From Silos to Solidarity: Case Study of a Patient-Centered, Integrative Approach to Opioid Tapering and Chronic Pain Mitigation in a Multidisciplinary AIDS Clinic.

BACKGROUND: People with HIV (PWH) are at a disproportionate risk for experiencing both chronic pain and opioid use disorder (OUD). Prescription opioid tapering is typically addressed within the "silo model" of medical care, whereby attention is focused solely on opioid addiction rather than also addressing chronic pain management, and limited communication occurs between patient and providers. OBJECTIVE: This descriptive case study examined an integrative, collaborative care model consisting of Provider, Physical Therapist (PT), and Patient aimed at decreasing chronic pain and opioid use within a multidisciplinary HIV/AIDS clinic. METHOD: A physical-therapy based model of chronic pain mitigation and physician-driven opioid tapering was implemented. The Provider, PT, and Patient worked collaboratively to address physiological pain, pain coping skills and opioid tapering. A patient case example was used to illustrate the implementation of the model for a future, larger study in the same patient population. RESULTS: This model was feasible in this case example in terms of clinic workflow and acceptability to both the Patient and Providers in this clinic. After the intervention, the Patient's pain was fully eliminated, and he had ceased all opioid use. CONCLUSION: Results of this case study suggest that utilizing an integrative, patient-centered approach to both chronic pain management and opioid tapering may be feasible within the context of a multidisciplinary HIV/AIDS clinic. Generalizability is limited by case study model; however, this gives insight into the value of a collaborative alternative compared to a "silo" model of opioid tapering and chronic pain management in preparation for a larger study.

The effect of exercise training on intrahepatic triglyceride and hepatic insulin sensitivity: a systematic review and meta-analysis.

This systematic review and meta-analysis determined the impact of structured exercise training, and the influence of associated weight loss, on intrahepatic triglyceride (IHTG) in individuals with non-alcoholic fatty liver disease (NAFLD). It also examined its effect on hepatic insulin sensitivity in individuals with or at increased risk of NAFLD. Analyses were restricted to studies using magnetic resonance spectroscopy or liver biopsy for the measurement of IHTG and isotope-labelled glucose tracer for assessment of hepatic insulin sensitivity. Pooling data from 17 studies (373 exercising participants), exercise training for one to 24 weeks (mode: 12 weeks) elicits an absolute reduction in IHTG of 3.31% (95% CI: -4.41 to -2.22%). Exercise reduces IHTG independent of significant weight change (-2.16 [-2.87 to -1.44]%), but benefits are substantially greater when weight loss occurs (-4.87 [-6.64 to -3.11]%). Furthermore, meta-regression identified a positive association between percentage weight loss and absolute reduction in IHTG (ß = 0.99 [0.62 to 1.36], P < 0.001). Pooling of six studies (94 participants) suggests that exercise training also improves basal hepatic insulin sensitivity (mean change in hepatic insulin sensitivity index: 0.13 [0.05 to 0.21] mg m-2  min-1 per µU mL-1 ), but available evidence is limited, and the impact of exercise on insulin-stimulated hepatic insulin sensitivity remains unclear.

Dynamic changes in dna methylation status in peripheral blood Mononuclear cells following an acute bout of exercise: Potential impact of exercise-induced elevations in interleukin-6 concentration.

The aim of the present study was to examine the relationship between interleukin (IL)-6 concentrations and DNA methylation in the peripheral blood mononuclear cells (PBMCs) of trained runners after a bout of prolonged, strenuous exercise. Eight healthy trained males completed a treadmill run at 60% vVO(2max) for 120 min followed by a 5-km time trial in a fasted condition. Whole blood samples were taken prior to, immediately before and 24 h following exercise. From these samples, PBMCs were isolated for analysis and plasma IL-6 concentrations were measured. The methylation status of DNA extracted from PBMCs was analysed using the Illumina 27k methylation beadchip platform. Global DNA methylation status was unaltered immediately and up to 24 hours following a bout of prolonged exercise in comparison to pre-exercise. Despite no change in global DNA methylation, plasma IL-6 concentrations were significantly related to the DNA methylation status of 11 genes. Our study demonstrates that the methylome is stable, while discovering a novel link between exercise-induced increases in circulating IL-6 and the DNA methylation status of 11 individual genes. Based on our preliminary findings, the mechanisms by which changes in plasma IL-6 concentrations and DNA methylation in response to exercise interact require further study.

Interleukin-6 in combination with the interleukin-6 receptor stimulates glucose uptake in resting human skeletal muscle independently of insulin action.

AIM: To examine if the physiological concentrations of both interleukin-6 (IL-6), in combination with IL-6 receptor (IL-6R), are able to stimulate glucose uptake in human skeletal muscle and to identify the associated signalling pathways. METHODS: Skeletal muscle tissue (~60 mg) obtained from healthy female volunteers via muscle biopsy was subjected to incubation in the absence or presence of insulin (60 µU/ml), recombinant human IL-6 (rhIL-6) (4 ng/ml) or a combination of rhIL-6 (4 ng/ml) and rhIL-6R (100 ng/ml) for 30 min, with glucose transport measured for each incubation. Western blot analysis was conducted on key signalling proteins, protein kinase B (PKB/Akt), adenosine monophosphate kinase (AMPK) and mammalian target of rapamycin (mTOR) to gain an early insight into any differing transport mechanisms. RESULTS: Human skeletal muscle exhibited increased glucose uptake with insulin (1.85-fold; p < 0.05) and stimulated phosphorylation of PKB/Akt and AMPK (0.98 ± 0.23 and 1.49 ± 0.13, respectively, phosphorylated: total; p < 0.05). IL-6/IL-6R increased phosphorylation of mTOR (fourfold, p < 0.05) compared to insulin, IL-6 alone and basal control. IL-6 did not stimulate glucose uptake but combined with IL-6R, induced 1.5-fold increase in glucose uptake (p < 0.05) and phosphorylation of AMPK (0.95 ± 0.19; phosphorylated: total, p < 0.05). CONCLUSIONS: IL-6 in combination with IL-6R and not IL-6 alone increased glucose uptake in human skeletal muscle. IL-6/IL-6R-mediated glucose uptake occurred independently of PKB/Akt phosphorylation, showing that IL-6/IL-6R-induced glucose uptake is dependent on a divergent pathway.

Type 2 diabetes mellitus and obesity in young adults: the extreme phenotype with early cardiovascular dysfunction.

AIM: A pilot study to phenotype young adults (< 40 years) with Type 2 diabetes mellitus. METHODS: Twenty people with Type 2 diabetes (aged 18-40 years), 10 lean and 10 obese control subjects underwent detailed assessment, including tagged cardiac magnetic resonance imaging, inflammatory proteins, lipids, vitamin D and maximal oxygen uptake. Outcomes were compared between the group with Type 2 diabetes and the control group. RESULTS: Mean (standard deviation) age, Type 2 diabetes duration and BMI in the group with Type 2 diabetes were 31.8 (6.6) years, 4.7 (4.0) years and 33.9 (5.8) kg/m(2) respectively. Compared with lean control subjects, those with Type 2 diabetes had more deleterious profiles of hyperlipidaemia, vitamin D deficiency, inflammation and maximal oxygen uptake relative to body mass. However, there was no difference between the group with Type 2 diabetes and the obese control group. The group with Type 2 diabetes had a higher left ventricular mass and a trend towards concentric remodelling compared with the lean control group (P = 0.002, P = 0.052) but not the obese control group (P > 0.05). Peak early diastolic strain rate was reduced in the group with Type 2 diabetes [1.51 (0.24)/s] compared with the lean control [1.97 (0.34)/s, P = 0.001] and obese control [1.78 (0.39)/s, P = 0.042] group. CONCLUSIONS: Young adults with Type 2 diabetes and those with obesity have similar adverse cardiovascular risk profiles, higher left ventricular mass and a trend towards left ventricular concentric remodelling. In addition, those with Type 2 diabetes demonstrate diastolic dysfunction, a known risk marker for future heart failure and mortality.

The effect of physical activity on mediators of inflammation.

Being physically active and undertaking exercise on a regular basis are critical lifestyle behaviours which protect against the development of numerous chronic metabolic conditions. One of the key mechanisms by which physical activity exerts favourable health effects appears to be due to its capacity to reduce chronic low-grade inflammation. Single bouts of exercise have a potent anti-inflammatory influence with recent advances describing important effects of acute exercise on inflammatory mediators produced within skeletal muscle (myokines), adipose tissue (adipokines) and leucocytes. The accumulated effects of physical activity or exercise training on systemic inflammation have been studied widely within epidemiological research; however, information from intervention trials is still emerging. Current data suggest that the most marked improvements in the inflammatory profile are conferred with exercise performed at higher intensities, with combined aerobic and resistance exercise training potentially providing the greatest benefit. The purpose of this review is to describe recent advances in our understanding surrounding the acute and chronic effects of physical activity on key mediators of inflammation. Within this, particular attention is given to the interleukin-6 system owing to its apparent centrality in mediating the anti-inflammatory effects of exercise.

Associations of objectively measured sedentary behaviour and physical activity with markers of cardiometabolic health.

AIMS/HYPOTHESIS: The study aimed to examine the associations between objectively measured sedentary time, breaks in sedentary time, moderate-to-vigorous physical activity (MVPA) and total physical activity with markers of cardiometabolic health in a population with known risk factors for type 2 diabetes mellitus. METHODS: This study reports data from two ongoing diabetes prevention programmes. Participants with known risk factors were recruited from primary care practices located within the East Midlands, UK, over the period 2010-2011. ActiGraph GT3X accelerometers (15 s epochs) were used to assess sedentary time (<25 counts per 15 s), MVPA (≥ 488 counts per 15 s) and total physical activity (total counts). A break was considered as any interruption in sedentary time (≥ 25 counts per 15 s). Linear regression examined the independent association of sedentary time, breaks in sedentary time, MVPA and total physical activity with markers of cardiometabolic health. RESULTS: The sample comprised 878 participants; 153 from Project STAND (Sedentary Time And Diabetes) (age 32.9 ± 5.6 years, 28.8% male) and 725 from Walking Away from Diabetes (age 63.7 ± 7.8 years, 64.8% male). Following adjustment for various covariates, including MVPA and BMI, there were detrimental linear associations of sedentary time with 2 h plasma glucose (standardised beta coefficient) (ß = 0.220, p < 0.001), triacylglycerol (ß = 0.206, p = 0.001) and HDL-cholesterol (ß = -0.123, p = 0.029). Breaks in sedentary time, total physical activity and MVPA were significantly inversely associated with measures of adiposity, but not with any other cardiometabolic variables after adjustment for sedentary time and BMI. CONCLUSIONS/INTERPRETATION: In adults at high risk of type 2 diabetes mellitus, time spent sedentary is strongly and adversely associated with cardiometabolic health and may be a more important indicator of poor health than MVPA.

Prevalence of diabetes and impaired glucose metabolism in younger 'at risk' UK adults: insights from the STAND programme of research.

AIMS: Rising rates of obesity have led to an increasing prevalence of Type 2 diabetes mellitus in young people. Uncertainty exists over the utility of screening younger adults for Type 2 diabetes, as existing data sets have focused on mature (> 40 years) cohorts. The aim of this study was to determine the prevalence of impaired glucose metabolism in higher risk younger adults. METHODS: Overweight (with an additional risk factor) or obese adults (18-40 years) were recruited for the Sedentary Time And Diabetes (STAND) randomized controlled trial. Measures included an oral glucose tolerance test, HbA1c , biochemical and anthropometric data. RESULTS: One hundred and ninety-three individuals (68% female; median age 33.8 years; median BMI 33.9 kg/m²) were recruited. Forty-three per cent had a first-degree family history of Type 2 diabetes. Previously undiagnosed Type 2 diabetes was present in 4.7% (n = 9). Of participants, 18.1% (n = 35) had impaired glucose metabolism: 4.7% (n = 9) HbA1c ≥ 48 mmol/mol (6.5%); 9.3% (n = 18) HbA1c 42-46 mmol/mol (6.0-6.4%); 3.1% (n = 6) Type 2 diabetes on oral glucose tolerance test; 6.2% (n = 12) isolated impaired glucose tolerance; 2.1% (n = 4) isolated impaired fasting glucose; 1% (n = 2) both impaired fasting glucose and impaired glucose tolerance. Of participants, 58.5% (n = 113) had dyslipidaemia, 28.0% (n = 54) had hypertension, 31.1% (n = 60) were vitamin D deficient and 7.3% (n = 14) had abnormal liver function. CONCLUSIONS: This study identified a high prevalence of Type 2 diabetes and impaired glucose regulation in overweight and obese younger adults. These findings require confirmation in a larger, representative, population.

Plasma IL-6, its soluble receptors and F2-isoprostanes at rest and during exercise in chronic fatigue syndrome.

The aim of the current study was to investigate the levels of interleukin-6 (IL-6), its soluble receptors (sIL-6R and sgp130) and F(2)-isoprostanes, at rest and during exercise, in patients with chronic fatigue syndrome (CFS). Six male CFS patients and six healthy controls performed an incremental exercise test to exhaustion and a submaximal exercise bout to exhaustion. Blood samples taken in the submaximal test at rest, immediately post-exercise and 24 h post-exercise were analyzed for IL-6, sIL-6R, sgp130 and F(2)-isoprostanes. A further 33 CFS and 33 healthy control participants gave a resting blood sample for IL-6 and sIL-6R measurement. During the incremental exercise test only power output at the lactate threshold was lower (P<0.05) in the CFS group. F(2)-isoprostanes were higher (P<0.05) in CFS patients at rest and this difference persisted immediately and 24 h post-exercise. The exercise study found no differences in IL-6, sIL-6R or sgp130 at any time point between groups. In the larger resting group, there were no differences in IL-6 and sIL-6R between CFS and control groups. This investigation has demonstrated that patients with CFS do not have altered plasma levels of IL-6, sIL-6R or sgp130 either at rest or following exercise. F(2)-isoprostanes, however, were consistently higher in CFS patients.

The response of circulating levels of the interleukin-6/interleukin-6 receptor complex to exercise in young men.

The formation of an interleukin-6/IL-6 receptor (IL-6/IL-6R) complex increases the biological activity and half-life of IL-6, with its response to exercise currently unknown. The aim of the present study was to determine the response of circulating levels of the IL-6/IL-6R complex to exercise. Nine healthy male participants performed 1h of cycling exercise at a workload required to elicit 90% lactate threshold. Venous blood samples were taken at rest, immediately post-exercise and after 1.5 h rest. Hemoglobin concentration and hematocrit were measured to estimate changes in plasma volume during exercise. The concentrations of IL-6, sIL-6R and the IL-6/IL-6R complex were measured via ELISA and corrected for changes in plasma volume. A single bout of acute exercise resulted in a 5-fold increase (P<0.05) in IL-6 and a 1.2-fold increase (P<0.05) in sIL-6R immediately after exercise. These returned to baseline at 1.5 h after the cessation of exercise. There was a 2.1-fold increase (P<0.05) in the levels of the IL-6/IL-6R complex post-exercise with levels remaining 1.8 times elevated (P<0.05) after 1.5 h rest. The present study has demonstrated, for the first time, that circulating levels of the IL-6/IL-6R complex are increased in response to acute exercise in young males.

Effect of moderate-intensity exercise session on preprandial and postprandial responses of circulating ghrelin and appetite.

Responses of plasma total ghrelin and appetite were investigated during preprandial and postprandial stages of recovery from a moderate-intensity cycling session. Healthy recreationally active men underwent one exercise and one control trial. In the exercise trial, subjects exercised for approximately 60 minutes, while in the control trial they rested quietly for the same duration. After the intervention, subjects rested for 120 minutes and then consumed a test meal. Measurements were obtained immediately and 120 minutes after the intervention and then during 180 minutes of the postprandial period. The post-intervention concentration of total ghrelin was lower (p<0.05) in the exercise than in the control trial. The modulating effect of exercise was related to the reduction in the postprandial rather than preprandial concentration. Post-intervention scores of appetite were not different between the two trials, but when preprandial and postprandial responses were considered separately, postprandial hunger and desire to eat was higher (p<0.05) in the exercise trial. In summary, during recovery from moderate-intensity exercise, total ghrelin does not respond in a compensatory manner to disturbances in energy balance. Thus, an exercise-induced increase in appetite during the later stages of recovery coinciding with the postprandial state cannot be explained by changes in the plasma concentration of total ghrelin.

Response of plasma IL-6 and its soluble receptors during submaximal exercise to fatigue in sedentary middle-aged men.

The pleiotropic cytokine interleukin-6 (IL-6) has been demonstrated to increase during exercise. Little is known regarding the response of the soluble IL-6 receptors (sIL-6R and sgp130) during such exercise. The aim of the current study was to investigate the response of plasma IL-6, sIL-6R and sgp130 during fatiguing submaximal exercise in humans. Twelve participants underwent an incremental exercise test to exhaustion and one week later performed a submaximal exercise bout (96 +/- 6% lactate threshold) to volitional exhaustion. Blood samples taken at rest and immediately post exercise were analyzed for IL-6, sIL-6R and sgp130. IL-6 increased (P < 0.01) by 8.4 +/- 8.9 pg ml(-1) (75.7%) during the exercise period. sIL-6R and sgp130 also increased (P < 0.05) by 2.7 +/- 3.9 ng ml(-1) (9.6%) and 37.7 +/- 55.6 ng ml(-1) (9.6%), respectively. The current study is the first investigation to demonstrate that alongside IL-6, acute exercise stress results in an increase in both sIL-6R and sgp130.

Fatigue and illness in athletes.

Adequate nutrition before, during, and after training and competition is a key element to maintaining health. During both sprint and endurance exercise, the availability of glycogen is fundamental to performance and any deficit will lead to early fatigue. In addition, strategies to offset the negative effects of the products of metabolism are presented. Although nutritional strategies can attenuate the immunosuppressive effects of exercise, there remains a period of susceptibility to infection after a hard exercise session and when this is repeated without sufficient recovery an athlete can enter a period of "overtraining" during which performance deteriorates. The aetiology and identification of this state is not clear and some current ideas are discussed. Finally, gastrointestinal problems during running can negate any training benefits and we propose some suggestions to reduce this problem.

Ataxia and the role of antigliadin antibodies.

BACKGROUND: Although it is acknowledged that patients with celiac disease can develop neurological complications such as ataxia, the association of antigliadin antibodies in the etiology of sporadic ataxia and the usefulness of this testing in diagnosis of ataxia is controversial. METHODS: We investigated this association by testing for the presence of IgG and IgA antigliadin antibodies in 56 ataxic patients and 59 controls. The ataxia patients were subsequently classified into three groups: sporadic, hereditary and MSA. RESULTS: Of the total ataxic patients, 6/56 (11%) were positive for either IgG or IGA antigliadin antibodies compared to the controls of which 5/59 (8%) were positive (p = 0.68). In a subgroup analysis, 4/29 (14%) of the samples in the sporadic ataxic subgroup were positive for antigliadin antibodies (IgG or IgA) compared to control (p = 0.44). Similar negative results were found in the remaining subgroup analyses. CONCLUSIONS: These results do not support an association between antigliadin antibodies and sporadic ataxias.

Spontaneous activity responses to exercise in males and females.

OBJECTIVE: This study examines the impact of a short-term exercise programme, prescribed on the basis of current exercise recommendations, on energy balance in males and females to assess whether this type of exercise induces compensatory changes in spontaneous activity energy expenditure (SAEE) and energy intake (EI). DESIGN: Individuals were monitored for 16 days, 8 days of habitual physical activity (C) and 8 days when exercise was imposed (E). Total energy expenditure (TEE) was calculated from individual relationships of VO2 and VCO2 to heart rate (HR) records of HR and physical activity obtained during waking hours of the C and E periods and basal metabolic rate (BMR) measurements (Deltatrac System, Datex Instrumentation). Changes in nude body mass (BM) were estimated by using a digital scale (Sartorius AG, Gottigen, Germany). SETTING: Laboratory and free-living. SUBJECTS: Eight lean females (body fat: 17.5+/-4.5%) and eight males of similar percentage body fat participated in this study. All subjects were Caucasian and aged between 20 and 25 years. INTERVENTION: During the E period, a supervised exercise session was conducted every second day, each consisting of a total net energy expenditure of 2092 kJ+BMR at 90% lactate threshold. RESULTS: During the E period, TEE was higher than C in males and females (exercise: 95.2+/-13.9, 78.3+/-15.9 MJ; control: 82.4+/-10.4, 68.8+/-16.7 MJ, respectively; P<0.00; P=0.02). SAEE, calculated as TEE minus the energy expended during exercise, was not significantly different between C (males: 82.4+/-4.8 MJ; females: 68.8+/-7.6 MJ) and E (males: 86.8+/-6.3 MJ; females: 70.0+/-7.2 MJ) periods in either gender. Males showed no change in BM over the C (pre-intervention: 83.4+/-7.2 kg; post-intervention: 83.1+/-6.8 kg) or E (pre-intervention: 83.4+/-6.8 kg; post-intervention: 83.4+/-6.8 kg) periods. Females' BM over the C period did not alter (pre-intervention: 63.3+/-2.8 kg; post-intervention 63.7+/-3.1 kg); however, there was a significant decrease (P<0.00) in BM over the E period (pre-intervention: 63.0+/-2.7 kg; post-intervention: 62.4+/-2.7 kg). CONCLUSION: The exercise programme was achieved in males and females without any impact on SAEE. Therefore, differences between genders in relation to BM reduction can be explained by differences in the EI response to exercise.

Combining HPLC pigment markers and ecological similarity indices to assess phytoplankton community structure: an environmental tool for eutrophication?

A new tool combining the use of HPLC pigment markers with ecological similarity indices, to provide a fast and effective environmental tool for monitoring water quality, was investigated. HPLC pigment concentrations from a 4-year time series data set (2000-2003) from the western English Channel were used to calculate six similarity indices to assess changes in phytoplankton community structure. Indices obtained from HPLC data were compared with those produced from the corresponding phytoplankton biomass derived from microscopic analysis. Multivariate RELATE analyses (P<0.001) suggested that there was little loss of information when species biomass data were grouped into higher taxonomic levels, thereby providing justification for the use of pigment markers. To test the proposed methodology, product moment (r) and Spearman's rank (r(s)) correlation analyses were performed. Highly significant correlations (P<0.01, Canberra Metric: P<0.05) between percentage similarities derived from phytoplankton class biomass and pigment markers were found for all indices when data were pooled (n=104). A Mann-Whitney U-test suggested that indices were more sensitive to changes in relative biomass than pigment concentrations; however, pigment data also produced statistically significant findings (P<0.05). Combining HPLC pigment markers and ecological similarity indices to assess phytoplankton community structure has advantages over microscopy in that it is rapid, reproducible and better suited to large-scale environmental monitoring. We present a basic protocol for implementing this new tool using a suite of similarity indices into environmental monitoring of phytoplankton communities.

Acute effects of dehydration on sweat composition in men during prolonged exercise in the heat.

AIM: To determine whether acute exercise-heat-induced dehydration affects sweat composition, eight males cycled for 2 h at 39.5 +/- 1.6% VO2peak on two separate occasions in a hot-humid environment (38.0 +/- 0.0 degrees C, 60.0 +/- 0.1% relative humidity). METHODS: During exercise, subjects ingested either no fluid (dehydration) or a 20 mmol L(-1) sodium chloride solution (euhydration). The volume of solution, calculated from whole-body sweat loss and determined in a familiarization trial, was ingested at 0 min and every 15 min thereafter. Venous blood was collected at 0, 60 and 120 min of exercise and sweat was aspirated from a patch located on the dominant forearm at 120 min. RESULTS: Following the 2-h cycling exercise, sweat [Na+] and [Cl-] was greater (P < 0.05) in the dehydration trial (Na+ 91.1 +/- 6.8 mmol L(-1); Cl- 73.3 +/- 3.5 mmol L(-1)) compared with the euhydration trial (Na+ 81.1 +/- 5.9 mmol L(-1); Cl- 68.5 +/- 3.3 mmol L(-1)). In addition, dehydration invoked a greater serum [Na+] (142.2 +/- 0.7 mmol L(-1); P < 0.05), [Cl-] (105.8 +/- 0.6 mmol L(-1); P < 0.05) and [K+] (5.27 +/- 0.2 mmol L(-1); P < 0.05) over the euhydration values for [Na+], [Cl-] and [K+], respectively (138.9 +/- 0.6, 102.9 +/- 0.5 and 4.88 +/- 0.1 mmol L(-1)). Plasma aldosterone was also significantly higher during exercise in the dehydration trial compared with the euhydration trial (53.8 +/- 3.8 vs. 40.0 +/- 4.3 ng dL(-1); P < 0.05). CONCLUSIONS: Acute exercise-heat stress without fluid replacement resulted in a greater sweat [Na+] and [Cl-] which was potentially related to greater extracellular fluid [Na+], plasma aldosterone or sympathetic nervous activity.

The use of ultrasound as an aid in the diagnosis of giant cell arteritis: a pilot study comparing histological features with ultrasound findings.

AIMS: We present our preliminary experience with the use of ultrasound in aiding the diagnosis of giant cell arteritis (GCA). Schmidt et al have previously described a hypoechoic or "halo" effect surrounding the walls of affected arteries on examination with ultrasound. We illustrate these features and explore the attributes and limitations of this technique. METHOD: Two groups of patients were recruited: (1) patients with suspected GCA awaiting temporal artery biopsy and (2) patients with no history or symptoms of GCA of a similar age group. All the recruited patients underwent ultrasound examination of both temporal arteries. The findings on ultrasound were compared with the results of the histological specimens in group 1. For this study, the histological findings alone were used to define if a patient was suffering from GCA. No biopsies were taken in the patients in group 2. RESULTS: Out of 26 patients with suspected GCA, seven patients were found to be positive on biopsy, of which six had been identified on ultrasound. Six patients were found to be false positive on ultrasound, but all had moderate-to-severe features of arteriosclerosis on histology. A total of 13 patients were found to be negative on ultrasound and negative on biopsy for GCA, two of these patients had histological features of arteriosclerosis. In the group with no symptoms of GCA (12 patients), in two patients hypoechoic areas were detected. The results presented give a sensitivity of 86%, specificity of 68%, and positive predictive value of 50% for the use of ultrasound in the diagnosis of GCA. CONCLUSIONS: This preliminary study indicates that this test may be helpful in those patients with symptoms suggestive of GCA, but currently we cannot recommend any change of present practice.

Trace metal uptake by the Chinese mitten crab Eriocheir sinensis: the role of osmoregulation.

Changes in salinity affect the bioavailability and consequent uptake of trace metals by euryhaline invertebrates. In many cases, salinity-related effects on metal uptake can be explained by changes in chemical speciation but salinity may also influence uptake indirectly through its action on osmoregulatory mechanisms. Specifically, it can be hypothesised that trace metal uptake may be reduced at salinities approaching the isosmotic point of a species because, at this point, there is reduced activity of ionic exchange pumps. The present study tested this hypothesis using the Chinese mitten crab, Eriocheir sinensis, a hyper-hypoosmoregulator with an isosmotic point around 33 per thousand. Crabs were exposed to radio-labelled cadmium and zinc at 23, 33 and 43 per thousand for 4 days. To eradicate speciation effects, crabs were exposed to the same concentration of the radio-labelled free metal ion (estimated using MineQL computer software) at each salinity. Haemolymph samples were taken daily and radio-labelled metal concentrations were estimated from radioactivity counts and used to provide relative measures of metal uptake. Neither cadmium nor zinc uptake was lowest at the isosmotic point. The uptake of cadmium increased significantly with increase in salinity, while the uptake of zinc showed no significant change with increased salinity. Thus changes in trace metal uptake rates in E. sinensis do not appear to be controlled only by changes in free metal ion concentrations. The different effects of salinity change on the uptake of cadmium and zinc (in the absence of free metal ion change) also indicate that physiological responses to osmotic change alone do not control metal uptake rates for this species.

Effects of central sympathetic inhibition on heart rate variability during steady-state exercise in healthy humans.

The profound reduction in heart rate variability (HRV) that occurs during exercise is thought to be, at least in part, the result of sympathetic nervous system activation. Moxonidine is a centrally acting anti-sympathetic drug, which suppresses sympathetic nervous system outflow by stimulation of central imidazoline receptors located in the rostral ventro-lateral medulla. This study was designed to investigate the combined effects of central sympathetic inhibition with moxonidine and steady-dynamic exercise on HRV. Ten normal males participated in a double-blind cross-over study, taking either placebo or 0.4 mg of moxonidine. The subjects were studied at rest and during steady-state exercise. HRV was measured considering both time and frequency domain parameters. As a non-linear measure, the Poincaré scatter-plot was measured and analysed quantitatively. Ventilation and gas exchange were also measured during exercise. In addition, plasma catecholamines were measured at rest and during exercise. The only parameter changed, at rest, by moxonidine was the blood pressure which was reduced. During exercise, moxonidine reduced plasma noradrenaline (NA), compared with the placebo (P<0.01). The only change observed in HRV during exercise was a significant reduction of the continuous long-term standard deviation (SD2) of the Poincaré scatter-plot of the R-R interval (P<0.05). However, the potential and prognostic significance of this result needs to be further assessed.