[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.

Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidney.

Erythropoietin (Epo)-producing cells were identified in the murine hypoxic kidney by in situ hybridization. Profound anemia was induced in order to greatly increase Epo production. This resulted in high levels of Epo mRNA in the kidney. 35S-labeled DNA fragments of the murine Epo gene were used as probes for in situ hybridization. Control experiments conducted in parallel included kidneys of nonanemic mice, RNase-treated hypoxic kidney sections, and 35S-labeled non-Epo-related DNA. The Epo probe gave a specific hybridization signal in the hypoxic kidney in the cortex and to a lesser extent in the outer medulla. Glomerular and tubular cells were not labeled. All positive cells were identified as peritubular cells. Using immunofluorescence, we showed that cells with the same topography contained Factor VIII-related antigen. These data demonstrated that peritubular cells, most likely endothelial cells, constitute the major site of Epo production in the murine hypoxic kidney.

Renin biosynthesis by human tumoral juxtaglomerular cells. Evidences for a renin precursor.

Renin biosynthesis was studied in a juxtaglomerular cell tumor. The tumoral tissue had a high renin content (180 Goldblatt Units/g of tissue), was heavily stained by immunofluorescence using human renin antiserum, and exhibited numerous characteristic secretory granules by electron microscopy. In one series of experiments, renin biosynthesis was studied in tissue slices, by following the incorporation of radiolabeled amino acids into specific immunoprecipitable renin. Time course studies showed that renin was first synthesized in a high molecular weight form, 55,000 mol wt, i.e., 10,000 mol wt higher than that of active renin, and was then converted into a 44,000-mol wt form. In a second series of experiments renin tumoral cells were cultured. Small, round, birefringent cells obtained after collagenase digestion produced renin in both primary culture and subculture media. After 5 d most of the renin found in the culture medium was inactive, but could be activated by trypsin treatment. The tumoral tissue exhibited a strong renin immunofluorescence and numerous secretory granules were observed by electron microscopy. In contrast, the renin-producing cells isolated from this tumor and grown in culture showed little renin immunofluorescence and no secretory granule could be observed. The renin-producing cells in primary culture and subculture were pulsed with radiolabeled amino acids, and immunoprecipitable radiolabeled renin was found in the culture media, thus demonstrating the actual biosynthesis of the enzyme. This renin was not stored inside cultured cells but was rapidly released into the medium and had a molecular weight of 55,000. No conversion of this inactive high molecular weight renin into the active, 44,000 mol wt form of renin was observed. We postulate the existence of two pathways for the processing, packaging, and secretion of renin in the tumoral cells: in juxtaglomerular cells of tumoral tissue renin is synthesized as a preprorenin and rapidly converted into prorenin (55,000 mol wt), which is in turn packaged in secretory granules where it is processed into active renin (44,000 mol wt) and finally secreted; in the cultured tumoral cells renin is still biosynthesized as a preprorenin molecule and then converted into prorenin, but is neither stored as granules nor processed into active renin. In this case the renin is released in an inactive form.

[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.

Genotyping human polymorphic arylamine N-acetyltransferase: identification of new slow allotypic variants.

Arylamine N-acetyltransferase catalyses the N-acetylation of primary arylamine and hydrazine drugs and chemicals. N-acetylation is subject to a polymorphism and humans can be categorized as either fast or slow acetylators according to their ability to N-acetylate polymorphic substrates in vivo. Previously, slow acetylation has been linked to four distinct polymorphic N-acetyltransferase (pnat) alleles each of which contains one or more point mutations within the coding region of the pnat gene. One new rare slow variant of pnat has been identified by cloning and sequencing the pnat DNA from an individual whose NAT phenotype was determined by in vivo acetylation of the polymorphic substrate sulphamethazine. This allele, designated S1c, differs from the wild type fast allele at nucleotide positions 341 and 803. A second new rare slow allotypic variant, designated S3, has been identified by resistance of the pnat specific DNA to digestion with the restriction enzymes Fok I and Bam HI. A method of genotyping individuals for the arylamine N-acetyltransferase (NAT) polymorphism is presented which correctly predicts the phenotype of greater than 95% (21 of 22) of individuals as measured by the extent of acetylation of sulphamethazine in urine. This refined genotyping method was applied to a clinical population of 48 Caucasians with classical or definite rheumatoid arthritis each receiving daily between 150 and 500 mg of the anti-rheumatic drug, D-penicillamine. There is no difference in the N-acetyltransferase phenotype of the individuals who developed proteinuria and the control group with no adverse effects.

Myocardial effect of converting enzyme inhibition in hypertensive and normotensive rats.

The effects of converting enzyme inhibition on the cardiac mass, isomyosins polymorphism, and collagen network in the left ventricle have been studied in renovascular, hypertensive, spontaneously hypertensive, and normotensive rats. The isoenzyme profile of left ventricular myosins was used as an indirect marker of the intrinsic property of contractility, whereas the collagen network, measured by a morphometric method, represented an indirect structural marker of the arrhythmogenic risk. One-clip, two-kidney renovascular hypertension was associated with cardiac hypertrophy, a shift in the isomyosin profile, and accumulation of collagen within the left ventricular myocardium. In this renin-angiotensin-dependent model, one month of treatment with converting enzyme inhibitor normalized blood pressure and consistently reversed cardiac hypertrophy and the isomyosin profile. Converting enzyme inhibitor treatment of 12-week-old spontaneously hypertensive rats for three months significantly decreased blood pressure but did not completely normalize it. The increase in cardiac mass observed in spontaneously hypertensive rats was not reversed by this short treatment. Nevertheless, the percentage of the V1 form of myosin increased slightly after treatment, and the collagen content of the left ventricle was considerably decreased. Converting enzyme inhibition did not decrease blood pressure in DOCA-salt hypertension, and no changes were observed in cardiac hypertrophy, isomyosin profile, or the collagen network. The cardiac hypertrophy that occurs with aging in normotensive rats was associated with a significant shift in isomyosin profile and a large accumulation of collagen. Thus, aging mimics several of the quantitative and qualitative changes in the left ventricular protein profile observed in hypertension. In young normotensive rats, converting enzyme inhibition significantly decreased blood pressure and left ventricular mass, increased the percentage of V1 isomyosin, and prevented the accumulation of collagen. In one-year-old normotensive rats, treatment for six months with converting enzyme inhibitor decreased blood pressure, decreased cardiac mass, and prevented the accumulation of collagen; the isomyosin profile was not modified. Converting enzyme inhibition, by acting on cardiac afterload, can bring about quantitative and qualitative changes in the cardiac proteins of both hypertensive and normotensive rats.

Renin-producing ovarian tumor. A case report with immunohistochemical and electron-microscopic study.

A 39-year-old woman presented with arterial hypertension. Examination of the patient revealed elevated plasma renin activity, hyperaldosteronemia, hypokalemia, and a pelvic mass. Subsequently, an 11-cm right ovarian tumor mass with histologic features of an unusual stromal cell tumor was resected. Immunohistochemical studies demonstrated renin production by tumor cells. Organelles resembling mature renin granules were identified by electron microscopy. Although blood pressure normalized after the initial surgery, the hypertension resumed with later recurrence of the tumor. We believe the tumor originated from renin-secreting ovarian stromal cells, possibly granulosa cells.

Use of a specific antiserum for renin detection in human kidney.

The use of anti-human renin antibodies made possible the intrarenal localization of renin in human kidney by immunofluorescence. In normal kidney, only some juxtaglomerular apparatus (JGA) were fluorescent. In these JGA, granular or diffuse fluorescence was only seen in afferent arterioles and was not present in all cells. In the ischemic areas of partially infarcted kidney, fluorescence was seen in all JGA and in interlobular arteries. In these arteries the most eccentric cells were often the most positive. In the nonischemic areas of the same kidneys, fluorescence was not seen in JGA, but was observed in proximal tubular cells, suggesting the reabsorption of filtered renin at this site.

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.

Glomerular matrix proteins in nodular glomerulosclerosis in association with light chain deposition disease and diabetes mellitus.

The diagnosis of light chain deposition nephropathy is based on the immunohistochemical demonstration of monoclonal light chain deposits within connective tissue matrix and on the presence at the ultrastructural level of electron-dense granular deposits along glomerular and tubular basement membranes. A nodular glomerulopathy characterized by amorphous periodic acid-Schiff-positive and argyrophilic widened mesangium and nodules is described in three patients with light chain deposition nephropathy. Light microscopic examination did not allow discrimination between the glomerular changes found in these specimens and the nodular glomerulosclerosis described in four patients with well-documented diabetes mellitus. Electron microscopic examination revealed microtubular fibrils 10 to 12 nm thick in mesangial areas in both groups. Such microfibrils could be glycoproteins. Immunofluorescence localization of matrix proteins, by staining with affinity-purified antibodies to types I, III, IV, and V (A, B) collagens, fibronectin, laminin, and heparan sulfate-containing proteoglycans, showed similar distributions in the two conditions. The mechanism of this abnormal accumulation of mesangial and glomerular basement membrane matrix proteins in two different conditions remains unknown.

Renin storage and cell differentiation in juxtaglomerular cell tumors: an immunohistochemical and ultrastructural study of three cases.

Three renin-secreting juxtaglomerular cell tumors were studied by ultrastructural and immunocytochemical methods. Both active and inactive renins were identified in tumor extracts. By immunofluorescence and the peroxidase-antiperoxidase (PAP) method with antirenin antiserum, immunolabeling was intracytoplasmic and irregularly distributed throughout the tumor tissue. Electron microscopic examination revealed various types of secretory granules, including atypical giant crystalloid protogranules in one case, and the postembedding PAP procedure showed labeling of all types of granules. Acid phosphatase staining was observed within secretory granules and autophagic vacuoles. The process of renin storage and release is discussed. The presence in one case of a neural component and a distal tubular structure supports the view of a hamartomatous lesion.

Takayasu's arteritis with bilateral pulmonary artery stenosis. Successful surgical correction.

The case of a 60-year-old patient with severe stenosis of both proximal pulmonary arteries resulting from Takayasu's arteritis is reported. The thoracic aorta and pulmonary artery were calcified. Patch enlargement of the pulmonary arteries was successfully performed. Operative biopsies confirmed the diagnosis of nonspecific arteritis consistent with Takayasu's disease.

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.

Aortocoronary bypass with homologous saphenous vein: long-term results.

Between February 1973, and February, 1979, 27 homologous saphenous veins were used in 20 patients (mean age, 54 years). Seven fresh grafts were used less than 24 hours after severance. They were kept at a temperature of 4 degrees C in saline solution containing penicillin. Twenty cryopreserved grafts were used within a period of eight days to 2 months from severance. They were preserved in glycerol at a temperature of -40 degrees C. One patient (5%) died postoperatively. A perioperative myocardial infarction developed in 3 patients (15%). Average follow-up is 27 months. No late mortality was registered. Fifteen patients are free from symptoms, and 3 patients have residual angina with exercise. Control angiograms were made in 13 patients 1 to 68 months after operation; 17 homografts were seen. Early occlusion of 1 graft and late occlusion of 8 grafts were registered. The poor late patency rate does not seem to be related to either histocompatibility or technical conditions. Conversely, microscopic examination of several cryopreserved grafts showed that the mode of preservation resulted in deterioration of intimal and medial tissues of the vein. Therefore, it appears to us that the use of homologous saphenous veins should be avoided for coronary bypass.

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.

Efficient clodronate entrapment within multilamellar and unilamellar liposomes.

Clodronate (dichloromethylene bisphosphonate) encapsulated within liposomes and administered intravenously eliminates resident macrophages within the liver and spleen. Macrophage depletion in the rat requires 20 mg of the encapsulated drug, and so far this has only been achieved using large multilamellar vesicles (MLV). Recent studies have shown that small unilamellar vesicles (SUV) when injected intravenously accumulate at inflamed joint sites in both animal models of arthritis and patients with rheumatoid arthritis; multilamellar vesicles were not able to do so. If phagocytic cells, such as macrophages, are responsible for SUV sequestration, then SUV containing clodronate may be targeted to the inflamed joint and may eliminate the macrophage population leading to reduction in the state of inflammation. We have adapted an existing technique to radiolabel clodronate with 99mTechnetium to use as a tracer to determine its encapsulation within liposomes, a technique that has advantages over other current methods. We have achieved a high-encapsulation efficiency of the drug within MLV and produced SUV containing sufficient clodronate to deplete macrophages in rats in a small enough volume to administer it intravenously as a single dose.

In vitro uptake of dicarboxylic porphyrins by human atheroma. Kinetic and analytical studies.

Human atheromatous aorta segments as well as presumably disease-free control aorta were obtained at autopsy. They were incubated with solutions of various purified dicarboxylic porphyrins including hematoporphyrin (HP) and hydroxyethylvinyldeuteroporphyrin (HVD), and with solutions of Photofrin. Selective labelling of the atheroma was shown by macroscopic and microscopic observations of the characteristic porphyrin fluorescence associated with the atheromatous plaques. The time dependence of the uptake, monitored by absorption spectrophotometry or by high performance liquid chromatography, was inferred from the disappearance of the porphyrins in the incubation medium. Significant binding was observed in the absence of albumin or serum proteins. The uptake of HP was less than that of the more hydrophobic compounds HVD or Photofrin when these porphyrins were used alone. The presence of albumin or serum drastically reduces atheroma labelling. Some competition between HP and HVD for binding sites is also seen. The present results do indicate that hydrophobic porphyrins have an intrinsic affinity for atheroma and that they can be taken up through passive processes. Taking into account previous data on animal models (Photochem. Photobiol. (1989), 731-737), it appears however that, in vivo, interactions with proteins and pharmacokinetics will primarily determine plaque labelling.

Active proliferation of telangiectases in skin of patients with progressive systemic sclerosis (PSS).

The labeling index of endothelial cells as measured by in vitro autoradiography with 3H-thymidine and the electron microscopic structure of microvessels were studied in telangiectases. The telangiectases of eight patients with progressive systemic sclerosis (PSS) were compared with the cherry angiomas of six healthy controls subjects. The ultrastructural features of telangiectases were similar in the two groups and were characteristic of capillaries and postcapillary venules of the dermis, with multilayering of the vascular basement membrane. However, a significant difference existed between these two groups in an autoradiographic study: in PSS telangiectases, the average labeling index was 5.9%, whereas in cherry angiomas it was around 0.8%. Thus, the telangiectases in PSS are structures with accelerated endothelial proliferation, as are the other endothelial cells of microvessels anywhere in dermis in this disease. However, the great heterogeneity of the labeling index (varying from 0.5% to 27%) must be emphasized in telangiectases.

Distinct phenotypic composition of diffuse interstitial and perivascular focal infiltrates in renal allografts: a morphometric analysis of cellular infiltration under conventional immunosuppressive therapy and under cyclosporine A.

Phenotypic analysis of interstitial mononuclear cell infiltrates was undertaken in 40 transplant renal specimens obtained from 38 patients in order to assess the influence of immunosuppressive therapy. Thirteen patients were given conventional immunosuppressive treatment (azathioprine and prednisone) and the other 25 received cyclosporine. The immunostaining was performed using seven antileucocyte antibodies by alkaline phosphatase-anti-alkaline phosphatase method. Interstitial infiltrates were distributed in two patterns: diffuse infiltrates and periglomerular/perivascular aggregates. The phenotypic composition was distinct in these two patterns: in diffuse infiltrates, monocytes/macrophages (EBM 11) represented the predominant inflammatory cell and were associated with a minor component of T cells (T 11). In contrast, aggregates had a major T lymphocyte phenotype in addition with few foci of B cells. T4 subset of T lymphocytes always predominated over T8 subset. The repartition and the proportion of each cell type were not significantly different in rejecting and not rejecting grafts and were not affected by the immunosuppressive regimen.

Glomerular extracellular roughly granular material (ERGM). Its autofluorescent property and the question of its nuclear origin.

A glomerular extra-cellular roughly granular material (ERGM) has been described by several authors, mainly in association with membranoproliferative glomerulonephritis. This material is clearly identified on light and electron microscopy. Another peculiar morphological character of ERGM is its property of autofluorescence detailed in this study. The precise nature of this granular material remains questionable. Immunostaining shows the lack of superposition of autofluorescent ERGM with C3 and with C5b9. Nuclear origin of ERGM suspected on ultrastructural features failed to be proven by using immunolabelling with an anti-DNA serum.