Peri-operative cardiac arrest in the older frail patient as reported to the 7th National Audit Project of the Royal College of Anaesthetists.

Frailty increases peri-operative risk, but details of its burden, clinical features and the risk of, and outcomes following, peri-operative cardiac arrest are lacking. As a preplanned analysis of the 7th National Audit Project of the Royal College of Anaesthetists, we described the characteristics of older patients living with frailty undergoing anaesthesia and surgery, and those reported to the peri-operative cardiac arrest case registry. In the activity survey, 1676 (26%) of 6466 patients aged > 65 y were reported as frail (Clinical Frailty Scale score ≥ 5). Increasing age and frailty were both associated with increasing comorbidities and the proportion of surgery undertaken as an emergency. Except in patients who were terminally ill (Clinical Frailty Scale score 9), increasing frailty was associated with an increased proportion of complex or major surgery. The rate of use of invasive arterial blood pressure monitoring was associated with frailty only until Clinical Frailty Scale score 5, and then plateaued or fell. Of 881 cardiac arrests reported to the 7th National Audit Project, 156 (18%) were in patients aged > 65 y and living with frailty, with an estimated incidence of 1 in 1204 (95%CI 1 in 1027-1412) and a mortality rate of 1 in 2020 (95%CI 1 in 1642-2488), approximately 2.6-fold higher than in adults who were not frail. Hip fracture, emergency laparotomy, emergency vascular surgery and urological surgery were the most common surgical procedures in older patients living with frailty who had a cardiac arrest. We report a high burden of frailty within the surgical population, requiring complex, urgent surgery, and the extent of poorer outcomes of peri-operative cardiac arrest compared with patients of the same age not living with frailty.

Peri-operative cardiac arrest in children as reported to the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project of the Royal College of Anaesthetists studied peri-operative cardiac arrest. An activity survey estimated UK paediatric anaesthesia annual caseload as 390,000 cases, 14% of the UK total. Paediatric peri-operative cardiac arrests accounted for 104 (12%) reports giving an incidence of 3 in 10,000 anaesthetics (95%CI 2.2-3.3 per 10,000). The incidence of peri-operative cardiac arrest was highest in neonates (27, 26%), infants (36, 35%) and children with congenital heart disease (44, 42%) and most reports were from tertiary centres (88, 85%). Frequent precipitants of cardiac arrest in non-cardiac surgery included: severe hypoxaemia (20, 22%); bradycardia (10, 11%); and major haemorrhage (9, 8%). Cardiac tamponade and isolated severe hypotension featured prominently as causes of cardiac arrest in children undergoing cardiac surgery or cardiological procedures. Themes identified at review included: inappropriate choices and doses of anaesthetic drugs for intravenous induction; bradycardias associated with high concentrations of volatile anaesthetic agent or airway manipulation; use of atropine in the place of adrenaline; and inadequate monitoring. Overall quality of care was judged by the panel to be good in 64 (62%) cases, which compares favourably with adults (371, 52%). The study provides insight into paediatric anaesthetic practice, complications and peri-operative cardiac arrest.

Independent sector and peri-operative cardiac arrest as reported to the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project (NAP7) of the Royal College of Anaesthetists studied peri-operative cardiac arrest including those that occurred in the independent healthcare sector, which provides around 1 in 6 NHS-funded care episodes. In total, 174 (39%) of 442 independent hospitals contacted agreed to participate. A survey examining provider preparedness for cardiac arrest had a response rate of 23 (13%), preventing useful analysis. An activity survey with 1912 responses (from a maximum of 45% of participating hospitals) showed that, compared with the NHS caseload, the independent sector caseload was less comorbid, with fewer patients at the extremes of age or who were severely obese, and with a large proportion of elective orthopaedic surgery undertaken during weekday working hours. The survey suggested suboptimal compliance rates with monitoring recommendations. Seventeen reports of independent sector peri-operative cardiac arrest comprised 2% of NAP7 reports and underreporting is likely. These patients were lower risk than NHS cases, reflecting the sector's case mix, but included cases of haemorrhage, anaphylaxis, cardiac arrhythmia and pulmonary embolus. Good and poor quality care were seen, the latter including delayed recognition and treatment of patient deterioration, and poor care delivery. Independent sector outcomes were similar to those in the NHS, though due to the case mix, improved outcomes might be anticipated. Assessment of quality of care was less often favourable for independent sector reports than NHS reports, though assessments were often uncertain, reflecting poor quality reports. Overall, NAP7 is unable to determine whether peri-operative care relating to cardiac arrest is more, equally or less safe than in the NHS.

Cardiac arrest in vascular surgical patients receiving anaesthetic care: an analysis from the 7th National Audit Project (NAP7) of the Royal College of Anaesthetists.

The 7th National Audit Project of the Royal College of Anaesthetists studied peri-operative cardiac arrest in the UK. We report the results of the vascular surgery cohort from the 12-month case registry, from 16 June 2021 to 15 June 2022. Anaesthesia for vascular surgery accounted for 2% of UK anaesthetic caseload and included 69 (8%) reported peri-operative cardiac arrests, giving an estimated incidence of 1 in 670 vascular anaesthetics (95%CI 1 in 520-830). The high-risk nature of the vascular population is reflected by the proportion of patients who were ASA physical status 4 (30, 43%) or 5 (19, 28%); the age of patients (80% aged > 65 y); and that most cardiac arrests (57, 83%) occurred during non-elective surgery. The most common vascular surgical procedures among patients who had a cardiac arrest were: aortic surgery (38, 55%); lower-limb revascularisation (13, 19%); and lower-limb amputation (8, 12%). Among patients having vascular surgery and who had a cardiac arrest, 28 (41%) presented with a ruptured abdominal aortic aneurysm. There were 48 (70%) patients who had died at the time of reporting to NAP7 and 11 (16%) were still in hospital, signifying poorer outcomes compared with the non-vascular surgical cohort. The most common cause of cardiac arrest was major haemorrhage (39, 57%), but multiple other causes reflected the critical illness of the patients and the complexity of surgery. This is the first analysis of the incidence, management and outcomes of peri-operative cardiac arrest during vascular anaesthesia in the UK.

Cardiac arrest in obstetric patients receiving anaesthetic care: results from the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project (NAP7) of the Royal College of Anaesthetists studied peri-operative cardiac arrest. Additional inclusion criteria for obstetric anaesthesia were: cardiac arrest associated with neuraxial block performed by an anaesthetist outside the operating theatre (labour epidural analgesia); and cardiac arrest associated with remifentanil patient-controlled analgesia. There were 28 cases of cardiac arrest in obstetric patients, representing 3% of all cardiac arrests reported to NAP7, giving an incidence of 7.9 per 100,000 (95%CI 5.4-11.4 per 100,000). Obstetric patients were approximately four times less likely to have a cardiac arrest during anaesthesia care than patients having non-obstetric surgery. The single leading cause of peri-operative cardiac arrest in obstetric patients was haemorrhage, with underestimated severity and inadequate early resuscitation being contributory factors. When taken together, anaesthetic causes, high neuraxial block and bradyarrhythmia associated with spinal anaesthesia were the leading causes overall. Two patients had a cardiac arrest related to labour neuraxial analgesia. There were no cardiac arrests related to failed airway management or remifentanil patient-controlled analgesia.

Peri-operative decisions about cardiopulmonary resuscitation among adults as reported to the 7th National Audit Project of the Royal College of Anaesthetists.

Current guidance recommends that, in most circumstances, cardiopulmonary resuscitation should be attempted when cardiac arrest occurs during anaesthesia, and when a patient has a pre-existing 'do not attempt cardiopulmonary resuscitation' recommendation, this should be suspended. How this guidance is translated into everyday clinical practice in the UK is currently unknown. Here, as part of the 7th National Audit Project of the Royal College of Anaesthetists, we have: assessed the rates of pre-operative 'do not attempt cardiopulmonary resuscitation' recommendations via an activity survey of all cases undertaken by anaesthetists over four days in each participating site; and analysed our one-year case registry of peri-operative cardiac arrests to understand the rates of cardiac arrest in patients who had 'do not attempt cardiopulmonary resuscitation' decisions pre-operatively. In the activity survey, among 20,717 adults (aged > 18 y) undergoing surgery, 595 (3%) had a 'do not attempt cardiopulmonary resuscitation' recommendation pre-operatively, of which less than a third (175, 29%) were suspended. Of the 881 peri-operative cardiac arrest reports, 54 (6%) patients had a 'do not attempt cardiopulmonary resuscitation' recommendation made pre-operatively and of these 38 (70%) had a clinical frailty scale score ≥ 5. Just under half (25, 46%) of these 'do not attempt cardiopulmonary resuscitation' recommendations were formally suspended at the time of anaesthesia and surgery. One in five of these patients with a 'do not attempt cardiopulmonary resuscitation' recommendation who had a cardiac arrest survived to leave hospital and of the seven patients with documented modified Rankin Scale scores before and after cardiac arrest, four remained the same and three had worse scores. Very few patients who had a pre-existing 'do not attempt cardiopulmonary resuscitation' recommendation had a peri-operative cardiac arrest, and when cardiac arrest did occur, return of spontaneous circulation was achieved in 57%, although > 50% of these patients subsequently died before discharge from hospital.

Peri-operative cardiac arrest: epidemiology and clinical features of patients analysed in the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project of the Royal College of Anaesthetists studied peri-operative cardiac arrest in the UK, a topic of importance to patients, anaesthetists and surgeons. Here we report the results of the 12-month registry, from 16 June 2021 to 15 June 2022, focusing on epidemiology and clinical features. We reviewed 881 cases of peri-operative cardiac arrest, giving an incidence of 3 in 10,000 anaesthetics (95%CI 3.0-3.5 per 10,000). Incidence varied with patient and surgical factors. Compared with denominator survey activity, patients with cardiac arrest: included more males (56% vs. 42%); were older (median (IQR) age 60.5 (40.5-80.5) vs. 50.5 (30.5-70.5) y), although the age distribution was bimodal, with infants and patients aged > 66 y overrepresented; and were notably more comorbid (73% ASA physical status 3-5 vs. 27% ASA physical status 1-2). The surgical case-mix included more weekend (14% vs. 11%), out-of-hours (19% vs. 10%), non-elective (65% vs. 30%) and major/complex cases (60% vs. 28%). Cardiac arrest was most prevalent in orthopaedic trauma (12%), lower gastrointestinal surgery (10%), cardiac surgery (9%), vascular surgery (8%) and interventional cardiology (6%). Specialities with the highest proportion of cases relative to denominator activity were: cardiac surgery (9% vs. 1%); cardiology (8% vs. 1%); and vascular surgery (8% vs. 2%). The most common causes of cardiac arrest were: major haemorrhage (17%); bradyarrhythmia (9%); and cardiac ischaemia (7%). Patient factors were judged a key cause of cardiac arrest in 82% of cases, anaesthesia in 40% and surgery in 35%.

The incidence of potentially serious complications during non-obstetric anaesthetic practice in the United Kingdom: an analysis from the 7th National Audit Project (NAP7) activity survey.

Complications and critical incidents arising during anaesthesia due to patient, surgical or anaesthetic factors, may cause harm themselves or progress to more severe events, including cardiac arrest or death. As part of the 7th National Audit Project of the Royal College of Anaesthetists, we studied a prospective national cohort of unselected patients. Anaesthetists recorded anonymous details of all cases undertaken over 4 days at their site through an online survey. Of 416 hospital sites invited to participate, 352 (85%) completed the survey. Among 24,172 cases, 1922 discrete potentially serious complications were reported during 1337 (6%) cases. Obstetric cases had a high reported major haemorrhage rate and were excluded from further analysis. Of 20,996 non-obstetric cases, 1705 complications were reported during 1150 (5%) cases. Circulatory events accounted for most complications (616, 36%), followed by airway (418, 25%), metabolic (264, 15%), breathing (259, 15%), and neurological (41, 2%) events. A single complication was reported in 851 (4%) cases, two complications in 166 (1%) cases and three or more complications in 133 (1%) cases. In non-obstetric elective surgery, all complications were 'uncommon' (10-100 per 10,000 cases). Emergency (urgent and immediate priority) surgery accounted for 3454 (16%) of non-obstetric cases but 714 (42%) of complications with severe hypotension, major haemorrhage, severe arrhythmias, septic shock, significant acidosis and electrolyte disturbances all being 'common' (100-1000 per 10,000 cases). Based on univariate analysis, complications were associated with: younger age; higher ASA physical status; male sex; increased frailty; urgency and extent of surgery; day of the week; and time of day. These data represent the rates of potentially serious complications during routine anaesthesia care and may be valuable for risk assessment and patient consent.

Predicting severe pain after major surgery: a secondary analysis of the Peri-operative Quality Improvement Programme (PQIP) dataset.

Acute postoperative pain is common, distressing and associated with increased morbidity. Targeted interventions can prevent its development. We aimed to develop and internally validate a predictive tool to pre-emptively identify patients at risk of severe pain following major surgery. We analysed data from the UK Peri-operative Quality Improvement Programme to develop and validate a logistic regression model to predict severe pain on the first postoperative day using pre-operative variables. Secondary analyses included the use of peri-operative variables. Data from 17,079 patients undergoing major surgery were included. Severe pain was reported by 3140 (18.4%) patients; this was more prevalent in females, patients with cancer or insulin-dependent diabetes, current smokers and in those taking baseline opioids. Our final model included 25 pre-operative predictors with an optimism-corrected c-statistic of 0.66 and good calibration (mean absolute error 0.005, p = 0.35). Decision-curve analysis suggested an optimal cut-off value of 20-30% predicted risk to identify high-risk individuals. Potentially modifiable risk factors included smoking status and patient-reported measures of psychological well-being. Non-modifiable factors included demographic and surgical factors. Discrimination was improved by the addition of intra-operative variables (likelihood ratio χ2 496.5, p < 0.001) but not by the addition of baseline opioid data. On internal validation, our pre-operative prediction model was well calibrated but discrimination was moderate. Performance was improved with the inclusion of peri-operative covariates suggesting pre-operative variables alone are not sufficient to adequately predict postoperative pain.

The impact of COVID-19 on anaesthesia and critical care services in the UK: a serial service evaluation.

Between October 2020 and January 2021, we conducted three national surveys to track anaesthetic, surgical and critical care activity during the second COVID-19 pandemic wave in the UK. We surveyed all NHS hospitals where surgery is undertaken. Response rates, by round, were 64%, 56% and 51%. Despite important regional variations, the surveys showed increasing systemic pressure on anaesthetic and peri-operative services due to the need to support critical care pandemic demands. During Rounds 1 and 2, approximately one in eight anaesthetic staff were not available for anaesthetic work. Approximately one in five operating theatres were closed and activity fell in those that were open. Some mitigation was achieved by relocation of surgical activity to other locations. Approximately one-quarter of all surgical activity was lost, with paediatric and non-cancer surgery most impacted. During January 2021, the system was largely overwhelmed. Almost one-third of anaesthesia staff were unavailable, 42% of operating theatres were closed, national surgical activity reduced to less than half, including reduced cancer and emergency surgery. Redeployed anaesthesia staff increased the critical care workforce by 125%. Three-quarters of critical care units were so expanded that planned surgery could not be safely resumed. At all times, the greatest resource limitation was staff. Due to lower response rates from the most pressed regions and hospitals, these results may underestimate the true impact. These findings have important implications for understanding what has happened during the COVID-19 pandemic, planning recovery and building a system that will better respond to future waves or new epidemics.

Regional anaesthesia practice for arteriovenous fistula formation surgery.

We conducted a survey and semi-structured qualitative interviews to investigate current anaesthetic practice for arteriovenous fistula formation surgery in the UK. Responses were received from 39 out of 59 vascular centres where arteriovenous access surgery is performed, a response rate of 66%. Thirty-five centres reported routine use of brachial plexus blocks, but variation in anaesthetic skill-mix and practice were observed. Interviews were conducted with 19 clinicians from 10 NHS Trusts including anaesthetists, vascular access and renal nurses, surgeons and nephrologists. Thematic analysis identified five key findings: (1) current anaesthetic practice showed that centres could be classified as 'regional anaesthesia dominant' or 'local anaesthesia/mixed'; (2) decision making around mode of anaesthesia highlighted the key role of surgeons as frontline decision makers across both centre types; (3) perceived barriers and facilitators of regional block use included clinicians' beliefs and preferences, resource considerations and patients' treatment preferences; (4) anaesthetists' preference for supraclavicular blocks emerged, alongside acknowledgement of varied practice; (5) there was widespread support for a future randomised controlled trial, although clinician equipoise issues and logistical/resource-related concerns were viewed as potential challenges. The use of regional anaesthesia for arteriovenous fistula formation in the UK is varied and influenced by a multitude of factors. Despite the availability of anaesthetists capable of performing regional blocks, there are other limiting factors that influence the routine use of this technique. The study also highlighted the perceived need for a large multicentre, randomised controlled trial to provide an evidence base to inform current practice.

Qualitative study of clinician and patient perspectives on the mode of anaesthesia for emergency surgery.

BACKGROUND: Although delivering a chosen mode of anaesthesia for certain emergency surgery procedures is potentially beneficial to patients, it is a complex intervention to evaluate. This qualitative study explored clinician and patient perspectives about mode of anaesthesia for emergency surgery. METHODS: Snowball sampling was used to recruit participants from eight National Health Service Trusts that cover the following three emergency surgery settings: ruptured abdominal aortic aneurysms, hip fractures and inguinal hernias. A qualitative researcher conducted interviews with clinicians and patients. Thematic analysis was applied to the interview transcripts. RESULTS: Interviews were conducted with 21 anaesthetists, 21 surgeons, 14 operating theatre staff and 23 patients. There were two main themes. The first, impact of mode of anaesthesia in emergency surgery, had four subthemes assessing clinician and patient ideas about: context and the 'best' mode of anaesthesia; balance in choosing it over others; change and developments in anaesthesia; and the importance of mode of anaesthesia in emergency surgery. The second, tensions in decision-making about mode of anaesthesia, comprised four subthemes: clinical autonomy and guidelines in anaesthesia; conforming to norms in mode of anaesthesia; the relationship between expertise, preference and patient involvement; and team dynamics in emergency surgery. The results highlight several interlinking factors affecting decision-making, including expertise, preference, habit, practicalities, norms and policies. CONCLUSION: There is variation in practice in choosing the mode of anaesthesia for surgery, alongside debate as to whether anaesthetic autonomy is necessary or results in a lack of willingness to change.

ANTECEDENTES: Si bien determinados tipos de anestesia en ciertos procedimientos quirúrgicos de urgencia pueden ser potencialmente beneficiosos para los pacientes, la decisión de su utilización es difícil de evaluar. Este estudio cualitativo exploró las perspectivas del clínico y del paciente sobre sobre el tipo de anestesia en cirugía de urgencia. MÉTODOS: Se utilizó un muestreo de bola de nieve para reclutar participantes de 8 corporaciones del National Health Service (NHS) que cubrían tres entornos de cirugía de urgencia: rotura de aneurismas aórticos abdominales, fracturas de cadera y hernias inguinales. Un investigador cualitativo realizó 79 entrevistas a 21 anestesistas, 21 cirujanos, 14 técnicos de quirófano y 23 pacientes. Se realizó un análisis de las transcripciones de la entrevista por temas. RESULTADOS: Dos fueron los temas principales. El primero era el impacto del tipo de anestesia en la cirugía de urgencia y tenía 4 subtemas que evaluaban las ideas del clínico y del paciente sobre: el contexto y el mejor tipo de anestesia, las ventajas e inconvenientes de la elección de un tipo sobre los otros, los cambios y avances en anestesia, y la importancia de la anestesia en cirugía de urgencias. El segundo era las dificultades en la toma de decisiones sobre el tipo de anestesia y comprendía 4 subtemas: la autonomía clínica y las guías de anestesia, el seguimiento de las normas en el tipo de anestesia, la relación entre experiencia, preferencia y opinión del paciente, así como las dinámicas del equipo en cirugía de urgencia. Los resultados resaltaron varios factores interconectados que afectan la toma de decisiones, incluyen la experiencia, las preferencias, los hábitos, algunos aspectos prácticos, las normas y las políticas. CONCLUSIÓN: En la práctica, existen variaciones en la elección del tipo de anestesia para la cirugía, junto con el debate sobre si la autonomía anestésica es necesaria o si resulta en una falta de voluntad para el cambio.

Survival in the pre-senile dementia frontotemporal lobar degeneration with TDP-43 proteinopathy: effects of genetic, demographic and neuropathological variables.

Factors associated with survival were studied in 84 neuropathologically documented cases of the pre-senile dementia frontotemporal dementia lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). Kaplan-Meier survival analysis estimated mean survival as 7.9 years (range: 1-19 years, SD = 4.64). Familial and sporadic cases exhibited similar survival, including progranulin (GRN) gene mutation cases. No significant differences in survival were associated with sex, disease onset, Braak disease stage, or disease subtype, but higher survival was associated with lower post-mortem brain weight. Survival was significantly reduced in cases with associated motor neuron disease (FTLD-MND) but increased with Alzheimer's disease (AD) or hippocampal sclerosis (HS) co-morbidity. Cox regression analysis suggested that reduced survival was associated with increased densities of neuronal cytoplasmic inclusions (NCI) while increased survival was associated with greater densities of enlarged neurons (EN) in the frontal and temporal lobes. The data suggest that: (1) survival in FTLD-TDP is more prolonged than typical in pre-senile dementia but shorter than some clinical subtypes such as the semantic variant of primary progressive aphasia (svPPA), (2) MND co-morbidity predicts poor survival, and (3) NCI may develop early and EN later in the disease. The data have implications for both neuropathological characterization and subtyping of FTLD-TDP.

Clustering and spatial correlations of the neuronal cytoplasmic inclusions, astrocytic plaques and ballooned neurons in corticobasal degeneration.

This study tested three hypotheses: (1) that there is clustering of the neuronal cytoplasmic inclusions (NCI), astrocytic plaques (AP) and ballooned neurons (BN) in corticobasal degeneration (CBD), (2) that the clusters of NCI and BN are not spatially correlated, and (3) that the lesions are correlated with disease 'stage'. In 50% of the regions, clusters of lesions were 400-800 mum in diameter and regularly distributed parallel to the tissue boundary. Clusters of NCI and BN were larger in laminae II/III and V/VI, respectively. In a third of regions, the clusters of BN and NCI were negatively spatially correlated. Cluster size of the BN in the parahippocampal gyrus (PHG) was positively correlated with disease 'stage'. The data suggest the following: (1) degeneration of the cortico-cortical pathways in CBD, (2) clusters of NCI and BN may affect different anatomical pathways and (3) BN may develop after the NCI in the PHG.

Spatial patterns of the pathological changes in neuronal intermediate filament inclusion disease (NIFID): an alpha-internexin immunohistochemical study.

Neuronal intermediate filament inclusion disease (NIFID) is characterized by alpha-internexin positive neuronal cytoplasmic inclusions (NCI), swollen achromatic neurons (SN), neuronal loss, and gliosis. This study tested: 1) whether the spatial patterns of the lesions was topographically organized in areas of the frontal and temporal lobe and 2) whether a spatial relationship exists between the NCI and SN. The NCI were distributed in regular clusters and in a quarter of these areas, the clusters were 400-800 microm in diameter approximating to the size of the cells of origin of the cortico-cortical pathways. Variations in the density of the NCI were positively correlated with the SN. Hence, cortical degeneration in NIFID appears to be topographically organized and may affect the cortico-cortical projections, the clusters of NCI and SN developing within the same vertical columns of cells.

Laminar degeneration of the frontal and temporal cortex in neuronal intermediate filament inclusion disease (NIFID): a study original using alpha-internexin immunohistochemistry.

OBJECTIVE: To determine the laminar distribution of the pathological changes in the frontal and temporal lobe in neuronal intermediate filament inclusion disease (NIFID). METHOD: The distribution of the alpha-internexin-positive neuronal cytoplasmic inclusions (NCI), surviving neurons, swollen achromatic neurons (SN) and glial cell nuclei was studied across the cortex in gyri of the frontal and temporal lobe in 10 cases of NIFID. RESULTS: The distribution of the NCI was highly variable within different gyri, a peak in the upper cortex, a bimodal distribution with peaks of density in the upper and lower laminae, or no significant variation in density across the cortex. The surviving neurons were either bimodally distributed or exhibited no significant change in density across the cortex. The SN and glial cell nuclei were most abundant in the lower cortical laminae. In half of the gyri, variations in density of the NCI across the cortex were positively correlated with the SN. In some gyri, the surviving neurons were positively correlated with the SN and negatively correlated with the glial cell nuclei. In addition, the SN and glial cell nuclei were positively correlated in over half the gyri studied. CONCLUSION: The data suggest that frontal and temporal lobe degeneration in NIFID characterized by NCI, SN, neuronal loss and gliosis extends across the cortical laminae with considerable variation between cases and gyri. alpha-internexin-positive neurons in the upper laminae appear to be particularly vulnerable. The gliosis appears to be largely correlated with the appearance of SN and with neuronal loss and not related to the NCI.

Fish oil before cardiac surgery: neutrophil activation is unaffected but myocardial damage is moderated.

Could pre-operative dietary intervention with fish oil reduce neutrophil activation and myocardial damage associated with cardiopulmonary bypass (CPB)? Patients were randomised to receive either 8 g/day fish oil (n=22) or placebo (n=18) for 6 weeks. Neutrophil activation, apoptosis and cardiac damage were measured. Demographics and operative variables were similar. Fish oil diet decreased plasma VLDL from 0.69+/-0.34 to 0.51+/-0.24 mmol/l and triglycerides from 1.68+/-0.70 to 1.39+/-0.54 mmol/l. HDL cholesterol increased from 0.94+/-0.27 to 1.03+/-0.26 mmol/l demonstrating significant treatment effects (P=0.007, 0.02 and 0.0003, respectively) as well as compliance with treatment. There were no significant differences in ex vivo N-formyl-methionyl-leucyl-phenylalanine-stimulated neutrophil superoxide anion generation or myeloperoxidase release at recruitment, pre-operatively and at end-CPB. Apoptosis at end-CPB was equally reduced in both groups from 23+/-9% to 13+/-4% in the fish oil group (P<0.001) and 35+/-14% to 15+/-3% in the placebo group (P=0.001). At end-CPB overall troponin I levels averaged 0.91+/-0.60 ng/ml which clearly exceeded diagnostic levels (0.15 ng/ml). At 24h troponin I fell significantly in the fish oil group to 46+/-23% of end-CPB levels (P=0.0002) whereas it peaked in the placebo group to 107+/-72% (P=0.098 vs. end-CPB); this difference was significant: P=0.013. At 48 h the placebo-treated patients had higher troponins but not significantly so (P=0.059). Area-under-the-curve analysis did not conclusively support this (P=0.068). We conclude that fish oil did not significantly decrease post-CPB neutrophil activation (as detected ex vivo) but may moderate post-operative myocardial damage.

Analysis of Acanthamoeba polyphaga surface carbohydrate exposure by FITC-lectin binding and fluorescence evaluation.

AIMS: Characterization of the representative protozoan Acanthamoeba polyphaga surface carbohydrate exposure by a novel combination of flow cytometry and ligand-receptor analysis. METHODS AND RESULTS: Trophozoite and cyst morphological forms were exposed to a panel of FITC-lectins. Population fluorescence associated with FITC-lectin binding to acanthamoebal surface moieties was ascertained by flow cytometry. Increasing concentrations of representative FITC-lectins, saturation binding and determination of K(d) and relative B(max) values were employed to characterize carbohydrate residue exposure. FITC-lectins specific for N-acetylglucosamine, N-acetylgalactosamine and mannose/glucose were readily bound by trophozoite and cyst surfaces. Minor incremental increases in FITC-lectin concentration resulted in significant differences in surface fluorescence intensity and supported the calculation of ligand-binding determinants, K(d) and relative B(max), which gave a trophozoite and cyst rank order of lectin affinity and surface receptor presence. CONCLUSIONS: Trophozoites and cysts expose similar surface carbohydrate residues, foremost amongst which is N-acetylglucosamine, in varying orientation and availability. SIGNIFICANCE AND IMPACT OF THE STUDY: The outlined versatile combination of flow cytometry and ligand-receptor analysis allowed the characterization of surface carbohydrate exposure by protozoan morphological forms and in turn will support a valid comparison of carbohydrate exposure by other single-cell protozoa and eucaryotic microbes analysed in the same manner.

The microbiology of the eye.

Infection of the external structures of the eye is one of the commonest types of eye disease worldwide. In addition, although relatively impermeable to microorganisms, infection within the eye can result from trauma, surgery or systemic disease. This article reviews the general biology of viruses, bacteria, fungi and protozoa and the major ocular infections that they cause. In addition, the effectiveness of the various antimicrobial agents in controlling ocular disease is discussed. Because of changes in the normal ocular flora, continuous monitoring of the microbiology of the eye will continue to be important in predicting future types of eye infection. Basic research is also needed into the interactions of microbes at the ocular surface. There is increasing microbial resistance to the antimicrobial agents used to treat ocular infections and hence, new antimicrobial agents will continue to be needed together with new methods of drug delivery to increase the effectiveness of existing antimicrobial agents.