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Diabetic retinopathy (DR) remains one of the leading risk factors and causes of blindness worldwide. Tight metabolic and blood pressure control has been shown to significantly decrease the risk of development as well as progression of retinopathy and remains a cornerstone in the medical management of DR. Laser photocoagulation and vitrectomy are important tools for preventing severe visual loss from sight-threatening DR and its complications. New pharmacological therapies to target the underlying biochemical mechanisms that cause DR are also being evaluated in order to overcome the limitations of current treatment modalities. In this context, the role of protein kinase C inhibitors, intravitreal injections of steroids, vascular endothelial growth factor inhibitors, angiotensin converting enzyme inhibitors such as candesartan, and growth hormone inhibitors is promising. Although treatment can help prevent blindness in a majority of cases, the key variable in the success of therapy lies in identifying patients with retinopathy before their vision is affected. This calls for timely eye examination of diabetic patients. The present article is a comprehensive review of DR with special emphasis on its pathophysiology and management aspects.

This study investigated the mechanisms of traumatic rupture of the aorta (TRA). Eight unembalmed human cadavers were tested using various dynamic blunt loading modes. Impacts were conducted using a 32-kg impactor with a 152-mm face, and high-speed seatbelt pretensioners. High-speed biplane x-ray was used to visualize aortic motion within the mediastinum, and to measure deformation of the aorta. An axillary thoracotomy approach was used to access the peri-isthmic region to place radiopaque markers on the aorta. The cadavers were inverted for testing. Clinically relevant TRA was observed in seven of the tests. Peak average longitudinal Lagrange strain was 0.644, with the average peak for all tests being 0.208 +/- 0.216. Peak intraluminal pressure of 165 kPa was recorded. Longitudinal stretch of the aorta was found to be a principal component of injury causation. Stretch of the aorta was generated by thoracic deformation, which is required for injury to occur. The presence of atherosclerosis was demonstrated to promote injury. The isthmus of the aorta moved dorsocranially during frontal impact and submarining loading modes. The aortic isthmus moved medially and anteriorly during impact to the left side. The results of this study provide a better understanding of the mechanisms associated with TRA, and can be used for the validation of finite element models developed for the examination and prediction of TRA.

To examine the effects of an auricular prosthesis on sound levels at the entrance of the ear canal by measuring the auricular prosthesis transfer function (APTF) and to determine the effect of the prosthesis on speech recognition in noisy hearing conditions.Eight prostheses were used to measure the APTF. A microphone at the entrance of the ear canal measured sound pressure levels with the prosthesis present or absent while the head was rotated 360 degrees at 30 degrees increments. The Hearing in Noise Test was modified by the APTF to simulate the absence of an auricular prosthesis. Speech recognition was measured by testing 11 subjects with the unmodified Hearing in Noise Test and the modified Hearing in Noise Test.The APTF changed with the head's position relative to the speaker. The mean (SD) maximal gain provided by an auricular prosthesis was 8.1 (2.7) dB at 4.6 (1.0) kHz and 9.7 (1.7) dB at 11.5 (0.9) kHz at 0 degrees rotation. During speech testing, the auricular prosthesis improved the mean (SD) signal to noise ratio by 1.7 (1.7) dB at 0 degrees (P.001), 0.9 (2.2) dB at 90 degrees (P=.04), and 0.5 (2.3) dB at 180 degrees (P=.52).The acoustic gain provided by an auricular prosthesis increases speech recognition in noisy environments. Auricular prostheses not only restore aesthetics but also improve hearing.

Objective: To evaluate if serum levels of candidate ovarian cancer biomarkers vary with individual characteristics of healthy women who are likely candidates for an ovarian cancer screening program. Methods: We analyzed serum CA125, mesothelin, and HE4 levels in a sample of 155 healthy postmenopausal women at increased risk for developing ovarian cancer based on personal and family cancer history. Information on reproductive, family and medical histories, lifestyle factors, and anthropometry was collected by self-report. Twenty-two factors were examined using univariate and multiple linear regression models for the three biomarker levels. Results: In the multivariate models, CA125 levels were significantly higher in women who had used talcum powder (P = 0.02) and were lower in women who were parous (P = 0.05). Mesothelin levels were significantly higher in older women (P = 0.01) and lower in heavier women (P = 0.03). HE4 levels were higher in older women (P = 0.001) and in women who began menstruating at an older age (P = 0.03). Conclusions: CA125, mesothelin, and HE4 levels in healthy, postmenopausal women at increased risk for ovarian cancer are significantly associated with a few ovarian cancer risk factors. Since the effects of these personal characteristics on these serum markers are not large, their incorporation in screening algorithms may be unnecessary. This is true especially if a longitudinal algorithm is used because the marker level at the previous screen reflects personal characteristics such as age, body mass index, and age of menarche. Understanding the influence of personal factors on levels of novel early detection markers in healthy, unaffected women may have clinical utility in interpreting biomarker levels. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2480–7)

Objective: The additional impact of development of acute lung injury on mortality in severely-injured trauma patients beyond baseline severity of illness has been questioned. We assessed the contribution of acute lung injury to in-hospital mortality in critically ill trauma patients. Design: Prospective cohort study. The contribution of acute lung injury to in-hospital mortality was evaluated in two ways. First, multivariable logistic regression models were used to test the independent association of acute lung injury with in-hospital mortality while adjusting for baseline confounding variables. Second, causal pathway models were used to estimate the amount of the overall association of baseline severity of illness with in-hospital mortality that is attributable to the interval development of acute lung injury. Setting: Academic level 1 trauma center. Patients: Two hundred eighty-three critically ill trauma patients without isolated head injury and with an Injury Severity Score ≥16 were evaluated for development of acute lung injury in the first 5 days after trauma. Measurements and Main Results: Of the 283 patients, 38 (13.4%) died. The unadjusted mortality rate was nearly three-fold greater in the acute lung injury group (23.9% vs. 8.4%; odds ratio = 3.36; 95% confidence interval 1.67-6.77; p = 0.001). Acute lung injury remained an independent risk factor for death after adjustment for age, baseline Acute Physiologic and Chronic Health Evaluation III score, Injury Severity Score, and blunt mechanism of injury (odds ratio = 2.87; 95% confidence interval 1.29-6.37; p = 0.010). Forty percent of the total association of the baseline Acute Physiologic and Chronic Health Evaluation III score with mortality occurred via an indirect association through acute lung injury, and the remaining 60% via a direct effect. Conclusions: Development of acute lung injury in critically ill trauma patients without isolated head injury contributes independently to in-hospital mortality beyond baseline severity of illness measures. In addition, a significant portion of the association between baseline illness severity and risk of death in these patients might be explained by the interval development of acute lung injury.

To investigate the short-term outcomes of 25-gauge pars plana vitrectomy (PPV) in 18 cases of complicated retinal detachment requiring silicone oil tamponade.In this retrospective noncomparative review, the primary outcome measures included postoperative anatomical status, preoperative and postoperative visual acuity and intraocular pressure (IOP), cataract progression, development of keratopathy, and other complications. The average follow-up was 5 months (142 days).Thirteen (72.2%) of 18 patients had attachment postoperatively. There was no difference between preoperative visual acuity and visual acuity at the end of follow-up (P = 0.851). One patient (5.6%) who underwent concomitant penetrating keratoplasty had hypotony (IOP,6 mmHg) postoperatively and until the end of follow-up. Ocular hypertension in two patients was controlled with antiglaucoma drops. Five (55.6%) of 9 patients who were initially phakic underwent cataract extraction or had documented cataract progression. There were no cases of keratopathy or endophthalmitis. Four patients had intraocular or retinal hemorrhage. Two patients developed significant macular epiretinal membranes, and one developed a parafoveal hole.Sutureless 25-gauge PPV with silicone oil is a relatively safe and comparable alternative to 20-gauge PPV with silicone oil for repair of complicated retinal detachment.

The objective of the study was to evaluate outcomes during the first year of a robotic surgery program in gynecologic oncology.We studied the initiation of a robotic surgery program with prospective data collection, including intraoperative times, estimated blood loss (EBL), length of stay (LOS), lymph node yields, and complications. Patients were compared with historical and contemporary open staging surgery for endometrial cancer.One hundred eighteen patients underwent robotic surgery (mean age 52.5 years, body mass index of 26.3 kg/m(2), hospital stay of 32.4 hours), with 8 major and 13 minor complications. Compared with open endometrial staging (n = 131), the robotic procedure (n = 25) was longer (283 vs 139 minutes, P.0001), had less blood loss (66.6 vs 197.6 mL, P.0001), and had shorter length of stay (40.3 vs 127 hours, P.0001) with comparable node yields (17.5 vs 13.1, P = .1109).Robotic surgery is feasible in gynecologic oncology and facilitated a dramatic expansion in our minimally invasive surgical practice. Despite longer operative times, EBL and LOS are reduced and lymph node yields are comparable.

Primary graft dysfunction (PGD), a form of acute lung injury occurring within 72 h following lung transplantation, is characterized by pulmonary edema and diffuse alveolar damage. We hypothesized that higher concentrations of intercellular adhesion molecule-1 (ICAM-1) and von Willebrand factor (vWF) would be associated with the occurrence of PGD. A total of 128 lung transplant recipients among 7 lung transplant centers were enrolled in a multicenter, prospective, cohort study. Blood specimens were collected preoperatively and at 6, 24, 48 and 72 h following lung transplantation. The primary outcome was Grade 3 PGD at 72 h after transplant. Logistic regression and generalized estimating equations (GEE) were used to analyze plasma ICAM-1 and vWF. At each postoperative timepoint, mean plasma ICAM-1 concentrations were higher for patients with PGD versus no PGD. The GEE contrast estimate for the association of plasma ICAM-1 with PGD was 107.5 ng/mL (95% CI 38.7, 176.3), p = 0.002. In the multivariate analyses, this finding was independent of all clinical variables except pulmonary artery pressures prior to transplant. There was no association between plasma vWF levels and PGD. We conclude that higher levels of plasma ICAM-1 are associated with PGD following lung transplantation.

High-speed biplane x-ray and neutral density targets were used to examine brain displacement and deformation during impact. Relative motion, maximum principal strain, maximum shear strain, and intracranial pressure were measured in thirty-five impacts using eight human cadaver head and neck specimens. The effect of a helmet was evaluated. During impact, local brain tissue tends to keep its position and shape with respect to the inertial frame, resulting in relative motion between the brain and skull and deformation of the brain. The local brain motions tend to follow looping patterns. Similar patterns are observed for impact in different planes, with some degree of posterior-anterior and right-left symmetry. Peak coup pressure and pressure rate increase with increasing linear acceleration, but coup pressure pulse duration decreases. Peak average maximum principal strain and maximum shear are on the order of 0.09 for CFC 60 Hz data for these tests. Peak average maximum principal strain and maximum shear increase with increasing linear acceleration, coup pressure, and coup pressure rate. Linear and angular acceleration of the head are reduced with use of a helmet, but strain increases. These results can be used for the validation of finite element models of the human head.

We have entered a new era of genomics in biomedical research with the availability of genome-wide sequences and expression data, resulting in the identification of a huge number of novel reproductive genes. The challenge we are facing today is how to determine the function of those novel and known genes and their roles in normal reproductive physiology, such as gamete production, pregnancy and fertilization, and the disease physiology such as infertility, spontaneous abortion and gynecological cancers. Mouse genetics has contributed tremendously to our understanding of the genetic causes of human diseases in the past decades. The establishment of mouse mutations is an effective way to understand the function of many reproductive proteins. One of the fast-growing mouse mutagenesis technologies—gene trap mutagenesis—represents a cost-effective way to generate mutations because of the public availability of mouse embryonic stem (ES) cell lines carrying insertional mutations and the continuing expansion of those ES gene trap cell lines. We review here the gene trapping technology and in particular examine its efficacy in generating mouse mutations for reproductive research. Even with the existing gene trap cell lines, many of the genes important for reproductive function through traditional knockout and chemical mutagenesis have been trapped, demonstrating gene trapping’s efficacy in mutating genes involved in reproductive development. Comparing genes expressed in specific reproductive sub-cellular organelles and in the entire testis and ovary with gene trap lines in the International Gene Trap Consortium (IGTC) database, we could identify a significant portion of those genes as having been trapped, representing a great resource for establishing mouse models for reproductive research. Establishment and analysis of these mouse models, for example, could help with identifying genetic abnormalities underlying male infertility and other reproductive diseases.

Aortic injuries during blunt thoracic impacts can lead to life threatening hemorrhagic shock and potential exsanguination. Experimental approaches designed to study the mechanism of aortic rupture such as the testing of cadavers is not only expensive and time consuming, but has also been relatively unsuccessful. The objective of this study was to develop a computer model and to use it to predict modes of loading that are most likely to produce aortic ruptures. Previously, a 3D finite element model of the human thorax was developed and validated against data obtained from lateral pendulum tests. The model included a detailed description of the heart, lungs, rib cage, sternum, spine, diaphragm, major blood vessels and intercostal muscles. However, the aorta was modeled as a hollow tube using shell elements with no fluid within, and its material properties were assumed to be linear and isotropic. In this study fluid elements representing blood have been incorporated into the model in order to simulate pressure changes inside the aorta due to impact. The current model was globally validated against experimental data published in the literature for both frontal and lateral pendulum impact tests. Simulations of the validated model for thoracic impacts from a number of directions indicate that the ligamentum arteriosum, subclavian artery, parietal pleura and pressure changes within the aorta are factors that could influence aortic rupture. The model suggests that a right-sided impact to the chest is potentially more hazardous with respect to aortic rupture than any other impact direction simulated in this study. The aortic isthmus was the most likely site of aortic rupture regardless of impact direction. The reader is cautioned that this model could only be validated on a global scale. Validation of the kinematics and dynamics of the aorta at the local level could not be done due to a lack of experimental data. It is hoped that this model will be used to design experiments that can reproduce field relevant aortic ruptures in the laboratory. Only after such experiments have been run, can local validation be examined and the model judged to be acceptable or unacceptable.

S-nitrosothiol compounds are important mediators of NO signalling and can give rise to various redox derivatives of NO: nitrosonium cation (NO+), nitroxyl anion (NO−) and NO• radical. Several enzymes and transporters have been implicated in the intracellular delivery of NO from S-nitrosothiols. In the present study we have investigated the role of GPx (glutathione peroxidase), the L-AT (L-amino acid transporter) system and PDI (protein disulfide-isomerase) in the delivery of NO redox derivatives into human platelets. Washed human platelets were treated with inhibitors of GPx, L-AT and PDI prior to exposure to donors of NO redox derivatives (S-nitrosoglutathione, Angeli's salt and diethylamine NONOate). Rapid delivery of NO-related signalling into platelets was monitored by cGMP accumulation and DAF-FM (4-amino-5-methylamino-2′7′-difluorofluorescein) fluorescence. All NO redox donors produced both a cGMP response and DAF-FM fluorescence in target platelets. NO delivery was blocked by inhibition of PDI in a dose-dependent manner. In contrast, inhibition of GPx and L-AT had only a minimal effect on NO-related signalling. PDI activity is therefore required for the rapid delivery into platelets of NO-related signals from donors of all NO redox derivatives. GPx and the L-AT system appeared to be unimportant in rapid NO signalling by the compounds used in the present study. This does not, however, exclude a possible role during exposure of cells to other S-nitrosothiol compounds, such as S-nitrosocysteine. These results further highlight the importance of PDI in mediating the action of a wide range of NO-related signals.

Traumatic rupture of the aorta (TRA) is an important transportation-related injury. This study investigated TRA mechanisms using in situ human cadaver experiments. Four quasi-static tests and one dynamic test were performed. The quasi-static experiments were conducted by perturbing the mediastinal structures of the cadavers. The mechanisms investigated included anterior, superior, and lateral displacement of the heart and aortic arch. The resulting injuries ranged from partial tears to complete transections. All injuries occurred within the peri-isthmic region. Intimal tears were associated with the primary injuries. The average failure load and stretch were 148 N and 30 percent for the quasi-static tests. This study illustrates that TRA can result from appropriate application of nominal levels of longitudinal load and tension. The results demonstrate that intraluminal pressure and whole-body acceleration are not required for TRA to occur. The results suggest that the role of the ligamentum arteriosum is likely limited, and that TRA can occur in the absence of pulmonary artery injury. Tethering of the descending thoracic aorta by the parietal pleura is a principal aspect of this injury. Language: en

It has been proven that HAART is effective in suppressing human immunodeficiency virus (HIV) replication, decreasing morbidity and mortality associated with HIV and improving quality of life in adults as well as children infected with HIV. However, drugs don’t work in patients who don’t take them and in the management of HIV infection it is now well established that optimum adherence to HAART is critical to successful outcome of patients receiving therapy. At least 95% adherence to HAART is optimum and studies have shown that 50 %. Important factors that influence adherence to HAART such as regimen related complexities, patient/family related issues and factors related to healthcare delivery system makes adherence to HAART challenging. Although numerous interventions to improve adherence have been investigated in developed as well as developing countries, majority of work in this area is focused on adherence in adults and data in children is limited. Therefore, in order to facilitate adherence and improve outcome of HAART in pediatric population, it is necessary to have a deep understanding of the factors influencing adherence and interventions that can improve adherence in children.

This study focuses on the biaxial mechanical properties of planar aorta tissue at strain rates likely to be experienced during automotive crashes. It also examines the structural response of the whole aorta to longitudinal tension. Twenty-six tissue-level tests were conducted using twelve thoracic aortas harvested from human cadavers. Cruciate samples were excised from the ascending, peri-isthmic, and descending regions. The samples were subjected to equibiaxial stretch at two nominal speed levels using a new biaxial tissue-testing device. Inertia-compensated loads were measured to facilitate calculation of true stress. High-speed videography and regional correlation analysis were used to track ink dots marked on the center of each sample to obtain strain. In a series of component-level tests, the response of the intact thoracic aorta to longitudinal stretch was obtained using seven aorta specimens. The aorta fails within the peri-isthmic region. The aorta fails in the transverse direction, and the intima fails before the media or adventitia. The aorta tissue exhibits nonlinear behavior. The aorta as complete structure can transect completely from 92 N axial load and 0.221 axial strain. Complete transection can be accompanied by intimal tears. These results have application to finite element modeling and the better understanding of traumatic rupture of the aorta.

Traumatic rupture of the aorta (TRA) is one of the leading causes of mortality in automobile crashes. Finite element (FE) modeling, used in conjunction with laboratory experiments, has emerged as increasingly important tool to understand the mechanisms of TRA. Appropriate material modeling of the aorta is a key aspect of such efforts. The current study focuses on obtaining biaxial mechanical properties of aorta tissue at strain rates typically experienced during automotive crashes. Five descending thoracic aorta samples from human cadavers were harvested in a cruciate shape. The samples were subjected to equibiaxial stretch at a strain rate of 44 s−1 using a new biaxial tissue-testing device. Inertially compensated loads were measured. High-speed videography was used to track ink dots marked on the center of each sample to obtain strain. The aorta tissue exhibited anisotropic and nonlinear behavior. The tissue was stiffer in the circumferential direction with a modulus of 10.64 MPa compared to 7.94 MPa in longitudinal direction. The peak stresses along the circumferential and longitudinal directions were found to be 1.89 MPa and 1.76 MPa, respectively. The tissue behavior can be used to develop a better constitutive representation of the aorta, which can be incorporated into FE models of the aorta.Copyright © 2005 by ASME

Traumatic rupture of the aorta (TRA) is responsible for 10% to 20% of motor vehicle fatalities [1]. Both finite element (FE) modeling and experimental investigations have enhanced our understanding of the injury mechanisms associated with TRA. Because accurate material properties are essential for the development of correct and authoritative FE model predictions, the objective of the current study was to identify a suitable material model and model parameters for aorta tissue that can be incorporated into FE aorta models for studying TRA. An Ogden rubber material (Type 77B in LS-DYNA 970) was used to simulate a series of high speed uniaxial experiments reported by Mohan [2] using a dumbbell shaped FE model representing human aortic tissue. Material constants were obtained by fitting model simulation results against experimentally obtained corridors. The sensitivity of the Ogden rubber material model was examined by altering constants G and alpha (α) and monitoring model behavior. One single set of material constants (α = 25.3, G = 0.02 GPa, and μ = 0.6000E-06 GPa) was found to fit uniaxial data at strain rates of approximately 100 s−1 for both younger and older aortic tissue specimens. Until a better material model is derived and other experimental data are obtained, it is recommended that the Ogden material model and associated constants derived from the current study be used to represent aorta tissue properties when using FE methods to investigate mechanisms of TRA.

OBJECTIVE: Guidelines for referring women with pelvic masses suspicious for ovarian cancers to gynecologic oncologists have been published jointly by Society of Gynecologic Oncologists (SGO) and the American College of Obstetricians and Gynecologists (ACOG). They are based on patient age, CA 125 level, physical findings, imaging study results, and family history. Although the guidelines are evidence-based, their predictive value in distinguishing cancers from benign masses is unknown. METHODS: Chart review for factors included in the guidelines of surgically evaluated women with pelvic masses at 7 tertiary care centers during a 12-month interval was performed. This information was used to estimate the predictive values of the SGO and ACOG guidelines in identifying patients with malignant pelvic masses. RESULTS: A total of 1,035 patients were identified, including 318 (30.7%) with primary malignancies of the ovary, fallopian tube, or peritoneum. Seventy-seven were younger than 50 years old (premenopausal group), and 240 were 50 years old or older (postmenopausal group). Fifty additional patients (4.8%) had cancers metastatic to the ovaries, and the remaining 667 (64.4%) had benign masses. The referral guidelines captured 70% of the ovarian cancers in the premenopausal group and 94% of the ovarian cancers in the postmenopausal group. The positive predictive value was 33.8% for the premenopausal group and 59.5% for the postmenopausal group, whereas the negative predictive values were more than 90% for both groups. Elevated CA 125 level was the single best predictor of malignancy in both groups. CONCLUSION: The SGO and ACOG referral guidelines effectively separate women with pelvic masses into 2 risk categories for malignancy. This distinction permits a rational approach for referring high-risk patients to a gynecologic oncologist for management.

Subepithelial nerves and stromal nerves of the cornea are damaged during LASEK surgery for the correction of myopia. This leads to a reduction in corneal sensation and to alterations of the tear film function in the early postoperative period. The aim of this study was to evaluate tear film function, corneal sensation and subjective symptoms of dry eye in the early postoperative period after LASEK for the correction of myopia.LASEK surgery was performed in 20 eyes of 10 consecutive patients for the correction of myopia (-1.0 to -9.0 D, mean -4.86 D). Subjective symptoms of a dry eye were evaluated with a standardised questionnaire. Schirmer test with and without local anaesthesia, tear film break-up time, fluorescein staining of the cornea and corneal esthesiometry (Cochet-Bonnet) were performed before surgery and 1 week, 1 month, 2 months and 3 months after LASEK. Additionally corneal staining and subjective symptom severity scores were assessed 3 days after surgery.Corneal sensation was reduced 1 week after LASEK and recovered during the first month after LASEK. The tear film break-up time was reduced 1 week and 1 month after LASEK and reached preoperative values 2 months after surgery. Fluorescein staining was increased 3 days and 1 week after LASEK. Subjective symptom severity scores were increased 3 days, 1 week, 1 month and 2 months after LASEK. Schirmer tests values with local anaesthesia were significantly reduced at 3 months after surgery, but not at 3 days, 1 month, or 2 months. Schirmer test values without local anaesthesia were significantly decreased 2 and 3 months after LASEK, but not after 3 days and 1 month after LASEK.LASEK alters ocular surface haemostasis and reduces corneal sensation in the early postoperative period. Subjective symptoms of dry eye were described during the first 2 months after surgery.

Objective To search for factors that contribute to the development of neovascularage-related macular degeneration (AMD). Methods In a matched-pair case-control study, we studied sib pairs in whichthe index sibling had neovascular AMD in at least 1 eye and the unaffectedsibling had normal maculae (or at most only a few small drusen) and was pastthe age at which the index case was diagnosed. Factors studied included sex,iris color, education, alcohol consumption, body mass index, vitamin use,smoking history, hypercholesterolemia, aspirin use, hypertension, other cardiovasculardisease, any autoimmune disease, and non–insulin-dependent diabetesmellitus. Conditional logistic regression was performed to identify predictorsof neovascular AMD. Results On the basis of 73 sib pairs, multivariate regression analysis revealeda statistically significant 2% increase in risk of neovascular AMD with eachpack-year of smoking (odds ratio, 1.02; 95% confidence interval, 1.01-1.04; P = .007). Suggestive but nonsignificant associations werealso observed for mean lifetime alcohol consumption, adult lifetime body massindex, and hypertension in multivariate regression analyses. Conclusion Using extremely discordant sib pairs to study risk factors for AMD,a novel approach in epidemiological design, we found evidence that smokingis a risk factor for neovascular AMD.

A finite element whole-body human model, which represents a 50th percentile male, was developed by integrating three detailed human component models previously developed at Wayne State University (WSU): a thorax model with detailed representation of the great vessels [1], an abdomen model [2], and a shoulder model [3]. This new model includes bony structures such as scapulae, clavicles, the vertebral column, rib cage, sternum, sacrum, and illium and soft tissue organs such as the heart, lungs, trachea, esophagus, diaphragm, kidneys, liver, spleen, and all major blood vessels including the aorta. In addition to model validations already reported at the component level, the new whole-body model was further validated against two sets of experimental data reported by Hardy [4]. In these experiments, human cadavers were loaded either by a seatbelt or by a surrogate airbag about the mid-abdomen, approximately at the level of umbilicus. It is believed that exercising a validated human model is an inexpensive and efficient way to examine potential injury mechanisms. In some cases, this can provide insight into the design of subsequent laboratory experiments.Copyright © 2004 by ASME

Objective To compare ELVIS (Enzyme Linked Virus Inducible System) (BioWhittaker, Walkersville, Md), a new, simple, 24-hour cell culture test for detecting herpes simplex virus (HSV), with standard cell culture and Herpchek (NEN, Boston, Mass) for detecting HSV in ocular specimens. Methods Retrospectively, 36 true-positive frozen-stock ocular samples that were cell-culture positive for HSV, and 25 true-negative samples (varicella-zoster virus, adenovirus,Pseudomonas aeruginosa,Staphylococcus aureus, andStreptococcus viridans) were tested with ELVIS. Herpchek was processed at the time of initial clinical laboratory testing. Prospectively, 422 patients were tested for HSV with standard cell culture, ELVIS, and Herpchek. The sensitivity, specificity, positive and negative predictive values, and efficacy of ELVIS based on positive and negative cell cultures were determined. Results Retrospectively, ELVIS was 86.1% sensitive (31/36), 100% specific (25/25), and 91.8% efficient (56/61). The positive predictive value was 100% (31/31), and the negative predictive value was 83.3% (25/30). The sensitivity of ELVIS was equivalent to Herpchek (80.5%, 29/36) (P= .53). Prospectively, the sensitivity of ELVIS (84.8%, 28/33) was equivalent to that of Herpchek (84.8%, 28/33). Conclusions ELVIS is an easy HSV diagnostic test that can provide faster positive culture results than standard cell culture, and it is equally sensitive but less time-consuming than Herpchek.

Intravascular catheter-associated bloodstream infections significantly increase rates of morbidity and hospital costs. Microbial colonization and development of biofilms, which are known to be recalcitrant to antibiotic therapy, often lead to the loss of otherwise patent vascular access systems. We evaluated a new taurolidine- and citrate-based catheter lock solution (Neutrolin; Biolink Corporation, Norwell, Mass.) for its activity against planktonic microbes, antimicrobial activity in a catheter model, and biofilm eradication activity. In studies of planktonic microbes, after 24 h of contact, 675 mg of taurolidine-citrate solution per liter caused >99% reductions in the initial counts of Staphylococcus aureus , Staphylococcus epidermidis , Pseudomonas aeruginosa , and Entercoccus faecalis. A solution of 13,500 mg/liter was cidal for Candida albicans . Ports and attached catheters inoculated with 50 to 600 CFU of these bloodstream isolates per ml were locked with heparin or the taurolidine-citrate solution. After 72 h, there was no growth in the taurolidine-citrate-treated devices but the heparin-treated devices exhibited growth in the range of 6 × 10 2 to 5 × 10 6 CFU/ml. Biofilms were developed on silicone disks in modified Robbins devices with broth containing 6% serum (initial counts, 10 6 to 10 8 CFU/cm 2 ). The axenic biofilms were treated for 24 h with taurolidine-citrate or heparin. Taurolidine-citrate exposure resulted in a median reduction of 4.8 logs, whereas heparin treatment resulted in a median reduction of 1.7 logs ( P < 0.01). No significant differences in the effects of the two treatments against P. aeruginosa and C. albicans were observed. These findings suggest that taurolidine-citrate is a promising combination agent for the prevention and treatment of intravascular catheter-related infections.

This paper summarizes component models of the human body, from head to foot, developed at WSU over the last decade. All of these models were validated against global response data obtained from relevant cadaveric tests. This report summarizes the capabilities and limitations of these models and points the direction for future developments.Copyright © 2002 by ASME

Leukemias with chromosomal translocation or partial tandem duplications involving the MLL (mixed lineage leukemia) gene have exceptionally poor prognosis (referred to as 11q23-leukemias). At the molecular level, 11q23-leukemias are characterized by aberrant expression of a set of homeodomain transcription factors in hematopoietic stem cells (HSC) and differentiating myeloid progenitor cells. This transcription factor set includes HoxB3, B4, A7-11, Cdx2-4 and Meis1. Cdx and Hox proteins are involved in regulating hematopoiesis. Transcription of HOX and CDX genes decreases normal myelopoiesis, but is aberrantly sustained in 11q23-leukemias. Cdx4 activates transcription of the HOXA9 and HOXA10 genes, and HoxA10 activates CDX4 transcription. The events that break this feedback loop, permitting a decrease in Cdx4-expression during normal myelopoiesis, were previously undefined. In the current study, we find that HoxA9 represses CDX4 transcription in differentiating myeloid cells; antagonizing activation by HoxA10. We determine that tyrosine phosphorylation of HoxA10 impairs transcriptional activation of CDX4, but tyrosine phosphorylation of HoxA9 facilitates repression of this gene. Since HoxA9 and HoxA10 are phosphorylated during myelopoiesis, this provides a mechanism for differentiation-stage-specific Cdx4 expression. HoxA9 and HoxA10 are increased in cells expressing Mll-Ell, a leukemia associated MLL1 fusion protein. We find that Mll-Ell induces a HoxA10-dependent increase in Cdx4-expression in myeloid progenitor cells. However, expression of Cdx4 decreases in a HoxA9-dependent manner upon exposure of Mll-Ell-expressing cells to differentiating cytokines. Leukemia associated, constitutively active mutants of Shp2 block cytokine-induced tyrosine phosphorylation of HoxA9 and HoxA10. In comparison to cells expressing Mll-Ell alone, we find that co-expression of Mll-Ell plus constitutively active Shp2 increases CDX4 transcription and Cdx4 expression in myeloid progenitor cells. And, increased Cdx4 expression is sustained upon exposure of these cells to differentiating cytokines. Our results identify a mechanism for increased and sustained CDX4 transcription in leukemias co-overexpressing HoxA9 and HoxA10 in combination with constitutive activation of Shp2. We also demonstrate that inhibition of Shp2-PTP activity decreases Cdx4 expression in Hox-overexpressing human myeloid leukemias. Disclosures No relevant conflicts of interest to declare.

To report the presenting features and clinical outcomes of a series of patients with noninfectious inflammation after intravitreal aflibercept injection.Noncomparative consecutive case series.Medical records of patients who presented with noninfectious inflammation after intravitreal aflibercept injection between November 18, 2011 and June 30, 2013 were retrospectively reviewed.A total of 20 cases of postinjection inflammation were identified in 5356 aflibercept injections. The patients presented 1-13 days after aflibercept injection (median 3 days); all noted decreased vision, while 3 of 20 (15%) had pain and 2 of 20 (10%) had conjunctival injection. One patient had a hypopyon (0.5 mm), and the average anterior chamber cell was 1.8+ (range 0 to 4+). All eyes had some degree of vitritis (average 1.8+; range 0.5+ to 4+). Patients on average had received 6 prior aflibercept injections (range 0-16). Only 1 patient-the first to present with inflammation in this series-received an intravitreal tap (culture negative) and injection of antibiotics. All patients were managed with frequent topical steroids and were followed closely for signs of improvement. All but 1 patient regained their preinjection visual acuity (average: 33 days; range: 7-73 days). Four patients were subsequently rechallenged with aflibercept, and 1 developed inflammation again after 5 additional aflibercept injections. The overall incidence of inflammation after intravitreal aflibercept injection was 20 of 5356 injections (0.37%) or 19 of 844 patients (2.25%). However, a disproportionate number of cases clustered around 1 provider (17/20, 85%; P.001 vs all other providers) and around the 2 office locations where this physician primarily worked (16/20, 75%; P.001 vs 5 other offices).Noninfectious inflammation after intravitreal aflibercept injection typically presents without pain, conjunctival injection, or hypopyon, and responds to topical steroid therapy. The visual outcomes are generally favorable, though the return to baseline acuity can take many weeks.

Purpose Dense, vision-obscuring calcification on the posterior aspect of silicone intraocular lenses (IOLs) is often not amenable to neodymium:yttrium-aluminum-garnet capsulotomy, and, in prior reports, has required IOL exchange. We report the successful removal of dense calcium deposition on the posterior surface of a three-piece silicone lens using pars plana vitrectomy (PPV). Materials and methods A 23-gauge PPV was performed using the Stellaris(®) vitrectomy system. A light pipe was used to retroilluminate the IOL, and a dense fibrous tissue setting with a low cut-rate and high aspiration rate was able to clear the visual axis of the dystrophic calcification without damaging the IOL optic. Results Visual acuity improved from 20/100 to 20/25. Conclusion Small-gauge PPV may be utilized to remove dense dystrophic calcium deposits on the lens surface in lieu of IOL exchange.

Objective Despite the rarity of uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC), they contribute disproportionately to endometrial cancer deaths. Sufficient clinical information regarding treatment and prognosis is lacking. The aim of this study is to evaluate treatment outcomes in a rare cancer cohort based on the experience at two tertiary care cancer centers.

PURPOSE: To report a case of fungal keratitis with consecutive endophthalmitis caused by Microsphaeropsis olivacea . METHODS: Case report. RESULTS: A 51-year-old man developed fungal keratitis and consecutive endophthalmitis after sustaining a penetrating injury to the right eye. Cultures of the aqueous humor yielded M. olivacea . Infection resolved after intraocular fungal debridement, intravitreous amphotericin B, and aggressive topical natamycin and oral fluconazole. Persistent, low-grade smoldering corneal and intraocular inflammation required topical corticosteroid therapy. CONCLUSION: M. olivacea is an exceedingly rare ocular pathogen. The intraocular portion of the infection responded quickly to intravitreal antifungal treatment; however, the course was prolonged by smoldering corneal inflammation. Prompt recognition of intraocular spread and aggressive treatment may be beneficial in fungal infections caused by unusual organisms with uncertain virulence.

Different surgical methods are used to fixate the subluxated sulcus intraocular lens (IOL) in the absence of in-bag fixation, ranging from iris and scleral suturing to optic capture of the IOL. A new technique, which we have termed capsule membrane suture fixation, provides an additional method for securing a subluxated or decentered sulcus-based IOL to the remnant capsule or a capsular membrane. This method can also be used in secondary surgery for fixation, repositioning, or removal and replacement of IOLs. In this technique, the IOL haptics are sutured to the fibrotic elements of the capsular membrane to center and secure the IOL to the capsular membrane and prevent complications associated with uveal touch.