Contact lens fitting following corneal graft surgery

Contact lens fitting may be required following keratoplasty for either optical or thera‐peutic reasons. Optical indications for contact lens fitting include the correction of irregular astigmatism, high regular astigmatism, anisometropia and secondary aniseikonia, as well as simple ametropia, where the patient desires to wear contact lenses in preference to spectacles. Therapeutic lenses are not routinely fitted following kerate plasty, although this management is advised in certain cases, such as when there are protruding sutures or epithelial healing is impaired. Designing a contact lens for a patient who has undergone keratoplasty will require the practitioner to carefully assess all the relevant features of the corneal graft. In this regard, there are many factors that need to be considered including the diameter of the graft zone, the topographical relationship between the host cornea and donor cornea, the corneal (graft) toricity and the location of the graft. Special designs, such as reverse geometry lenses, or more complex contact lens modalities, such as piggyback contact lens systems, may be required to achieve success in fitting.     

Chronic Inhalation Toxicity and Carcinogenicity Testing of Respirable Fibrous Particles

On May 8–10, 1995, a workshop on chronic inhalation toxicity and carcinogenicity testing of respirable fibrous particles was held in Chapel Hill, North Carolina. The workshop was sponsored by the Office of Pollution Prevention and Toxics, U.S. Environmental Protection Agency (EPA), in collaboration with the National Institute of Environmental Health Sciences (NIEHS), the National Institute for Occupational Safety and Health (NIOSH), and the Occupational Safety and Health Administration (OSHA). The goal of the workshop was to obtain input from the scientific community on a number of issues related to fiber testing. Major issues for discussion were: (i) the optimal design and conduct of studies of the health effects of chronic inhalation exposure of animals to fibers; (ii) preliminary studies which would be useful guides in designing the chronic exposure study; (iii) mechanistic studies which would be important adjuncts to the chronic exposure study to enable better interpretation of study results and extrapolation of potential effects in exposed humans; and (iv) available screening tests which can be used to develop a minimum data set for (a) making decisions about the potential health hazard of the fibers and (b) prioritizing the need for further testing in a chronic inhalation study. After extensive discussion and debate of the workshop issues, the general consensus of the expert panel is that chronic inhalation studies of fibers in the rat are the most appropriate tests for predicting inhalation hazard and risk of fibers to humans. A number of guidances specific for the design and conduct of prechronic and chronic inhalation studies of fibers in rodents were recommended. For instance, it was recommended that along with other information (decrease in body weight, systemic toxicity, etc.), data should be obtained on lung burdens and bronchoalveolar lavage fluid analysis to assist in establishing the chronic exposure levels. Lung burden data are also important for quantifying aspects of risk assessment related to dosimetric adjustments before extrapolation. Although mechanistic studies are not recommended as part of the standard chronic inhalation studies, the expert panel stressed the need for obtaining mechanistic information as far as possible during the course of subchronic or chronic inhalation studies. At present, no single assay and battery of short-term assays can predict the outcome of a chronic inhalation bioassay with respect to carcinogenic effects. Meanwhile, several short-termin vitroandin vivostudies that may be useful to assess the relative potential of fibrous substances to cause lung toxicity/carcinogenicity have been identified.     

Analysis of susceptibility of mature human T lymphocytes to dexamethasone-induced apoptosis

We present evidence that dexamethasone (Dex), a synthetic glucocorticosteroid, causes apoptosis in mature human T cells, similarly to what has been reported for murine T lymphocytes. Human T cell clones and short-term activated T lymphocytes treated with Dex show the characteristic pattern of apoptotic cells, such as hypodiploid nuclei, chromatin condensation and DNA fragmentation into oligonucleosomal fragments. However, Dex susceptibility of T cells to apoptosis is cell cycle-dependent. The progression in the proliferative cell cycle (G1 versus S) rescues Dex-treated T cells from apoptosis. Moreover, occupancy of the T cell receptor reverses Dex-induced apoptotic phenomena. These observations suggest that glucocorticoids contribute to the regulation of the proliferative or the suicidal response of antigen-activated human T cells.     

Factors That Predict 1-Year Incident Hip and Non-Hip Fractures for Home Care Recipients: A Linked-Data Retrospective Cohort Study

ObjectivesThe purpose of our study was to identify factors that predict 1-year incident hip and major osteoporotic non-hip fractures (ie, wrist, spine, pelvis, humerus) for home care recipients while accounting for the competing risk of death.DesignWe conducted a retrospective cohort study with linked population data.Setting and ParticipantsAll home care recipients in Ontario, Canada, receiving services for more than 6 months with an admission assessment between April 1, 2011, and March 31, 2015, were included.MethodsClinical data from the Resident Assessment Instrument Home Care were linked to fracture data from the Discharge Abstract Database and the National Acute Care Reporting System. Competing risk proportional hazard regressions using the Fine and Grey method were performed to model the association between potential risk factors and fracture.ResultsPrevious fall, previous fracture, cognitive impairment, unsteady gait, alcohol use, tobacco use, and Parkinson disease were consistently associated with all fracture types. Cognitive impairment (hazard ratio 2.09; 95% confidence interval 1.86–2.36) and wandering [1.66 (1.06–1.27)] were most predictive of hip fractures and being female [1.86 (1.76–1.98)] and experiencing a previous fracture [1.86 (1.76–1.98)] were most predictive of non-hip fractures. Risk factors unique to non-hip fractures as compared with hip fractures were locomotion ability outdoors and psychotropic medication use.Conclusions and ImplicationsOur results indicate that, in addition to typical fracture risk factors, home care recipients have unique characteristics that increase their risk. Fracture risk assessment tools and subsequent prevention strategies should be modified to accurately identify home care recipients at risk for imminent 1-year fracture.     

Mediation Analysis of a Theory-Based Culture and Age-Appropriate HIV/STI Prevention

Few studies have investigated mediator effects of HIV prevention interventions on adolescents in sub-Saharan Africa. Herein, we report on a secondary analysis of an intervention that increased intentions to use condoms, abstain from sexual intercourse, and seek safe male circumcision among adolescents in Botswana. In a study conducted in Botswana, 806 grade 9 students from 21 public Junior Secondary Schools were randomly assigned to either the OWN THE FUTURE: Pulling Together We Will” ( PTWW) intervention group or a health promotion control group. Both conditions consisted of 12 1-h modules, with two modules delivered during each of the six sessions on six consecutive school days. The students in both groups completed confidential computer-based surveys at several time points: pre-, immediately post-, 3, 6, and 12 months post-intervention. Mediation was assessed using the product-of-coefficients approach in a generalized estimating equations (GEE) framework. The analyses showed that condom use beliefs were significant mediators of the intervention effect on the intention to consistently use condoms over time. Also, negative socio-cultural beliefs, prevention beliefs, and HIV/STI knowledge were significant mediators of the intervention’s effects on the intention to abstain from sex. Additionally, normative beliefs, prevention beliefs, parental negotiation, and circumcision knowledge were significant mediators of the intervention’s effect on intention to seek safe male circumcision. The mediation analysis delineated a theoretical model and isolated activities that positively impact condom use, abstinence from sex, and circumcision intentions of Batswana middle school adolescents.

     

Inhibitory action of natural carrageenans on Herpes simplex virus infection of mouse astrocytes

The effects of the carrageenans 1T1 (lambda-type), 1C1 (kappa/iota-type) and 1C3 (upsilon/nu-type), isolated from the red seaweed Gigartina skottsbergii, on herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infection of murine astrocytes were investigated. The three compounds were effective inhibitors of virus replication, as determined by a virus yield inhibition assay, in astrocytes as well as in Vero cells. The 50% inhibitory concentration was in the range of 0.9-3.6 and 0.4-3.2 microg/ml for astrocytes and Vero cells, respectively, whereas the 90% inhibitory concentration ranged from 6.5 to 17.0 microg/ml in astrocytes and from 3.5 to 22.2 microg/ml in Vero cells. No cytotoxicity was detected at concentrations of up to 1,000 microg/ml, indicating high selectivity indices for these compounds. Inhibition of viral cytopathology and antigen expression was also detected in the presence of the carrageenans. The increase in the expression of glial fibrillary acidic protein (GFAP), an activated astrocyte marker, produced during the course of HSV-1 infection in astrocytes, was reversed in the presence of 1C1 and 1C3. By contrast, the lambda-carrageenan 1T1 increased the expression of GFAP, independently of HSV-1 infection.     

Phase II trial of VP16-213 in non-small cell lung cancer (NSCLC)

Summary Fifty-one patients with non-small cell lung cancer (NSCLC) were treated, during a phase II trial, with 4 demethylepipodophyllotoxin--d-ethylidene glucoside (VP16-213). Forty-nine were evaluable for response, and of these two (4%) had partial responses lasting 5 and 6 months. Prior treatment with chemotherapy may have adversely affected response rate; none of the 24 previously treated patients had a major response. Myelosuppression was the dose limiting toxicity. Anorexia, nausea and vomiting, partial alopecia, and chills plus hypotension during drug infusion were the other toxic effects. We conclude that VP16-213 has only minimal activity as a single agent in NSCLC.Supported in part by NIH Grant No. CA-05826 and CA-09027, and by NCI Contract NO-1-CM 972744Demethylepipodophyllotoxin--d-Ethylidene Glucoside (NSC141540) was supplied by the Drug Evaluation Branch of the National Cancer Institute