Randomized trial of near-infrared spectroscopy for personalized optimization of cerebral tissue oxygenation during cardiac surgery.

BACKGROUND: We assessed whether a near-infrared spectroscopy (NIRS)-based algorithm for the personalized optimization of cerebral oxygenation during cardiopulmonary bypass combined with a restrictive red cell transfusion threshold would reduce perioperative injury to the brain, heart, and kidneys. METHODS: In a randomized controlled trial, participants in three UK centres were randomized with concealed allocation to a NIRS (INVOS 5100; Medtronic Inc., Minneapolis, MN, USA)-based 'patient-specific' algorithm that included a restrictive red cell transfusion threshold (haematocrit 18%) or to a 'generic' non-NIRS-based algorithm (standard care). The NIRS algorithm aimed to maintain cerebral oxygenation at an absolute value of > 50% or at > 70% of baseline values. The primary outcome for the trial was cognitive function measured up to 3 months postsurgery. RESULTS: The analysis population comprised eligible randomized patients who underwent valve or combined valve surgery and coronary artery bypass grafts using cardiopulmonary bypass between December 2009 and January 2014 ( n =98 patient-specific algorithm; n =106 generic algorithm). There was no difference between the groups for the three core cognitive domains (attention, verbal memory, and motor coordination) or for the non-core domains psychomotor speed and visuo-spatial skills. The NIRS group had higher scores for verbal fluency; mean difference 3.73 (95% confidence interval 1.50, 5.96). Red cell transfusions, biomarkers of brain, kidney, and myocardial injury, adverse events, and health-care costs were similar between the groups. CONCLUSIONS: These results do not support the use of NIRS-based algorithms for the personalized optimization of cerebral oxygenation in adult cardiac surgery. CLINICAL TRIAL REGISTRATION: http://www.controlled-trials.com , ISRCTN 23557269.

SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes.

OBJECTIVES: To understand SARS-Co-V-2 infection and transmission in UK nursing homes in order to develop preventive strategies for protecting the frail elderly residents. METHODS: An outbreak investigation involving 394 residents and 70 staff, was carried out in 4 nursing homes affected by COVID-19 outbreaks in central London. Two point-prevalence surveys were performed one week apart where residents underwent SARS-CoV-2 testing and had relevant symptoms documented. Asymptomatic staff from three of the four homes were also offered SARS-CoV-2 testing. RESULTS: Overall, 26% (95% CI 22-31) of residents died over the two-month period. All-cause mortality increased by 203% (95% CI 70-336) compared with previous years. Systematic testing identified 40% (95% CI 35-46) of residents as positive for SARS-CoV-2, and of these 43% (95% CI 34-52) were asymptomatic and 18% (95% CI 11-24) had only atypical symptoms; 4% (95% CI -1 to 9) of asymptomatic staff also tested positive. CONCLUSIONS: The SARS-CoV-2 outbreak in four UK nursing homes was associated with very high infection and mortality rates. Many residents developed either atypical or had no discernible symptoms. A number of asymptomatic staff members also tested positive, suggesting a role for regular screening of both residents and staff in mitigating future outbreaks.

A fuzzy logic based apnoea monitor for SIDS risk infants.

A unit has been designed which monitors newborn infants at risk of Sudden Infant Death Syndrome (SIDS) in a home environment. The unit monitors respiration, electrocardiogram (ECG) and haemoglobin oxygen saturation (SpO2) in combination, in order to detect any potentially life threatening event at an early stage. Provision is made for the generation of both audible and silent alarms and for the storage of signals and other information before, during and after an alarm episode for diagnostic purposes. An intelligent fuzzy logic algorithm is used to process the signals monitored and to implement several propositions concerning their status in order to determine the probability of an apnoea event and initiate the appropriate action. This has substantially reduced the number of false alarms and of undetected dangerous situations compared with previous units, which greatly improves the reliability and usefulness of such a monitor.

Riboflavin status of adolescent vs elderly Gambian subjects before and during supplementation.

Riboflavin status was measured by activation coefficient of erythrocyte glutathione reductase (EGRAC) in elderly and adolescent rural Gambians whose intakes were low. Fifty-one adolescents and 52 elderly subjects were each subdivided into six supplementation groups to receive 0.25, 0.5, 0.75, 1.0, 1.5, or 2.5 mg riboflavin/d on 5 consecutive days weekly for 5 wk. Before supplementation, EGRAC values were grossly abnormal and differed (p less than 0.005) between the two female groups [elderly subjects, 1.94 +/- 0.33 (means +/- SD); adolescents. 1.72 +/- 0.27] but not between the two male groups. With supplementation greater than 0.25 mg/d the values became nearly equal in the two age groups. Only at total intakes between 1.8 and 2.5 mg riboflavin/d did the subjects attain acceptable status, with a mean EGRAC of 1.3-1.4. Clearly there is a need for further study of the discrepancy between observed index values during supplementation and the accepted ranges of normality at intakes close to the recommended amounts.

Grooming and vacuous chewing induced by SK&F 83959, an agonist of dopamine 'D1-like' receptors that inhibits dopamine-sensitive adenylyl cyclase.

The benzazepine SK&F 83959 demonstrates high affinity for dopamine D1 receptors and potently inhibits the stimulation of adenylyl cyclase by dopamine. This compound induced the same intense grooming behaviour identified previously as a characteristic response to typical dopamine D1 receptor agonists such as SK&F 77434 that stimulate adenylyl cyclase; it also induced vacuous chewing. These findings constitute direct evidence for a behaviourally relevant subtype of 'D1-like' receptor that is not linked to adenylyl cyclase.

Behavioural pharmacology of 'D-1-like' dopamine receptors: further subtyping, new pharmacological probes and interactions with 'D-2-like' receptors.

1. D-1 receptors are now recognised to play a critical psychopharmacological role in the regulation of unconditioned motor and numerous other aspects of behaviour. 2. There appears to exist a broad family of 'D-1-like' receptors in terms both of differential coupling to distinct messenger/transduction mechanisms and of gene cloning, whose behavioural roles remain to be clarified. 3. The adenylyl cyclase-inhibiting benzazepine SK&F 83959 induces behavioural responses in rats that are similar to those induced by the full efficacy cyclase-stimulating isochroman A 68930 but not to those induced by its high efficacy partial agonist benzazepine congener R-6-Br-APB; these data indicate roles for individual 'D-1-like' receptors in mediating distinct elements of dopaminergic behaviour. 4. The putative D-1 autoreceptor agonist B-HT 920 and the putative D-3 agonist 7-OH-DPAT demonstrate different behavioural profiles when given both alone and in combination with the selective 'D-1-like' antagonist BW 737C; D-3 receptors may participate in cooperative/synergistic but not in oppositional 'D-1-like': 'D-2-like' interactions. 5. Such interactions apparent at the level of behaviour are complemented by evidence for similar interactions at numerous alternative levels of function, though these may differ between rodent and primate species. 6. A broader range of more selective agonists and antagonists, able to distinguish between individual members of the 'D-1-like' and of the 'D-2-like' receptor families are needed to clarify these issues.

Trachoma and water use; a case control study in a Gambian village.

Trachoma is prevalent in many arid areas but data assessing the relationship between water use and trachoma are very scarce. This study compared 18 families having one or more active trachoma cases among the children with 16 trachoma-free families in the same village with respect to water use. Potential confounders such as family size, distance to water source, socio-economic indicators, and hygiene behaviour were assessed in the 2 groups. The families with trachoma were found to use significantly less water per person per day for washing children than did the control group (P = 0.033) with no evidence of confounding by the other measured variables. Low amounts of water for washing were also associated with unclean faces and impetigo in the children. If such a relationship can be substantiated it might provide the basis for effective and cheap interventions against trachoma.

Recent developments in the nutritional management of diarrhoea. 2. Chronic diarrhoea and malnutrition in The Gambia: studies on intestinal permeability.

Chronic diarrhoea and malnutrition in Gambian children is associated with persisting damage to the mucosa of the small intestine. Intestinal permeability tests suggest that mucosal status gradually deteriorates with age throughout the first year of life in tandem with increasingly severe growth faltering. The ability of the dual sugar permeability test to assess intestinal mucosal status frequently in a non-invasive way makes the technique a valuable tool for future studies into the aetiology of this syndrome.

Tracker-assisted photorefractive keratectomy for myopia of -1 to -6 diopters.

BACKGROUND: The Autonomous Technologies T-PRK (Tracker-assisted Photorefractive Keratectomy) excimer laser system uses a small beam scanner that allows flexibility in the ablation pattern that is applied to the cornea and incorporates a sophisticated LADARVision eye tracker that is capable of following saccadic movements. This paper describes the first clinical results on sighted eyes for the correction of low myopia. METHODS: Forty-two normal sighted eyes of 42 patients were treated for spherical myopia between -1.00 diopters (D) and -6.00 D with 6 mm ablations. Visual acuity, refractive error, contrast sensitivity (with and without glare), corneal haze, endothelial cell density, and patient satisfaction were measured. RESULTS: Mean manifest refraction was -0.39 D +/- 0.68 D at 1 month with regression to -0.94 D at 3 months and -1.05 D at 6 months. At 6 months, 5 (20%) eyes were +/- 0.50 D and 14 (56%) eyes were +/- 1.00 D. Consistent with this undercorrection and regression, uncorrected visual acuity (UCVA) of 20/20 and 20/40 or better was achieved by 10 (40%) and 34 (85%) eyes at 3 months and 16 (40%) and 17 (68%) eyes at 6 months. None of the eyes lost 2 or more lines of spectacle corrected visual acuity. Corneal haze was graded as 1/2 trace or less in 89% to 100% of eyes at all intervals. There was no loss of endothelial cells (mean +/- SD cell density centrally: preop 3115 +/- 322 and 6 months 3220 +/- 333) and contrast sensitivity recovered to baseline levels at 3 months. CONCLUSIONS: The Autonomous Technologies T-PRK excimer laser system is safe and effective for the reduction or correction of myopia from -1.00 D or -6.00 D. The refractive results may be improved by adjusting the calibration to reduce the undercorrection and by instituting use of topical corticosteroids on an individual basis for those who regress.

The Mersilene mesh sling--a new concept in ptosis surgery.

The use of a Mersilene mesh sling in brow suspension ptosis surgery is presented. Seventeen cases of severe blepharoptosis have been treated by means of this sling with favourable results. Materials used in brow suspension procedures are categorised and discussed, and it is concluded that the Mersilene sling is an alternative to those currently available for the management of severe blepharoptosis requiring brow suspension surgery.

Endonasal laser dacryocystorhinostomy--medium term results.

BACKGROUND/AIMS: Endonasal laser dacryocystorhinostomy (ELDCR) has many potential advantages over conventional external DCR. Although the short term results of this technique have been reported, little is yet known of the long term results, and the occurrence of late rhinostomy failure. The aim of this study was to examine the results at 3 and 12 months following ELDCR. METHOD: The notes of all consecutive ELDCRs performed between November 1993 and May 1995 were retrieved. Demographic information, details of surgery, and the postoperative results were noted. RESULTS: ELDCR procedures which did not undergo lacrimal stenting showed a short term success rate of 67% at 3 months, and a further failure rate of 9% at 12 months. ELDCRs which did undergo lacrimal stenting showed a short term success rate of 82% at 3 months, and a further failure rate of 21% at 12 months. Lacrimal intubation increased the long term success rate by 8%. The success rate was lower in the presence of local risk factors for nasal mucosal scarring. CONCLUSIONS: ELDCR requires some adjunctive treatment to improve maintenance of the nasal mucosal ostia if it is to complete successfully with external DCR on grounds other than cosmesis and patient convenience.

Running performance in Gambian children: effects of water-soluble vitamins or iron.

Sixty-nine boys and girls between 10 and 14 years, with evidence of subclinical vitamin deficiencies and poor iron status were enrolled into the study at the beginning of the rainy season. Children were allocated to three treatment groups to receive five times weekly either a placebo, 200 mg ferrous sulphate or 5 mg riboflavin and 150 mg ascorbic acid. Before receiving the supplement, and 9 weeks later, children performed an exercise regimen on a treadmill during which expired air was collected and heart rate measured. There was a general deterioration in the running performance of the children during the study period which was not affected by either the iron or the vitamin supplement.

Inflammatory mediators in alkali-burned corneas: preliminary characterization.

Leukocyte chemotactic factors (LCF) are important inflammatory mediators which activate and recruit leukocytes from the circulation into sites of tissue damage. These factors were recently detected in the tear fluid of inflamed eyes induced by alkali burn. It remains unclear, however, whether the detected LCF are released from injured corneal tissues or leaked from the circulation. Using a corneal cup model developed in our laboratory, we began examining the capability of corneal tissues to produce LCF in response to alkali injury. We also evaluated the influence of citric acid on the production of LCF from corneas preinjured by the alkali sodium hydroxide (NaOH). For these studies, the epithelial surfaces of corneas isolated from bovine and human eyes were exposed to 1N NaOH for 35 seconds at room temperature. The NaOH was then removed and the epithelial surfaces washed once with buffer and incubated with culture medium for 1, 2, 4, and 6 hours at 37 degrees C/5% CO2 atmosphere. Our results showed that (1) NaOH2 induced corneal epithelial cell injury ranging from cell discoloration and moderate damage of the upper half of the epithelium (1-4 hrs) to total destruction of the epithelium (6 hrs); (2) NaOH-injured corneas (2 hr incubation post injury) produced significant levels of chemotactic activity (via checkerboard analysis) specific for neutrophils (115% maximum chemotactic response [MCR]) and mononuclear cells (94% MCR); (3) preliminary characterization of these factors revealed that they are protease and heat sensitive, extractable by organic solvents, and possess molecular weight values greater than 100,000 daltons; and (4) incubation of NaOH-pretreated corneas with 0.01% citric acid for 2 hours markedly inhibited the production of LCF for both neutrophils (98% inhibition) and mononuclear cells (91% inhibition). Results of these studies indicate that alkali-burned bovine and human corneas generate leukocyte chemoattractants which differ in their biochemical characteristics from previously known low molecular weight chemotactic factors such as C5a, interleukin-1, or leukotriene B4.

An investigation into the effect of different intakes of vitamin C on drug metabolism in Gambian men.

Hepatic mixed-function oxidase activity was measured in Gambian men during a period of low seasonal vitamin C intake and after vitamin C supplementation. Demethylation of methoxyphenylacetamide (methacetin) was followed using a breath test, in which the exhalation of 13C-enriched CO2 was measured following an oral dose of 13C-methacetin. Vitamin C supplementation, sufficient to increase plasma levels significantly, did not influence methacetin metabolism. However, methacetin metabolism in unsupplemented men appeared normal in the majority of cases. Hepatic tissue may not have been sufficiently depleted of vitamin C to impair the activity of the mixed function oxidase system.

Enophthalmos secondary to maxillary sinus disease: single-stage operative management.

Maxillary sinus disease can lead to dehiscence of the orbital floor. Using endoscopic sinus surgery it is possible to simultaneously reconstruct the orbital floor and to assess and treat the underlying sinus disease.

Endoscopic holmium:YAG laser dacryocystorhinostomy-safe and effective as a day-case procedure.

Endoscopic holmium laser dacryocystorhinostomy can be used safely and efficiently to relieve symptoms of distal nasolacrimal duct obstruction. It has great advantages over the conventional external approach as it can be done as a day-case procedure under local anaesthesia. The excellent ablation of bone and soft tissue using this type of laser contribute to the fact that the procedure can be performed in a mean time of 20 minutes. We report on the results of our first 50 patients and review the literature on the subject.

Wegener's granulomatosis: The ocular manifestations revisited.

AIM. To investigate whether the extent of ocular morbidity had de-creased as a result of improved diagnosis, awareness and treatment of Wegener 's granulomatosis (WG). MATERIALS AND METHODS. A retrospective study of all patients with ophthalmic involvement due to WG over an 8-year period. RESULTS. Forty-nine patients were diagnosed to have WG. Of these, 28 had ocular involvement: 21 patients had focal ocular involvement (conjunctivitis, episcleritis, scleritis, keratitis, iritis, retinitis)and 7 had orbital involvement. Permanent visual loss occurred in three patients with orbital involvement, but in no patients with focal ocular disease. Up to 90% of patients had systemic involvement. Three deaths oc- curred among those with ocular involvement. CONCLUSIONS. Patients with WG have a much improved visual prog- nosis as a result of early diagnosis and intervention with systemic im- munosuppression. A combination of assays for ANCA and tissue biop-sies were needed to establish the diagnosis of WG. Treatment with immunosuppressive agents (usually prednisolone and cyclophospha- mide)led to a good response in the majority of cases.

Issues raised by a case of orbital metastatic disease.

The clinical, radiological and histopathological findings in an 81-year-old man presenting with lung carcinoma metastatic to the orbit are described. Orbital biopsy was complicated by postoperative visual loss and failed to contribute significantly to the final diagnosis. The authors believe that in cases of possible orbital metastases a primary neoplasm should be excluded by means of a complete oncological assessment before proceeding to biopsy.

Dacryocystorhinostomy in nasolacrimal duct obstruction secondary to sarcoidosis.

Over the past 3 years we have treated 4 patients with nasolacrimal duct obstruction secondary to sarcoidosis. These patients have had mixed outcomes following endonasal laser-assisted dacryocystorhinostomy (DCR). A literature search from 1966 to the present yielded a further 11 cases of patients thought to have sarcoid who underwent DCR. The outcome of these 15 patients indicate that while all were initially successful, the subsequent failure rate is high. These patients are older than the majority of patients with sarcoidosis and there is a female preponderance. Systemic steroids reversed obstruction in one patient. We recommend nasal examination in all patients with nasal symptoms in whom DCR is proposed to help identify sarcoidosis or other intranasal disease and/or to allow treatment of specific diseases prior to surgery.

Quality of life outcomes following dacryocystorhinostomy: external and endonasal laser techniques compared.

AIMS/BACKGROUND. Endonasal laser dacryocystorhinostomy (ELDCR) has recently become established as an alternative technique to conventional external DCR (EXDCR) for relief of epiphora. The aim of this study was to compare quality of life and symptomatic outcomes in patients treated by these two methods. METHODS. A postal questionnaire was sent to 204 ELDCR and 78 EXDCR patients who had undergone surgery under our care more than 6 months previously. The questionnaire included the validated 18-item Glasgow Benefit Inventory (GBI) and 5 further questions addressing ocular symptomatology. RESULTS. Fully completed questionnaires were received from 156 ELDCR and 50 EXDCR patients. Mean GBI scores of +16.8 (ELDCR) and +23.2 (EXDCR) were obtained (Mann-Whitney U test = NS). Ocular symptom scores were +33 (ELDCR) and +54 (EXDCR) (p=0.005). CONCLUSION. Patients undergoing either ELDCR or EXDCR experience significant benefit in their healthcare status as detected by the GBI. There is no significant difference between the scores obtained by the two groups of patients. There were improvements in ocular symptom scores in both groups, with patients who had EXDCR scoring significantly better than the ELDCR group.