Retinopathy in patients with diabetic ophthalmoplegia

PURPOSE: To review the clinical characteristics, prevalence, and severity of retinopathy in diabetics with cranial nerve (CN) 3, 4, and/or 6 palsies, and to determine the relationship between type and duration of diabetes mellitus (DM), presence of retinopathy, and occurrence of CN palsy. DESIGN: Retrospective, comparative cohort study. PARTICIPANTS: Chart reviews of 2229 patients with CN 3, 4, and/or 6 palsies were performed at the Bascom Palmer Eye Institute (BPEI) from January 1991 through December 1997 and at the Dean A. McGee Eye Institute (DMEI) from January 1994 through July 2001. A total of 306 patients qualified for the study group. The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) was used as a control. METHODS: Demographic and clinical data were extracted to determine characteristics of patients with diabetic ophthalmoplegia. The subsets of data regarding type of DM and level of diabetic retinopathy in the study population were compared with the WESDR control data for statistical analysis. MAIN OUTCOME MEASURES: The prevalence of diabetic retinopathy in patients with diabetic ophthalmoplegia. RESULTS: Of 2229 patients at both institutions with ocular motor CN palsy, 306 (13.7%) were associated with DM. The frequency of CN involvement was 6 (50.0%), 3 (43.3%), and 4 (6.7%). There was a total of 12 patients (3.9%) with consecutive palsies and 8 patients (2.6%) with simultaneous palsies (5 unilateral and 3 bilateral). At both institutions, the prevalence of retinopathy controlling for duration of DM was lower in both insulin-dependent DM (IDDM) and non-IDDM (NIDDM) type II diabetics as compared with controls (BPEI, P = 0.009 and P = 0.005; DMEI, P = 0.004 and P = 0.29). When data from both locations were combined, the difference was even more significant (IDDM, P = 0.001 and NIDDM, P = 0.006). There were no significant differences between the two institutions in gender, type or duration of DM, age at presentation, or frequency of CN involvement. CONCLUSIONS: Diabetic ophthalmoplegia most commonly involves CN 3 and 6, with relative sparing of CN 4. Multiple cranial nerves are affected simultaneously in 2.6% of cases, and consecutive palsies occurred in 3.9% of cases. Type II diabetics with ocular motor CN palsy have significantly less diabetic retinopathy than do controls. This may imply a different pathophysiologic mechanism for these two microvascular complications of DM.     

The effects of antibodies to heat shock protein 70 in fertilization and embryo development

The role of heat shock proteins in shielding organisms from environmental stress is illustrated by the large-scale synthesis of these proteins by the organisms studied to date. However, recent evidence also suggests an important role for heat shock proteins in fertilization and early development of mammalian embryos. We found that the presence of anti-HSP70 antibody significantly reduced tight binding of spermatozoa to the zona pellucida of bovine oocytes and interrupted completion of meiosis II and pronuclear formation. Furthermore, the presence of anti-HSP70 in culture medium from day 3 to day 9 of development increased apoptosis and significantly reduced the number of embryos reaching the blastocyst stage. We further observed that the proportion of apoptotic cells in bovine blastocysts was significantly lower after in-vitro culture with a prior exposure to increased temperature. However, nuclear localization of the p53 protein, which is thought to be essential for the up-regulation of genes involved in apoptosis and cell cycle arrest, was detected in the majority of nuclei in blastocysts exposed to increased temperature, whereas in their untreated (control) counterparts, p53 protein was only detected in the cytoplasm. The decrease in apoptosis after exposure of blastocysts to increased temperature may be attributed to cell cycle arrest resulting from nuclear localization of the p53 protein and/or to an increase in heat shock protein synthesis. We propose that HSP70 plays a critical role in fertilization and early embryonic development.     

Exposure information in European industry: implications for future occupational research

A survey has been carried out among European industry to investigate the collection and retention of records which might be used for epidemiological research. Exposure information results are reported. Approximately 1,000 questionnaires focusing on exposure information were sent to seven countries, with a 42 percent response rate. Eighty-two percent of companies reported that exposure measurements were taken to comply with legal requirements. Measurements were most often made for noise (84%), with 48% of companies measuring chemicals, 48 percent particulates but only 10 percent vibration. Measurements were most often taken for specific locations (73%), rather than for particular jobs (54%) or individual workers (50%). Eighty percent recorded location, sampling date, agents measured, and units of measurement, with about 70 percent recording job being sampled, sampling method, and duration and plant process, but less than 60 percent recording environmental conditions or worker details. Overall, only 10 percent of companies kept their exposure information forever, and 71 percent kept it for 10 years or less. Legislative requirements were most often cited as the reason for retention of records. The variation in the quantity and quality of measurements and the early destruction of records poses considerable problems for European research. Inaccuracy and misclassification of exposure limits the ability to establish causal relationships between effect and disease. Records should uniquely identify an individual worker and facilitate linkage to exposure and health effects information. Their format should be accessible, linkable, and secure. Data should be kept by an identifiable organization and there should be a secure chain of custody if a company goes out of business. Unless industry can be motivated to follow these guidelines the future of research into occupational causes of ill health, and in particular, the evaluation of exposure, will be limited.     

Assessment of Ilizarov correction of club-foot deformity using pedobarography. A preliminary report

Relapsed congenital talipes equinovarus is difficult to assess and treat. Pedobarography provides dynamic measurement of the pressures under the foot, and may be used in the assessment of these patients both before and after operation. Our findings showed a statistically significant difference in the distribution of pressure across the foot after treatment by the Ilizarov technique.     

Negative charge distribution and density on the surface of oxygenated normal and sickle red cells

Negative charges on the external surface of red cells were visualized by colloidal iron hydroxide labelling of 50% of the membrane area after osmotic hemolysis and glutaraldehyde fixation. Counts were made over randomly selected areas on electron micrographs at 350,000 x magnification. Statistical analyses showed that at the 95% level of confidence there was no significant difference between oxygenated normal (AA) and sickle (SS) cells in either the distribution or the density of negative charges.     

Number needed to treat and costs per responder among biologic treatments for moderate-to-severe psoriasis: a network meta-analysis

Background: The clinical benefits of biologic therapies for moderate-to-severe psoriasis are well established, but wide variations exist in patient response.

Objectives: To determine the number needed to treat (NNT) to achieve a 75% and 90% reduction in the Psoriasis Area and Severity Index (PASI-75/90) with FDA-approved agents and evaluate the incremental cost per PASI-75 or PASI-90 responder.

Methods: The relative probabilities of achieving PASI-75 and PASI-90, as well as NNTs, were estimated using a network meta-analysis. Costs (2017 USD) included drug acquisition and administration. The incremental cost per PASI-75 or PASI-90 responder for each treatment was estimated for the clinical trial period, and annually.

Results: Compared with supportive care, the NNT to achieve PASI-75 was 1.18 for ixekizumab, 1.29 for secukinumab 300?mg, 1.37 for infliximab, 1.48 for adalimumab, 1.53 for secukinumab 150?mg, 1.58 for ustekinumab, 2.25 for etanercept, and 3.71 for apremilast. The one-year incremental cost per PASI-75 responder relative to supportive care was $59,830 for infliximab, $88,775 for secukinumab 300?mg, $91,837 for adalimumab, $95,898 for ixekizumab, $97,363 for ustekinumab, $105,131 for secukinumab 150?mg, $129,665 for apremilast, and $159,328 for etanercept. Results were similar for PASI-90.

Conclusion: The NNT and incremental cost per responder are meaningful ways to assess comparative effectiveness and cost effectiveness among psoriasis treatments.     

Dendritic cells and skin sensitisation hazard assessment.

Allergic contact dermatitis is an important occupational and environmental health disease. There is a need, therefore, to identify skin sensitisation hazard, and to assess accurately likely risks to human health. During the past 15 years very significant advances have been made in our understanding of the cellular and molecular mechanisms that serve to initiate and regulate cutaneous immune responses, including the acquisition of skin sensitisation. This has facilitated parallel advances in the identification and characterisation of skin sensitising chemicals and the development of more robust approaches to risk assessment. It is relevant to consider whether advances in immunobiology provide opportunities also for the design of alternative approaches to the toxicological evaluation of skin sensitisation, including the development of in vitro methods. Here we review the potential use of strategies based on analysis of responses induced in Langerhans cells and dendritic cells; professional antigen processing and presenting cells that are known to play pivotal roles during the induction phase of adaptive immune responses.     

The reduced local lymph node assay: the impact of group size

The local lymph node assay (LLNA) is a skin sensitization test that provides animal welfare benefits. To reduce animal usage further, a modified version (rLLNA) was proposed. Conducting the rLLNA as a screening test with a single high dose group and vehicle control differentiated accurately between skin sensitizers and non-sensitizers. This study examined whether a reduction in animal number/group is feasible. Historical data were utilized to examine the impact of conducting the rLLNA with two mice/group. To assess the effect on the stimulation index (SI) 41 datasets with individual animal data derived using five mice/group were analysed. SIs were calculated on all possible combinations of two control and two high dose group disintegrations per minute (dpm) values. For 25 of 33 sensitizer datasets, > 96% of possible dpm combinations resulted in a calculated SI > 3. The lowest percentages of positive SIs were observed with weak allergens when, in the standard LLNA, the mean SIs would have been nearer to the threshold value of 3. The results indicate that moderate, strong and extreme allergens are more likely than weak allergens to be identified as sensitizers when group sizes of two mice are used within the rLLNA. It is concluded that a rLLNA with two mice/group would display decreased sensitivity and is inappropriate for use in hazard identification.     

Duration of improved muscle glucose uptake after acute exercise in obese Zucker rats

Skeletal muscle is insulin resistant in the obese Zucker rat. Endurance training reduces muscle insulin resistance, but the effects of a single acute exercise session on muscle insulin resistance in the obese Zucker rat are unknown. Therefore, insulin responsiveness of muscle glucose uptake was measured in 15-week-old obese rats either 1, 48, or 72 hours after two hours of intermittent exercise (30:30 min; work:rest). Hindlimbs of sedentary lean (LS) and obese (OS) rats and exercised obese (OE) rats were perfused after a 10-hour fast under both basal (0 mU x ml(-1)) and maximal (20 mU x ml(-1)) insulin concentrations to measure net glucose uptake. Insulin responsiveness of net glucose uptake was significantly reduced in OS compared to LS (8.5 +/- 1.6 vs 15.3 +/- 2.0 micromol x g(-1) x h(-1), respectively). Compared to OS, insulin responsiveness of net glucose uptake was significantly increased by 56% and 80% at 1 hour and 48 hours after acute exercise. However, 72 hours after acute exercise, the increased insulin responsiveness of net glucose uptake was no longer evident. These results indicate that improved responsiveness of muscle glucose uptake persists for at least 48 hours after two hours of acute intermittent exercise in 15-week-old obese Zucker rats.