHOD: Five hundred and forty-one patients with definite or classical rheumatoid arthritis were entered into an open randomized controlled trial with a flexible dose regimen designed to reflect clinical practice. Decisions to stop treatment with any one of the disease-modifying anti-rheumatic drugs (DMARDs) were based on an agreed trial protocol which defined criteria for adverse reactions and therapeutic failure. The managing physicians' decisions were confirmed in a separate monitor clinic. RESULTS: The proportion of patients who remained on their first DMARD or who were in remission at 5 yr was 53% for penicillamine, 34% for sodium aurothiomalate, 31%, for auranofin and 30% for hydroxychloroquine (P < 0.001). In patients who stayed on their first DMARD, all groups showed a 30-50% improvement in C-reactive protein, erythrocyte sedimentation rate, Ritchie Index and joint stiffness, and a deterioration in their Larsen score. There was no evidence of physician bias to explain the larger proportion of patients remaining on penicillamine for 5 yr. CONCLUSION: Despite the increased popularity of sulphasalazine and inmmunosuppressives, the drugs in this study continue to be used worldwide. The natural history of rheumatoid arthritis requires long-term follow up to establish drug efficacy. Evidence is needed as to whether the newer regimens will prove to be more effective and safer in the longer term than the commonly prescribed DMARDs. The data from this trial will provide a reference for comparison with future studies.

Influence of the HLA-DRB1 locus on susceptibility and severity in rheumatoid arthritis.

We examined HLA-DR genotype risk in 288 patients with rheumatoid arthritis who were carefully categorized for disease severity. Five hundred ethnically-matched bone-marrow donors were controls. A hierarchy of positive allelic associations was noted with DRB1*0401 (p < 10(-38), *0404,8 (p < 10(-43), *0405 (p < 10(-8), *10 (p < 10(-3) and *0101,2 (p < 10(-2), while DRB1*0403 was negatively associated (p = 0.02). The DRB1 genotype relative risks (and 95% CIs) for RA were: *0404,5,8/*0404,5,8 = 36.2 (15-87), *0401/*0404,5,8 = 31.3 (18-55), *401/*0401 = 18.8 (11-35), *0101,2/*0404,5,8 = 6.0 (2-14), *0101,2/*0401 = 6.4 (3-12), *0101,2/*0101,2 = 1.3 (0.3-6), *10/*0404,5,8 = 27.8 (5-148), *10/*0401 = 20.8 (5-89), *10/*0101,2 = 22.3 (5-96), *0404,5,8/DRX = 5.0 (3-8), *0401/DRX = 4.7 (3-7), *0101,2/DRX = 2.3 (1.4-4), *10/DRX = 3.4 (0.8-14). No significant correlation of DRB1 genotypes was found with severity of RA as judged by nodules or articular erosions.

A single intra-articular injection of liposomally conjugated methotrexate suppresses joint inflammation in rat antigen-induced arthritis.

In this study, we sought to determine whether liposomal preparations containing a phospholipid conjugate of methotrexate and dimyristoylphosphatidylethanolamine (MTX-gamma-DMPE) incorporated within their lipid membranes are effective in suppressing established joint inflammation in a monoarticular model of arthritis in the rat. Arthritis was induced in the right knee joint of Lewis rats. The rats were treated with a single intra-articular injection of either free methotrexate (MTX), liposomal MTX [MTX-multilamellar vesicles (MLV)-1.2 microns or MTX-small unilamellar vesicles (SUV)-100 nm], control liposomes (E-LIPO) or saline into the inflamed knee 7 days after arthritis induction. There was no significant difference in knee swelling in MTX-, saline- and E-LIPO-treated rats up to 21 days after treatment. However, MTX-MLV treatment produced a significant reduction in knee swelling (26.5 +/- 6.0%: mean +/- S.E.M.) 1 day after intra-articular injection compared with MTX (3.5 +/- 3.5%) and MTX-SUV (14.4 +/- 2.4%), respectively. Over the next 20 days, knee swelling in MTX-MLV-treated rats fell progressively and almost returned to normal. MTX-MLV treatment also inhibited the cellular infiltration associated with the arthritis. Large multilamellar liposomal preparations of MTX-gamma-DMPE are more effective than free MTX and MTX-SUV in suppressing inflammation. Their differential effects in treating the antigen-induced arthritis model are related to their retention within the joint space.

Differential effects of methotrexate and liposomally conjugated methotrexate in rat adjuvant-induced arthritis.

In this study we evaluated the comparative efficacy of free and liposomally conjugated methotrexate on both disease induction and suppression of acute inflammation in rat adjuvant-induced arthritis. Rats were given either empty liposomes (E-LIPO), free methotrexate (MTX) or the liposomally conjugated methotrexate (MTX-LIPO) at a dose of 100 micrograms/day for 7 consecutive days by the intravenous route. When MTX treatment was initiated on the day of arthritis induction the drug suppressed but did not abolish the development of joint inflammation. Free MTX had no significant anti-inflammatory effect upon an established arthritis when dosing was commenced on day 11 post-adjuvant induction. Conversely, MTX-LIPO did not affect the progression of the arthritis when dosing was started on day 0, but exerted a significant anti-inflammatory effect on an established arthritis. MTX-LIPO treatment was significantly less haematotoxic than free MTX.

Methods for assessing splenic macrophage depletion by liposome encapsulated clodronate.

Small unilamellar vesicles containing clodronate (SUVc) injected intravenously will deplete splenic macrophages and the degree of histological depletion can be assessed by determining the clearance and uptake of monoclonal antibody coated erythrocytes. Splenic Fc dependent clearance, assessed in decomplemented animals, provides a more sensitive index of the effects of large multilamellar liposome encapsulated clodronate (MLVc) and SUVc than does the clearance of complement coated erythrocytes on macrophage depletion in the spleen. MLVc were more efficient than SUVc in inducing a reduction in the number of red pulp macrophages within the spleen. Receptor specific red cell uptake in the spleen could be used as an alternative to histology when assessing splenic macrophage depletion. Encapsulation of clodronate is crucial to its depleting effect since the free drug in saline does not change splenic macrophage number or function.

The effect of free and liposome-encapsulated clodronate on the hepatic mononuclear phagocyte system in the rat.

Clodronate, encapsulated within small unilamellar vesicles (SUVc) will deplete hepatic macrophages after intravenous injection. Functional studies, using probes to evaluate hepatic Fc and C3b uptake, showed a close correlation between the inhibition of receptor-mediated uptake and the depletion of hepatic macrophages. Twenty milligrams of clodronate encapsulated within SUVc produced > or = 90% inhibition of uptake and clearance of Fc- and C3b-coated erythrocytes and a comparable reduction of hepatic macrophage numbers. Inhibition of macrophage receptor-mediated uptake of these erythrocytes was closely related to the reduction in macrophage numbers. Repopulation of macrophages within the liver took place over 2 weeks. At 1 week after depletion, although repopulation was taking place, receptor-mediated function remained suppressed. In a preliminary experiment, treatment of rats with adjuvant arthritis with 20 mg clodronate encapsulated in SUV suppressed the inflammation and reversed the course of the disease, while treatment with 20 mg free clodronate in saline or 20 mg clodronate in multilamellar vesicles (MLVc) did not.

Prostaglandin and tumor necrosis factor secretion by peritoneal macrophages isolated from normal and arthritic rats treated with liposomal methotrexate.

The effect of a novel liposomal preparation containing a phospholipid conjugate of methotrexate (MTX-LIPO) upon macrophage mediator release was investigated in normal and arthritic rats ex vivo. Peritoneal macrophages isolated from MTX-LIPO-treated arthritic rats and stimulated with lipopolysaccharide produced significantly less tumor necrosis factor (TNF) and prostaglandin (PGE2) than did macrophages isolated from saline-treated controls. In the same experimental system, free methotrexate only inhibited prostaglandin release, but it was more potent than MTX-LIPO in this respect. Additional studies are presently underway to investigate the effect of MTX-LIPO and MTX treatment upon the lipopolysaccharide-induced rise in plasma levels of various proinflammatory mediators in vivo. Haematopoietic toxicity was demonstrated in blood isolated from rats treated with free MTX, and this was as characterized by a significant reduction in reticulocyte count compared with MTX-LIPO and saline-treated rats.

Suppression of adjuvant-induced arthritis by liposomally conjugated methotrexate in the rat.

A phospholipid conjugate of methotrexate was synthesized and liposomally formulated in order to determine whether such a formulation could modulate the severity of experimentally induced arthritis in the rat. Lewis rats were immunized with Mycobacterium butyricum and after the onset of joint inflammation were treated intravenously with methotrexate liposomes (MTX-LIPO). This preparation was significantly better in reducing established joint inflammation than comparable doses of the free drug or empty liposomes of identical lipid composition. Haematopoietic toxicity associated with MTX-LIPO was significantly less than seen with comparable doses of the free drug.

Juxtaglomerular cell tumor of the kidney: report of two cases with a papillary pattern.

We report the clinicopathologic, immunohistochemical, and electron microscopic study of two cases of juxtaglomerular cell tumor of the kidney with a hitherto unreported dominant papillary pattern. Both tumors were associated with high blood pressure that did not respond to medical therapy, but that returned to normal after removal of the kidney. They were well delineated, tan, and had no necrosis. The cores of the papillary structures consisted of polygonal cells found to express renin by immunohistochemistry and to contain renin protogranules by electron microscopy. The papillary fronds were covered by one layer of cuboidal epithelial cells that did not stain for renin and had ultrastructural features reminiscent of the collecting duct epithelium. These tumors must be differentiated from malignant papillary tumors of the kidney, such as papillary clear cell carcinoma, transitional cell carcinoma, and collecting duct carcinoma.