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To determine differences in hip geometry in adults with type 1 diabetes (T1D) compared with healthy adults without diabetes.In this cross-sectional study, 43 adults with T1D (mean age 56 years, 84 % female, 92 % White, mean duration of diabetes of 39 years, A1c of 7.8 %) and 40 adults without diabetes (mean age 60 years, 80 % female, 77 % white) who had hip dual-energy x-ray absorptiometry (DXA) scans from previous studies were included. Areal bone mineral density (aBMD) and measures of hip structural properties at the narrow neck, intertrochanteric and femoral shaft regions of the left proximal femur were analyzed between adults with T1D and controls using linear models controlled for age, sex, and body mass index.There were no significant differences in DXA-based aBMD at the hip (0.769 ± 0.132 vs. 0.900 ± 0.139 g/cmAdults with T1D have several significant differences in proximal femur morphology compared with controls. These morphological differences may adversely affect the mechanical integrity of the proximal femur, thereby contributing to an increased risk of fracture in the event of a fall.

Osteocytes can participate in systemic mineral homeostasis through perilacunar maintenance and remodeling, where changes to osteocyte lacunar morphology may affect bone structural integrity, tissue strains, and osteocyte mechanosensitivity. Though aging is associated with both decreased bone quality and altered mineral metabolism, it is not known if osteocyte lacunae undergo age-related changes in geometry. In order to survey lacunar changes with age, we developed an open-source program whereby 3D osteocyte lacunae are automatically segmented and then subsequently reconstructed from confocal laser scanning microscopy (CLSM) depth stacks for quantitative analysis of geometry and orientation. This approach takes advantage of the availability and speed of CLSM while avoiding time-consuming and bias-prone manual segmentation. Unlike conventional approaches used to quantify osteocyte lacunar morphology, CLSM enables facile analysis in three-dimensions with clear identification of osteocyte lacunae. We report that 3D osteocyte lacunae measured by CLSM become smaller, more spherical, more oblate, more spatially disorganized, and more sparsely populated with increased age in C57Bl/6 mouse cortical bone in groups spanning 6–24 months old. Critically, these age-related changes are in large part not observed in 2D analyses from the same samples. These results (1) demonstrate proof-of-concept of an efficient method to quantitatively assess osteocyte lacunae in 3D for application to a wide range of studies and (2) motivate further inquiry into how changes to osteocyte lacunar geometries and perilacunar material contribute to diminished bone quality in aging.

Objectives:To study and review the short- and long-term effects of intranasal steroids on obstructive adenoids.Methods:In this prospective cohort study, 19 children previously treated with mometasone furoate for 3 months were contacted at 3, 6 and 12 months after cessation of treatment. Main outcome measures included: change in severity of nasal obstruction, allergic rhinitis and obstructive symptoms. A systematic review of literature was also performed.Results:By one year, 25 per cent of patients required adenoidectomy; the remaining children had no significant change in clinical score (p= 0.464), obstruction severity (p= 0.191) or allergic symptoms (p= 0.284). Fourteen pertinent studies were identified; all but one study showed improvement in the patients’ symptoms and/or degree of obstruction. Two studies with follow up reaching 25 months showed positive effects.Conclusion:The short-term positive effect of some intranasal steroids on obstructive adenoids seems to persist in a significant number of patients after the cessation of treatment.

Current implant materials and designs used in spinal fusion show high rates of subsidence. There is currently a need for a method to predict the mechanical properties of the endplate using clinically available tools. The purpose of this study was to develop a predictive model of the mechanical properties of the vertebral endplate at a scale relevant to the evaluation of current medical implant designs and materials. Twenty vertebrae (10 L1 and 10 L2) from 10 cadavers were studied using dual-energy X-ray absorptiometry to define bone status (normal, osteopenic, or osteoporotic) and computed tomography (CT) to study endplate thickness (μm), density (mg/mm3), and mineral density of underlying trabecular bone (mg/mm3) at discrete sites. Apparent Oliver–Pharr modulus, stiffness, maximum tolerable pressure (MTP), and Brinell hardness were measured at each site using a 3 mm spherical indenter. Predictive models were built for each measured property using various measures obtained from CT and demographic data. Stiffness showed a strong correlation between the predictive model and experimental values (r = 0.85), a polynomial model for Brinell hardness had a stronger predictive ability compared to the linear model (r = 0.82), and the modulus model showed weak predictive ability (r = 0.44), likely due the low indentation depth and the inability to image the endplate at that depth (≈0.15 mm). Osteoporosis and osteopenia were found to be the largest confounders of the measured properties, decreasing them by approximately 50%. It was confirmed that vertebral endplate mechanical properties could be predicted using CT and demographic indices.

Poly(para-phenylene) (PPP) is a novel aromatic polymer with higher strength and stiffness than polyetheretherketone (PEEK), the gold standard material for polymeric load-bearing orthopaedic implants. The amorphous structure of PPP makes it relatively straightforward to manufacture different architectures, while maintaining mechanical properties. PPP is promising as a potential orthopaedic material; however, the biocompatibility and osseointegration have not been well investigated. The objective of this study was to evaluate biological and mechanical behavior of PPP, with or without porosity, in comparison to PEEK. We examined four specific constructs: 1) solid PPP, 2) solid PEEK, 3) porous PPP and 4) porous PEEK. Pre-osteoblasts (MC3T3) exhibited similar cell proliferation among the materials. Osteogenic potential was significantly increased in the porous PPP scaffold as assessed by ALP activity and calcium mineralization. In vivo osseointegration was assessed by implanting the cylindrical materials into a defect in the metaphysis region of rat tibiae. Significantly more mineral ingrowth was observed in both porous scaffolds compared to the solid scaffolds, and porous PPP had a further increase compared to porous PEEK. Additionally, porous PPP implants showed bone formation throughout the porous structure when observed via histology. A computational simulation of mechanical push-out strength showed approximately 50% higher interfacial strength in the porous PPP implants compared to the porous PEEK implants and similar stress dissipation. These data demonstrate the potential utility of PPP for orthopaedic applications and show improved osseointegration when compared to the currently available polymeric material. Statement of significance PEEK has been widely used in orthopaedic surgery; however, the ability to utilize PEEK for advanced fabrication methods, such as 3D printing and tailored porosity, remain challenging. We present a promising new orthopaedic biomaterial, Poly(para-phenylene) (PPP), which is a novel class of aromatic polymers with higher strength and stiffness than polyetheretherketone (PEEK). PPP has exceptional mechanical strength and stiffness due to its repeating aromatic rings that provide strong anti-rotational biaryl bonds. Furthermore, PPP has an amorphous structure making it relatively easier to manufacture (via molding or solvent-casting techniques) into different geometries with and without porosity. This ability to manufacture different architectures and use different processes while maintaining mechanical properties makes PPP a very promising potential orthopaedic biomaterial which may allow for closer matching of mechanical properties between the host bone tissue while also allowing for enhanced osseointegration. In this manuscript, we look at the potential of porous and solid PPP in comparison to PEEK. We measured the mechanical properties of PPP and PEEK scaffolds, tested these scaffolds in vitro for osteocompatibility with MC3T3 cells, and then tested the osseointegration and subsequent functional integration in vivo in a metaphyseal drill hole model in rat tibia. We found that PPP permits cell adhesion, growth, and mineralization in vitro. In vivo it was found that porous PPP significantly enhanced mineralization into the construct and increased the mechanical strength required to push out the scaffold in comparison to PEEK. This is the first study to investigate the performance of PPP as an orthopaedic biomaterial in vivo. PPP is an attractive material for orthopaedic implants due to the ease of manufacturing and superior mechanical strength.

ObjectiveTo assess the ‘real-world’ performance of the newer generation of hydrogel coils in ruptured aneurysms.MethodsA multicenter retrospective study was carried out of angiographic and clinical outcome data on consecutive patients with ruptured aneurysms treated with at least 70% of the newer generation of hydrogel coils. Demographics and data on clinical grade, smoking, use of statins, aneurysm size, location, technique used, packing density, immediate angiographic result, angiographic follow-up, rebleeding and clinical outcome were obtained and analyzed.ResultsEighty patients (54F; 26M) with an average age of 55.1 years were entered in the study. Forty-four presented good clinical grade (Hunt and Hess 1 or 2). Forty-two (52.5%) aneurysms were ≤5 mm. 56.7% of the aneurysms were treated with simple coil embolization and 39.6% with balloon-assisted coil. The packing density ranged from 9.3% to 92.6% (mean 48.5%). Immediate occlusion rates (Raymond–Roy Scale) were: complete occlusion (class I) in 57.5%, residual neck (class II) in 32.5% and residual aneurysm (class III) in 10%. Intraoperative rupture occurred in 3 cases (3.75%). Clinical follow-up, available in 73 patients, showed a good outcome (modified Rankin Scale 0–2) in 76.3%. Preliminary data on imaging follow-up were available in 54 patients (average 6.8 months) with complete occlusion in 77.8%, residual neck in 20.3% and residual aneurysm in 1.9%. There was no re-hemorrhage.ConclusionsOur data show that the use of the newer-generation hydrogel coils in the treatment of ruptured aneurysms is feasible, safe and effective with high immediate and mid-term occlusion rates and low morbidity.

Simulated partial weight bearing during magnetic resonance imaging of the knee was used to measure patellar tilt, medial-lateral patellar shift, and patellofemoral contact area in three groups of subjects; patients with posterior cruciate retaining (PCR) TKA, patients with bicruciate substituting (BCS) TKA, and healthy controls. Contact stress was also calculated based on the contact area and body weight-based estimates of contact force. Contact stress was significantly (p0.05) higher in PCR knees (2.5+/-3.0 MPa) than in BCS knees (0.2+/-0.1 MPa) when knees were fully extended, but this difference was not significant (3.7+/-3.5 MPa for PCR knees vs. 1.4+/-1.9 MPa for BCS knees; p0.05) in early flexion. The results also indicate that patellar tilt (normal=2.4 degrees +/-4.8 degrees, BCS=5.5 degrees +/-5.5 degrees, PCR=-3.0 degrees +/-6.9 degrees change in lateral tilt when moving from full extension to early flexion) and contact area (full extension: normal=267+/-111 mm(2), BCS=344+/-201 mm(2), PCR=83+/-80 mm(2); early flexion: normal=723+/-306 mm(2), BCS=417+/-290 mm(2), PCR=246+/-108 mm(2)) in BCS TKA mimic those in the normal knees more closely than PCR knees do. These results suggest that the patellar component in BCS TKA may be expected to experience less wear than the patellar component in PCR TKA over time.

Purpose The purpose of this study was to use magnetic resonance imaging (MRI) to determine 3-dimensional knee kinematics after anterior cruciate ligament (ACL) reconstruction. Methods Nine ACL-reconstructed and contralateral knees were tested 12 ± 8 months after surgery. MRI was performed at full extension and 40° of knee flexion under simulated weight-bearing conditions. Femoral condyle positions, tibial rotation, contact area, and contact location were analyzed by use of MRI-based 3-dimensional models. Results When knees were fully extended, tibiae in ACL-reconstructed knees were externally rotated by 3.6° ± 4.2° compared with contralateral knees. The external rotation was due to anterior subluxation of the medial side of the tibia. At 40° of knee flexion, tibiae in ACL-reconstructed knees and contralateral knees were both internally rotated by 5.3°. There were no significant differences in contact area or contact location between ACL-reconstructed and contralateral knees. When moving from extension to flexion, ACL-reconstructed knees exhibited 3.5° ± 5.9° more internal tibial rotation than contralateral knees. Conclusions Reconstruction of the ACL restored normal motion on the lateral side of the knee but not on the medial side, resulting in increased internal tibial rotation when moving from full extension to 40° of flexion. These results suggest that ACL reconstruction does not restore normal kinematics on the medial side of the knee, which may lead to early cartilage degeneration. Level of Evidence Level IV, therapeutic case series.

Osteoarthritis (OA) is associated with increased mechanical damage to joint cartilage. We have previously found that extracellular superoxide dismutase (ECSOD) is decreased in OA joint fluid and cartilage, suggesting oxidant damage may play a role in OA. We explored the effect of forced running as a surrogate for mechanical damage in a transgenic mouse with reduced ECSOD tissue binding. Transgenic mice heterozygous (Het) for the human ECSOD R213G polymorphism and 129-SvEv (wild-type, WT) mice were exposed to forced running on a treadmill for 45 min/day, 5 days/wk, over 8 wk. At the end of the running protocol, knee joint tissue was obtained for histology, immunohistochemistry, and protein analysis. Sedentary Het and WT mice were maintained for comparison. Whole tibias were studied for bone morphometry, finite element analysis, and mechanical testing. Forced running improved joint histology in WT mice. However, when ECSOD levels were reduced, this beneficial effect with running was lost. Het ECSOD runner mice had significantly worse histology scores compared with WT runner mice. Runner mice for both strains had increased bone strength in response to the running protocol, while Het mice showed evidence of a less robust bone structure in both runners and untrained mice. Reduced levels of ECSOD in cartilage produced joint damage when joints were stressed by forced running. The bone tissues responded to increased loading with hypertrophy, regardless of mouse strain. We conclude that ECSOD plays an important role in protecting cartilage from damage caused by mechanical loading.

Background We evaluated military personnel who developed dermatologic reactions suggestive of generalized vaccinia (GV) after smallpox vaccination. Methods We conducted surveillance and retrospective analysis of cases from the Vaccine Adverse Event Reporting System (a passive reporting system managed by the Centers for Disease Control and Prevention), and the military's preventive medicine channels, vaccine healthcare centers, clinical laboratory network, dermatology clinics, and pathology departments from December 2002 to December 2004. Results Of 74 cases investigated in 753,226 vaccinations, 50 (67.6%) met the case definition of possible GV (rate 66/million), 95% confidence interval (49-88/million), consistent with historically reported rates. Cases of possible GV occurred more frequently in primary vaccinees (81/million) than in those revaccinated (32/million) (relative risk 2.6, 95% confidence interval 1.2-5.9, P = .013). None met the case definition of probable or confirmed GV, including 15 with virologically negative laboratory evaluations (eg, culture, skin biopsy, or polymerase chain reaction). Limitations The methods of case collection and retrospective nature of this study are its limitations. The clinical diagnosis of possible GV was made on the basis of the authors' interpretation of clinical notes and adverse events submitted by more than 100 different providers. Only 15 of the 74 cases of possible GV had laboratory attempts for virological confirmation. Conclusion GV is still a rarely reported complication of smallpox vaccination. True GV, strictly defined, may be even less common than previously reported. We named one self-limited dermatologic manifestation confused with GV "postvaccinial nonviral pustulosis." Properly screened individuals considering smallpox vaccination may be assured most exanthemata after vaccination are benign.

Background/aim: Human tears contain hundreds of proteins that may exert a significant influence on tear film stability, ocular surface integrity, and visual function. The authors hypothesise that many of these proteins originate from the meibomian gland. This study’s aim was to begin to develop the proteomic methodology to permit the testing of their hypothesis. Methods: Meibomian gland secretions were collected from the lower eyelids of adult volunteers and placed in a chloroform-methanol mixture. Samples were partitioned in a biphasic system and non-lipid phase materials were reduced, alkylated, and trypsin digested to obtain peptides for protein identification. This peptide mixture was separated by µ-capillary reverse phase chromatography and the effluent examined by nano-electrospray MS and data dependent MS/MS. SEQUEST software was used to identify proteins from the MS/MS spectra. Results: The methodological approach to date has permitted the identification of more than 90 proteins in human meibomian gland secretions. Proteins include the α2-macroglobulin receptor, IgA α chain, farnesoid X activated receptor, interferon regulatory factor 3, lacritin precursor, lactotransferrin, lipocalin 1, lysozyme C precursor, potential phospholipid transporting ATPase IK, seven transmembrane helix receptor (also termed somatostatin receptor type 4), testes development related NYD-SP21 (also termed high affinity IgE receptor β subunit), and TrkC tyrosine kinase. Conclusions: These findings indicate that the meibomian gland secretes a number of proteins into the tear film. It is quite possible that these proteins contribute to the dynamics of the tear film in both health and disease.

The effects of an antioxidant mixture of mineral ascorbates (MA) on the state of neurons in the temporal area of the cortex and the behavior of mice subjected to bulbectomy (BE) were studied; these mice, as demonstrated previously, are characterized by deficiency of spatial memory and the development of a neurodegenerative process in brain structures showing pathological changes in Alzheimer's disease. One month after BE, there were abnormalities in the cytoarchitectonics of the temporal area of the cortex, with loss of clarity of the boundaries between its layers because of dystrophy of pyramidal neurons and foci of loss of these cells. There were sharp increases in the numbers of neurons showing pyknosis, karyolysis, and vacuolysis on the background of decreases in neuronal density. Three weeks of treatment by addition of MA to the diet prevented the degradation of spatial memory in mice after BE and protected neurons in the temporal area of the cortex from degenerative changes. These results provide evidence for the possibility of prophylaxis of neurodestructive changes of the Alzheimer's type.

This article describes a public health leadership certificate curriculum developed by the Commonwealth Public Health Training Center for employees in public health and medical trainees in primary care to share didactic and experiential learning. As part of the program, trainees are involved in improving the health of their communities and thus gain a blended perspective on the effectiveness of interprofessional teams in improving population health. The certificate curriculum includes eight one-credit-hour didactic courses offered through an MPH program and a two-credit-hour, community-based participatory research project conducted by teams of trainees under the mentorship of health district directors. Fiscal sustainability is achieved by sharing didactic courses with MPH degree students, thereby enabling trainees to take advantage of a reduced, continuing education tuition rate. Public health employee and primary care trainees jointly learn knowledge and skills required for community health improvement in interprofessional teams and gain an integrated perspective through opportunities to question assumptions and broaden disciplinary approaches. At the same time, the required community projects have benefited public health in Virginia.

Purpose: The purpose of the study is to delineate the visual prognosticators in sarcoid-associated uveitis given the current standards of care. Methods: The records of 60 patients with sarcoid-associated uveitis who were observed for at least 6 months were studied retrospectively. Multivariate regression models using the generalized estimating equations approach to adjust for the correlation between fellow eyes were applied to determine disease, patient, and treatment characteristics that altered the odds of visual rehabilitation. Results: One hundred twelve eyes of 43 women and 17 men who met the inclusion criteria were identified. Seventy-seven percent of patients were white, 15% black, and 8% of Hispanic origin. Uveitis developed in the patients at a mean age of 42 (range, 482) years. Of the 112 affected eyes, 81% had granulomatous and 15% nongranulomatous uveitis. Most patients (66%) had anterior or intermediate uveitis alone. Ninety-one percent had chronically smoldering disease; another 7% had recurrent flares, and only 1 patient had a monophasic acute course to her uveitis. Vision-threatening complications developed in many patients, including 58% in whom cystoid macular edema developed and 25% in whom media opacities developed, requiring cataract surgery or vitrectomy or both. Overall, 34% of treated eyes and 51% of patients had final visual acuities that were superior to their acuities at presentation. The factors most significantly associated with a final visual acuity of worse than 20/40 after controlling for potential confounders were as follows: delay in presentation to a subspecialist (odds ratio [OR] = 2.94, P=0.05), total duration of uveitis (OR = 1.04, P = 0.09), development of cystoid macular edema (OR = 0.37, P = 0.07) or glaucoma (OR = 4.54, P = 0.02), presence of intermediate (OR = 5.00, P = 0.01) or posterior uveitis (OR = 8.33, P = 0.04), and systemic steroid use (OR = 0.30, P = 0.03) were the parameters most strongly correlated with a lack of visual acuity improvement. Delay in presentation to a subspecialist (OR = 20.00, P = 0.01), development of glaucoma (OR = 50.00, P = 0.005), presence of intermediate (OR = 25.00, P = 0.02) or posterior uveitis (OR = 50.00, P = 0.02), black race (OR = 11.11, P = 0.02), (log) visual acuity at presentation (OR = 0.05, P = 0.0001), and use of systemic steroids (OR = 0.07, P = 0.02). Conclusion: Multivariate outcomes analysis, particularly after correcting for the correlation between fellow eyes, is a useful analytic tool for optimization of standards of care and for disease risk stratification to aid both physicians and patients.

Surgery is indicated for keratoconus when management with contact lenses fails. The authors sought to determine the relative contribution of various preoperative patient and ocular factors to the ultimate causes of contact lens failure.The records of unoperated eyes of keratoconus patients whose contact lenses were managed intensively before undergoing penetrating keratoplasty (PK) at the authors' institution between 1981 and 1990 were selected for study. Univariate and multivariate analyses were performed to identify risk factors for early contact lens failure.The records of 99 keratoconic eyes of 75 patients with an average age of 34 years and average keratometry readings of 57.5 diopters at presentation were studied. Cases had been followed for an average of 27 months before PK. The primary reasons for PK were a best-corrected visual acuity of under 20/40 (despite good contact lens fit) causing disability for the patient (43%), contact lens intolerance (32%), frequent lens displacement (13%), and significant peripheral thinning of the cornea (12%). The referral source of the patient, sex, a history of PK in the fellow eye, or of contact lens wear in either eye did not alter the relative contributions of these parameters to surgery.Poor best-corrected visual acuity at presentation, higher keratometry readings (greater than or equal to 55 D), age (greater than or equal to 40 years), and duration of disease (greater than 5 years) were significantly associated with failure due to poor functional acuity and peripheral thinning, frequently leading to surgery within the first 12 months after presentation.

to bring back the clinical and therapeutic aspects of 6 cases of DPC in the service of surgery A of the hospital of the POINT G.descriptive retrospective study of 5 years and 6 months in the service. All the patients presenting a duodéno-pancreatic malignant tumour treated by DPC with histological diagnostic confirmation were included in the study. The palliative techniques of biliary and digestive derivations were not retained.6 files of patients were collected. The average age of the patients was 63 years. The average time of consultation was 8 months. The abdominal pains, the jaundice and the cutaneous prurit were the reasons for consultation of first order. The functional signs were the cutaneous prurit and vomiting, the faded saddles (2 cases, 33.3%), and the dark urines (a case, 16,7% of the cases). The seat of pain was epigastric among 3 patients (50%), diffuse with epigastric starting point in a case, pain of the right hypochondre in one case. An epigastric mass was palpated by 4 patients (66,6%). A hepatomegaly and a large blister were palpated once (16,7% of the cases). High blood amylase rates are noted by 4 patients (66,7%). The rates of bilirubine free and total in blood were very high. The echographic image was that of a mass of the head of the pancreas and a dilation of the bile ducts will intra and extrahepatic as well as channel of Wirsung (4 cases, 66.7%). The computer tomodensitometry did not objectify local vascular invasion, hepatic metastases, or of ascite. The tomodensitometric images of the lesions were a cystic tumour of the head of the pancreas (one case), a pancreatic tumour + cholestase (one case), a tumour of the head of the pancreas with compression of duodenum (4 cases). Classes ASA II (4, 66.7%) and III (2, 33.3%) were only represented. The procedures of resection were practised according to the technique of WHIPPLE or its alternatives. The ganglionic clearing out related to the 5 classical chains. The early continuations were simple for 4 patients (66,6%). A case of parietal suppuration, a pancreatic leak (operated again at J3) and a death were recorded. The average duration of the hospital stay was 16 days. Two patients died between 0 and 3 months into postoperative, and 2 others died between the 3rd month (33,33%) and the 10th month (33,3%). The results of the histological examination were 4 cases of adenocarcinomists of the pancreas (66,6%), a adenocarcinomist inflammatory and necrotic, a fairly differentiated adenocarcinomist.the tumours of the head of the pancreas very often diagnosed at a late stage are of weak frequency in our context of exercise. The DPC is burdened with a made morbidity of pancréato-jejunal dents. The rate of survival at 5 years remains around 5%.

The purpose of this study was to test whether (1) the 3-dimensional in vivo patellofemoral kinematics and patellofemoral contact area of anterior cruciate ligament (ACL)-deficient knees are different from those of normal, contralateral knees and (2) ACL reconstruction restores in vivo patellofemoral kinematics and contact area.Ten ACL-deficient knees and twelve ACL-reconstructed knees, as well as the contralateral uninjured knees, were tested. Magnetic resonance imaging was performed at full extension and 40 degrees of flexion under simulated partial weight-bearing conditions. Six-degrees of freedom patellofemoral kinematics, patellofemoral contact area, and contact location were analyzed by use of magnetic resonance image-based 3-dimensional patellofemoral knee models.The patella in the ACL-deficient knees underwent significantly more lateral tilt during flexion (P.05) and tended to translate more laterally (P = .083) than the patella in contralateral knees. After ACL reconstruction, no kinematic parameters were significantly different from those in contralateral knees. The patellofemoral contact areas of ACL-deficient knees at both the extended and flexed positions (37 +/- 22 mm(2) and 357 +/- 53 mm(2), respectively) were significantly smaller than those of contralateral knees (78 +/- 45 mm(2) and 437 +/- 119 mm(2), respectively) (P.05). After reconstruction, the patellofemoral contact area of ACL-reconstructed knees in the extended position (86 +/- 41 mm(2)) was significantly larger (P.05) than that of contralateral knees (50 +/- 34 mm(2)), but no difference was detected in the flexed position. Reproducibility of all patellofemoral kinematic parameters, contact centroid translation, and contact area showed coefficients of variation of less than 6.8%.ACL injuries alter patellofemoral kinematics including patellar tilt and patellar lateral translation, but ACL reconstruction with hamstring or allograft restores altered patellar tilt. ACL injuries reduce the patellofemoral contact area at both the extended and flexed positions, but ACL reconstruction enlarges the patellofemoral contact area at extension and restores the normal contact area at low angles of flexion.Level III, case-control study.

To examine the effects of race and sex on bone density and geometry at specific sites within the proximal femur and lumbar spine, we used quantitative computed tomography to image 30 Caucasian American (CA) men, 25 African American (AA) men, 30 CA women, and 17 AA women aged 35-45 yr. Volumetric integral bone mineral density (BMD), trabecular BMD (tBMD), and cross sectional area were measured in the femoral neck, trochanter, total femur, and L1/L2 vertebrae. Volumetric cortical BMD (cBMD) was also measured in the femur regions of interest. Differences were ascertained using a multivariate regression model. Overall, AA subjects had denser bones than CA subjects, but there were no racial differences in bone size. Men had larger femoral necks but not larger vertebrae than women. The AA men had higher tBMD and cBMD in the femur than CA men, whereas AA women had higher femoral tBMD but not higher femoral cBMD than CA women. These data support the idea that higher hip fracture rates in women compared with men are associated with smaller bone size. Lower fracture rates in AA elderly compared with CA elderly are consistent with higher peak bone density, particularly in the trabecular compartment, and potentially lower rates of age-related bone loss rather than larger bone size.

Corneal transplants normally enjoy a high percentage of survival, mainly because the eye is an immune-privileged site. When allograft failure occurs, it is most commonly due to rejection, an immune-mediated reaction that targets the corneal endothelium. While the exact mechanism by which the endothelium is targeted is still unknown, we postulate that corneal endothelial cell loss during allograft failure is mediated by apoptosis. Furthermore, because corneal endothelial cells do not normally regenerate, we hypothesize that suppressing apoptosis in the graft endothelium will promote transplant survival. In a murine model of transplantation, TUNEL staining and confocal microscopy showed apoptosis of the graft endothelium occurring in rejecting corneas as early as 2 weeks posttransplantation. We found that bcl-xL protected cultured corneal endothelial cells from apoptosis and that lentiviral delivery of bcl-xL to the corneal endothelium of donor corneas significantly improved the survival of allografts. These studies suggest a novel approach to improve corneal allograft survival by preventing apoptosis of the endothelium.

The influence of fall orientation on femur strength has important implications for understanding hip fracture risk. A new image analysis technique showed that the strength of the femoral neck in 37 males varied significantly along the neck axis and that bending strength varied by a factor of up to 2.8 for different loading directions. Introduction: Osteoporosis is associated with decreased BMD and increased hip fracture risk, but it is unclear whether specific osteoporotic changes in the proximal femur lead to a more vulnerable overall structure. Nonhomogeneous beam theory, which is used to determine the mechanical response of composite structures to applied loads, can be used along with QCT to estimate the resistance of the femoral neck to axial forces and bending moments. Materials and Methods: The bending moment {My(θ)} sufficient to induce yielding within femoral neck sections was estimated for a range of bending orientations (θ) using in vivo QCT images of 37 male (mean age, 73 years; range, 65–87 years) femora. Volumetric BMD, axial stiffness, average moment at yield (My,avg), maximum and minimum moment at yield (My,max and My,min), bone strength index (BSI), stress-strain index (SSI), and density-weighted moments of resistance (Rx and Ry) were also computed. Differences among the proximal, mid-, and distal neck regions were detected using ANOVA. Results: My(θ) was found to vary by as much as a factor of 2.8 for different bending directions. Axial stiffness, My,avg, My,max, My,min, BSI, and Rx differed significantly between all femoral neck regions, with an overall trend of increasing axial stiffness and bending strength when moving from the proximal neck to the distal neck. Mean axial stiffness increased 62% between the proximal and distal neck, and mean My,avg increased 53% between the proximal and distal neck. Conclusions: The results of this study show that femoral neck strength strongly depends on both fall orientation and location along the neck axis. Compressive yielding in the superior portion of the femoral neck is expected to initiate fracture in a fall to the side.

To determine the effect of systemic anti-CD154 monoclonal antibody on the survival of orthotopic murine corneal transplants.BALB/c mice were used as recipients of syngeneic, multiple minor histocompatability (H)-disparate, or major histocompatibility complex MHC-mismatched corneal transplants. Recipient beds were either avascular (normal risk) or neovascularized (high risk). Mice were randomized to receive either anti-CD154 antibody or control immunoglobulin by intraperitoneal injection at surgery and once weekly after surgery. After orthotopic corneal transplantation, all grafts were evaluated for signs of rejection by slit lamp biomicroscopy over 8 weeks. The high-risk transplants were continuously observed until week 18 after the therapy was discontinued at week 8. Allospecific delayed-type hypersensitivity (DTH) was evaluated after transplantation in high-risk graft recipients. Frequency of interferon (IFN)-gamma-secreting T cells in the hosts was measured by enzyme-linked immunospot (ELISPOT) assay.In normal-risk transplantation, the 8-week survival rate improved from 25% in control mice to 88% in anti-CD154-treated hosts of minor H-disparate grafts (P = 0.0087) and from 78% in control mice to 100% in anti-CD154-treated recipients of MHC-mismatched transplants (P = 0.177). Of particular significance, in high-risk transplantation, anti-CD154 therapy dramatically enhanced the survival of both minor H- and MHC-disparate corneal transplants to 100% (P = 0.0001) and 92% (P = 0.0002), respectively. In addition, the anti-CD154-treated mice did not exhibit allospecific immunity. However, termination of anti-CD154 led to some loss in graft survival, especially among high-risk minor H-disparate grafts. The frequency of IFN-gamma-producing T cells was significantly reduced in anti-CD154-treated hosts.Continuous suppression of the CD40-CD154 costimulatory pathway promotes the acceptance of corneal transplants, regardless of the degree of allodisparity or preoperative risk. The beneficial effect of anti-CD154 treatment may be due in part to inhibition of Th1-mediated responses.

We used a murine model of orthotopic corneal transplantation to determine whether host deficiency in ICAM-1 promotes survival of corneal grafts with different degrees of allodisparity.ICAM-1-/- and wild-type C57BL/6 (ICAM-1+/+) received corneal grafts from the following strains of mice: BALB/c (fully mismatched), BALB.b (mismatched at multiple minor H only), or B10.D2 [including major histocompatibility complex (MHC) mismatch]. Graft rejection, induction of allospecific delayed-type hypersensitivity (DTH) responses, and leukocytic infiltration of grafts were measured.There were no differences in long-term survival of allografts that were either fully mismatched or had only minor H disparity in ICAM-1+/+ vs. ICAM-1-/-hosts. However, whereas B10.D2 grafts were accepted in only 58% of the ICAM-1+/+ hosts, graft survival in ICAM-1-/- recipients was 100% (P=0.006). Moreover, none of the ICAM-1-/- mice receiving B10.D2 grafts developed allospecific DTH.Prolonged survival seen in MHC-mismatched grafts in ICAM-1-/- mice, along with a suppressed DTH response to donor alloantigens after transplantation, suggest that ICAM-1 is associated with recipient sensitization to MHC alloantigens.

The purpose of this study was to determine whether the chronic use of antiandrogen medications leads to meibomian gland dysfunction, altered lipid profiles in meibomian gland secretions, decreased tear film stability, and evaporative dry eye. Subjects taking antiandrogen therapy for prostatic indications, as well as age-related controls, were asked to complete a questionnaire that assessed dry eye symptoms and then were given a complete anterior segment examination. Moreover, meibomian gland secretions were obtained from each eye and analyzed by high-performance liquid chromatography/mass spectrometry for the relative content of cholesterol, cholesterol esters, wax esters, diglycerides, triglycerides, and specific molecular species in the diglyceride fraction. Our results demonstrate that patients taking antiandrogen treatment, compared with age-related controls, had a: 1) significant increase in the frequency of appearance of tear film debris, an abnormal tear film meniscus, irregular posterior lid margins, conjunctival tarsal injection, and orifice metaplasia of the meibomian glands; 2) significant increase in the degree of ocular surface vital dye staining; 3) significant decrease in the tear film breakup time and quality of meibomian gland secretions; and 4) significant increase in the frequency of light sensitivity, painful eyes, and blurred vision. In addition, the use of antiandrogen pharmaceuticals was associated with significant changes in the relative amounts of lipids in meibomian gland secretions. Our findings indicate that chronic androgen deficiency is associated with meibomian gland dysfunction and dry eye.

Topical treatment with interleukin 1 receptor antagonist (IL-1ra) can promote corneal allograft survival by suppressing induction of allodestructive immunity. The purpose of these experiments was to determine whether IL-1ra could also promote induction of allo-protective tolerogenic pathways, including anterior chamber-associated immune deviation (ACAID), which has been shown to participate in long-term survival of corneal transplants.Corneal buttons from BALB/c (syngeneic) or C57BL/6 (fully mismatched allogeneic) mice were orthotopically grafted onto BALB/c recipients. Topical IL-1ra or vehicle alone was applied to grafts three times daily. Donor-specific ACAID was measured in allogeneic grafted mice at 4 and 8 weeks after transplantation by ear-challenging grafted hosts with donor-derived splenocytes 1 week after SC immunization. In separate experiments, grafted mice were treated for 4 weeks before injecting ovalbumin (OVA) into their anterior chambers to determine their capacity to induce antigen-specific ACAID.Treatment with IL-1ra did not promote, or inhibit, induction of donor-specific ACAID compared with vehicle-treated controls at either the early or late time points studied. However, IL-1ra treatment after transplantation led to significantly earlier restoration of the grafted eyes' capacity for inducing ACAID to soluble antigen (OVA).Promotion of OVA-specific ACAID by IL-1ra suggests that suppression of IL-1-mediated mechanisms contributes to recovery of the anterior segment's immunosuppressive microenvironment at least 1 month earlier than would otherwise be seen after corneal transplantation. However, IL-1ra treatment does not alter induction of donor-specific ACAID after transplantation, suggesting that its anti-inflammatory activities do not lead to an ACAID-inducing signal per se. This suggests that IL-1ra promotes graft survival almost exclusively by virtue of suppressing inflammation and not by directly promoting tolerance or antigen-specific regulatory pathways.

To evaluate the differential gene expression of chemokines after corneal transplantation and to determine the chemokines associated with allograft rejection.Orthotopic mouse corneal transplantation was performed in two fully mismatched-strain combinations using C57BL/6 (H-2b) and BALB/c (H-2d) mice as recipients and BALB/c and C57BL/6 mice as donors. Normal nonsurgical eyes served as negative control specimens and syngeneic transplants (isografts) as control specimens for the alloimmune response. Chemokine gene expression in accepted and rejected allografts and appropriate control specimens was determined by a multiprobe RNase protection assay system.In eyes with rejected allografts, there was overexpression of regulated on activation normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, MIP-2, and monocyte chemotactic protein (MCP)-1 in both C57BL/6 and BALB/c recipients. In addition, C57BL/6 eyes with rejected allografts expressed very high levels of interferon-gamma-inducible protein of 10 kDa (IP-10) mRNA, in contrast to BALB/c eyes with rejected allografts, in which IP-10 expression remained very low. In contrast, lymphotactin gene expression increased only slightly in rejected allografts, and eotaxin mRNA, which was also detected in normal eyes, remained unchanged among isograft and allograft groups. T-cell activation gene (TCA)-3 mRNA was not detected in any of the assayed eyes.Increased expression of mRNA for select chemokines of the CXC (alpha) and CC (beta) families is associated with corneal allograft rejection. Significantly elevated IP-10 gene expression in high-rejector C57BL/6, but not in low-rejector BALB/c, hosts suggests that differential activation of chemokines may be related to differences in alloimmune reactivity observed among different murine strains.

To determine the role of tumor necrosis factor-alpha (TNF-alpha) receptor (TNFR) function in corneal allograft immunology.Animals with gene-targeted deficiency in TNFR-I (p55-/-), TNFR-II (p75-/-), or combined TNFR-I/TNFR-II deficiency (p55-/-p75-/-) and their wild-type controls were used as recipients of fully-mismatched (BALB/c; n=88) or multiple minor alloantigen-mismatched (BALB.b; n=62) orthotopic corneal transplants to determine the effect of selective deficiency in one or both TNF-alpha receptors on corneal allograft survival. Grafted recipients were followed biomicroscopically for signs of rejection, and survival data were analyzed by the Kaplan-Meier method.There was no discernible difference in survival of fully-mismatched BALB/c corneal grafts in p55-/- (n=12; P=0.76) or in double-knockout p55-/-p75-/- (n=13; P=0.41) as compared with wild-type C57BL/6.129 hosts. However, the survival of BALB/c allografts was lower in p75-/- (n=10; median survival 20 days) as compared with control C57BL/6 (n=30; median survival 30 days) hosts (P=0.02). In contrast, there was no discernible effect in survival of minor alloantigen-disparate BALB.b corneal grafts in p75-/- (n=13; P=0.95) or in combined p55-/-p75-/-(n=10; P=0.17) hosts as compared with C57BL/6 (n=9) and C57BL/6.129 (n=10) wild-type controls, respectively. However, there was a profound enhancement in the survival of BALB.b allografts in p55-/- recipients (n= 10; median survival 35 days) as compared to wild-type C57BL/6.129 (n=10; median survival 25 days) controls (P0.01).Our data suggest that the two TNF-alpha receptors largely play discrete roles in mediating rejection of murine corneal allografts. TNFR-I (p55) function seems to be integral to the rejection of minor-disparate grafts, and its selective suppression leads to enhancement of allograft survival. In contrast, TNFR-II (p75) function appears to be associated with enhanced survival of major histocompatibility complex-disparate allografts. The combined deletion of TNFR functionality in p55-/-p75-/- confers no net advantage or disadvantage to major histocompatibility complex or minor alloantigen-disparate grafts.

To investigate the expression of cell-adhesion molecules on corneolimbal and neovascular endothelium and the associated leukocyte infiltration in an experimental model of inflammatory corneal neovascularization (NV).Corneal NV was induced in BALB/c mice by placement of nylon sutures. Interleukin-1 receptor antagonist (IL-1ra) was used topically to determine whether suppression of IL-1 could affect adhesion molecule expression and leukocytic infiltration. At set time points, corneal samples were analyzed immunohistochemically for expression of P-selectin, E-selectin, intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, and platelet- endothelial adhesion molecule (PECAM)-1. Leukocytic infiltration at different time points was quantified histologically. In companion experiments mice deficient in ICAM-1 were investigated to determine the functional relevance of this molecule in corneal leukocyte infiltration.Significant enhanced expression of ICAM-1 was detected on the corneolimbal vascular endothelium as early as 8 hours and on the newly formed corneal NV by day 3, and treatment with IL-1ra led to significant suppression of this expression. IL-1ra-induced suppression of ICAM-1 expression was accompanied by a profound decrease in corneal leukocytic infiltration by 44.6% at day 1 (P0.003), 71.8% at day 3 (P0.001), 60.1% at day 7 (P0.001), and 63.8% at day 14 (P0.001), compared with control corneas. Similarly, in ICAM-1 knockout mice, the corneal leukocytic infiltration was 50.3%, 52.9%, and 36.4%, compared with wild-type control animals on day 1 (P0.001), day 7 (P0.005), and day 14 (P0.001), respectively. Expression of PECAM-1 was constitutively present on perilimbal vascular endothelium and had no response to IL-1ra treatment. No significant expression of P-selectin, E-selectin, or VCAM-1 was detected in this experimental model.These results suggest that leukocytic infiltration in this model of inflammatory corneal NV is closely associated with ICAM-1 expression, and that topical IL-1ra displays corneal anti-inflammatory effects, largely by suppressing ICAM-1 expression on vascular endothelial cells.

The current investigators have shown that androgen treatment suppresses inflammation and stimulates the function of lacrimal glands in mouse models of Sjögren's syndrome. Recently, others have hypothesized that androgen insufficiency induces an autoimmune process in lacrimal tissue, leading to inflammation, a Sjögren's syndrome-like pathology, and aqueous tear deficiency. The purpose of the present study was to test this hypothesis.Lacrimal glands were obtained from adult testicular feminized (Tfm) and control mice; castrated rats, guinea pigs, and rabbits; and castrated rats without anterior or whole pituitary glands and were processed for histology and image analysis. Tear volumes were measured in mice, in patients taking antiandrogen medications, and in age-matched human control subjects.Tfm mice, which are completely resistant to classical androgen action, did not have increased lymphocyte infiltration in their lacrimal glands or decreased tear volumes. No inflammation was evident in lacrimal tissues of male or female rats, guinea pigs, or rabbits 12 to 31 days after castration, no inflammation existed in rat lacrimal glands 15 to 31 days after orchiectomy and pituitary removal, and no aqueous tear deficiency was apparent in patients receiving antiandrogen therapy.Androgen deficiency may promote the progression of Sjögren's syndrome and its associated lacrimal gland inflammation, meibomian gland dysfunction, and severe dry eye. However, androgen insufficiency alone does not cause lacrimal gland inflammation, a Sjögren's syndrome-like pathology in lacrimal tissue, or aqueous tear deficiency in nonautoimmune animals and humans.

Langerhans cells (LC) belong to the dendritic cell family and mediate Ag presentation in the cornea and ocular surface. Under normal physiological conditions, the central cornea is devoid of LC. Centripetal migration of LC plays a critical role in promoting immunoinflammatory responses in the eye including allograft rejection and herpetic keratitis. The molecular mechanisms responsible for ocular LC migration are poorly understood. To examine whether TNF-alpha mediates corneal LC migration and to establish the interaction of IL-1 and TNF-alpha in regulating LC migratory capacity, we utilized gene-targeted knockout mice lacking IL-1 receptor I (IL-1RI-/-), TNF receptor I (p55-/-), TNF receptor II (p75-/-), or both (p55-/-p75-/-). LC migration was induced by thermal cautery or cytokine injection and enumerated by an immunofluorescence assay. Migration of LC after cauterization and TNF-alpha injection was significantly depressed in both p55-/- and p75-/- mice. Similarly, in the first 72 h after intracorneal injection of IL-1alpha, LC migration was reduced in p55-/-, p75-/-, and p55-/-p75-/- mice. In contrast, injection of TNF-alpha in IL-1RI-/- mice led to normal migration of corneal LC indistinguishable from wild-type controls. These results suggest that the IL-1 induction of corneal LC migration is largely mediated by TNFR function, whereas TNF-alpha induction of LC migration is independent of IL-1RI activity. Moreover, the data suggest that both p55 and p75 signaling pathways are important in mediating LC migration in the cornea.

The purpose of the study is to describe graft and visual outcomes of penetrating keratoplasty among young children with Peters anomaly and associated mesenchymal dysgeneses.The design was a multicenter retrospective analysis of the indications and outcome in pediatric keratoplasty.The records of all children aged 12 years and younger who underwent penetrating keratoplasty for mesenchymal dysgenesis between January 1975 and May 1993 at the participating centers were reviewed.The data were analyzed regarding graft survival and postoperative visual acuity.Forty-seven corneal transplants in 36 eyes of 29 patients with mesenchymal dysgenesis were studied. The majority of eyes operated on (30) had Peters anomaly (83%). Patients' mean age at the time of keratoplasty was 7 months. After a mean follow-up period of 38 months, 61% of eyes retained full graft clarity. One and 3-year survival rates were 79% (95% confidence interval [CI] = 65%-93%) and 62% (95% CI = 45%-79%), respectively. Postoperative corneal ulcers/nonhealing epithelial defects (P = 0.03), and additional noncorneal surgical procedures at the time of transplantation (P = 0.05) were associated with graft failure. Provision of postoperative optical aids (P = 0.01) was associated with better postoperative visual acuity levels.Penetrating keratoplasty for Peters anomaly and related mesenchymal dysgeneses in young children has a reasonable chance of success during the critical years of visual maturation and is associated with satisfactory visual results in one third to half the cases. The data suggest that complicated cases requiring additional surgical procedures have a worse prognosis.

The purpose of this study was to delineate the patient and surgical factors that contribute to the development of corneal neovascularization (CNV) after penetrating keratoplasty (PK). Thirty-six eyes of 36 patients with no antecedent CNV were enrolled in the study. Grafts were sutured to the host with 16 10-0 nylon sutures with the knots buried alternately in either the host or donor corneal stroma. Multiple perioperative factors were recorded for each patient, and at each postoperative visit systematic corneal drawings were used to follow the development of neovascularization. The stroma adjacent to each suture of each graft was given a neovascularization score based on the extent of vessel growth toward the wound interface. Univariate and multivariate analyses were performed, including generalized estimating equations logistic regression where each eye is considered a cluster of observations. Thirty-four patients without preoperative CNV or inflammation were followed prospectively for 6-9 (mean, 7) months after PK. Fourteen eyes (41%) developed some degree of CNV. Indication for keratoplasty, age, gender, phakic status, and size of donor button were not risk factors for CNV development. The most significant risk factor identified for any degree of CNV was placement of the suture knot in the host stroma (p = 0.00007), with the overall relative risk of CNV associated with these knots over 2 (95% confidence interval, 1.1-4.2). Furthermore, the mean recipient size in eyes with postoperative CNV was larger than eyes that did not develop neovascularization (p = 0.015), and active blepharitis was associated with a fivefold increase in the risk of developing CNV to the wound edge (p = 0.008). Embedding suture knots in the host stroma, active blepharitis, and a large recipient bed are significantly associated with postkeratoplasty CNV.

A 3-year retrospective study on the risk factors of positive donor rim cultures in penetrating keratoplasty was performed. One thousand and ninety-seven consecutive donor rim cultures were reviewed from the period between June 1990 and October 1993 to determine the rate of culture positivity. The sex, age, diabetes status, use of respirator at time of death, cause of death, harvesting technique, storage time, and corneal storage medium utilized for the donors with positive donor rim culture were compared to those for 100 randomly selected culture negative donor controls. Logistic analysis was performed to eliminate confounding effects. Forty-six of the 1,097 (4.19%) donor rim cultures were positive. We found an association between the in situ technique for donor harvesting and culture negativity (p = 0.03). None of the other donor characteristics was associated with culture positivity. None of the 46 recipients who received the positive culture corneas developed endophthalmitis. In situ cornea harvesting promotes less contamination than enucleation and enriched gentamicin and streptomycin storage medium may further decrease donor rim culture positivity.

A multicenter study was undertaken to delineate the indications for and outcome of pediatric keratoplasty.The authors retrospectively studied 164 grafts in 131 eyes of 108 children younger than 12 years of age, with an average follow-up of 45 months. Multivariate linear and logistic regression was performed to evaluate potential risk factors for poor visual outcome and graft failure. Graft survival was depicted in terms of the Kaplan-Meier survival curve.Corneal opacities were grouped into three diagnostic categories: congenital (64%), traumatic (17%), and acquired nontraumatic (19%) opacities. Overall graft survival was 80% at 12 months and 67% at 24 months postoperatively. There was no significant difference in retention of clarity among diagnostic groups. Vitrectomy-lensectomy, regrafts, and postoperative complications were associated significantly with poor allograft survival. Eighteen percent of all eyes had worse vision at the time of the last visit than preoperatively. Amblyopia treatment was the only independently significant prognosticator for visual improvement after surgery. Timing of keratoplasty was not demonstrated to be associated with visual outcome. Visual acuity in 33% of eyes that could be quantified was better than 20/200 at the last visit, whereas 62% of eyes retained full graft clarity.The authors conclude that keratoplasty can be successful in most children, especially when combined with appropriate amblyopia management.

A population-based survey of 1136 subjects aged 40 years and older was conducted in a rural valley of Kentucky to determine the nature and extent of visual disability in an underserved area of rural America. Data on corrected visual acuity and ocular history, along with demographic, socioeconomic, and health care utilization parameters, were gathered. Those subjects with an acuity below 20/60 in either eye underwent a comprehensive ophthalmologic examination. The prevalence of binocular blindness (acuity worse than 20/400 in the better eye) was 0.44% and of monocular blindness (acuity worse than 20/400 in one eye) was 3.3%, approximately twice the national rates. The chief cause of bilateral visual impairment was macular degeneration among men and cataract among women. Cataract, trauma, and amblyopia were the major causes of monocular visual impairment in both sexes. Risk factor analysis revealed younger age, higher education, active employment, access to a health care facility, and comprehensive health insurance coverage to be inversely associated with visual impairment.

To review from a historical perspective the recent epidemic of Acanthamoeba keratitis and its association with the use of contact lenses and to provide a summary of recent techniques that have allowed earlier diagnosis and treatment.The authors reviewed available literature on Acanthamoeba keratitis from 1973 to the present, with emphasis on the history of the epidemic and its association with contact lenses, identification of risk factors, preventive measures, and current diagnostic techniques. We also estimated the annual incidence of Acanthamoeba keratitis during 1985 through 1987 from available data.Before the popularization of soft-contact-lens wear, Acanthamoeba keratitis was extremely rare; however, an epidemic began in the early 1980s, and the number of cases increased dramatically beginning in 1984. By 1985, the association of this infection with the use of contact lenses was firmly established, and in 1987, the infection was shown to occur more commonly among men, as well as in contact-lens wearers who failed to disinfect their lenses as frequently as recommended, swam while wearing lenses, or used homemade instead of commercially prepared saline solution. Adoption of "disposable" contact lenses in the late 1980s did not decrease the risk of Acanthamoeba keratitis, and concerns remain regarding the effectiveness of some contact-lens disinfectants; however, recent advances in diagnosis and treatment have improved the prognosis. The annual incidence during 1985 through 1987 was conservatively estimated at 1.65 to 2.01 cases per million contact-lens wearers. It is unclear whether the incidence is declining.Acanthamoeba keratitis has now been recognized worldwide, and there are clear associations of this infection with improper contact-lens hygiene, particularly contact with water. Recent methods allow earlier diagnosis and thus improved outcomes. The epidemic provides a valuable lesson on how a new technology can be associated with unforeseen complications and exemplifies how rapid dissemination of epidemiologic information can aid in controlling an emergent epidemic.

The retrograde barium enema is considered to be contraindicated in patients with acute colitis because of the risk of precipitating toxicity. The purpose of this study was to investigate the antegrade evaluation of the colon in such patients. Thirteen patients were examined by antegrade barium study. The right and left colon to the level of the descending colon-sigmoid junction were well seen in all (100%), the sigmoid in 77% and the rectum in 54%. Excellent correlation between the extent of disease seen on antegrade study and retrograde enema, endoscopy, and surgery was achieved. The antegrade study was found to be a safe and effective study in patients with acute colitis.

Central administration of corticotropin releasing factor (CRF) in rats produces pituitary-adrenal activation and a variety of "anxiogenic-like" effects. The present study was designed to explore the contribution of the peripheral pituitary-adrenocortical axis in mediating these CRF responses. Intraventricularly administered CRF produced suppression of responding in the conflict test and a marked locomotor activation. Neither behavioral effect was altered by the prior administration of dexamethasone in a dose that blocked pituitary-adrenal activation to CRF. These results support the hypothesis that behavioral effects of CRF are mediated by its action at central sites and not via an action on the pituitary-adrenocortical system.