Carbon Monoxide and Driving Skills

Eighty milliliters of carbon monoxide (CO) or 80 ml of air was administered doubleblind to 50 adults (32 men, 18 women). Blood carboxyhemoglobin (COHb) levels increased by 3.4% in those receiving CO. Brake reaction time, night vision, glare vision, glare recovery, hand-steadiness, and depth perception all showed small and individually insignificant deterioration in the group receiving CO; grouping data in a nonparametric analysis, the performance difference became significant (P < .005). During operation of a driving simulator, the CO-exposed group showed a highly significant deficit in “careful driving” skills (P < .005), with a statistically insignificant facilitation of emergency-type movements. Since a 3.4% increase of COHb level is sufficient to prejudice safe driving, there is a need to revise the permitted eight-hour industrial CO exposure level of 50 ppm.     

"Early-peak" carbon monoxide production in certain erythropoietic disorders

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.     

Peak oxygen intake and cardiac mortality in women referred for cardiac rehabilitation

OBJECTIVES: This study investigated the prognostic importance of measured peak oxygen intake (VO(2peak)) in women with known coronary heart disease referred for outpatient cardiac rehabilitation. BACKGROUND: Exercise capacity is a powerful predictor of prognosis in men with known or suspected coronary disease. Similar findings are described in women, but fewer studies have utilized measured VO(2peak), the most accurate measure of exercise capacity. METHODS: A single-center design took data from 2,380 women, age 59.7 +/- 9.5 years (1,052 myocardial infarctions, 620 coronary bypass procedures, and 708 with proven ischemic heart disease), who underwent cardiorespiratory exercise testing. They were followed for an average of 6.1 +/- 5 years (median 4.5 years, range 0.4 to 25 years) until cardiac and all-cause death. RESULTS: We recorded 95 cardiac deaths and 209 all-cause deaths. Measured VO(2peak) was an independent predictor of risk, values > or =13 ml/kg/min (3.7 multiples of resting metabolic rate) conferring a 50% reduction in cardiac mortality (hazard ratio [HR] 0.5, p = 0.001). Considered as a continuous variable, a 1 ml/kg/min advantage in initial VO(2peak) was associated with a 10% lower cardiac mortality. Adverse predictors were diabetes (HR 2.73, p = 0.0005) and antiarrhythmic therapy (HR 3.93, p = 0.0001). CONCLUSIONS: As in men, measured VO(2peak) is a strong independent predictor of cardiac mortality in women referred for cardiac rehabilitation.     

Investigation of susceptibility loci identified in the UK rheumatoid arthritis whole-genome scan in a further series of 217 UK affected sibling pairs

OBJECTIVE: A previous whole-genome scan (WGS) of 182 UK rheumatoid arthritis (RA) affected sibling pair (ASP) families suggested linkage to HLA and 11 other chromosome regions. Replication of such findings in an independent cohort can help to distinguish true linkages from false-positive linkages. Since RA is a heterogeneous disease, some loci may be linked only in subsets of patients. Thus, the aim of this study was to investigate in an additional set of RA ASP families linkage to regions showing deviation in expected allele-sharing ratios in the UK WGS and to perform subset analysis on the combined cohort. METHODS: Twenty loci were investigated for linkage in 217 Caucasian UK RA ASPs. Stratification analysis was performed on the combined cohort of 377 RA ASP families to account for sex, RA severity, and the shared epitope (SE). RESULTS: None of the regions of linkage identified in the initial WGS achieved statistical significance in the second cohort. In contrast, after stratification analysis, 14 regions showed nominal evidence of linkage (logarithm of odds score >0.8) in one or more subgroups. In particular, the strength of evidence for linkage to chromosome 16p was increased in subsets of ASPs with younger age at disease onset (LOD score 2.38) and for linkage to chromosome 6q in female-female ASPs (LOD score 2.31) and in ASPs in which both siblings had 2 copies of the SE (LOD score 3.03). CONCLUSION: These results support the evidence for heterogeneity of RA. This information will inform the future design of association-based investigations as the search for disease genes in the linked regions begins.     

Angiotensinogen gene T235 variant: a marker for the development of persistent microalbuminuria in children and adolescents with type 1 diabetes mellitus

AIM: We examined genetic polymorphisms in the renin-angiotensin system (RAS) coding for angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) for angiotensinogen (AGT) M235T and angiotensin II receptor type 1 (AGTR1) A1166C as predictors for the development of microalbuminuria (MA) in children with type 1 diabetes mellitus (T1DM). METHODS: Four hundred fifty-three (215 males, 238 females) T1DM children [median (interquartile range): age, 16.7 years (13.9-18.3); diabetes duration, 6.9 years (3.3-10.8); age at diagnosis, 9.1 years (5.8-11.8)] were followed prospectively from diagnosis until the development of MA (two of three consecutive overnight urine samples with albumin excretion rates of > or =20 and <200 microg/min). Kaplan-Meier survival curves and Cox proportional multivariate model estimated the probability of developing MA and the relative risk for MA among different variables. RESULTS: MA developed in 41 (9.1%) subjects. The frequencies of genotypes were as follows: ACE-II 112 (25%), ACE-ID 221 (49%), and ACE-DD 117 (26%) (n=450); AGT-MM 144 (32%), AGT-MT 231 (51%), and AGT-TT 77 (17%) (n=452); AGTR1-AA 211 (47%), AGTR1-AC 204 (45%), and AGTR1-CC 37 (8%) (n=452). The cumulative risk for the development of MA was higher in ACE-DD versus ACE-ID/II groups (log-rank test, P=.05), and a trend was noticed when AGT-TT was compared to AGT-MT/MM groups (log-rank test, P=.08). AGT-TT polymorphism conferred a fourfold increased risk for MA compared to AGT-MM/MT (hazard ratio=3.8; 95% confidence interval=1.43-10.3; P=.008). INTERPRETATION: Our findings suggest that RAS gene polymorphism at AGT M235T is a strong predictor for early MA in young T1DM subjects.     

Clinical features of kidney cancer in primary care: a case-control study using primary care records

Background

Kidney cancer accounts for over 4000 UK deaths annually, and is one of the cancer sites with a poor mortality record compared with Europe.

Aim

To identify and quantify all clinical features of kidney cancer in primary care.

Design

Case-control study, using General Practice Research Database records.

Method

A total of 3149 patients aged ≥40 years, diagnosed with kidney cancer between 2000 and 2009, and 14 091 age, sex and practice-matched controls, were selected. Clinical features associated with kidney cancer were identified, and analysed using conditional logistic regression. Positive predictive values for features of kidney cancer were estimated.

Results

Cases consulted more frequently than controls in the year before diagnosis: median 16 consultations (interquartile range 10–25) versus 8 (4–15): P<0.001. Fifteen features were independently associated with kidney cancer: visible haematuria, odds ratio 37 (95% confidence interval [CI] = 28 to 49), abdominal pain 2.8 (95% CI = 2.4 to 3.4), microcytosis 2.6 (95% CI = 1.9 to 3.4), raised inflammatory markers 2.4 (95% CI = 2.1 to 2.8), thrombocytosis 2.2 (95% CI = 1.7 to 2.7), low haemoglobin 1.9 (95% CI = 1.6 to 2.2), urinary tract infection 1.8 (95% CI = 1.5 to 2.1), nausea 1.8 (95% CI = 1.4 to 2.3), raised creatinine 1.7 (95% CI = 1.5 to 2.0), leukocytosis 1.5 (95% CI = 1.2 to 1.9), fatigue 1.5 (95% CI = 1.2 to 1.9), constipation 1.4 (95% CI = 1.1 to 1.7), back pain 1.4 (95% CI = 1.2 to 1.7), abnormal liver function 1.3 (95% CI = 1.2 to 1.5), and raised blood sugar 1.2 (95% CI = 1.1 to 1.4). The positive predictive value for visible haematuria in patients aged ≥60 years was 1.0% (95% CI = 0.8 to 1.3).

Conclusion

Visible haematuria is the commonest and most powerful single predictor of kidney cancer, and the risk rises when additional symptoms are present. When considered alongside the risk of bladder cancer, the overall risk of urinary tract cancer from haematuria warrants referral.     

Effects of physical activity upon the liver

European Journal of Applied Physiology - To review the responses of the liver to acute and chronic physical activity and to summarize relationships between physical activity and liver health. A...