Treatments of avascular osteonecrosis of the hip: Current treatments.

Conservative treatments for aseptic osteonecrosis of the femoral head have their ancestor in the core decompression of the femoral neck, recommended by Ficat. Due to inconsistent results, this treatment has been optimized by either vascularized fibular grafting, or by injecting autologous stem cells into the necrotic zone. The French promoters have published long-term results, showing efficacy in the early stages of the disease, where the femoral head has not yet lost its sphericity. Over the last 10years, comparative studies, sometimes randomized, opposing them to simple core decompression, have been published by non-promoters, confirming the possibility of stabilization or even regression of necrosis area. But these techniques are not easy to implement. Cell therapy requires treatment of marrow samples by centrifugation to obtain a pellet with a high concentration of haematopoietic cells. The now proven long-term efficacy as well as the safety of this technique make it the method of choice for treating young patients detected at the sub-radiological stage by MRI. Unfortunately, many are seen late with detached cephalic cartilage or collapsed femoral head and have no other option than total hip arthroplasty. This technique is very reliable. With alumina ceramics, results of more than 20years show the absence of wear and osteolysis, although other complications such as instability or periprosthetic fractures may occur in these young and active patients.

Wear products of total hip arthroplasty: The case of polyethylene.

Among the bearing surfaces involved in a total hip arthroplasty, ultra-high molecular weight polyethylene (UHMWPE) is the weak link. It is submitted to the friction of a harder bearing, producing wear particles, which, in turn, initiate an inflammatory reaction ultimately leading to osteolysis. This kind of bone deterioration sometimes turns out to an aggressive granuloma and may provoke implant loosening. Wear resistance of UHMWPE depends on its molecular weight and crystallinity. Some steps of the manufacturing process were improved to optimize its tribological properties and to slow down degradation resulting from mechanical (abrasion) and chemical (oxidation) phenomena. Its preparation and conservation must be performed in an inert atmosphere, i.e. without ambient oxygen. Its resistance to abrasion depends on its cross-linking degree. Its cross-linking rate was observed to increase proportionally to the irradiation doses, improving its wear resistance. However, its mechanical properties are impaired and moreover, it becomes oxidation sensitive. It is therefore necessary to submit it to a thermal treatment to eliminate free radicals that were produced during irradiation. More recently impregnation by vitamin E, a powerful anti-oxidant product, was proposed to preserve the polymer from in vivo oxidation while maintaining its mechanical properties. We raised the hypothesis that last-generation UHMWPE could offer the same wear resistance as the most performing bearings (ceramic-on-ceramic). Recent clinical results confirm the tribological performance of highly crosslinked UHMWPE in vivo. However, it remains to be seen whether this excellent wear resistance would persist under eccentric load such as edge loading, and if, in the long run, this kind of bearing proves capable of reducing the risk of osteolysis in young and active patients.

Infection recurrence factors in one- and two-stage total knee prosthesis exchanges.

PURPOSE: Revision of infected total knee replacements (TKR) is usually delayed for a period in which the joint space is filled with an antibiotic-loaded acrylic spacer. In contrast, one-stage re-implantation supposes immediate re-implantation. Formal comparisons between the two methods are scarce. A retrospective multi-centre study was conducted to investigate the effects of surgery type (one-stage vs. two-stage) on cure rates. It was hypothesised that this parameter would not influence the results. METHOD: All infected TKR, treated consecutively between 2005 and 2010 by senior surgeons working in six referral hospitals, were included retrospectively. Two hundred and eighty-five patients, undergoing one-stage or two-stage TKR, with more than 2-year follow-up (clinical and radiological) were eligible for data collection and analysis. Of them, 108 underwent one-stage and 177 received two-stage TKR. Failure was defined as infection recurrence or persistence of the same or unknown pathogens. Factors linked with infection recurrence were analysed by uni- and multi-variate logistic regression with random intercept. RESULTS: Factors associated with infection recurrence were fistulae (odds ratio (OR) 3.4 [1.2-10.2], p = 0.03), infection by gram-negative bacteria (OR 3.3 [1.0-10.6], p = 0.05), and two-stage surgery with static spacers (OR 4.4 [1.1-17.9], p = 0.04). Gender and type of surgery interacted (p = 0.05). In men (133 patients), type of surgery showed no significant linkage with infection recurrence. In women (152 patients), two-stage surgery with static spacers was associated independently with infection recurrence (OR 5.9 [1.5-23.6], p = 0.01). Among patients without infection recurrence, International Knee Society scores were similar between those undergoing one-stage or two-stage exchanges. CONCLUSION: Two-stage procedures offered less benefit to female patients. It suggests that one-stage procedures are preferable, because they offer greater comfort without increasing the risk of recurrence. Routine one-stage procedures may be a reasonable option in the treatment of infected TKR. LEVEL OF EVIDENCE: III.

Control of paradoxical kinematics in posterior cruciate-retaining total knee arthroplasty by increasing posterior femoral offset.

PURPOSE: Balancing the posterior cruciate ligament (PCL) with posterior cruciate-retaining total knee replacement (PCR-TKR) aims to restore femoral rollback. In practice, paradoxical roll forward persists. The purpose of this study is to propose a technique for optimizing PCL tension. Because PCL function starts above 60° of flexion, we hypothesize that PCL balancing requires flexion gap tightening by oversizing the femoral component and increasing posterior condylar offset (PCO). METHODS: PCR-TKR was performed in 21 osteoarthritis patients with a gap-balancing technique. The femoral component was oversized if more than a 5-mm posterior drawer existed after tibial component implantation. Kinematics was recorded intra-operatively in two steps with dedicated navigation software (Praxim, La Tronche, Isère, France): antero-posterior (AP) displacements of condylo-tibial contact points were observed in native and implanted knees, with each knee serving as its own control. The absence of paradoxical displacements was verified once the final implants were inserted. RESULTS: Paradoxical medial condyle displacement (11 mm) persisted in a single case. On average, posterior displacement of the medial condyle decreased from 9 ± 9 to 1 ± 6 mm (p = 0.001) and that of the lateral condyle from 16 ± 14 to 6 ± 6 mm (p = 0.006). In the 0°-30° flexion interval, posterior displacement was 2 times less than before implantation for the medial condyle (p = 0.001), and 4 times less for the lateral condyle (p = 0.004). The course of the lateral condyle decreased from 2 ± 3 to 0 ± 4 mm in the 90°-120° flexion interval (p = 0.046). Six-month flexion was 124° ± 17°. CONCLUSION: Femoral component oversizing allows us to control paradoxical forward displacements in 95 % of cases. When balancing PCR prostheses, AP laxity should be taken into account. Increasing PCO appears to be a reliable technique for adjusting PCL balance. Thus, it may optimize extensor mechanism action and, subsequently, the functional results of PCR-TKR. LEVEL OF EVIDENCE: Diagnostic study, Level II.

Arthroscopic double-row cuff repair with suture-bridging: a structural and functional comparison of two techniques.

PURPOSE: The aim of this study was to compare the functional and structural outcomes of 2 techniques for double-row, suture-bridging cuff repair. METHODS: A consecutive series of 73 patients who underwent arthroscopic, double-row, suture-bridge primary rotator cuff repair of full-thickness supraspinatus tear were evaluated. Thirty-eight shoulders were repaired by the arthroscopic, tied, suture-bridging technique (group A), and 35 shoulders by knot-less bridging with suture tape material (group B). Constant scores, pain, range of motion, strength, and complications were measured after a minimum follow-up period of 12 months post-operatively. Structural integrity of the repairs was evaluated systematically by either magnetic resonance imaging or computed tomography arthrography. RESULTS: Median follow-up after surgery was 29 (23-32) months in group A, and 21 (12-23) months in group B. Mean pain relief, range of motion, strength, and constant score improved significantly in both groups. No statistical differences were found between groups in the post-operative period. According to control imaging, the re-tear rate trended to be higher in group A (23.4 %) than in group B (17.1 %), although not significantly. CONCLUSION: Both bridging repair techniques achieved successful functional outcomes. In terms of structural outcome, the knot-less tape-bridging construct showed a lower but not significant re-tear rate. Longer follow-up is needed to confirm these results and to evaluate potential differences between the two techniques. LEVEL OF EVIDENCE: A prospective, non-randomized, comparative study, Level III.

Satisfactory long-term MRI after autologous chondrocyte implantation at the knee.

PURPOSE: Autologous chondrocyte implantation (ACI) to address isolated condylar lesions is supposed to limit degenerative deterioration in neutrally aligned knees. Here, we report long-term results of the first-generation ACI technique with periosteal flap. METHODS: Twelve patients, 29 years old on average, were included on the basis of pre-operative MRI selection of lesions >2 cm2. Cartilage carrots were harvested arthroscopically, then cultured and finally re-implanted within a mean time interval of 12 weeks. Ten-year MRI results were analysed according to a semi-quantitative scale, along with functional assessment based on International Knee Documentation Committee score, Lysholm et al. score and the Tegner et al. activity scale. RESULTS: One patient secondarily required valgus tibial osteotomy with mosaic plasty. Another incurred graft hypertrophy that necessitated arthroscopic peeling. MRI showed that cartilage repair filled more than 50% of the initial defect in 9 patients. Standard radiographs revealed slight narrowing of the joint line. Overall, functional scores improved durably by 50%, although activity level decreased substantially. CONCLUSION: ACI contained degenerative changes within moderate stages while maintaining durable functional improvement. However, in the absence of controls, it was difficult to differentiate between these findings and the spontaneous evolution of non-treated lesions. LEVEL OF EVIDENCE: Case series, Level IV.

Microvascular retinal abnormalities in acute intracerebral haemorrhage and lacunar infarction.

BACKGROUND: Retinal microvascular changes have been previously associated with cerebral MRI markers of small vessel disease (SVD). Whether retinal changes differ between patient with intracerebral haemorrhage (ICH) and patients with lacunar infarction (LI) caused by small vessel disease has been poorly investigated. OBJECTIVE: The study aims to compare the frequency of retinal changes between patients with LI and patients with ICH at the acute stage of stroke-related SVD. METHODS: Microvascular wall signs (arteriolar occlusion, arteriovenous nicking, focal arterial narrowing) and retinopathy lesions (microanevrysms, cotton wool spots, retinal haemorrhages, hard exudates) were assessed by retinography up to three months after stroke onset. RESULTS: Forty-eight non-diabetic patients with acute stroke-related to SVD (26 LI, 22 ICH) were recruited prospectively in the study. Retinal wall signs (arteriovenous nicking, and focal arterial narrowing) were found in more than three quarters of subjects and most often bilaterally in both groups. Retinopathy lesions (cotton wool spots, retinal haemorrhages) were found more frequently in ICH patients than in LI patients (22.2% vs. 15.4%, 50% vs. 34% respectively, P>0.005). The frequency of bilateral cotton wool spots and of bilateral retinal haemorrhages was significantly higher in ICH patients than in LI patients (12.5% vs. 0%, P=0.012, 41.2% vs. 7.7%, P=0.029 respectively). CONCLUSION: These results confirm the high frequency of microvascular alterations in patients with hypertension-related SVD leading to LI or ICH and suggest that retinal tissue alterations are more frequent in ICH than in LI. Further investigations are needed to investigate the mechanisms underlying this difference.

[Treatment switch in diabetic macular edema: Literature review and management algorithm]. / Les switchs de traitement dans l'œdème maculaire diabétique : revue de la littérature et algorithme de prise en charge.

Initial management of diabetic macular edema (DME) is well-defined, but there is a lack of national or international consensus for patients who do not respond or respond only partially to these treatments. Several studies, mostly retrospective, have assessed medication switches, but currently, the literature contains no randomized studies. The goal of this article is to present an algorithm for switching medications, which can be proposed to DME patients treated with anti-VEGF agents, as defined by a group of French retina experts, supported by the existing literature on the subject. After initiation of an anti-VEGF treatment for DME, the response is usually assessed after 5 monthly injections. A partial anatomical response (reduction of central retinal thickness between 10 and 20%), seen in 30 to 40% of patients, is associated with a favorable visual prognosis according to randomized studies. Continuation of the anti-VEGF injections after the induction phase is thus possible. If the response remains incomplete after 3 additional anti-VEGF injections, a complete ophthalmologic examination should be performed, and a switch to another therapeutic class (corticosteroids) may be proposed in the absence of contraindications. If a complete non-response is seen initially (reduction of central retinal thickness<10%), the switch is proposed immediately after the induction phase.

Benefits of Ophdiat, a telemedical network to screen for diabetic retinopathy: a retrospective study in five reference hospital centres.

AIM: One objective of Ophdiat, a telemedical network using digital non-mydriatic cameras in Ile-de-France, is to develop a comprehensive screening programme that provides access to annual fundus examinations to all diabetic patients. The aim of this study was to evaluate the benefits of this programme in a hospital setting. METHODS: A retrospective analysis of 500 case reports of diabetic patients hospitalized before and after Ophdiat setup was performed in five reference hospital centres. At each centre, 100 case reports (50 before, 50 after) of patients aged greater than 18 years, hospitalized for their annual check-up, with no known diabetic retinopathy (DR) before hospitalization and with the last fundus examination performed greater than 11 months previously, were randomly selected. The primary endpoint was the proportion of patients whose fundus examinations were performed during hospitalization; secondary endpoints were the number of cases of DR found and the time taken by ophthalmologists to make the diagnosis. RESULTS: The mean proportion of patients with fundus examinations was 50.4% and 72.4% before and after, respectively, Ophdiat (P<0.01). The prevalence of DR was 11.1% before and 12.7% after (not significant). The mean time taken by an ophthalmologist per diagnosis of DR was 0.90 half-day before and 0.32 half-day after Ophdiat. CONCLUSION: This evaluation shows that Ophdiat, combined with the availability of modern and effective devices, has improved DR screening in diabetology departments in hospitals. Additional human resources would certainly ensure more effective use of the system.

Total knee replacement in the fixed valgus deformity using a lateral approach: role of the automatic iliotibial band release for a successful balancing.

The purpose of this work was to document eleven years of experience in knee replacement for fixed knee valgus through a lateral approach with special emphasis on the balancing procedures. At a mean follow-up of seven years, only one revision for sepsis was required in this series of 63 knee replacements. The mean knee score improved from 37 (range 20-45) to 91 (range 65-100) at the last review (p < 0.01) while the function score increased from 29.5 (range 0-50) to 78.7 (range 10-100) (p = 0.01). The mean mechanical axis (HKA) was 14.7 degrees of valgus preoperatively and 1 degrees of valgus postoperatively. After the iliotibial band was automatically released in the approach, only four of 63 knees required additional release for tightness in extension. These results underline the appeal of the lateral approach with the automatic release of the iliotibial band. If required, additional ligament release is recommended step-by-step after bone section to avoid postoperative instability.

Cerebral immunoglobulin light chain amyloid angiopathy-related hemorrhages.

INTRODUCTION: Cerebral amyloid angiopathy (CAA) is a common cause of intracerebral hemorrhage (ICH) particularly in elderly patients. In CAA-related hemorrhages, amyloid deposits in the brain vessel walls mainly contain amyloid beta-protein (A-beta). Rarely other forms of amyloid substances have been reported in sporadic CAA-related hemorrhages. METHODS: We report the case of a 44-year-old patient with recurrent ICH who had surgical evacuation of a large frontal hematoma. Following surgery, samples from the hematoma and adjacent cerebral cortex were obtained for histopathological examination. RESULTS: Within the recent hemorrhage, a few arteriolar walls were thickened with an amyloid deposit that was immunostained for immunoglobulin (Ig) M and light chain lambda. In the wall of some vessels, around the amyloid deposits, as well as in the adjacent cerebral cortex, there was an infiltration by monotypic lymphocytes and plasma cells expressing IgM and light chain lambda. No amyloid deposition was found outside the hemorrhage. There was no evidence of multiple myeloma, B-cell malignancy, or systemic amyloidosis. CONCLUSIONS: Recurrent ICH may be due to amyloid deposition of IgM lambda produced by monotypic proliferation of lymphocytes and plasma cells purely localized to the brain.

Long-term stability of 5-Fluorouracil in 0.9% sodium chloride after freezing, microwave thawing, and refrigeration.

OBJECTIVE: To investigate the stability of 5-fluorouracil diluted in 0.9% sodium chloride (normal saline [NS]) after freezing, microwave thawing, and storage for 28 days at 5°C ± 3°C. METHODS: Polyvinylchloride (PVC) infusion bags (n = 5) containing 5-fluorouracil 800 mg/100 mL were frozen for 79 days at -20°C. The bags were then thawed in a microwave oven and stored at 5°C ± 3°C for 28 days. The concentration of 5-fluorouracil was measured by high-performance liquid chromatography. Visual and microscopic inspections were performed and pH was measured periodically during storage. Solutions were considered stable if the lower limit of the 95% confidence interval of the concentration versus time profile remained greater than 90% of the initial concentration. RESULTS: No colour change or precipitation was observed in any of the solutions. Slight changes in pH were observed during refrigeration. 5-Fluorouracil solutions were stable during storage at 5°C ± 3°C for 28 days, as indicated by the results of high-performance liquid chromatography. CONCLUSION: 5-Fluorouracil 8 mg/mL in NS may be prepared in advance, frozen and stored in PVC bags, and thawed before use. The solutions remained stable after freezing at -20°C for 79 days followed by storage at 5°C ± 3°C for up to 28 days.

OPHDIAT: quality-assurance programme plan and performance of the network.

AIMS: There is a need for evaluation of screening and grading services for diabetic retinopathy (DR) in compliance with quality-assurance (QA) standards. We describe the screening/grading QA programme set up for OPHDIAT over the 2005-2006 period. METHODS: Screening and grading objectives, evaluation criteria and minimum acceptable QA standards were set. To ensure the quality of DR photos, the proportion of nongradable photos in at least one eye had to be less than 10%. To ensure grading accuracy, intergrading agreement had to be greater than 90%. Grader-generated reports had to be available in less than 48 h for more than 80% photos. Readers had to grade 500 to 3000 photos per year. RESULTS: Sixteen screening centres were opened between June 2004 and December 2006, and 14,769 patients were screened. Percentages of nongradable photos were consistently below the QA requirement (less than 10%). Overall, 800 photos were graded a second time by a reader blinded to original grading; agreement between graders ranged from 92 to 99%. More than 90% of grader-generated reports were produced within 48 h. The number of readings by each grader nearly achieved the QA standard. CONCLUSION: QA for DR telescreening should be a continuous process to provide performance feedback, thus guaranteeing a high standard for delivered results. Almost all of the predetermined QA standards in OPHDIAT for screening and grading were met. Besides the quality/sensitivity of the screening/grading modalities, it is important to evaluate at-risk patients so that they can be treated efficiently; this should be addressed in a global QA programme.

Severity of diabetic microvascular complications is associated with a low soluble RAGE level.

AIMS: The receptor for advanced glycation end-products (RAGE) has been implicated in diabetic microvascular complications, but several lines of evidence suggest that the soluble isoform of RAGE (sRAGE) may protect against AGE-mediated vessel damage. The characterized AGE Nepsilon-carboxymethyllysine (CML) is associated with diabetic microvascular complications. In the present study, we measured blood levels of sRAGE and CML-protein in diabetic patients with and without microvascular complications. METHODS: Thirty patients with type-2 diabetes were recruited into the study, comprising 20 who had no microvascular complications, and 10 who had both retinal and renal complications. sRAGE was measured in serum by ELISA, and CML by competitive ELISA. RESULTS: sRAGE blood levels were similar in both the controls and diabetic patients without microvascular complications. In patients with complications, the mean sRAGE blood level was significantly decreased (1068+/-231pg/mL) compared with diabetic patients without complications (P=0.028). CML-protein was increased in all diabetic patients, but to a higher extent in those who had microvascular complications. CONCLUSION: The association of low sRAGE with high CML-protein levels in diabetic patients who developed severe diabetic complications supports the hypothesis that sRAGE protects vessels against AGE-mediated diabetic microvascular damage.

Macular pattern dystrophy in MIDD: long-term follow-up.

A case of maternally inherited diabetes and deafness (MIDD)-associated macular pattern dystrophy with a 15-year follow-up is reported. On initial examination at age 37, visual acuity was normal, but chorioretinal atrophy at the posterior pole was already present in both eyes. At age 52, visual acuity remained normal in the right eye and was only slightly decreased in the left eye despite notable extension of the areas of chorioretinal atrophy in that eye. No evidence of diabetic retinopathy was present at any time. This case shows that visual acuity can remain stable in the long term despite extensive lesions of macular pattern dystrophy.

OPHDIAT: a telemedical network screening system for diabetic retinopathy in the Ile-de-France.

OBJECTIVE: International and national guidelines recommend an annual funduscopic examination for all diabetic patients, but such annual fundus examinations are not sufficiently performed in France. Non-mydriatic fundus photography is a valid method of evaluation for diabetic retinopathy (DR) and a viable alternative to ophthalmoscopy. After two pilot studies demonstrated the feasibility of telemedical screening for diabetic retinopathy in both hospital and primary-care settings, we developed a regional telemedical network, OPHDIAT, designed to facilitate access to regular annual evaluations of patients with diabetes while saving medical time. MATERIALS AND METHODS: OPHDIAT comprises peripheral screening centres equipped with non-mydriatic cameras, where fundus photographs are taken by technicians linked by telemedicine to a reference centre, where ophthalmologists grade the images. Currently in the Ile-de-France region, 16 screening centres are linked through a central server to an ophthalmologic reading centre and includes 11 centres located in the diabetes departments of 11 hospitals, one diabetic retinopathy screening centre located in northern Paris, three in healthcare centres and one in a prison. RESULTS: During the 28-month evaluation period, 15,307 DR screening examinations were performed. Retinal photographs of at least one eye could not be graded in 1332 patients (9.7%) and diabetic retinopathy was detected in 3350 patients (23.4%). After the screening examination, 3478 patients (25.2%) were referred to an ophthalmologist for either DR, cataract and/or non-gradable photographs. CONCLUSION: Fundus photography combined with telemedicine has the potential to improve the regular annual evaluation for diabetic retinopathy. The organization of the network around a central reading centre serves to guarantee quality control.

Early worsening of diabetic retinopathy after rapid improvement of blood glucose control in patients with diabetes.

AIM: To review the frequency, importance of and risk factors for "early worsening of diabetic retinopathy" (EWDR) after rapid improvement of blood glucose in patients with diabetes. METHODS: This was a systematic review of key references (PubMed 1980-2016) and the current international recommendations for the above-mentioned topics. RESULTS: EWDR has been described during intensive treatment (IT) in patients with uncontrolled type 1 or 2 diabetes, and after pancreas transplantation or bariatric surgery. EWDR arises in 10-20% of patients within 3-6 months after abrupt improvement of glucose control, and in nearly two times that proportion in patients with advanced baseline diabetic retinopathy (DR). While EWDR is often transient and predominantly driven by the development of cotton-wool spots and intraretinal microvascular abnormalities in patients with no or minimal DR, it can lead to irreversible retinal damage in patients with advanced DR before IT. Its identified risk factors include higher baseline levels and larger magnitudes of reduction of HbA1c, longer diabetes durations and previous severity of DR. CONCLUSION: Intensive diabetes treatment inducing a rapid fall in glucose should prompt vigilance and caution, particularly in patients with long-term and uncontrolled diabetes and DR prior to IT. Careful retinal examination should be performed in all patients before initiating IT; however, in patients with severe non-proliferative or proliferative DR, panretinal photocoagulation therapy should be performed promptly. During the year following IT, quarterly eye monitoring is required in patients at high risk of EWDR (long-term uncontrolled diabetes, previous advanced DR), whereas follow-up every 6 months can be applied in patients with short-term diabetes and no/minimal DR before IT. To date, there is no evidence that controlling the speed or magnitude of HbA1c decreases will reduce the risk of EWDR in patients with diabetes.

Emergence and multiple reassortments of French 2015-2016 highly pathogenic H5 avian influenza viruses.

From November 2015 to August 2016, 81 outbreaks of highly pathogenic (HP) H5 avian influenza virus were detected in poultry farms from South-Western France. These viruses were mainly detected in farms raising waterfowl, but also in chicken or guinea fowl flocks, and did not induce severe signs in waterfowl although they did meet the HP criteria. Three different types of neuraminidases (N1, N2 and N9) were associated with the HP H5 gene. Full genomes sequences of 24 H5HP and 6 LP viruses that circulated in the same period were obtained by next generation sequencing, from direct field samples or after virus isolation in SPF embryonated eggs. Phylogenetic analyses of the eight viral segments confirmed that they were all related to the avian Eurasian lineage. In addition, analyses of the "Time of the Most Recent Common Ancestor" showed that the common ancestor of the H5HP sequences from South-Western France could date back to early 2014 (±1 year). This pre-dated the first detection of H5 HP in poultry farms and was consistent with a silent circulation of these viruses for several months. Finally, the phylogenetic study of the different segments showed that several phylogenetic groups could be established. Twelve genotypes of H5HP were detected implying that at least eleven reassortment events did occur after the H5HP cleavage site emerged. This indicates that a large number of co-infections with both highly pathogenic H5 and other avian influenza viruses must have occurred, a finding that lends further support to prolonged silent circulation.

Comparative effects of five bisphosphonates on apoptosis of macrophage cells in vitro.

Bisphosphonates (BPs) inhibits bone resorption by reducing osteoclastic activity; they induce osteoclast apoptosis. Pathophysiology of prostheses loosening is complex and implies an inflammatory reaction secondary to the phagocytosis of wear debris by macrophages with a secondary increased bone resorption by osteoclasts. BPs inhibit proliferation and cause cell death in macrophages by induction of apoptosis. We have used mouse macrophage-like J774.1 cells to evaluate the effects of five BPs. J774A.1 cells were cultured in a standard culture medium for 2-days. BPs (alendronate, pamidronate, etidronate, risedronate, zoledronic acid) were added in the medium at concentration of 10(-6) to 10(-4)M during 3 days. Cells were studied by fluorescence microscopy after staining with the fluorescent dye Hoescht H33342 and the percentage of apoptotic cells was determined on 300 nuclei. Cells were analyzed by flow cytofluorometry after staining with annexin V-FITC (for counting apoptotic cells) and propidium iodide (for necrotic/late-apoptotic cells) on 2000 cells. Etidronate did not cause significant apoptosis or necrosis, at any concentration. Alendronate and pamidronate caused apoptosis and death only at very high concentration [10(-4)M]. On the contrary, apoptotic and necrotic cells were evidenced with risedronate or zoledronic acid at lower concentrations. These effects were dose-dependant and occurred when concentration reached [10(-5)M]. The number of apoptotic cells was higher with zoledronic acid and then with risedronate. Cytofluorometry appeared superior to cytologic analysis in the investigation of macrophage apoptosis, since necrotic cells loose contact with the glass slides and are not identifiable in cytological counts. Some amino-BPs appear to induce apoptosis in macrophages.

The elderly diabetic's eyes.

This review article attempts to clarify current and future issues concerning diabetic retinopathy in the elderly. This retinopathy is often part of multiple geriatric ophthalmological diseases (cataract, glaucoma, age-related macular degeneration [ARMD]). Current management is insufficient. A variety of factors come together to aggravate the situation: the increase in the number of elderly diabetic patients and the decrease in the number of ophthalmologists. Through a review of the literature, seriously lacking in prospective studies specific to the geriatric population, we discuss the epidemiology, the screening problems, and the various issues concerning the overall ophthalmologic and diabetologic management inherent to these patients' age and condition. We stress the seriousness of the visual disability of the older subject, but also the overall morbidity and mortality. We observe that recommendations can only be based on expert opinion. Each section includes a warning on the high iatrogenic risk in this area. The caregiver should avoid two pitfalls: a lax attitude related to fear or defeatism and excessive interventionism that may be inappropriate to the patient's condition.