Relationships between markers of inflammation and bone density: findings from the Hertfordshire Cohort Study.

Among 365 Hertfordshire Cohort Study participants (aged 59-71 years at baseline), higher adiponectin and adiponectin to leptin ratios were associated with lower baseline lumbar spine and femoral neck bone mineral density (BMD). Lower IL-10 was associated with accelerated decline in lumbar spine BMD. This suggests that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis. INTRODUCTION: The aim of this study was to examine the association between indices of inflammation and BMD in a population-based cohort of older adults in the UK. METHODS: Analyses were based on a sample of 194 men and 171 women of the Hertfordshire Cohort Study (community-living, older adults). Dual energy X-ray absorptiometry (DXA) was performed at the lumbar spine and proximal femur at baseline and repeated at a median of 4.5 years (inter-quartile range 3.6 to 5.2). Inflammatory markers (CRP, TNF, IL-1ß, IL-6, IL-8, IL-10, adiponectin and leptin) were ascertained at baseline using enzyme-linked immunosorbent assay (ELISA) techniques and Bio-Plex Pro Assays. Gender-adjusted linear regression was used to examine the associations between markers of inflammation and outcomes with and without adjustment for anthropometric and lifestyle factors. RESULTS: The mean (SD) ages at baseline were 64.4 (2.5) and 66.5 (2.7) years for men and women respectively. Higher levels of adiponectin and adiponectin to leptin ratios were each associated with lower baseline lumbar spine and femoral neck BMD in gender-adjusted (p < 0.01) and fully adjusted (p < 0.05) analyses. Lower levels of IL-10 and TNF were each associated with accelerated decline in lumbar spine BMD in both gender-adjusted (p ≤ 0.05) and fully adjusted (p < 0.05) analyses. CONCLUSIONS: In a cohort of older adults, high levels of adiponectin and adiponectin to leptin ratios were both associated with lower BMD at the lumbar spine and femoral neck at baseline, and lower IL-10 was associated with accelerated decline in BMD at the lumbar spine. This adds weight to the theory that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis.

Correlates of Level and Loss of Grip Strength in Later Life: Findings from the English Longitudinal Study of Ageing and the Hertfordshire Cohort Study.

Characterisation of grip strength (GS) using isometric dynamometry is central to the definition of sarcopenia. Determinants of low GS include: older age, shorter stature, low physical activity, poor nutrition, socioeconomic disadvantage and multimorbidity. Less is known about risk factors for accelerated loss of GS. We investigated determinants of level and 8-year loss of GS in 3703 men and women (aged 52-82 years) in the English Longitudinal Study of Ageing (ELSA). Four hundred and forty-one men and women (aged 59-71 years) who participated in a 10-year follow-up of the Hertfordshire Cohort Study (HCS) were used for replication. Variables were harmonised between cohorts. Change in GS was characterised using mixed-effects models in ELSA and a residual change approach in HCS and analysed for men and women combined. Men in ELSA and HCS had higher average levels of GS at baseline, and accelerated rates of loss, compared with women. In ELSA, older age, shorter stature and multimorbidity were correlated with lower level, and accelerated rate of loss, of GS in both sexes (accelerated loss of 0.04 (95% CI 0.00-0.08) standard deviation scores per additional morbidity after multivariable adjustment). Socioeconomic disadvantage, low level of physical activity and poorer self-reported health were also correlated with low GS level, but not loss rate, after multivariable adjustment. Analysis in HCS yielded similar results. Our results identify multimorbidity as a modifiable determinant of loss of muscle strength in later life, and raise the possibility that developmental influences may impact on rate of involutional decline in muscle strength.

Relationships Between Markers of Inflammation and Muscle Mass, Strength and Function: Findings from the Hertfordshire Cohort Study.

We investigated the longitudinal relationships between inflammation markers and the following outcomes in a UK cohort study: appendicular lean mass (ALM); walking speed; level and change in grip strength; and sarcopenia defined by the European Working Group on Sarcopenia in Older People. Analyses were based on 336 community-dwelling older men and women (aged 59-70 years) who participated in the Hertfordshire Cohort Study (HCS). Inflammation markers were ascertained at baseline using enzyme-linked immunosorbent assay techniques and Bio-Plex Pro Assays. Grip strength was measured at baseline and follow-up [median follow-up time: 10.8 years (inter-quartile range 10.2-11.6)] and change in grip strength was ascertained using a residual change approach. At follow-up, ALM was ascertained using dual-energy X-ray absorptiometry, customary walking speed was measured and sarcopenia status was ascertained. Gender-adjusted linear and Poisson regression was used to examine the associations between inflammation markers and outcomes with and without adjustment for anthropometric and lifestyle factors. Higher C-reactive protein was associated (p < 0.04) with lower grip strength and accelerated decline in grip strength from baseline to follow-up. Higher cortisol was associated with lower ALM (p < 0.05). Higher interleukin-8 (IL-8) was associated with lower ALM (p < 0.05) and increased risk of sarcopenia [fully-adjusted relative risk per SD increase in IL-8: 1.37 (95% CI 1.10, 1.71), p = 0.005]. All associations were robust in fully-adjusted analyses. Inflammation markers were associated with measures of muscle mass, strength and function in HCS. Further work is required to replicate these associations and to delineate the underlying mechanisms.

Diet Quality and Bone Measurements Using HRpQCT and pQCT in Older Community-Dwelling Adults from the Hertfordshire Cohort Study.

There are few data describing associations between dietary patterns and bone microarchitecture. This study investigated the relationship between diet quality and HRpQCT and pQCT measures in older adults. Data were available for 184 men and 166 women. Dietary data were collected at baseline (1998-2003) using an administered food frequency questionnaire. A 'prudent' diet score (PDS) was identified using principal component analysis and used as an indicator of dietary quality. HRpQCT and pQCT images were acquired at follow-up in 2012, from the non-dominant distal radius and tibia using Scanco XtremeCT and Stratec XCT2000 instrument scanners, respectively. The mean (SD) PDS was - 0.24 (1.23) for men and 0.62 (1.14) for women. In women, a significant positive relationship was found between baseline dietary pattern and total and trabecular area at both the radius and the tibia, measured by HRpQCT. Similar trends were observed with pQCT parameters. Positive associations were observed for tibia total area (38% slice). At the radius, significant positive associations were found for total area (4% slice) and polar strength strain index (33% slice). All relationships remained robust to adjustment. For men, although patterns were similar, there were no significant associations for HRpQCT outcomes. Significant associations were observed for baseline PDS and polar strength strain and total area (66% slice) at the radius, measured by pQCT. Our data suggest that diets high in fruit, vegetables, oily fish and whole grain cereals in early old age are associated with greater bone size but not volumetric bone density or microarchitecture in later life in women.

Parameatal urethral cyst.

Parameatal urethral cyst is a rare clinical entity, resulting in asymptomatic cosmetic concerns, distortion of urinary stream or difficulty in urination. Though they cause considerable parental concerns, natural history is to resolve spontaneously or rarely surgical excision is needed. We report a neonate with asymptomatic parameatal urethral cyst.

Nutrition and physical activity in the prevention and treatment of sarcopenia: systematic review.

This systematic review summarizes the effect of combined exercise and nutrition intervention on muscle mass and muscle function. A total of 37 RCTs were identified. Results indicate that physical exercise has a positive impact on muscle mass and muscle function in subjects aged 65 years and older. However, any interactive effect of dietary supplementation appears to be limited. INTRODUCTION: In 2013, Denison et al. conducted a systematic review including 17 randomized controlled trials (RCTs) to explore the effect of combined exercise and nutrition intervention to improve muscle mass, muscle strength, or physical performance in older people. They concluded that further studies were needed to provide evidence upon which public health and clinical recommendations could be based. The purpose of the present work was to update the prior systematic review and include studies published up to October 2015. METHODS: Using the electronic databases MEDLINE and EMBASE, we identified RCTs which assessed the combined effect of exercise training and nutritional supplementation on muscle strength, muscle mass, or physical performance in subjects aged 60 years and over. Study selection and data extraction were performed by two independent reviewers. RESULTS: The search strategy identified 21 additional RCTs giving a total of 37 RCTs. Studies were heterogeneous in terms of protocols for physical exercise and dietary supplementation (proteins, essential amino acids, creatine, ß-hydroxy-ß-methylbuthyrate, vitamin D, multi-nutrients, or other). In 79% of the studies (27/34 RCTs), muscle mass increased with exercise but an additional effect of nutrition was only found in 8 RCTs (23.5%). Muscle strength increased in 82.8% of the studies (29/35 RCTs) following exercise intervention, and dietary supplementation showed additional benefits in only a small number of studies (8/35 RCTS, 22.8%). Finally, the majority of studies showed an increase of physical performance following exercise intervention (26/28 RCTs, 92.8%) but interaction with nutrition supplementation was only found in 14.3% of these studies (4/28 RCTs). CONCLUSION: Physical exercise has a positive impact on muscle mass and muscle function in healthy subjects aged 60 years and older. The biggest effect of exercise intervention, of any type, has been seen on physical performance (gait speed, chair rising test, balance, SPPB test, etc.). We observed huge variations in regard to the dietary supplementation protocols. Based on the included studies, mainly performed on well-nourished subjects, the interactive effect of dietary supplementation on muscle function appears limited.

Epidemiology of Sarcopenia: Determinants Throughout the Lifecourse.

Sarcopenia is an age-related syndrome characterised by progressive and generalised loss of skeletal muscle mass and strength; it is a major contributor to the risk of physical frailty, functional impairment in older people, poor health-related quality of life and premature death. Many different definitions have been used to describe sarcopenia and have resulted in varying estimates of prevalence of the condition. The most recent attempts of definitions have tried to integrate information on muscle mass, strength and physical function and provide a definition that is useful in both research and clinical settings. This review focuses on the epidemiology of the three distinct physiological components of sarcopenia, and highlights the similarities and differences between their patterns of variation with age, gender, geography and time and the individual risk factors that cluster selectively with muscle mass, strength and physical function. Methods used to measure muscle mass, strength and physical functioning and how differences in these approaches can contribute to the varying prevalence rates will also be described. The evidence for this review was gathered by undertaking a systematic search of the literature. The descriptive characteristics of muscle mass, strength and function described in this review point to the urgent need for a consensual definition of sarcopenia incorporating these parameters.

Pompe's Disease in Childhood: A Metabolic Myopathy.

BACKGROUND: Myopathy of metabolic origin in childhood occurs due to a variety of conditions. Pompe's Disease also known as Glycogen storage disease Type II, is a rare storage disorder with clinical presentation akin to spinal muscular atrophy. METHODS: A series of patients with suspected metabolic myopathy were reviewed at a tertiary care service hospital over a period of three years. The diagnosis was confirmed by estimation of acid alpha glucosidase activity. RESULT: At our centre, these cases presented with generalized hypotonia, organomegaly (hepatomegaly, cardiomegaly) and congestive cardiac failure. Infantile onset, the most severe form of Pompe's disease, was the commonest form accounting for 75% of the cases. Four of the babies with infantile onset Pompe's disease expired, three due to refractory heart failure and one to fulminant respiratory infection before 15 months of age. CONCLUSION: Pompe's Disease is now being increasingly diagnosed, due to definitive enzyme estimation facilities. With the recent availability of enzyme replacement therapy with Myozyme, the prognosis is likely to change for the better.

Development and validation of a new standardised data collection tool to aid in the diagnosis of canine skin allergies.

Canine atopic dermatitis (cAD) is a common hereditary clinical syndrome in domestic dogs with no definitive diagnostic tests, which causes marked morbidity and has a high economic impact internationally. We created a novel questionnaire for Labrador (LR) and Golden retriever (GR) owners to evaluate canine skin health with respect to clinical signs of cAD. 4,111 dogs had fully completed questionnaires (2,803 LR; 1,308 GR). 'Cases' (793) had a reported veterinary diagnosis of cAD, and 'controls' (1652) had no current or past clinical signs of cAD and were aged >3 years. Remaining dogs (1666) were initially categorised as 'Other'. Simulated annealing was used comparing 'Cases' and 'Others' to select a novel set of features able to classify a known case. Two feature sets are proposed, one for use on first evaluation and one for dogs with a history of skin problems. A sum for each list when applied to the whole population (including controls) was able to classify 'Cases' with a sensitivity of 89% to 94% and specificity of 71% to 69%, respectively, and identify potentially undiagnosed cases. Our findings demonstrate for the first time that owner questionnaire data can be reliably used to aid in the diagnostic process of cAD.

Does nutrition play a role in the prevention and management of sarcopenia?

There is a growing body of evidence that links nutrition to muscle mass, strength and function in older adults, suggesting that it has an important role to play both in the prevention and management of sarcopenia. This review summarises the discussions of a working group [ESCEO working group meeting 8th September 2016] that met to review current evidence and to consider its implications for preventive and treatment strategies. The review points to the importance of 'healthier' dietary patterns that are adequate in quality in older age, to ensure sufficient intakes of protein, vitamin D, antioxidant nutrients and long-chain polyunsaturated fatty acids. In particular, there is substantial evidence to support the roles of dietary protein and physical activity as key anabolic stimuli for muscle protein synthesis. However, much of the evidence is observational and from high-income countries. Further high-quality trials, particularly from more diverse populations, are needed to enable an understanding of dose and duration effects of individual nutrients on function, to elucidate mechanistic links, and to define optimal profiles and patterns of nutrient intake for older adults.

Canine lymphomatoid granulomatosis: an immunophenotypic analysis of three cases.

Three dogs had a history of multiple progressive lesions affecting the skin, subcutis or skeletal muscles. The lesions developed over a period of several months, and each case demonstrated late cardiopulmonary complications. Post-mortem examination revealed multicentric, angio-destructive, lymphohistiocytic, proliferative lesions typical of the rare disorder lymphomatoid granulomatosis. Immunohistochemical examination demonstrated variable CD3 antigen expression by the atypical cell population in two of the three cases. This provides the first evidence that canine lymphomatoid granulomatosis may be a form of atypical T-cell lymphoma similar to the comparable disorder that occurs in man.

Vitamin K-dependent coagulopathy in a British Devon rex cat.

Deficiencies of the vitamin K-dependent coagulation factors were identified in a Devon rex cat which had bled after castration. Haemorrhage was controlled by plasma transfusion. Clotting times were normalised by oral administration of vitamin K. This report confirms the existence of this bleeding disorder in a Devon rex cat in the United Kingdom.

Von Wille-brand's disease in UK dobermanns: possible correlation of a polymorphic DNA marker with disease status.

Ninety-one dobermanns have been typed for a polymorphic microsatellite DNA marker situated within an intron of the von Willebrand factor gene and the alleles correlated with von Wille-brand's disease status. Two alleles were identified, one associated only with the normal gene and the other with both normal and disease genes.

Lessons from pilot tests of computer self-help for agora/claustrophobia and panic.

Two pilot tests were made of computer-aided self-help for chronic agora/claustrophobia diagnosed by a psychiatrist. Test 1 was of 17 patients at the Institute of Psychiatry (IoP). They had no human clinical help, getting ideas only from the computer on how to do self-exposure therapy and set exposure goals week by week. Patients could attend for 12 sessions. Outcome data were inconsistent across ratings, not always matching clinical impression of progress. Of the 15 patients for whom outcome data were available, 6 improved markedly or moderately on clinical impression. Test 2 was of 6 patients in a rural general practice (GP) in Wales who were given help and support from a nonclinical administrator. Of the 4 Welsh patients with follow-up data, 3 improved markedly or moderately. The test results suggest desirable changes. Patients first need to do practice ratings before rating on the computer and to check computer ratings. Some rating instructions need to be clarified. Most importantly, synergism comes from giving patients access to brief human help if they encounter problems when using computer-aided self-help.