HLA typing of a Hong Kong Chinese family with intermediate uveitis.
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Biomedical subjects
Publications and source records attributed to A C Browning.
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PURPOSE: To determine whether topical ketorolac (Acular) is more effective than artificial tears in treating the signs and symptoms of idiopathic episcleritis. METHODS: In this prospective, randomised, double-blind study, 38 eyes of 37 patients presenting with idiopathic episcleritis were allocated to receive either topical ketorolac (0.5%) or artificial tears three times a day for 3 weeks. The severity of patients' signs (episcleral injection and the number of clock hours affected) were recorded at weekly intervals. Patients' symptoms (perceived redness and pain scores) were recorded using a daily diary. RESULTS: There was no significant difference in the ophthalmic signs between the two groups at each assessment, including intensity of episcleral injection and the number of clock hours affected. No significant difference was found in the time to halve the baseline redness intensity scores (4.4 vs 6.1 days, P=0.2) or pain scores (3.6 vs 4.3 days, P=0.55). Significantly more patients on ketorolac reported stinging at the first follow-up visit (P<0.001). CONCLUSION: Topical ketorolac is not significantly better than artificial tears in treating the signs or symptoms of idiopathic episcleritis.
AIM: To develop a method for the reliable isolation of adult human macular inner choroidal endothelial cells (ICECs) and to subsequently characterise them for their expression of a range of endothelial cell associated surface markers. METHOD: Human ICECs were isolated after manual dissection of maculas from fresh human posterior segments. Following enzyme digestion to form a single cell suspension, the ICECs were isolated using anti-CD31 coated Dynabeads. The isolated cells were grown in culture and examined for typical endothelial cell morphology, surface expression of vWf, CD 31, CD 105, VEGF receptors 1 and 2, and expression of E-selectin after stimulation with TNF-alpha. The cells were also examined for their ability to form fenestrations and capillary-like tubes in Matrigel. RESULTS: The method enabled the rapid isolation of viable cells that demonstrated typical endothelial cobblestone morphology in culture. The cells stained positive for CD31, vWf, CD105, VEGF receptors 1 and 2, and E-selectin (after stimulation with TNF-alpha). The cells stained negative for alpha smooth muscle actin and fibroblast surface protein. The cells also developed fenestrations when cultured on fibronectin coated plates and formed capillary-like tubes structures when cultured on Matrigel. CONCLUSIONS: This technique isolates cells from the human macular inner choroid that display features consistent with vascular endothelial cells. These cells could subsequently be used to further the understanding of the pathophysiological mechanisms of diseases of the inner choroid, such as choroidal neovascularisation.
BACKGROUND/AIM: To compare intraocular pressure (IOP) measurements taken by the Goldmann applanation tonometer, the Tono-Pen and the ocular blood flow pneumotonometer in eyes with varying central corneal thickness (CCT) due to penetrating keratoplasty (PK), keratoconus (KC), and Fuchs' endothelial dystrophy (FED). METHODS: IOP was measured with the Goldmann applanation tonometer, Tono-Pen XL, and OBF pneumotonometer in 127 eyes with the following corneal abnormalities. There were 56 eyes that had undergone PK, 37 eyes with KC, and 34 eyes with FED. CCT was measured using an ultrasound pachymeter after IOP determinations had been made. RESULTS: Mean IOP measurements in all three patient groups were significantly higher when measured by OBF pneumotonometer. Linear regression analysis showed that patients with FED had a significant increase in IOP with increasing CCT of 0.18 mm Hg/10 microm using the Goldmann tonometer, 0.15 mm Hg/10 microm with the Tono-Pen, and 0.26 mm Hg/10 microm with the OBF pneumotonometer. In patients with KC and after PK, linear regression analysis did not show a significant effect of CCT on IOP. A multivariate linear regression model controlling for age, sex, graft size, and patient group, showed that the effect of CCT on IOP for Tono-Pen (0.13 mm Hg/10 microm CCT) and Goldmann (0.14 mm Hg/10 microm CCT) were significantly lower than for the OBF pneumotonometer (0.26 mm Hg/10 microm CCT). CONCLUSIONS: This study found that mean IOP measurements using the OBF pneumotonometer were significantly higher than those made using the Goldmann applanation tonometer or Tono-Pen in eyes with a variety of cornel pathologies. The OBF pneumotonometer was found to be most affected by variation in CCT. For all three instruments, the relation between IOP and CCT depended on the corneal pathology and was greatest for FED.
The expression of enzymes involved in fatty acid beta-oxidation (FAO), the principal source of energy production in the adult mammalian heart, is controlled at the transcriptional level via the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). Evidence has emerged that PPARalpha activity is activated as a component of an energy metabolic stress response. The p38 mitogen-activated protein kinase (MAPK) pathway is activated by cellular stressors in the heart, including ischemia, hypoxia, and hypertrophic growth stimuli. We show here that PPARalpha is phosphorylated in response to stress stimuli in rat neonatal cardiac myocytes; in vitro kinase assays demonstrated that p38 MAPK phosphorylates serine residues located within the NH(2)-terminal A/B domain of the protein. Transient transfection studies in cardiac myocytes and in CV-1 cells utilizing homologous and heterologous PPARalpha target element reporters and mammalian one-hybrid transcription assays revealed that p38 MAPK phosphorylation of PPARalpha significantly enhanced ligand-dependent transactivation. Cotransfection studies performed with several known coactivators of PPARalpha demonstrated that p38 MAPK markedly increased coactivation specifically by PGC-1, a transcriptional coactivator implicated in myocyte energy metabolic gene regulation and mitochondrial biogenesis. These results identify PPARalpha as a downstream effector of p38 kinase-dependent stress-activated signaling in the heart, linking extracellular stressors to alterations in energy metabolic gene expression.
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PURPOSE: To assess the effect of sub-Tenon's anaesthesia on intraocular pressure (IOP) prior to cataract surgery. METHODS: Fifty consecutive patients undergoing phacoemulsification of cataract were recruited. Routine sub-Tenon's anaesthesia was administered with 5 ml unpreserved 2% lignocaine. IOPs were measured immediately prior to and at 1, 3, 5 and 10 min after injection. Efficacy was assessed subjectively by the operating surgeon. No ocular compression was used. Pre- and post-injection IOPs were compared using the Wilcoxon signed rank test, whereas all other results were compared with baseline using Student's two-tailed paired t-tests. RESULTS: All patients achieved good analgesia and akinesis. There was no significant difference between the IOP prior to and 1 min after injection. At all time intervals after 3 min there was a significant reduction in IOP compared with the pre-injection measurement. At 5 min, the mean IOP reduction was 2.72 mmHg and at 10 min IOP was lowered by 2.92 mmHg. Both reductions were statistically significant compared with baseline. CONCLUSIONS: Sub-Tenon's anaesthesia does not cause any significant rise in IOP, thereby possibly making it the anaesthetic technique of choice when an increase in IOP is undesirable. There is no indication for the use of an ocular pressure-reducing device when sub-Tenon's anaesthesia is employed.
A retrospective review was carried out of patients under 16 years old with malignant hypertension, who had been referred to a teaching hospital ophthalmology department because of reduced visual acuity. Four patients (three girls, one boy) were seen between 1994 and 2000 with a mean age at presentation of 11.5 years (range 9-15). In the short term, visual acuity improved after control of blood pressure in all four patients. However, in the long term, two patients were registered blind one to two years after presentation, one because of a choroidal neovascular membrane developing at the macula, and the other because of progressive optic neuropathy. Both of these patients had a longer duration of symptoms before diagnosis, worse visual acuity, and higher blood pressure at presentation when compared with the patients who made a good visual recovery. These observations suggest that early diagnosis of malignant hypertension in children is essential in reducing the likelihood of permanent severe visual damage.
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PURPOSE: To compare a new automated system for the measurement of erythrocyte sedimentation rate (ESR) with the established manual Seditainer method. METHODS: Two hundred and twelve patients undergoing investigation for giant cell arteritis or other systemic vasculitides had ESR measurements by both the established manual Seditainer and the new laboratory-based automated system. The results were compared by correlation coefficient and mean difference. The limits of agreement with confidence intervals were also calculated. RESULTS: Across the range of results from 1 to 120 mm/h, the correlation coefficient was 0.844. The automated method had a mean negative bias of -9.8 mm/h (95% confidence interval: -12.2 to -7.4 mm/h). The wide scatter of results produced limits of agreement (+/- 2 standard deviations) between the two methods of -45 to 26 mm/h. There were seven results that were underestimated by the automated system which were clinically significant. CONCLUSIONS: There is a wide degree of scatter between the two sets of results. The automated system has a negative bias when compared with the manual method. There is a propensity for the automated system to sporadically underestimate the true result, sometimes to a degree that is clinically significant. The authors therefore cannot recommend replacement of the manual Seditainer system at the present time.
It is well established that bispecific antibodies (BsAbs) can be used effectively in targeting the ribosome-inactivating protein (RIP), saporin, against neoplastic B cells. We have now extended this delivery system for use with gelonin. By measuring antigen-binding characteristics and epitope mapping a panel of anti-gelonin MAbs using the IAsys resonant mirror bisensor, we were able to rapidly select the most suitable for making BaAbs. The Fab' fragments from these MAbs were chemically conjugated with Fab' from either anti-CD22 or anti-CD38. Cytotoxicity assays showed that BsAbs were highly efficient at delivering gelonin to cultured Daudi cells and achieved levels of toxicity which correlated closely with the affinity of the BsAbs. Using pairs of anti-CD22 BsAbs we were able to generate bivalent BsAb-gelonin complexes which achieved IC50 values of 2 x 10(-11) M gelonin, a potency which is equivalent to that reached by saporin in this targeting system. However, because gelonin is 5-10 times less toxic than saporin, the therapeutic ratio for gelonin is superior, making it potentially a more useful agent for human treatment. Cytotoxicity assays and kinetic analysis showed that targeting gelonin via CD38 was 2-5 times less effective than delivery through CD22. However, with a pair of BsAbs designed to co-target gelonin via CD22 and CD38, the cytotoxicity achieved equalled that obtained with a pair of anti-CD22 BsAbs (IC50 = 1 x 10(-11) M). This important result suggests that the anti-CD38 helps bind the gelonin to the cell and is then 'dragged' or 'piggy-backed' into the cell by the anti-CD22 BsAb. The implication of these findings for cancer therapy is discussed.
This is the second part of an article on an unusual form of passenger transport, the moving pavement or pedestrian conveyor running at speeds up to 16 km/h. Part 1, "Ergonomic considerations of acceleration, deceleration and transfer sections," was published in the December, 1974, issue.
In this article, an uncommon form of passenger transport is considered, the moving pavement or pedestrian conveyor running at speeds of up to 16 km/h. There are very little relevant ergonomic data for such devices and some specific laboratory experiments have been carried out using 1000 subjects to represent the general public. It is concluded that whilst high speed pedestrian conveyors are quite feasible, stations along them are likely to be large. The most attractive type is a set of parallel surfaces moving at different speeds and with handholds provided in the form of poles. This type could be extremely convenient for certain locations but will probably have to be restricted in its use to fairly fit adults carrying little luggage, and would find applications in situations where a large number of people need to travel in the same direction. Part 2, Ergonomic considerations of complete conveyor systems, will follow.