Asymmetry indicates more severe and active disease in Graves' orbitopathy: results from a prospective cross-sectional multicentre study.

PURPOSE: Patients with Graves' orbitopathy can present with asymmetric disease. The aim of this study was to identify clinical characteristics that distinguish asymmetric from unilateral and symmetric Graves' orbitopathy. METHODS: This was a multi-centre study of new referrals to 13 European Group on Graves' Orbitopathy (EUGOGO) tertiary centres. New patients presenting over a 4 month period with a diagnosis of Graves' orbitopathy were included. Patient demographics were collected and a clinical examination was performed based on a previously published protocol. Patients were categorized as having asymmetric, symmetric, and unilateral Graves' orbitopathy. The distribution of clinical characteristics among the three groups was documented. RESULTS: The asymmetric group (n = 83), was older than the symmetric (n = 157) group [mean age 50.9 years (SD 13.9) vs 45.8 (SD 13.5), p = 0.019], had a lower female to male ratio than the symmetric and unilateral (n = 29) groups (1.6 vs 5.0 vs 8.7, p < 0.001), had more active disease than the symmetric and unilateral groups [mean linical Activity Score 3.0 (SD 1.6) vs 1.7 (SD 1.7), p < 0.001 vs 1.3 (SD 1.4), p < 0.001] and significantly more severe disease than the symmetric and unilateral groups, as measured by the Total Eye Score [mean 8.8 (SD 6.6) vs 5.3 (SD 4.4), p < 0.001, vs 2.7 (SD 2.1), p < 0.001]. CONCLUSION: Older age, lower female to male ratio, more severe, and more active disease cluster around asymmetric Graves' orbitopathy. Asymmetry appears to be a marker of more severe and more active disease than other presentations. This simple clinical parameter present at first presentation to tertiary centres may be valuable to clinicians who manage such patients.

Trends in serious ocular trauma in Scotland.

PURPOSE: To report trends in serious, sight-threatening ocular trauma in Scotland. METHODS: A prospective, population-based, observational study of patients with ocular trauma admitted to hospital in Scotland during a 12-month period (2008-2009), conducted through the British Ophthalmic Surveillance Unit. Data on circumstances of the injuries and visual outcomes were collected using protocols standardised to those from an earlier study (1991-1992) to allow direct comparisons over time. RESULTS: In all, 0.3% of all emergency admissions in Scotland were for ocular trauma. Significant differences were observed between the time periods in where an injury occurred (P=0.009): a reduction of those occurring in a sports/leisure facility (8.2%) and an increase in those occurring on the street (21.4%). Assaults remained the most common cause of injury (31%). Gender differences persisted with females more likely to have an injury from falls (OR=8.67; 95% CI: 2.41-31.49; P=0.002), or in the home (OR=5.40; 95% CI: 1.69-17.16; P=0.009 ), and less likely to have one in the workplace (P=0.06). Poor visual outcome was associated with injuries occurring in the home (OR=4.33, P=0.047), in a public place (OR=6.25, P=0.047), and those caused by a fall (OR 42.75, P<0.001); or assault (OR 7.29, P=0.019). Half of those with a poor outcome have no perception of light. CONCLUSION: Serious ocular trauma remains an infrequent, sight-threatening event, associated with significant monocular visual morbidity. The findings suggest a shift from corporate to personal responsibility for risk awareness, health, and safety.

The incidence of serious eye injury in Scotland: a prospective study.

PURPOSE: Ocular trauma remains an important cause of visual morbidity worldwide. A previous population-based study in Scotland reported a 1-year cumulative incidence of 8.14 per 100 000 population. The purpose of this study was to identify any change in the incidence and pattern of serious ocular trauma in Scotland. METHODS: This study was a 1-year prospective observational study using the British Ophthalmological Surveillance Unit reporting scheme among Scottish ophthalmologists. Serious ocular trauma was defined as requiring hospital admission. Data were collected using two questionnaires for each patient 1 year apart. RESULTS: The response rate from ophthalmologists was 77.1%. There were 102 patients reported with complete data giving an incidence of 1.96 per 100 000 population, four times less than in 1992. In patients younger than 65 years, the age-adjusted incidence ratio (males/females) indicated a ninefold higher risk of trauma in males. In 25 patients (27.2%), the injured eye was blind (final visual acuities (FVA) <6/60), 24 being attributable to the eye injury. Standardised morbidity ratios suggested a threefold decrease in risk of poor visual outcome in 2009 compared with 1992. CONCLUSIONS: The incidence of serious ocular trauma has fallen; this study has shown hospital admission for serious eye injury in Scotland has decreased fourfold in 17 years. Young adult males continue to be at highest risk, which needs to be specifically addressed in future health-prevention strategies. This study also observed a reduction in visual loss from serious ocular injuries, although the reasons for this require further exploration.

The carbon footprint of cataract surgery.

BACKGROUND: Climate change is predicted to be one of the largest global health threats of the 21st century. Health care itself is a large contributor to carbon emissions. Determining the carbon footprint of specific health care activities such as cataract surgery allows the assessment of associated emissions and identifies opportunities for reduction. AIM: To assess the carbon footprint of a cataract pathway in a British teaching hospital. METHODS: This was a component analysis study for one patient having first eye cataract surgery in the University Hospital of Wales, Cardiff. Activity data was collected from three sectors, building and energy use, travel and procurement. Published emissions factors were applied to this data to provide figures in carbon dioxide equivalents (CO2eq). RESULTS: The carbon footprint for one cataract operation was 181.8 kg CO2eq. On the basis that 2230 patients were treated for cataracts during 2011 in Cardiff, this has an associated carbon footprint of 405.4 tonnes CO2eq. Building and energy use was estimated to account for 36.1% of overall emissions, travel 10.1% and procurement 53.8%, with medical equipment accounting for the most emissions at 32.6%. CONCLUSIONS: This is the first published carbon footprint of cataract surgery and acts as a benchmark for other studies as well as identifying areas for emissions reduction. Within the procurement sector, dialogue with industry is important to reduce the overall carbon footprint. Sustainability should be considered when cataract pathways are designed as there is potential for reduction in all sectors with the possible side effects of saving costs and improving patient care.

Changes to colour vision on exposure to high altitude.

OBJECTIVES: Several studies have shown deterioration in colour vision at altitudes above 3,000m. These studies have been conducted in photopic (bright daylight) conditions, whereas many military operations take place in mesopic (dim light) conditions. Data suggests that the tritan colour vision axis (blue cones, TA) are more susceptible to hypoxic insult than protan axis (red cones, PA). The objective of this study was to examine colour vision at high altitude, in mesopic conditions, and using a novel method of assessment to discriminate between the tritan and protan axis. METHODS: We examined 42 eyes (21 subjects, mean age 44, range 22-71), at sea level and within 12-36 hours of exposure to 3300m. This was done in a darkened room, with refractive error correction. Colour vision was studied using ChromaTest, a software programme that analyzes colour contrast threshold (CCT) of both TA and PA. We planned to repeat CCT measurement at 4,392m, but technology failure prevented this. Non-parametric paired data was examined using the Wilcoxon signed rank test. RESULTS: There was found to be no change to either the PA (p = 0.409) or the TA (p = 0.871) upon ascent. Within the PA 16 eyes had a lower CCT at high altitude, whilst 26 were higher. In the TA 20 eyes had a lower CCT and 22 were higher. At sea level, mean CCT for PA was 4.21 (SD 2.29) TA was 7.06 (SD 1.77). At 3,300m mean CCT for PA was 4.36 (SD 2.86) and TA was 6.93 (SD 2.39). CONCLUSIONS: This experiment revealed no changes to colour vision with exposure to 3,300m. This may be below the threshold altitude for cone dysfunction, alternatively colour vision deterioration may be less significant in mesopic conditions.

Periocular basal cell carcinoma: 5-year outcome following Slow Mohs surgery with formalin-fixed paraffin-embedded sections and delayed closure.

AIM: The aim of the study was to determine the 5-year outcome of periocular basal cell carcinoma (BCC) managed by Mohs surgery using formalin-fixed, paraffin-embedded sections (Slow Mohs). METHODS: This was a prospective, non-comparative, interventional case series of all patients with periocular BCC treated by Slow Mohs in Newcastle upon Tyne, UK, between 1985 and 1999. Data collected included demographic information, indication for Slow Mohs, tumour site, histology, recurrence rate after 5 years and cosmetic outcome. RESULTS: Of 287 BCCs in 278 patients, 5-year follow-up data were available for 173 (60.2%). Recurrence following Slow Mohs occurred in one patient: 0.34% of total and 0.58% of those with 5-year follow-up. The main indication for Slow Mohs was most frequently due to the tumour site. Cosmetic outcome was deemed excellent in 56%, good in 18%, adequate in 8%, unknown in 14% and revision advised in only 4%. CONCLUSION: The low 5-year recurrence rate (0.58%) reported in this prospective series confirms the importance of margin-controlled removal of recurrent, poorly defined or critically sited BCCs, and illustrates that Slow Mohs is equivalent to standard Mohs. While delayed closure does not appear to compromise cosmetic outcome, this technique offers a histologically superior and cheaper alternative to frozen-section Mohs surgery.

Optic nerve sheath diameter, intracranial pressure and acute mountain sickness on Mount Everest: a longitudinal cohort study.

OBJECTIVE: To investigate the association of optic nerve sheath diameter (ONSD), as a correlate of intracranial pressure (ICP), with acute mountain sickness (AMS). DESIGN: Longitudinal cohort study of mountaineers from sea level to 6400 m. SETTING: Mount Everest (North side). PARTICIPANTS: 13 mountaineers (10 men, 3 women; aged 23-52 years) on a British expedition to climb Mount Everest. INTERVENTIONS: ONSD was measured ultrasonically, 3 mm behind the globe using B scans recorded with an OTI-Scan 3D scanner (Ophthalmic Technologies, Canada). Serial binocular scans were recorded at sea level, and 2000, 3700, 5200 and 6400 m. All ONSDs were measured by a blinded observer. MAIN OUTCOME MEASURES: ONSD, AMS score (using the Lake Louise scoring system), heart rate, and oxygen saturation levels. RESULTS: All results were analysed by regression analysis with adjustment. ONSD was positively associated with increasing altitude above sea level (0.10 mm increase in ONSD per 1000 m, 95% CI 0.05 to 0.14 mm) and AMS score (0.12 mm per score, 95% CI 0.06 to 0.18 mm); further associations were found with resting heart rate (0.29 mm per 20 beats/min, 95% CI 0.17 to 0.41 mm) and oxygen saturations (0.20 mm per 10% decrease, 95% CI 0.11 to 0.29 mm). CONCLUSIONS: ONSD increases at high altitude, and this increase is associated with more severe symptoms of AMS. Given the linkage between ONSD and ICP, these results strongly suggest that intracranial pressure plays an important role in the pathophysiology of AMS.

Ocular blunt trauma: loss of sight from an ice hockey injury.

A case of ocular blunt trauma is described in which a 17 year old male ice hockey player collided with an opponent during a game. The opponent's stick travelled under the patient's half face visor and struck his left eye causing hyphema, angle recession, lens subluxation, and choroidal rupture over the macula, permanently reducing his vision to counting fingers. Sequelae of ocular blunt trauma are discussed along with methods of injury prevention by addressing players' behaviour and safety equipment. This injury is unlikely to have occurred with properly used full face protection.

Embryonic chick muscle produces an FGF-like activity.

Normal and pathological formation of blood vessels is of considerable interest both in terms of basic scientific processes and clinical applications. Angiogenic events in the adult are likely to represent persistence of developmental mechanisms, and embryos are therefore a suitable experimental model for these processes. Among embryonic tissues, muscle is particularly appropriate for investigation, since it is highly vascularised from early stages. There are a number of competing explanations of how this process is controlled. Bioassays offer advantages over conventional molecular localisation techniques, in that they reveal the presence of active processed forms of the molecules under study, rather than non-processed forms, or non-translated messages. Using these techniques, we report here that embryonic chick muscle, taken from the stages at which blood vessels are forming, produces an angiogenic activity on the chick chorioallantoic membrane (CAM), and transforms NR6 cells in soft agar. Basic fibroblast growth factor (bFGF) is shown to be angiogenic on the CAM in the same way, and also transforms NR6 cells (NR6 cells lack functional epidermal growth factor/transforming growth factor-a receptors, and are believed to respond only to bFGF in this way). Anti-bFGF removes the transforming activity of the embryonic muscle. We conclude that this represents evidence that embryonic chick muscle is producing an FGF-like molecule which is capable of acting as an angiogenic agent at the appropriate times in development.

Surgeons and the International Committee of the Red Cross.

The International Committee of the Red Cross (ICRC) is at the forefront in the provision of surgical care to the victims of war. In 1990 twenty-two surgical teams were deployed in 14 hospitals in eight countries and 18,450 patients were treated. This article reviews the contribution made by ICRC, and the experience that can be gained by New Zealand and Australian surgeons and anaesthetists.

Abdominal injuries in the war wounded of Afghanistan: a report from the International Committee of the Red Cross Hospital in Kabul.

This report is from the hospital opened by the International Committee of the Red Cross, in Kabul, which receives acute war-wounded patients from the Afghanistan conflict. Of more than 1000 operations carried out by the New Zealand team in a 6-month period, there were 70 laparotomies for penetrating wounds. These injuries were dealt with by established surgical techniques. The main area of controversy was the management of colonic wounds where the recent trend away from mandatory colostomy was followed by good results. Selective primary repair was achieved in 16 of 27 patients with colonic injury with no mortality and minimal morbidity. The right colon was considered particularly favourable for primary anastomosis. The overall mortality rate for all laparotomies was 13 per cent, with injuries to the liver, major veins and rectum particularly being fatal. There were eight negative laparotomies.

2(1H)-quinolinones with cardiac stimulant activity. 3. Synthesis and biological properties of 6-imidazol-1-yl derivatives.

A series of 6-imidazol-1-yl-8-methyl-2(1H)-quinolinones was synthesized and evaluated for cardiac stimulant activity in dogs. The majority of compounds were prepared from an appropriate 6-imidazol-1-yl-2(1H)-quinolinone precursor or by sulfuric acid catalyzed cyclization of an N-(4-heteroarylphenyl)-3-ethoxypropenamide. Introduction of a range of 5-substituents into 6-(2,4-dimethylimidazol-1-yl)-8-methyl-2(1H)-quinolinone (1) reduced inotropic activity in anesthetized dogs (percentage increase in dP/dtmax) although replacement of the 2-methyl group by iodo (10) or cyano (11) substituents was well tolerated. The 2-methyl-4-chloro (15) and 2-methyl-4-(methylthio) (22) derivatives displayed similar potency to 1 (40-50% increase in dP/dtmax, 10-12.5 micrograms/kg) and these compounds were 3-5 times more potent than milrinone. Introduction of iodo (14), cyano (16), or acetyl (17) substituents into the 4-position approximately halved inotropic activity. In conscious dogs, 11 (0.25 mg/kg) and 16 and 17 (0.125 mg/kg) produced similar increases in cardiac contractility (decrease in the QA interval) to 1 (0.125 mg/kg) and maximum responses were maintained for at least 3 h. Dose-related (25, 125, 250 micrograms/kg) cardiac stimulant activity was demonstrated by 17 and after the higher doses a marked response (approximately 30% increase in dP/dtmax) was still observed after 7 h, in contrast to milrinone. The substantial increases in cardiac contractility observed with 16 and 17 in the conscious dog were not accompanied by any tachycardia. These compounds also displayed an overwhelming selectivity for increasing the force of cardiac contraction (greater than 120% increase in dP/dtmax) rather than heart rate (5-10 beats/min decrease) in the Starling heart-lung preparation. As a result of this beneficial pharmacological profile, 6-(4-acetyl-2-methylimidazol-1-yl)-8-methyl-2(1H)-quinolinone (17, UK-66,838) was selected for preclinical development studies.

2(1H)-quinolinones with cardiac stimulant activity. 2. Synthesis and biological activities of 6-(N-linked, five-membered heteroaryl) derivatives.

A series of 6-(N-linked, five-membered heteroaryl)-2(1H)-quinolinone derivatives was synthesized and evaluated for cardiotonic activity. Most compounds were prepared by sulfuric acid catalyzed cyclization of an N-(4-heteroarylphenyl)-3-ethoxypropenamide or by condensation of a 2-amino-5-heteroarylbenzaldehyde or -acetophenone derivative with the ylide derived from triethyl phosphonoacetate. In anesthetized dogs, 6-imidazol-1-yl-8-methyl-2(1H)-quinolinone (3; 25 micrograms/kg) produced a greater increase in cardiac contractility (percentage increase in dP/dt max) than alternative 6-(five-membered heteroaryl)-substituted analogues (4-8). Introduction of 4-methyl (10) or 2,4-dimethyl (13) substituents into the imidazole ring of 3 produced a marked increase in inotropic activity, and these compounds were some 10 and 5 times more potent than milrinone. Most of these quinolinones also displayed positive inotropic effects (decrease in QA interval) in conscious dogs after oral administration (0.0625-1 mg/kg) and in many cases (3, 5-7, 9, 11, 13, 16) there was little difference in activities at both the 1- and 3-h time points. Compound 13 (62.5, 125, 250 micrograms/kg po) demonstrated dose-related cardiac stimulant activity which, in contrast to milrinone, was maintained over the whole 7-h test period. No changes in heart rate were detected at any dose level and compounds 3, 9, 10, and 13 also displayed high selectivity for the stimulation of cardiac contractile force rather than heart rate in the Starling dog heart-lung preparation. Increases in dP/dt max of approximately 50% were accompanied by heart rate changes of less than 10 beats/minute. Physicochemical measurements gave a log P of 1.64 for 13 with pKa values of 7.13 +/- 0.04 and 11.5 +/- 0.2 for the imidazole and quinolinone moieties, respectively. X-ray structural analysis of 13 showed the imidazole and quinolinone rings at 52 degrees to one another in close agreement with the minimum-energy conformation (30 degrees) suggested by PCILO calculations. 6-(2,4-Dimethylimidazol-1-yl)-8-methyl-2-(1H)-quinolinone (13, UK-61,260) is currently undergoing phase II clinical evaluation in congestive heart failure patients.

Colonoscopy and the followup of colorectal carcinoma.

The colonoscopy findings in 100 patients who had had a previous resection for colorectal carcinoma are reviewed. This postoperative surveillance was aimed at discovering benign or malignant neoplastic growth within the remaining large bowel. Six patients had further carcinoma discovered at colonoscopy followup, five of these were symptomless. Twenty-eight patients had one or more adenomas. A special risk group was confirmed: patients with multiple neoplasia in the original resected specimen have over a 50% chance of further adenomas being present. This represents a worthwhile yield and colonoscopy surveillance of the remaining colon should be part of the followup programme in these patients.