Selection of baseline blood pressure to guide management of hypotension during spinal anaesthesia for caesarean section.

INTRODUCTION: Recommendations on vasopressor management during caesarean section under spinal anaesthesia suggest maintaining systolic arterial pressure ≥90% of an accurately measured baseline value. The baseline is often taken as the first reading in the operating room. We hypothesise that this reading may not reflect an accurate baseline value. METHODS: A retrospective case note review of 300 non-hypertensive women undergoing caesarean section with neuraxial anaesthesia, including spinal anaesthesia for elective delivery (n=100), and spinal (n=100) and epidural top-up anaesthesia (n=100) for emergency delivery. Systolic arterial pressure values recorded at various time points between the last antenatal visit and the first blood pressure value recorded in the operating room were compared. RESULTS: There was a stepwise and significant increase in systolic arterial pressure over three time points (last antenatal clinic, morning of surgery, operating room) before elective caesarean section (all P <0.001). In women having emergency caesarean under spinal anaesthesia, a stepwise increase over four time points (last antenatal clinic, first reading in labour, final reading in labour, operating room) was observed. A similar trend was seen over these time points for women having emergency caesarean under epidural top-up, although the systolic blood pressure did not rise during labour. CONCLUSIONS: Using the initial blood pressure reading in the operating room as the baseline value may lead to unnecessary vasopressor use and hypertension. Prospective research is required to clarify which reading represents the most accurate baseline to maintain homeostasis and reduce the hypotensive sequelae of neuraxial anaesthesia for both the mother and fetus.

Dynapenic Abdominal Obesity Increases Mortality Risk among English and Brazilian Older Adults: A 10-Year Follow-Up of the ELSA and SABE Studies.

BACKGROUND/OBJECTIVE: There is little epidemiological evidence demonstrating that dynapenic abdominal obesity has higher mortality risk than dynapenia and abdominal obesity alone. Our main aim was to investigate whether dynapenia combined with abdominal obesity increases mortality risk among English and Brazilian older adults over ten-year follow-up. DESIGN: Cohort study. SETTING: United Kingdom and Brazil. PARTICIPANTS: Data came from 4,683 individuals from the English Longitudinal Study of Ageing (ELSA) and 1,490 from the Brazilian Health, Well-being and Aging study (SABE), hence the final sample of this study was 6,173 older adults. MEASUREMENTS: The study population was categorized into the following groups: non-dynapenic/non-abdominal obese, abdominal obese, dynapenic, and dynapenic abdominal obese according to their handgrip strength (< 26 kg for men and < 16 kg for women) and waist circumference (> 102 cm for men and > 88 cm for women). The outcome was all-cause mortality over a ten-year follow-up. Adjusted hazard ratios by sociodemographic, behavioural and clinical characteristics were estimated using Cox proportional hazards models. RESULTS: The fully adjusted model showed that dynapenic abdominal obesity has a higher mortality risk among the groups. The hazard ratios (HR) were 1.37 for dynapenic abdominal obesity (95% CI = 1.12 - 1.68), 1.15 for abdominal obesity (95% CI = 0.98 - 1.35), and 1.23 for dynapenia (95% CI = 1.04 - 1.45). CONCLUSIONS: Dynapenia is an important risk factor for mortality but dynapenic abdominal obesity has the highest mortality risk among English and Brazilian older adults.

Histological assessment of ß-amyloid precursor protein immunolabelled rectal biopsies aids diagnosis of equine grass sickness.

BACKGROUND: An accurate, minimally invasive, ante-mortem diagnostic test for equine grass sickness (EGS) is currently lacking. Although histological examination of haematoxylin and eosin-stained rectal biopsies for chromatolytic neurons is insensitive as a diagnostic test for EGS, we hypothesised that its diagnostic accuracy could be improved by immunolabelling for ß-amyloid precursor protein (ß-APP), which has increased expression in cranial cervical ganglia (CCG) neuronal perikarya in EGS. OBJECTIVES: To develop a grading scheme for assessing the distribution and intensity of ß-APP immunoreactivity within individual rectal submucosal neurons and subsequently to determine the value of the distribution of different grades of neurons in EGS diagnosis. STUDY DESIGN: Retrospective case-control diagnostic accuracy study. METHODS: Initially, a standardised grading scheme was developed and ß-APP immunoreactivity in individual neuronal perikarya and axons was compared in sections of CCG and ileum from EGS and control horses. The grading scheme was then refined before being blindly applied to submucosal neurons in rectal biopsies derived from 21 EGS and 23 control horses. RESULTS: ß-APP immunoreactivity was increased in neuronal perikarya and axons in sections of CCG, ileum and rectum from EGS horses compared with controls. For rectal biopsies, a mean immunoreactivity grade exceeding 1.1 was 100% specific and sensitive for EGS, and the presence of at least one neuron with diffuse labelling of the entire cytoplasm (grade 3) was 95% sensitive and 100% specific for EGS. MAIN LIMITATIONS: Although the diagnostic criteria facilitated the discrimination of the EGS and control biopsies evaluated in this study, further prospective validation using a larger sample set is required. CONCLUSIONS: Histological assessment of ß-APP immunolabelled rectal biopsies is more sensitive than conventional histological examination in EGS diagnosis. Further validation is required before this technique can be advocated for use in clinical decision making.

Type 2 diabetes remission 2 years post Roux-en-Y gastric bypass and sleeve gastrectomy: the role of the weight loss and comparison of DiaRem and DiaBetter scores.

AIMS: The comparative efficacy of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy on Type 2 diabetes remission and the role of weight loss are unclear. The DiaRem diabetes remission prediction score uses HbA1c , age and diabetes medications but not diabetes duration. The aim of this study was to compare the DiaRem with the DiaBetter score that includes diabetes duration, upon combined (complete plus partial) 2-year post-surgery diabetes remission in people following RYGB and sleeve gastrectomy, and to investigate the relationship between weight loss and diabetes remission. METHODS: A retrospective single-centre cohort study of obese people with diabetes who underwent RYGB (107) or sleeve gastrectomy (103) and a validation cohort study (173) were undertaken. Diabetes remission, % weight loss, DiaRem, DiaBetter scores and areas under receiving operator characteristic (ROC) curves were calculated. The relationship between % weight loss and diabetes remission was investigated using logistic regression. RESULTS: The proportion of people achieving diabetes remission was highest for those with the lowest DiaBetter and DiaRem scores. Areas under the ROC curves were comparable [DiaBetter: 0.867 (95%CI: 0.817-0.916); DiaRem: 0.865 (95%CI: 0.814-0.915), P=0.856]. Two-year % weight loss was higher post RYGB [26.6 (95%CI: 24.8-28.4)] vs post-sleeve gastrectomy [20.6 (95%CI: 18.3-22.8), P<0.001]. RYGB had 151% higher odds of diabetes remission [OR 2.51 (95%CI: 1.12-5.60), P=0.025]. This association became non-significant when adjusted for % weight loss. CONCLUSION: DiaBetter and DiaRem scores predict diabetes remission following both procedures. Two-year % weight loss plays a key role in determining diabetes remission.

Role of Schmallenberg virus infection in congenital malformations in ruminants in Scotland in 2017.

Scotland's Rural College (SRUC), together with the Moredun Research Institute, carries out surveillance for Schmallenberg virus (SBV) infection in cattle and sheep. This article reports findings relating to diagnoses of fetopathy associated with SBV infection and other congenital malformations in these species made between January 1 and May 5, 2017.

Explant analysis of the Biomet Magnum/ReCap metal-on-metal hip joint.

OBJECTIVES: The high revision rates of the DePuy Articular Surface Replacement (ASR) and the DePuy ASR XL (the total hip arthroplasty (THA) version) have led to questions over the viability of metal-on-metal (MoM) hip joints. Some designs of MoM hip joint do, however, have reasonable mid-term performance when implanted in appropriate patients. Investigations into the reasons for implant failure are important to offer help with the choice of implants and direction for future implant designs. One way to assess the performance of explanted hip prostheses is to measure the wear (in terms of material loss) on the joint surfaces. METHODS: In this study, a coordinate measuring machine (CMM) was used to measure the wear on five failed cementless Biomet Magnum/ReCap/ Taperloc large head MoM THAs, along with one Biomet ReCap resurfacing joint. Surface roughness measurements were also taken. The reason for revision of these implants was pain and/or adverse reaction to metal debris (ARMD) and/or elevated blood metal ion levels. RESULTS: The mean wear rate of the articulating surfaces of the heads and acetabular components of all six joints tested was found to be 6.1 mm3/year (4.1 to 7.6). The mean wear rate of the femoral head tapers of the five THAs was 0.054 mm3/year (0.021 to 0.128) with a mean maximum wear depth of 5.7 µm (4.3 to 8.5). CONCLUSION: Although the taper wear was relatively low, the wear from the articulating surfaces was sufficient to provide concern and was potentially large enough to have been the cause of failure of these joints. The authors believe that patients implanted with the ReCap system, whether the resurfacing prosthesis or the THA, should be closely monitored.Cite this article: S. C. Scholes, B. J. Hunt, V. M. Richardson, D. J. Langton, E. Smith, T. J. Joyce. Explant analysis of the Biomet Magnum/ReCap metal-on-metal hip joint. Bone Joint Res 2017;6:113-122. DOI: 10.1302/2046-3758.62.BJR-2016-0130.R2.

A novel astrovirus associated with encephalitis and ganglionitis in domestic sheep.

In June 2013, a 4-year-old Welsh Mountain ewe and in March 2014 a 10-day-old lamb of the same breed and the same flock presented progressive neurological signs including depressed sensorium, tremor, and unusual behaviour. Neuropathological examination of the brain and spinal cord detected non-suppurative polioencephalomyelitis and dorsal root ganglionitis, characteristic of a neurotropic viral agent in both sheep. Metagenomic analysis of different tissue samples from both animals identified a novel Ovine Astrovirus (OvAstV). The presence of viral genome in the central nervous system was confirmed by RT-qPCR. Although the cases presented nine months apart, the identified OvAstV shared nearly identical sequences, differing in only three nucleotide positions across the complete genome. Phylogenetic analysis revealed a close relation of OvAstV to neurotropic bovine astroviruses and an enteric OvAstV. In conclusion, these are the first reported cases of astrovirus infection in domestic sheep that were associated with encephalitis and ganglionitis.

Equine grass sickness, but not botulism, causes autonomic and enteric neurodegeneration and increases soluble N-ethylmaleimide-sensitive factor attachment receptor protein expression within neuronal perikarya.

REASONS FOR PERFORMING STUDY: Equine grass sickness (EGS) is of unknown aetiology. Despite some evidence suggesting that it represents a toxico-infection with Clostridium botulinum types C and/or D, the effect of EGS on the functional targets of botulinum neurotoxins, namely the soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, is unknown. Further, while it is commonly stated that, unlike EGS, equine botulism is not associated with autonomic and enteric neurodegeneration, this has not been definitively assessed. OBJECTIVES: To determine: 1) whether botulism causes autonomic and enteric neurodegeneration; and 2) the effect of EGS on the expression of SNARE proteins within cranial cervical ganglion (CCG) and enteric neuronal perikarya. STUDY DESIGN: Descriptive study. METHODS: Light microscopy was used to compare the morphology of neurons in haematoxylin-eosin stained sections of CCG and ileum from 6 EGS horses, 5 botulism horses and 6 control horses. Immunohistochemistry was used to compare the expression of synaptosomal-associated protein-25, synaptobrevin (Syb) and syntaxin within CCG neurons, and of Syb in enteric neurons, from horses with EGS, horses with botulism and control horses. The concentrations of these SNARE proteins in extracts of CCG from EGS and control horses were compared using quantitative fluorescent western blotting. RESULTS: EGS, but not botulism, was associated with autonomic and enteric neurodegeneration and with increased immunoreactivity for SNARE proteins within neuronal perikarya. Quantitative fluorescent western blotting confirmed increased concentrations of synaptosomal-associated protein-25, Syb and syntaxin within CCG extracts from EGS vs. control horses, with the increases in the latter 2 proteins being statistically significant. CONCLUSIONS: The occurrence of autonomic and enteric neurodegeneration, and increased expression of SNARE proteins within neuronal perikarya, in EGS but not botulism, suggests that EGS may not be caused by botulinum neurotoxins. Further investigation of the aetiology of EGS is therefore warranted.

In vitro wear testing of a contemporary design of reverse shoulder prosthesis.

Reverse shoulder arthroplasty is an increasingly common surgical intervention. However there are concerns and known limitations in relation to such joint replacement, while novel designs of reverse shoulder prostheses continue to appear on the market. Many claim to offer improvements over older designs but such assertions are difficult to validate when there is no consensus as to how such implants should be tested in vitro or even if such testing is necessary. In order to permit appropriate in vitro testing of reverse shoulder prostheses a unique, multi-station test rig was designed which was capable of applying motion in three axes to test prostheses. The shoulder simulator can apply up to 110° of motion in the flexion-extension and abduction-adduction axes and up to 90° in the internal-external rotation axis. Dynamic loading of up to 1500 N can be provided. The simulator is computer controlled so that the motions and loading associated with particular activities of daily living can be applied. A 4.5 million cycle wear test of commercially available reverse shoulder prostheses was undertaken using a 'mug to mouth' activity of daily living. Gravimetric analysis was used to characterise wear. After 4.5 million cycles of 'mug to mouth', the average wear rate of the test components was 14.3mm(3)/million cycles. Polyethylene test components showed a reduction in roughness and the median wear particle diameter was 167 nm. A three axis shoulder simulator has been designed and used to successfully test multiple samples of a commercially available reverse shoulder prosthesis.

The contribution of primary prevention medication and dietary change in coronary mortality reduction in England between 2000 and 2007: a modelling study.

OBJECTIVE: To analyse the falls in coronary heart disease (CHD) mortality in England between 2000 and 2007 and quantify the relative contributions from preventive medications and population-wide changes in blood pressure (BP) and cholesterol levels, particularly by exploring socioeconomic inequalities. DESIGN: A modelling study. SETTING: Sources of data included controlled trials and meta-analyses, national surveys and official statistics. PARTICIPANTS: English population aged 25+ in 2000-2007. MAIN OUTCOME MEASURES: Number of deaths prevented or postponed (DPPs) in 2007 by socioeconomic status. We used the IMPACTSEC model which applies the relative risk reduction quantified in previous randomised controlled trials and meta-analyses to partition the mortality reduction among specific treatments and risk factor changes. RESULTS: Between 2000 and 2007, approximately 20 400 DPPs were attributable to reductions in BP and cholesterol in the English population. The substantial decline in BP was responsible for approximately 13 000 DPPs. Approximately 1800 DPPs came from medications and some 11 200 DPPs from population-wide changes. Reduction in population BP prevented almost twofold more deaths in the most deprived quintile compared with the most affluent. Reduction in cholesterol resulted in approximately 7400 DPPs; approximately 5300 DPPs were attributable to statin use and approximately 2100 DPPs to population-wide changes. Statins prevented almost 50% more deaths in the most affluent quintile compared with the most deprived. Conversely, population-wide changes in cholesterol prevented threefold more deaths in the most deprived quintile compared with the most affluent. CONCLUSIONS: Population-wide secular changes in systolic blood pressure (SBP) and cholesterol levels helped to substantially reduce CHD mortality and the associated socioeconomic disparities. Mortality reductions were, in absolute terms, greatest in the most deprived quintiles, mainly reflecting their bigger initial burden of disease. Statins for high-risk individuals also made an important contribution but maintained socioeconomic inequalities. Our results strengthen the case for greater emphasis on preventive approaches, particularly population-based policies to reduce SBP and cholesterol.

GM2 gangliosidosis in British Jacob sheep.

GM2 gangliosidosis (Tay-Sachs disease) was diagnosed in 6- to 8-month-old pedigree Jacob lambs from two unrelated flocks presenting clinically with progressive neurological dysfunction of 10 day's to 8 week's duration. Clinical signs included hindlimb ataxia and weakness, recumbency and proprioceptive defects. Histopathological examination of the nervous system identified extensive neuronal cytoplasmic accumulation of material that stained with periodic acid--Schiff and Luxol fast blue. Electron microscopy identified membranous cytoplasmic bodies within the nervous system. Serum biochemistry detected a marked decrease in hexosaminidase A activity in the one lamb tested, when compared with the concentration in age matched controls and genetic analysis identified a mutation in the sheep hexa allele G444R consistent with Tay-Sachs disease in Jacob sheep in North America. The identification of Tay-Sachs disease in British Jacob sheep supports previous evidence that the mutation in North American Jacob sheep originated from imported UK stock.

Brain lesions associated with clostridium perfringens type D epsilon toxin in a Holstein heifer calf.

A 6-month-old dairy heifer calf with no premonitory signs was acutely down after the morning feeding and could not rise. On presentation, the heifer was in right lateral recumbency and moribund with opisthotonus and left hind limb paddling. Following euthanasia, gross examination of the brain revealed multifocal loss of gray-white matter distinction and extensive petechiae throughout the brainstem. On histopathological examination, there was striking white matter edema and marked perivascular proteinaceous edema surrounding many arterioles and venules (microangiopathy), mainly in the white matter of the internal capsule, thalamus, midbrain, cerebellum, and cerebellar peduncles. The perivascular neuropil was strongly positive for Alzheimer precursor protein A4. Clostridium perfringens epsilon toxin was detected in the intestinal contents. This is the first report of microangiopathy in postneonatal cattle associated with the detection of epsilon toxin in the intestinal contents.

Identification of congenital muscular dystonia 2 associated with an inherited GlyT2 defect in Belgian Blue cattle from the United Kingdom.

Two newborn Belgian Blue calves from a farm in the United Kingdom exhibited lateral recumbency, low head carriage and transient muscle spasms following tactile or auditory stimulation. DNA sequence analysis indicated that both calves were homozygous for the recessive congenital muscular dystonia type 2 (CMD2) mutation (c.809T>C, p.Leu270Pro) in SLC6A5, encoding the neuronal glycine transporter GlyT2. Further testing of animals from the index farm and a sample of Belgian Blue sires revealed an unexpectedly high frequency of CMD2 carriers. This implies that linked quantitative trait loci may be influencing the prevalence of CMD2 in the estimated 55,000 Belgian Blue cattle in the United Kingdom. We have therefore developed new inexpensive tests for the CMD2 allele that can be used to confirm diagnosis, identify carriers and guide future breeding strategy, thus avoiding animal distress/premature death and minimizing the future economic impact of this disorder.

Increased immunohistochemical labelling for prion protein occurs in diverse neurological disorders of sheep: relevance for normal cellular PrP function.

The classical prion diseases (e.g. scrapie of sheep and goats and bovine spongiform encephalopathy of cattle) are characterized by the accumulation of abnormal forms of the prion protein (PrP), usually recognized by their relative resistance to proteolysis compared with the physiological cellular forms of PrP. However, novel prion diseases have been detected in sheep, cattle and man, in which the abnormal PrP has less resistance to proteolysis than identified previously. These more subtle differences between abnormal and normal forms of PrP can be problematic in routine diagnostic tests and raise questions in respect of the range of PrP disorders. Abnormal accumulations of PrP in atypical and classical prion diseases can be recognized by immunohistochemistry. To determine whether altered PrP expression or trafficking might occur in nosological entities not previously connected with prion disease, the brains of sheep affected with diverse neurological conditions were examined for evidence of altered PrP labelling. Such altered immunolabelling was detected in association with either basic lesions or specific diseases. Some reactive glial cells and degenerate neurons found in several different recognized disorders and non-specific inflammatory processes were associated with abnormal PrP labelling, which was absent from brains of healthy, age-matched sheep. The results agree with previous indications that normal PrP function may be linked with the oxidative stress response, but the data also suggest that PrP functions are more extensive than simple protective responses against stress insults.

Clinical, ultrasonographic and pathological findings in a bull with segmental aplasia of the mesonephric duct.

On assessment for use in an AI stud, a 12-month-old bull was found to produce low volume ejaculates with 41% of the sperm having morphological abnormalities. No left epididymal tail was palpable and the head of the epididymis on the left was twice the size compared with the right. Ultrasound examination showed the left testis to contain a large central area of decreased echogenicity, which could be followed proximally to a 15-mm echolucent lesion at the site of the epididymal head. Postmortem examination revealed a 15-mm diameter cyst in the region of the left epididymal head, and absence of the body and tail of the epididymis. The mediastinum testis of the left testis was dilated, corresponding to the area of decreased echogenicity observed on ultrasonography. No left seminal vesicle was present and the ampulla was significantly smaller than the same structure on the right. Histological examination revealed incomplete or absent spermatogenesis involving the majority of seminiferous tubules in the left testis, and a small proportion of those of the right testis. The cystic structure at the site of the left epididymal head was lined by irregular, sometimes attenuated, epithelium and contained sparse spermatozoa. This case demonstrates the adverse impact, which segmental aplasia of the mesonephric duct had on the testicular and epididymal function of a bull, and highlights the importance of careful clinical assessment in its diagnosis.