Bone density and functional results after femoral revision with a cementless press-fit stem.

INTRODUCTION: The influence of radiographic bone density changes in the area surrounding a total hip arthroplasty (THA) revision with a cementless press-fit stem is unknown, notably in terms of functional results. We have therefore conducted a study aiming to (1) propose a radiographic method to assess bone density, (2) measure the functional effects of reduced bone density, and (3) determine the factors contributing to these modifications. HYPOTHESIS: A reduction in radiographic bone density has a negative influence on the functional result after revision using a cementless press-fit stem. MATERIAL AND METHODS: We retrospectively assessed 150 THA revisions at a mean follow-up of 6.3 ± 3.2 years (range, 2-15 years). The clinical assessment was based on the Harris Hip Score. Bone density modifications were measured radiographically and the method was evaluated. The change in bone density was classified into two groups: (1) bone density not reduced or < 2 Gruen zones (118 cases [79%]); (2) bone density reduced ≥ 2 zones (32 cases [21%]). The variables showing a potential influence were the Cortical Index (CI), the type of primary stability with the press-fit system, and the femoral implant length. RESULTS: Inter- and intraobserver reliability of radiographic bone density measurement was evaluated as moderate or good (Kappa, 0.58; 0.60 and 0.67, respectively). For the Harris Hip Score at follow-up, there was a borderline statistical relation between stages 1 and 2: for the 118 stage 1 patients, this score was 83.62 ± 11.54 (range, 27-99) versus 78.34 ± 15.98 (range, 62-91) for stage 2 patients (P = 0.09). A CI ≤ 0.44 showed mediocre bone quality contributing to decreased bone density (P < 0.02). On the other hand, there was no statistically significant relation with the type of primary fixation (P = 0.34) or the length of the implant (P = 0.23). CONCLUSIONS: A cementless revision femoral stem can induce a reduction in bone density with possible functional effects. The negative role played by bone scarcity on the functional score is confirmed, and even though the difference is not statistically significant, we suggest using a short stem when this is possible.

Flow cytometric analysis of inflammatory markers in KCS: 6-month treatment with topical cyclosporin A.

PURPOSE: Immune-based inflammation has been observed as a common mechanism of keratoconjunctivitis sicca (KCS). In KCS-affected eyes, upregulated expression of HLA DR and various immune- or apoptosis-related markers by conjunctival epithelial cells has been demonstrated in an earlier study, by a technique of flow cytometry in impression cytology (IC) specimens. The purpose of this study was to monitor the effects of topical cyclosporin A on the expression of these markers throughout a 6-month period of treatment. METHODS: Patients with moderate to severe KCS included in a large European multicenter clinical trial (Cyclosporin Dry Eye Study, Allergan, Irvine, CA) underwent collection of IC specimens at baseline, month 3, and month 6. For 6 months, they randomly received 0.05% or 0.1% cyclosporin A or vehicle. Specimens were processed and analyzed in a masked manner by flow cytometry, using monoclonal antibodies directed to HLA DR, CD40, CD40 ligand, Fas, and the apoptotic marker APO2.7. Percentages of positive cells were calculated and levels of expression quantified after conversion into standardized units of fluorescence. RESULTS: One hundred fifty-eight patients had at least two IC specimens available for flow cytometry analysis. HLA DR expression, both in percentage of positive cells and level of expression, was highly significantly reduced after 0.05% and 0.1% cyclosporin A treatment at months 3 and 6 compared with baseline values, whereas vehicle did not induce any change in HLA DR expression over time. The 0.05% and 0.1% cyclosporin emulsions were significantly more effective than the vehicle in reducing HLA DR at months 3 and 6 (0.05%), and at month 6 (0.1%). CD40 expression was significantly reduced at month 3 and partially at month 6, compared with baseline, with no reduction in patients who received the vehicle. CD40 ligand expression also decreased at months 3 and 6 in patients taking both concentrations of cyclosporin A. APO2.7 expression was significantly increased in all three groups, whereas percentage of Fas-positive cells decreased only in patients treated with 0.05% cyclosporin A at months 3 and 6. CONCLUSIONS: Flow cytometry provided an objective technique to monitor the effects of topical cyclosporin A on immune- and apoptosis-related markers in the conjunctival epithelium of patients with KCS enrolled in a large multicenter trial. Topical cyclosporin A strikingly reduced HLA DR and to a lesser extent, other inflammatory and apoptotic markers, whereas the vehicle, used as a control tear substitute, had almost no effect. This study confirms that cyclosporin A may be efficient in reducing conjunctival inflammation in moderate to severe KCS and is consistent with clinical results in this indication.

Flow cytometric analysis of inflammatory markers in conjunctival epithelial cells of patients with dry eyes.

PURPOSE: To investigate in impression cytology (IC) specimens the expression of inflammatory and apoptosis-related markers by conjunctival epithelial cells from patients with dry eye as a rationale for treatment with topical cyclosporine. METHODS: Immunologic anomalies were identified at baseline, before treatment with the masked medication, in a homogeneous series of patients with dry eye syndrome, who were enrolled in a large European multicenter clinical trial (Cyclosporin A Dry Eye Study; Allergan, Irvine, CA). IC specimens were collected in 243 patients with moderate to severe keratoconjunctivitis sicca (KCS), with or without Sjogren's syndrome (SS). Fifty normal subjects were separately examined to provide normal control values. Specimens were analyzed in a masked manner by flow cytometry, using antibodies directed to markers of the immune system and/or apoptotic pathway: HLA DR, CD40, CD40 ligand, Fas, and APO2.7. Levels of expression were quantified, and results were compared with those obtained in the 50 normal patients. RESULTS: One hundred sixty-nine specimens were successfully interpreted at baseline, including 41% from patients with SS. A highly significant increase of HLA DR expression by conjunctival cells was found in KCS-affected eyes compared with normal eyes, which did not express this marker or did so very weakly. HLA DR expression in eyes with SS was significantly higher than in KCS-affected eyes without SS. Fas and APO2.7 were found at low levels in all normal and KCS-affected eyes. CD40 and CD40 ligand expressions were significantly increased in eyes with KCS compared with normal eyes. HLA DR, CD40 and Fas were found at significantly higher levels in the SS group than in the non-SS group. CONCLUSIONS. Conjunctival cells from patients with dry eye with moderate to severe KCS, with or without SS, overexpress inflammatory and apoptosis-related markers. Whether inflammation is a primary phenomenon in KCS or is the consequence of repetitive abrasion of the ocular surface after tear film deficiency remains to be determined. These data, nevertheless, support the use of immunomodulatory and/or anti-inflammatory drugs in the treatment of patients with KCS.

Correlation between tear IgE levels and HLA-DR expression by conjunctival cells in allergic and nonallergic chronic conjunctivitis.

BACKGROUND: Chronic conjunctival inflammatory diseases may depend upon various mechanisms. Discriminating allergy from nonspecific inflammation has become of striking importance for diagnosis and treatment. We investigated conjunctival inflammatory response by comparing two objective biological tools, tear IgE and HLA-DR expression by conjunctival epithelium, as indirect indicators of activation of the Th2 and Th1 subsets, respectively. METHODS: Eighty-two patients with chronic conjunctivitis underwent tear IgE measurement by an ELISA technique and quantitation of HLA-DR expression in impression cytology specimens. Forty-two had direct or indirect clinical indications of allergic mechanisms, 26 had chronic conjunctivitis without any sign of allergy, and 14 suffered from isolated nonallergic dry eyes. RESULTS: Patients clinically considered as allergic only showed positive IgE in 47 of 84 eyes (56%), whereas 21% and 25% of eyes with nonspecific conjunctivitis and dry eyes respectively were also positive. IgE levels were significantly higher in the allergic group than in the other two groups. HLA-DR positivity in epithelial cells was found in 28.5%, 48% and 50% of eyes, respectively. HLA-DR expression by epithelial cells was negatively correlated with tear IgE, as most specimens positive to one criterion were negative to the other one (49 eyes DR+, IgE-; 47 eyes DR-, IgE+; only 9 eyes positive to both criteria; chi-square: P = 0.0001). CONCLUSION: As IgE synthesis and HLA-DR induction may represent indirect indicators of the activation of the Th2 and Th1 subsets, association of these two simple tests could be interesting for the routine assessment of the mechanisms of inflammatory ocular surface diseases.

Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies.

OBJECTIVES: To investigate conjunctival and trabecular specimens from patients with glaucoma according to the duration and number of drugs received before filtration surgery, and to confirm, in a complementary experimental model, the role of preservative by comparing the effects of preserved and nonpreserved timolol. STUDY DESIGN: Experimental animal and human tissue study. PARTICIPANTS: Paired specimens of conjunctiva and trabeculum were taken from 61 patients undergoing trabeculectomy. Twenty-six patients were treated with 2 or more drugs for at least 1 year; 30 had received a beta-blocker for more than 1 year and 5 underwent primary surgery. A second study was performed in 25 rats receiving topical solutions in both eyes for 1 month. INTERVENTION: Immunohistochemistry was performed in all biopsy specimens using 12 different monoclonal antibodies. Ocular structures from rats treated for 1 month with preserved 0.5% timolol, nonpreserved 0.5% timolol, or 0.01% benzalkonium chloride were similarly investigated in an experimental study. MAIN OUTCOME MEASURES: Inflammatory cell infiltrates and fibroblasts were evaluated in biopsies, as well as in animal specimens, together with histologic changes induced by the drugs applied. RESULTS: Twenty-four of 26 conjunctivae and 21 of 24 trabecular pieces from multitreated patients were found to be abnormally infiltrated by cells expressing inflammatory or fibroblastic markers or both. Nineteen of 30 conjunctivae and 9 of 22 trabeculums in the monotherapy group and only 1 of 5 specimens from the primary surgery group were abnormal. In rats, preserved timolol and benzalkonium similarly showed infiltrates together with toxic histopathologic changes as compared to the nonpreserved timolol and control groups. CONCLUSIONS: These two combined studies confirmed histopathologic effects of antiglaucomatous drugs on the conjunctiva and showed similar effects in the trabecular meshwork. The experimental study showed that benzalkonium chloride is at least, to a large part, responsible for these toxic or immunoinflammatory effects or both on the ocular structures.

Effects of EGb761 and superoxide dismutase in an experimental model of retinopathy generated by intravitreal production of superoxide anion radical.

BACKGROUND: A study was carried out to investigate the effect of two antioxidants--Ginkgo biloba extract (EGb761) and superoxide dismutase (SOD)--in an experimental model of vitreoretinopathy obtained by direct production of oxygen free radicals in the vitreous cavity. METHODS: Twenty-eight pigmented rabbits were used. Vitreoretinopathy was induced by intravitreal injection of 50 microliters of a mixture composed of 40 nmol of xanthine and 0.001 IU of xanthine oxidase. Rabbits were randomly distributed into four groups: Group 1 (n = 8) did not receive any treatment and served as a positive control. Groups 2 (n = 8) and 3 (n = 8) received for 1 month EGb761 given orally at a dose of 100 mg/kg/day, respectively 1 day after and 1 week before induction of retinopathy. Group 4 (n = 4) was treated by three intramuscular injections of 15,000 IU/kg of SOD, 24 h before induction and 24 and 48 h thereafter. Clinical evaluations and electroretinograms (ERG) were repeatedly performed until the animals were killed at day 28. Histological examinations and immunohistological procedures were performed to ascertain the origin and characteristics of the cellular proliferation and to compare vitreoretinal structures in the four groups. RESULTS: Intravitreal injection of xanthine-xanthine oxidase produced a strong inflammatory response with vitreous infiltrates and epiretinal membrane formation, inconstantly associated with retinal detachment. ERG showed a decrease of the a-, b- and c-waves beginning within a few hours after injection. Histologic evaluation found an intravitreal and epiretinal infiltration by leukocytes and epithelial-derived cells, dense vitreoretinal membranes and retinal detachments with occasional neovascularization. In the treated groups (groups 2-4), all clinical, electric and histologic data were significantly improved compared to the control group. However, no difference could be found among the three treated groups. CONCLUSION: This study demonstrates the strong pathologic effects of free radical production on the retina and the close relationships between free radicals, inflammatory pathways and vitreoretinal proliferative disorders. It also confirms the pharmacological interest of prevention by antioxidants and free radical scavengers.

Bone mineral density in sixty adult patients with Marfan syndrome.

Sixty adult patients (40 women, 20 men) with Marfan syndrome (MFS) according to the Berlin criteria had a full clinical examination and bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry of the hip and nondominant forearm. BMD was expressed as a Z-score and compared with the reference population of the Hologic database. In MFS men, BMD (g/cm(2)) was compared with the BMD of 45 normal tall Caucasian adults. Osteocalcin was measured by radioimmunoassay. In patients with MFS, BMD was compared between patients with and without previous fractures and according to the phenotypic severity of MFS. The mean age of the patients was 32.9 +/- 9.3 years (women 32.5 +/- 9.7, men 33.4 +/- 8.6), mean height was 180.3 +/- 10.3 cm (women 176.3 +/- 9.2, men 188.1 +/- 7.5) and mean body mass index 20.9 +/- 3.6 kg/m(2) (women 20.8 +/- 3.4, men 20.95 +/- 3.97). Hyperlaxity score (Beighton criteria) was 6.9 +/- 1. 1. Six patients (10%) had a previous fracture. Thirty per cent of patients had had at least one previous operation for scoliosis, aortic dilatation or eye problems. BMD values in the 60 patients were as follows: Z-score of the hip, -1.26 +/- 0.93, p<10(-9) (neck, -0.93 +/- 1.09, p<10(-9); trochanter, -1.31 +/- 0.85, p<10(-9); intertrochanter, -1.39 +/- 0.99, p<10(-9); Ward's triangle, -0.93 +/- 1.88, p<10(-9)); Z-score of the radius: -1.6 +/- 1.06, p<10(-9) (1/3 proximal, -1.29 +/- 1.03; mid-radius, -1.94 +/- 1.04; ultradistal, -0.68 +/- 1.1, p<10(-9)). The decrease in BMD was similar in men and women at both the hip and the radius. BMD in MFS patients was significantly decreased at cortical compared with trabecular sites (radius 1/3 proximal vs ultradistal, p<0.0001; total femur vs Ward's triangle, p<0.0005). No difference in BMD was found between MFS patients with or without previous fractures and those with severe or less severe phenotypic expression of MFS. An influence of height and weight in MFS on BMD is suspected. Osteocalcin was not increased in our group of MFS patients. Thus both men and women with MFS have a significant deficit of BMD at the hip and radius. The decrease in BMD is present equally in both sexes and is more pronounced at predominantly cortical sites. In our group of patients we found no increase in fractures and no relation between decreased BMD and phenotypic expression of the syndrome.

[Value of lacrymal IgE determination and conjunctival cytology in the diagnosis of chronic conjunctivitis]. / Intérêt du dosage des IgE lacrymales et des empreintes conjonctivales dans le diagnostic des conjonctivites chroniques.

PURPOSE: Chronic conjunctival inflammatory diseases may depend upon various strongly intricated mechanisms. Discriminating allergy from nonspecific inflammation has become of striking importance for diagnosis and treatment. We investigated conjunctival inflammatory response by comparing two objective biological tools, tear IgE detection and HLA DR expression by conjunctival epithelium, as indirect indicators of activation of the Th1 and Th2 subsets, respectively. METHODS: Sixty-eight patients (135 eyes) with chronic conjunctivitis underwent tear IgE dosage by an ELISA technique and quantification of HLA DR expression in impression cytology specimens. 34 had direct or indirect clinical indications of allergic mechanisms, 22 had chronic conjunctivitis without any sign of allergy, and 12 suffered from isolated nonallergic dry eyes. RESULTS: Patients clinically considered as allergic only showed positive IgE in 31 out pf 68 eyes (46 per cent), whereas 11/44 (25%) and 7/24 (29%) eyes with nonspecific conjunctivitis and dry eyes respectively were also positive. HLA DR positivity in epithelial cells was found in 18/61 (29.5%), 15/40 (37.5%) and 9/22 (41%) eyes, respectively. HLA DR expression by epithelial cells was negatively correlated with tear IgE, as most specimens positive to one criterion were negative to the other one (37 eyes DR+ IgE-, 35 eyes DR- IgE+, and 5 eyes DR+ IgE+; chi-square: p = 0.0001). CONCLUSION: As IgE synthesis and HLA DR induction may represent indirect indicators of the activation of the Th1 and Th2 subsets, association of these two simple tests could be interesting for the routine assessment of the mechanisms of inflammatory ocular surface diseases.

[Evaluation by laser flare meter of the inflammatory response after cataract surgery]. / Evaluation par laser flare meter de la réponse inflammatoire après chirurgie de la cataracte.

PURPOSE: To prospectively evaluate use of the laser flare meter the inflammatory response after phacoemulsification with four different types of intraocular lenses. METHODS: Measurements with the Kowa laser flare meter FC-500 were done before surgery and at 1, 6 and 21 days following standard phacoemulsification with corneal incision in 157 patients. The patients were randomized in four groups to receive HSM IOL (group I), foldable acrylic IOL (group II), foldable three-piece silicone (group III), and foldable single-piece silicone (group IV). RESULTS: Overall, mean flare values were increased at D1, and decreased rapidly to normal values at D21. Intragroup analysis showed a slight increase of flare value observed in the PMMA group (p = 0.0015) and silicone monobloc group (p = 0.001) at D21 compared to D0. There was no statistical difference found between D0 and D21 in the acrylic and the silicone three pieces groups. At D1, a significant increase of flare values was observed in the PMMA (28.9 ph/ms) and silicone three pieces (28.8 ph/ms) groups, as compared to silicone monobloc group (22 ph/ms). At D21, the acrylic group had a significantly lower mean value than PMMA and silicone monobloc groups. No statistical difference was observed between acrylic and three-piece silicone at D21. CONCLUSION: This study shows that the inflammation in the four groups was very low after phacoemulsification by a corneal incision and attempts to explain the impact of the incision length on the breakdown of blood-aqueous barrier.

[Value of multidisciplinary consultation in diagnosis and survival of Marfan syndrome]. / Apport d'une consultation multidisciplinaire dans le diagnostic et le suivi d'un syndrome de Marfan.

OBJECTIVES: To facilitate diagnosis, define a strategy for prevention and treatment and obtain further insight concerning Marfan's disease, we conducted a series of multidisciplinary consultations in French clinics. PATIENTS AND METHODS: Five specialists (a genetics specialist, a pediatrician or a rheumatologist, an ophthalmologist, and a psychologist) saw all the patients successively in the same clinic. A synthesis of the clinical files was prepared for analysis. Since the first consultation on 1 January 1995 and the study end on 30 June 1997, 494 patients (67% adults) participated in primary consultations, 143 were seen at follow-up consultations. RESULTS: The diagnosis of Marfan's disease was affirmed in 41% of the patients, disaffirmed in 48% and uncertain in 11%. Among the Marfan's patients, 75% were seen again within the framework of a multidisciplinary follow-up consultations. Annual work-up included cardiology (echocardiography with measurement of the proximal aorta diameter in search for indication for beta-blocker therapy or preventive valve replacement), ophthalmology (lens, retina) and rheumatology examinations (skeletal involvement). CONCLUSION: Early diagnosis and rigorous follow-up can help prevent ocular and cardiac complications in Marfan's disease. The multidisciplinary approach provides more precise data for diagnosis and possible phenotype-genotype correlations.

Histopathological effects of topical ophthalmic preservatives on rat corneoconjunctival surface.

PURPOSE: Long term use of topical drugs has clearly been shown to induce toxic immunopathological changes in the ocular surface. However, little is known concerning the respective roles of active compounds and preservatives. Benzalkonium chloride (BAC) is the most used preservative and its cytotoxicity is well known, but other preservatives have not yet been clearly evaluated. We thus performed a comparative study to investigate toxic side effects induced in the rat ocular surface by applications of various preservatives, with special attention to inflammatory infiltrates. METHODS: A total of 35 brown Norway rats were divided into seven groups of five each. They received, for one month, in both eyes, either 0.01% cetrimonium chloride, 0.01% benzalkonium chloride, 0.01% benzododecinium bromide, 0.004% thiomersal, 0.05% methyl parahydroxybenzoate or phosphate-buffered saline (PBS), the last group remaining untreated. Then, animals were sacrificed and eyes were processed for histological and immunological procedures with monoclonal antibodies to rat immunocompetent cells. RESULTS: When compared to controls, all preservative-treated eyes consistently showed corneal and conjunctival damage, including epithelial alterations, various degrees of keratinization and inflammatory infiltrates at the limbus and within the conjunctival stroma and epithelium. No difference was found between the five tested drugs. CONCLUSIONS: This study confirms that most preservatives used in ophthalmic eyedrops may similarly induce strong histopathological and inflammatory changes in the ocular surface after short term use. Although obtained in animal model, these results confirm strong toxic side effects in patients with preexisting ocular surface disorders and/or receiving topical drugs for long periods.

Expression of Fas-Fas ligand antigens and apoptotic marker APO2.7 by the human conjunctival epithelium. Positive correlation with class II HLA DR expression in inflammatory ocular surface disorders.

Fas antigen (CD95) is a membrane receptor that plays a major role in induction of apoptosis. In surface conjunctival epithelial cells the expressions of Fas, Fas ligand, the apoptotic marker APO2.7 and of HLA DR class II antigen, a membrane marker known to be expressed in inflammatory conditions were investigated. Impression cytology specimens were collected in 65 patients: 20 normal ones, 15 contact lens wearers, 20 receiving chronic topical antiglaucoma treatment and 10 with nonspecific chronic conjunctivitis. Cells were processed for flow cytometry, using monoclonal antibodies to Fas, Fas ligand, APO2.7, HLA DR antigens and a negative isotypic control. Percentages of positive cells were recorded and levels of fluorescence quantified using fluorescent beads at standardized fluorescence intensities. In addition, a human conjunctival cell line was incubated with anti-Fas stimulating antibodies in order to test Fas-induced apoptosis in vitro. Fas was found in all specimens in most of the conjunctival cells, but quantitation of levels of fluorescence showed a significantly higher expression in pathologic eyes than in normal ones. Fas ligand and APO2.7 were variably expressed by conjunctival cells, but in a significantly higher percentage of cells in pathological eyes than in normal ones. In these eyes a strong expression of HLA DR was also observed, whereas normal eyes showed lowest levels. Highly significant correlations were found between Fas, Fas ligand, APO2.7 and HLA DR levels. Anti-Fas antibodies in vitro induced strong apoptosis in epithelial cells as confirmed by APO2.7 expression and DAPI staining. This study confirms that conjunctival epithelial cells normally express Fas antigen, and more inconstantly its ligand, as do corneal ones or keratinocytes. Fluorescence quantitation by flow cytometry showed much higher expression in inflammatory eyes than in normal ones, and demonstrated a strong correlation between apoptotic and inflammatory pathways in the ocular surface.

[Contribution of nidus fluorescence in the surgical treatment of osteoid osteoma. Apropos of 17 cases]. / Apport de la fluorescence du nidus dans le traitement chirurgical de l'ostéome ostéoïde. A propos de 17 cas.

PURPOSE OF THE STUDY: The severity of pain and functional disability contrast with the benignity and small size which characterize the osteoid osteoma. This study evaluates the clinical and histological efficiency of an intraoperative localization of the nidus by the tetracycline fluorescence test which is based on histomorphometric bone labeling techniques. MATERIAL AND METHODS: 17 out 25 osteoïd osteoma, operated between 1987 and 1995, had tetracycline fluorescence test. The patients received 1 gram orally during each of the 3 pre-operative days. Fluorescence under ultraviolet light was assessed on the removed specimen, and on the tumor site, before and after surgical resection. RESULTS: At a mean follow-up of 39 months (12-85), 15 of the 17 patients (88 per cent) were painless. The result was always acquired within the first weeks after procedure. 2 patients had a primary failure due to incomplete removal of fluorescent nidus, and one was reoperated with success after one year. One patient had a false negative test although there was histological evidence of osteoid osteoma on the removed tissues with a complete relief of pain. In summary, the test was helpful in 14 cases (82 per cent) guiding "en bloc" resection or curetage, and allowing 70 per cent of histological nidus diagnosis. DISCUSSION: This test is easy to carry out by pre-operative ingestion of tetracycline and only requires an ultra-violet light source. It demonstrated a good reliability which can be compared with that of more complex radio-labeling techniques or CT guided drill resections which impede histological confirmation in half of the cases. The fluorescence test allows a secure and precise procedure without complication, and we use it mainly for cancellous and superficial osteoid osteoma, and for revision of previous failed excisions. When the nidus is cortical and deeply located, radioguided techniques must be discussed.