Instrument-based Tests for Measuring Anterior Chamber Cells in Uveitis: A Systematic Review

ABSTRACT

Purpose

New instrument-based techniques for anterior chamber (AC) cell counting can offer automation and objectivity above clinician assessment. This review aims to identify such instruments and its correlation with clinician estimates.     

Ultrasonography for assessment of subcutaneous nodules

OBJECTIVE: To characterize a variety of subcutaneous lesions by their ultrasonographic (US) appearance, and establish these images as a starting point to measure changes with treatments. METHODS: Twenty-six patients with 48 subcutaneous nodular swellings of various types were imaged using a portable US machine equipped with a 10 MHz linear transducer. All patients had a known diagnosis of a rheumatic disease. We used US to examine subcutaneous lesions and the underlying cortical surface of the bone or joint. Two measurements of some tophi and rheumatoid nodules were done on different dates to examine reproducibility of the measurements. RESULTS: Nodular lesions included 20 tophi and 20 rheumatoid nodules, 2 sarcoid nodules, 2 lipomas, and 4 synovial cysts. Tophi most often appeared as heterogeneous masses; hypoechoic areas in 2 tophi were decreased after aspiration of chalky liquid tophaceous material. Occasionally tophi had calcifications appearing hyperechoic with acoustic shadowing. Cortical bone erosions could be seen adjacent to some tophi. The nodules in patients with rheumatoid arthritis were often attached closely to the bone surface and less erosive to bone, allowing the cortical bone to be seen easily. The nodules were more homogeneous. Some showed a central sharply demarcated hypoechoic area, possibly corresponding to necrosis inside the rheumatoid nodules. Nodules were easily measured. The repeated measurements of both tophi and rheumatoid nodules showed excellent reproducibility. Lipomas had different echogenic patterns depending on composition of the associated connective tissue and position of the mass. They could be hypoechogenic, hyperechogenic, or mixed, but were easily distinguished by oval shapes with well demarcated capsules. Synovial cysts seen in this study had a characteristic hypoechoic pattern. CONCLUSION: Subcutaneous nodules examined by sonography show characteristics and patterns that, although not diagnostic, can be used to help distinguish their etiology. Tophi and rheumatoid nodules can be easily measured and these measurements used to help follow disease progression or response to therapy.     

The use of focus groups in the development of the PROMIS pediatrics item bank

PURPOSE: To understand differences in perceptions of patient-reported outcome domains between children with asthma and children from the general population. We used this information in the development of patient-reported outcome items for the Patient-Reported Outcomes Measurement Information System Pediatrics project. METHODS: We conducted focus groups composed of ethnically, racially, and geographically diverse youth (8-12, 13-17 years) from the general population and youth with asthma. We performed content analysis to identify important themes. RESULTS: We identified five unique and different challenges that may confront youth with asthma as compared to general population youth: (1) They experience more difficulties when participating in physical activities; (2) They may experience anxiety about having an asthma attack at anytime and anywhere; (3) They may experience sleep disturbances and fatigue secondary to their asthma symptoms; (4) Their health condition has a greater effect on their emotional well-being and interpersonal relationships; and (5) Youth with asthma report that asthma often leaves them with insufficient energy to complete their school activities, especially physical activities. CONCLUSIONS: The results confirm unique experiences for children with asthma across a broad range of health domains and enhance the breadth of all domains when creating an item bank.     

Glomerular endothelial dysfunction in chronic kidney disease

A dysfunctioning glomerular endothelium was demonstrated in chronic kidney disease (CKD) patients by means of in vitro endothelial cell cytotoxicity test and of in vivo intrarenal hemodynamic study. An enhanced endothelial cell cytotoxicity in CKD patients was 26.5 +/- 12% as compared to 0.4 +/- 1% of control. An altered intrarenal hemodynamics revealed 1) a reduction in renal plasma flow, 190 +/- 67 mL/min/1.73 m2 versus control 595 +/- 45 mL/min/1.73 m2, and in peritubular capillary flow, 149 +/- 55 mL/min/1.73 m2 versus control 479 +/- 46 mL/min/1.73 m2, 2) an elevated intraglomerular hydrostatic pressure, 55 +/- 2 mmHg versus control 51 mmHg, elevated afferent arteriolar resistance, 13184 dyne x s x cm(-5) versus control 2443 +/- 154 dyne x s x cm(5), and elevated efferent arteriolar resistance, 13591 +/- 7591 dyne x s x cm(-5) versus control 3062 +/- 177 dyne x s x cm(-5). Both enhanced endothelial cell cytotoxicity and altered intrarenal hemodynamics reflect glomerular endothelial dysfunction which is likely responsible for the renal disease progression in CKD.     

Synergistic cytotoxicity and apoptosis induced in human cholangiocarcinoma cell lines by a combined treatment with tumor necrosis factor-alpha (TNF-alpha) and triptolide

Cholangiocarcinoma is known to be relatively resistant to chemotherapy. One alternative approach is to use a combination of an immunomodulating agent with an anticancer drug. Here we studied the synergistic actions of TNF-alpha and triptolide (a diterpene epoxide prepared from Tripterygium wilfordii), previously shown to have antitumor activity against hamster cholangiocarcinoma (CCA) cells. Three human CCA cell lines (HuCCA-1, HubCCA-1, KKU-100 cell lines) were subjected to a combined treatment of TNF-alpha (0.1-10 ng/ml) and triptolide (5-50 ng/ml) for 24 hours in microculture plates. The combination of TNF-alpha and triptolide had a significantly increased cytotoxic activity over that of triptolide alone (p < 0.05). Under the same conditions, TNF-alpha by itself was not cytotoxic to these cell lines. Similarly, the combined treatment could also accelerate apoptotic cell death in all three human cholangiocarcinoma cell lines. The combined treatment of TNF-alpha at 10 ng/ml and triptolide at 50 ng/ml for 6-10 hours achieved a percentage of apoptotic cells shown by DAPI staining of 18-65%, compared to only 6-20% apoptotic cells for triptolide alone. Analyzing the possible mechanisms of the combined treatment, we found by Western blot that at 6 hours, there was a poly (ADP-ribose) polymerase (PARP) cleavage which was not detectable by the treatment of either TNF-alpha or triptolide alone. The cleavage of PARP was inhibited when the cells were pretreated with the enzyme inhibitor AC-DEVD-CMK, suggesting that apoptosis induced by the combination of TNF-alpha and triptolide involved activation of caspase 3. These results indicate that apoptosis of human cholangiocarcinoma cell lines as induced by a combination of TNF-alpha and triptolide is mediated through caspase 3 activation.     

Development of a monoclonal antibody-based enzyme-linked immunosorbent assay for the diagnosis of Penicillium marneffei infection

A monoclonal antibody (MAb)-based sandwich enzyme-linked immunosorbent assay was developed for the detection of Penicillium antigen in clinical specimens from patients with Penicillium marneffei infection. The IgM from clone 8C3, reactive with both yeast and mycelial antigens, was immobilized on a microtiter plate. The antigen in serum or urine was captured and detected with biotinylated polyclonal rabbit anti-P. marneffei antibody. The test was sensitive in detecting soluble yeast exoantigen at a concentration as low as 4.88 ng/mL. The reliability of the assay method was evaluated using sera at a dilution of 1:2 from 18 patients with culture-proven penicilliosis, 23 patients with other fungal and bacterial infections, and 125 healthy volunteers. The method exhibited a sensitivity of 72%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 97%, and an accuracy of 97%. However, the sensitivity could be increased to 90% when the specimens were used undiluted. The method was also useful for the detection of antigen secreted in the urine of the patients. The results showed that the newly described assay method can be used in the diagnosis of P. marneffei infection with a high degree of reliability.     

Multiple deprivation,vision loss,and ophthalmic disease in adults: global perspectives

The association between socioeconomic position and morbidity and mortality has long been recognized. We evaluate the evidence for an association between multiple aspects of deprivation and ocular health in a global context. This is a systematic review of studies that evaluated deprivation in the adult population in the context of the major acquired causes of visual loss such as cataract, diabetic eye disease, glaucoma, age-related macular degeneration, and ocular trauma. The search strategy identified relevant studies reported between 1946 and August 2016, with randomized control trials, case-control, cohort, and cross-sectional study designs being selected for inclusion. The studies identified in this review from across the world demonstrate the extent to which the common themes such as low educational attainment and low income may be associated with increased incidence of various sight-threatening conditions and may adversely affect access to specialist assessment and delivery of treatment. Health inequality may always persist, but an increased recognition of the importance of the various impacts of deprivation may empower policy makers to target limited resources to the most vulnerable groups in order to deliver the greatest benefit.     

Thai herbal antipyretic 22 formula (APF22) inhibits UVA‐mediated melanogenesis through activation of Nrf2‐regulated antioxidant defense

Thai herbal antipyretic 22 formula (APF22), a polyherbal formula, has been traditionally used to treat dermatologic problems including hyperpigmentation. Exposure of the skin to ultraviolet A (UVA) causes abnormal melanin production induced by photooxidative stress. This study thus aimed to investigate the protective effects of APF22 extracts and phenolic compounds, ferulic acid (FA), and gallic acid (GA; used as positive control and reference compounds), on melanogenesis through modulation of nuclear factor E2‐related factor 2 (Nrf2) signaling and antioxidant defenses in mouse melanoma (B16F10) cells exposed to UVA. Our results revealed that the APF22 extracts, FA, and GA reduced melanin synthesis as well as activity and protein levels of tyrosinase in UVA‐irradiated B16F10 cells. Moreover, APF22 extracts and both FA and GA were able to activate Nrf2‐antioxidant response element signaling and promote antioxidant defenses including glutathione, catalase, glutathione peroxidase, and the glutathione‐S‐transferase at both mRNA and enzyme activity levels in irradiated cells. In conclusion, APF22 extracts suppressed UVA‐mediated melanogenesis in B16F10 cells possibly via redox mechanisms involving activation of Nrf2 signaling and upregulation of antioxidant defenses. Moreover, pharmacological action of the APF22 extracts may be attributed to the phenolic compounds, FA, and GA, probably serving as the APF22's active compounds.     

The prevalence and severity of diabetic retinopathy, associated risk factors and vision loss in patients registered with type 2 diabetes in Luganville, Vanuatu

AIM: To determine the prevalence and severity of diabetic retinopathy in patients with type 2 diabetes in Luganville, the second largest town in Vanuatu. Additionally, to investigate risk factors for retinopathy and the effect of retinopathy on visual acuity (VA) within this group. METHOD: All 83 registered patients with type 2 diabetes in Luganville, a town of 13 121 people, were invited for an interview and anthropometric measurements. A questionnaire including assessment of hypertension and glycaemic control, which are known risk factors for diabetic retinopathy, was administered. This sample accounted for approximately 1.07% of Luganville's adult population. Presenting VA was measured. The retina was photographed with a non-mydriatic fundus camera and images later independently graded for the extent of retinopathy. RESULTS: 68 (82%) of the 83 patients attended. The mean (SD) age was 54 (11) years and 31 (46%) were male. Diabetic retinopathy was present in 36 (52.9%) of the sample. Sight-threatening retinopathy requiring urgent referral was present in 15 (22.1%) patients. Presenting VA was worse than 6/12 in the better eye in n = 32 (47%) and in up to half of these cases the principal cause was retinopathy. In addition, four people had uniocular blindness resulting from diabetes. The mean body mass index was lower in those patients with diabetes with retinopathy than in those without (p = 0.010), but there were no other significant differences between the two groups and, specifically, no difference in the frequency of retinopathy risk factors. 42 (61.8%) patients had hypertension (>or=135/85 mm Hg) or were taking antihypertensive therapy. CONCLUSIONS: The prevalence of registered patients with diabetes in Luganville's adult population was 1.07%. Diabetic retinopathy was highly prevalent in the sample (in 36, 52.9%), and in 15 (22.1%) there was a significant threat to sight, with up to 25% of the sample possibly already affected by decreased VA or blindness resulting from diabetes-related eye disease. Retinopathy risk factors were also prevalent. A diabetes screening programme with baseline ophthalmic assessment and follow-up are urgently needed to enable timely intervention and treatment.