Undifferentiated febrile illnesses amongst British troops in Helmand, Afghanistan.

OBJECTIVES: Undifferentiated febrile illnesses have been a threat to British expeditionary forces ever since the Crusades. The infections responsible were identified during the Colonial Era, both World Wars and smaller conflicts since, but nearly all remain a significant threat today. Undiagnosed febrile illnesses have occurred amongst British troops in Helmand, Afghanistan since 2006 and so a fever study was performed to identify them. METHODS: From May to October 2008, all undifferentiated fever cases seen at the British field hospital in Helmand, Afghanistan were assessed using a standard protocol. Demographic details, clinical features and laboratory results were recorded and paired serum samples were sent for testing at the UK Special Pathogens Reference Unit (SPRU). RESULTS: Over 6 months, there were 26 cases of"Helmand Fever" assessed and 23 diagnoses were made of which 12 (52%) were sandfly fever, 6 (26%) were acute Qfever and 5 (22%) were rickettsial infections. Four cases had co-infections and 7 cases were not diagnosed (mostly due to inadequate samples). The clinical features and laboratory results available at the British field hospital did not allow these diseases to be distinguished from each other. The exact type of rickettsial infection could not be identified at SPRU. CONCLUSIONS: These cases probably represent the "tip of an iceberg" for British and Allied forces. More resources for diagnostic facilities and follow-up of patients are required to improve the management and surveillance of "Helmand Fever" cases; until then doxycycline 100 mg twice daily for 2 weeks should be given to all troops who present with an undifferentiated febrile illness in Helmand, Afghanistan. Patients with acute Q fever should be followed-up for at least 2 years to exclude chronic Q fever. Prevention of these diseases requires a better understanding of their epidemiology, but prophylaxis with doxycycline and possibly Q fever vaccine should be considered.

Are the adverse effects of glitazones linked to induced testosterone deficiency?

BACKGROUND: Adverse side-effects of the glitazones have been frequently reported in both clinical and animal studies, especially with rosiglitazone (RGZ) and pioglitazone (PGZ), including congestive heart failure, osteoporosis, weight gain, oedema and anaemia. These led to consideration of an evidence-based hypothesis which would explain these diverse effects, and further suggested novel approaches by which this hypothesis could be tested. PRESENTATION OF HYPOTHESIS: The literature on the clinical, metabolic and endocrine effects of glitazones in relation to the reported actions of testosterone in diabetes, metabolic syndrome, and cardiovascular disease is reviewed, and the following unifying hypothesis advanced: "Glitazones induce androgen deficiency in patients with Type 2 Diabetes Mellitus resulting in pathophysiological changes in multiple tissues and organs which may explain their observed clinical adverse effects." This also provides further evidence for the lipocentric concept of diabetes and its clinical implications. TESTING OF THE HYPOTHESIS: Clinical studies to investigate the endocrine profiles, including measurements of TT, DHT, SHBG, FT and estradiol, together with LH and FSH, in both men and women with T2DM before and after RGZ and PGZ treatment in placebo controlled groups, are necessary to provide data to substantiate this hypothesis. Also, studies on T treatment in diabetic men would further establish if the adverse effects of glitazones could be reversed or ameliorated by androgen therapy. Basic sciences investigations on the inhibition of androgen biosynthesis by glitazones are also warranted. IMPLICATIONS OF THE HYPOTHESIS: Glitazones reduce androgen biosynthesis, increase their binding to SHBG, and attenuate androgen receptor activation, thus reducing the physiological actions of testosterone, causing relative and absolute androgen deficiency. This hypothesis explains the adverse effects of glitazones on the heart and other organs resulting from reversal of the action of androgens in directing the maturation of stem cells towards muscle, vascular endothelium, erythroid stem cells and osteoblasts, and away from adipocyte differentiation. The higher incidence of side-effects with RGZ than PGZ, may be explained by a detailed study of the mechanism by which glitazones down-regulate androgen biosynthesis and action, resulting in a state of androgen deficiency.

The cost-effectiveness of cardiac computed tomography for patients with stable chest pain.

OBJECTIVE: To assess the cost-effectiveness of cardiac CT compared with exercise stress testing (EST) in improving the health-related quality of life of patients with stable chest pain. METHODS: A cost-utility analysis alongside a single-centre randomised controlled trial carried out in Northern Ireland. Patients with stable chest pain were randomised to undergo either cardiac CT assessment or EST (standard care). The main outcome measure was cost per quality adjusted life year (QALY) gained at 1 year. RESULTS: Of the 500 patients recruited, 250 were randomised to cardiac CT and 250 were randomised to EST. Cardiac CT was the dominant strategy as it was both less costly (incremental total costs -£50.45; 95% CI -£672.26 to £571.36) and more effective (incremental QALYs 0.02; 95% CI -0.02 to 0.05) than EST. At a willingness-to-pay threshold of £20 000 per QALY the probability of cardiac CT being cost-effective was 83%. Subgroup analyses indicated that cardiac CT appears to be most cost-effective in patients with a likelihood of coronary artery disease (CAD) of <30%, followed by 30%-60% and then >60%. CONCLUSIONS: Cardiac CT is cost-effective compared with EST and cost-effectiveness was observed to vary with likelihood of CAD. This finding could have major implications for how patients with chest pain in the UK are assessed, however it would need to be validated in other healthcare systems. TRIAL REGISTRATION NUMBER: (ISRCTN52480460); results.

A comparison of cardiac computerized tomography and exercise stress electrocardiogram test for the investigation of stable chest pain: the clinical results of the CAPP randomized prospective trial.

AIMS: To determine the symptomatic and prognostic differences resulting from a novel diagnostic pathway based on cardiac computerized tomography (CT) compared with the traditional exercise stress electrocardiography test (EST) in stable chest pain patients. METHODS AND RESULTS: A prospective randomized controlled trial compared selected patient outcomes in EST and cardiac CT coronary angiography groups. Five hundred patients with troponin-negative stable chest pain and without known coronary artery disease were recruited. Patients completed the Seattle Angina Questionnaires (SAQ) at baseline, 3, and 12 months to assess angina symptoms. Patients were also followed for management strategies and clinical events. Over the year 12 patients withdrew, resulting in 245 in the EST cohort and 243 in the CT cohort. There was no significant difference in baseline demographics. The CT arm had a statistical difference in angina stability and quality-of-life domains of the SAQ at 3 and12 months, suggesting less angina compared with the EST arm. In the CT arm, there was more significant disease identified and more revascularizations. Significantly, more inconclusive results were seen in the EST arm with a higher number of additional investigations ordered. There was also a longer mean time to management. There were no differences in major adverse cardiac events between the cohorts. At 1 year in the EST arm, there were more Accident and Emergency (A&E) attendances and cardiac admission. CONCLUSION: Cardiac CT as an index investigation for stable chest pain improved angina symptoms and resulted in fewer investigations and re-hospitalizations compared with EST. CLINICAL TRIAL REGISTRATION: http://www.controlled-trials.com/ISRCTN52480460.

Experience of a quality assessment scheme for non-laboratory glucose meters.

In late 1989 a quality assessment scheme was introduced for glucose meters at 12 non-laboratory sites in a unit of management. The overall monthly imprecision of the meters varied from 3.4% to 17.1%, the highest coefficients of variation being recorded for glucose concentrations outside the range 3-20 mmol/l. In the same period 37% of results fell outside +/- 10% of laboratory set target limits; 13% fell outside +/- 20% of these limits. Participants have been advised of the unreliability of results outside the range 3-20 mmol/l. The main benefit of the scheme has been the improved confidence of users in the results obtained.

Measurement of serum albumin by capillary zone electrophoresis, bromocresol green, bromocresol purple, and immunoassay methods.

BACKGROUND/AIMS: The introduction of capillary zone electrophoresis (CZE) to this laboratory has highlighted discrepancies in albumin measured on an Abbott Aeroset by bromocresol green (BCG) and that calculated by CZE on the basis of total protein measured by Biuret. METHODS: This study examined differences in albumin estimation by CZE, Abbott Aeroset BCG, and Aeroset bromocresol purple (BCP), and compared these with albumin estimated by Beckman Array immunoassay. RESULTS: Altman and Bland analysis of results showed a positive bias of BCG with CZE (4.51 g/litre; 95% limits of agreement, 3.77 to 5.26; n = 72) and BCP (3.85 g/litre; 95% limits of agreement, -1.42 to 9.12; n = 72). CZE and BCP agreed closely (0.67 g/litre; 95% limits of agreement, -4.39 to 3.06; n = 72). Analysis of 57 of those samples in which BCG and CZE differed > or = 5 g/litre showed a positive bias of BCG with immunoassay (8.35 g/litre; 95% limits of agreement, 1.54 to 15.16; n =57), with good agreement between CZE and immunoassay (-0.44 g/litre; 95% limits of agreement, -2.82 to 1.94; n = 57). CONCLUSIONS: BCP is superior to BCG for the assay of albumin and has replaced BCG as the routine test for albumin in this laboratory.

Total radical trapping antioxidant potential (TRAP) and exercise.

The relationship between physical activity, physical fitness and total radical trapping antioxidant potential (TRAP) was examined in the Northern Ireland Health and Activity Survey. This was a cross-sectional population study (n = 1600) using a two-stage probability sample of the population. TRAP was calculated using the sum of the individual serum antioxidant concentrations (urate, protein thiols, ascorbate, alpha tocopherol and bilirubin) multiplied by their respective stoichiometric values. Physical fitness was determined by estimation of VO2max by extrapolation from submaximal oxygen uptake, and physical activity was recorded by computer-assisted interview. Mean serum TRAP concentrations were significantly higher in males (653 +/- 8.2 mumol/l, mean +/- SEM) compared to females (564 +/- 8.0 mumol/l) (p < 0.0001). Both male and female smokers had significantly lower TRAP values than non-smokers (males p < 0.0001, females p = 0.02). In females, there was a positive relationship of TRAP with age (p < 0.001) and body mass index (p < 0.001) but a negative relationship with physical fitness (p < 0.05). The known beneficial effects of exercise and activity do not appear to be directly mediated through increased antioxidant status.

Physical activity, physical fitness, blood pressure, and fibrinogen in the Northern Ireland health and activity survey.

STUDY OBJECTIVE: To investigate the relationship between physical activity, physical fitness, blood pressure, and fibrinogen. DESIGN: This was a cross sectional population study using a two stage probability sample. SETTING: Northern Ireland. PARTICIPANTS: A sample of 1600 subjects aged 16-74 years from the population of Northern Ireland. MAIN OUTCOME MEASURES: Physical activity profile from computer assisted interview using the Allied Dunbar national fitness survey scales. Physical fitness using estimation of VO2 max by extrapolation from submaximal oxygen uptake while walking on a motor driven treadmill. Systolic and diastolic blood pressure measured with a Hawksley random zero sphygmomanometer. Measurement of fibrinogen using the Clauss method. MAIN RESULTS: There were significant relationships between both current and past activity and blood pressure. These were of a magnitude that would have been clinically significant, but for the fact that, with the exception of the relationship between habitual activity and diastolic pressure (p = 0.03) and past activity and systolic pressure (p = 0.03) in men, they were not sustained after adjustment for the effect of age using analysis of variance. After adjustment for other potentially confounding factors using multiple regression, there was an inverse relationship between systolic blood pressure and past activity in men, so that those with a life-time of participation compared with a life-time of inactivity had a lower systolic blood pressure of 6 mmHg (p < 0.05). There was a highly significant (p < 0.001) inverse association between both systolic and diastolic blood pressure and physical fitness (VO2 max) which was not sustained after adjustment for possible confounding factors. There were relationships between fibrinogen and highest recorded activity (p < 0.001), habitual activity (p < 0.01), and past activity (p < 0.01) in men but no significant relationship in women. The relationship between fibrinogen and activity was no longer sustained after adjustment for possible confounding factors. There was a highly significant (p < 0.001) inverse relationship with physical fitness using VO2 max. This relationship was sustained after adjustment for possible confounding factors in both men (p < 0.05) and women (p < 0.001). CONCLUSIONS: There was a relationship between physical activity, physical fitness, and blood pressure but the relationship was greatly influenced by age. A reduction of 6 mmHg in systolic blood pressure associated with past activity is of clinical significance and supports the hypothesis that physical activity is of benefit in reducing cardiovascular risk. There was a lower level of fibrinogen in those who were most active but this relationship was not significant after adjustment for possible confounding factors. There was also a lower level of fibrinogen those who were most fit (VO2 max) and this relationship persisted even after adjustment for possible confounding factors.

Effects of isotretinoin on serum lipids and lipoproteins, liver and thyroid function.

Seven patients with severe rosacea were treated with 1 mg/kg per day isotretinoin for 12 wk. There were significant increases in serum triglyceride (p less than 0.001) and cholesterol (p less than 0.001). Triglyceride associated with very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) increased (p less than 0.01), cholesterol in VLDL and LDL increased (p less than 0.01), and levels of HDL cholesterol decreased (p less than 0.01). There were changes in indices of liver function, with increased levels of gamma-glutamyltransferase (GGT) (p less than 0.01), alkaline phosphatase (ALP) (p less than 0.01) and aspartate aminotransferase (AST) (p less than 0.01), and decreased bilirubin levels (p less than 0.05). Although levels of thyroxine and triiodothyronine were lower after treatment (p less than 0.05), there were no changes in basal levels of thyroid-stimulating hormone (TSH), luteinizing hormone (LH) or follicle-stimulating hormone (FSH), and responses to thyrotrophin releasing hormone (TRH) and luteinizing hormone releasing hormone (LHRH) were unchanged. These changes may partially be explained by induction of hepatic microsomal enzymes by isotretinoin.

Physical fitness, lipids, and apolipoproteins in the Northern Ireland Health and Activity Survey.

The objective of this study was to investigate the relationship between physical fitness, lipids, and apolipoproteins in a cross-sectional study using a two-stage probability sample of the population of Northern Ireland. The main outcome measures were physical fitness using VO2max estimated by extrapolation from submaximal oxygen uptake while walking on a motor driven treadmill, and total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, HDL2 and HDL3, and Lp(a). There were no significant relationships with fitness, after adjustment for possible confounders, with the exception of a positive relationship with HDL2 in males (P < or = 0.01) and Lp(a) in females (P < or = 0.05). There was also a relationship between physical fitness and HDL:apo AI ratio in males and females after adjustment for possible confounders (P < or = 0.05). We concluded that there were few relationships between lipid parameters and physical fitness after adjustment for possible confounders. The relationship between physical fitness and Lp(a) in females suggests a benefit associated with physical fitness and the relationship between physical fitness and HDL:apo AI ratio was in keeping with improved HDL cholesterol transport.

Vitamin E and exercise in the Northern Ireland population.

Serum vitamin E, vitamin E/cholesterol and physical activity and fitness were examined in a representative cross section (n = 1600) of the Northern Ireland population as part of the Northern Ireland health and activity survey. Serum vitamin E levels were measured by high-performance liquid chromatography, cholesterol by an enzymatic method, physical activity profile was recorded by computer assisted interview and physical fitness was determined by estimation of VO2 max. The levels of serum vitamin E and vitamin E/cholesterol ratio in the Northern Irish population were similar or higher than in other populations with lower incidences of coronary heart disease. The assessment of activity showed that 75% of the population fell below recommended activity levels likely to confer a cardioprotective effect. A significant relationship (P = 0.01) was found in males between serum vitamin E levels and lifetime participation in physical activity. Otherwise no relationship was found between serum vitamin E or vitamin E/cholesterol ratio and physical activity or fitness in the population.

APO E genotype and familial hypercholesterolaemia.

Apolipoprotein E genotypes were measured in 83 patients with familial hypercholesterolaemia (FH) and in 175 blood donor controls. Following DNA extraction from peripheral blood, each sample was genotyped for the Apo E polymorphism by polymerase chain reaction. No significant differences were found in the levels of the epsilon 2 and epsilon 3 alleles between the two groups, while the epsilon 4 allele was approximately twice as prevalent in the FH patients as in controls (P = 0.006, df = 1). Of the FH patients, 8.4% were homozygous for the epsilon 4 allele while this genotype was rare in controls (P = 0.009, df = 1). These results suggest that the epsilon 4 allele is over represented in the FH population and may contribute to increased cholesterol levels and consequent vascular disease.

Ascorbate and exercise in the Northern Ireland population.

The relationship between physical activity, physical fitness and serum ascorbate was examined in the Northern Ireland Health and Activity Survey. This was a cross sectional population study (n = 1600), using a two stage probability sample, of the population of N. Ireland. Physical activity profile was recorded by computer assisted interview and physical fitness was determined by estimation of VO2 max by extrapolation from submaximal oxygen uptake. Serum ascorbate was measured using a colorimetric reaction of 2,4 dinitrophenylhydrazine with dehydroascorbate. Mean serum ascorbate was greater in females than males (p < 0.001), and was lower in smokers than non-smokers in both males (p = 0.01) and females (p < 0.001). There was no statistically significant relationship between serum ascorbate and age, social class, body mass index, physical activity or physical fitness in males but there was a relationship with age (p < 0.01) and physical fitness (p < 0.05) in females.

Hepatic function and indocyanine green clearance during and after prolonged anaesthesia with propofol.

We have studied the effects of propofol on hepatic function and clearance of indocyanine green (ICG) in 13 consecutive patients undergoing prolonged plastic and reconstructive surgery. Hepatic function was assessed using serum concentrations of liver-specific glutathione-S-transferase (GST). There were no significant changes in GST activity or plasma clearance of ICG throughout the study.

Plasma fluoride concentrations during and after prolonged anesthesia: a comparison of halothane and isoflurane.

Serum inorganic fluoride concentrations were studied in 19 adult patients undergoing prolonged head and neck surgery with either halothane or isoflurane anesthesia (mean 19.5 and 19.2 MAC-hours, respectively). In the group of nine patients anesthetized with isoflurane, plasma inorganic fluoride increased from a mean concentration of 3.5 mumols/L (baseline) to a peak of 43.2 mumols/L. Forty percent of the patients in the isoflurane group had peak plasma inorganic fluoride concentrations of more than 50 mumol/L. In the group that received halothane, plasma inorganic fluoride concentrations increased from a mean of 3.8 mumols/L to a peak of 12.6 mumols/L. Despite similar exposures to both anesthetics, the differences in serum inorganic fluoride concentrations between the two groups were significant at 10, 24, and 48 h after induction of anesthesia (P = 0.035, P = 0.003, and P = 0.003, respectively). Serum electrolyte, urea, and creatinine concentrations and urine output rates during and after surgery were similar in both groups. We conclude that, after anesthesia of up to 20 MAC-hours, metabolism of isoflurane to inorganic fluoride may be of a greater magnitude than has previously been realized. Although no clinical or biochemical evidence was found to suggest postoperative renal dysfunction, we recommend caution using isoflurane when prolonged anesthesia and surgery are planned.

Indocyanine green clearance and hepatic function during and after prolonged anaesthesia: comparison of halothane with isoflurane.

Specific biochemical and physiological tests of liver function were used to assess 20 consecutive patients undergoing prolonged head and neck surgery with halothane or isoflurane anaesthesia. Hepatic function was assessed by measurement of serum concentrations of total bilirubin and albumin, and plasma activity of pseudocholinesterase, gamma-glutamyl transferase (GGT), aspartate transaminase (AST), alkaline phosphatase (ALP) and hepatic glutathione S-transferase. Plasma clearance of indocyanine green was used as an estimate of hepatic blood flow. No major differences were observed in serum concentrations of GGT, ALP, bilirubin, albumin or pseudocholinesterase. Serum AST activity in those patients receiving halothane was increased at 24 h and at 48 h compared with those who received isoflurane (not statistically significant). Glutathione S-transferase activity was increased significantly in the halothane group throughout the period of study, compared with those who received isoflurane. Similarly, there was a significant difference between the two groups as measured by plasma clearance of indocyanine green: in the halothane group there was a slower disappearance rate of the dye from plasma at specific times than in the patients who received isoflurane. Our data support the use of isoflurane rather than halothane for prolonged anaesthesia.

Serum antioxidant potential, and lipoprotein oxidation in female smokers following vitamin C supplementation.

A single blind placebo controlled trial was carried out to assess the effect of high dose vitamin C supplementation on the antioxidant potential, and extent of lipoprotein oxidation of serum in female smokers. Sixteen apparently healthy subjects were randomised into two groups of eight. One group received 1 g of vitamin C for 14 days the other group received a placebo for 14 days. Serum antioxidant potential (TRAP) was measured and lipoprotein oxidation was assessed by measuring serum malondialdehyde like material. Despite significant increases in serum C concentrations in the supplemented group, serum TRAP values did not change significantly over the course of the trial. Serum malondialdehyde like material also failed to show any temporal variation.