Femoral atherosclerosis in an older British population: prevalence and risk factors

Most estimates of the prevalence of peripheral atherosclerosis have been based on intermittent claudication or lower limb blood flow. The aim of this study was therefore to determine the prevalence of underlying femoral plaque, and to determine its association with other cardiovascular disease and risk factors. Presence of plaque was identified using ultrasound in a random sample of men (n=417) and women (n=367) aged 56-77 years. Coexistent cardiovascular disease, exercise and smoking were determined by questionnaire, blood pressure was recorded, and serum cholesterol and plasma fibrinogen were determined. Of the 784 subjects that were scanned, 502 (64%) demonstrated atherosclerotic plaque. Disease prevalence increased significantly with age (P<0.0001), and was more common in men (67.1 vs. 59.4%, P<0.05). Subjects with femoral plaque had a significantly greater odds of previous ischaemic heart disease (OR 2. 2, 95% CI 1.3, 3.7) and angina (OR 1.7, 95% CI 1.03, 2.7), but not of stroke or leg pain on exercise. Current and ex-smoking, raised serum total cholesterol and plasma fibrinogen levels, but not blood pressure, were associated with an increased risk of femoral plaque, independent of age and sex. Frequent exercise and a high HDL cholesterol were significantly associated with lower risk. In conclusion, therefore, atherosclerotic disease of the femoral artery affects almost two-thirds of the population in late middle age. It is associated with an increased prevalence of ischaemic heart disease and angina, but whether detecting at risk individuals using ultrasound offers advantages over simpler and less expensive risk factor scoring requires evaluation in trials.     

Childhood anaplastic large cell lymphoma has a high incidence of ALK gene rearrangement as determined by immunohistochemical staining and fluorescent in situ hybridisation: a genetic and pathological correlation

Anaplastic large cell lymphoma (ALCL) comprises 10-15% of childhood non-Hodgkin lymphomas (NHL). Systemic ALCL is highly associated with anaplastic lymphoma kinase (ALK) gene translocations with over-expression of ALK protein. We studied ALK rearrangements using fluorescence in situ hybridisation (FISH) and ALK immunohistochemical staining in 43 paediatric systemic ALCLs. FISH (performed on 35 cases) identified a translocation in 29 cases (83%). Immunohistochemistry identified ALK over-expression in 42/43 cases (97%) with the single ALK-negative case demonstrating an ALK rearrangement by FISH, indicating 100% incidence of ALK translocations.     

Effects of lipids and lipoproteins on thrombosis and rheology

Atherosclerotic plaque rupture and erosions precipitate thrombus formation and may lead to an acute ischemic syndrome. Lipids and lipoproteins modulate the expression and/or function of thrombotic, fibrinolytic and rheologic factors, and thereby influence hemostasis and potential tissue damage resulting from vascular injury. Triglyceride-enriched lipoproteins are accompanied by elevations in factor VII clotting activity, plasminogen activator inhibitor (PAI-1) and viscosity of blood and plasma. Low density lipoprotein (LDL) promotes platelet activation and tissue factor expression and LDL levels correlate with levels of vitamin K dependent coagulation factors and fibrinogen. Conversely, LDL inhibits tissue factor pathway inhibitor (TFPI) which limits activation of the extrinsic coagulation pathway. High density lipoprotein (HDL) has anti-atherothrombotic properties that result from inhibition of platelet and erythrocyte aggregation, reduced blood viscosity and suppression of tissue factor activity and PAI-1 activity and antigen levels. The effects of lipids and lipoproteins on hemostasis and rheology may have important implications for the clinical sequelae following plaque disruption and erosion.     

Mapping of quantitative trait loci for hypnotic sensitivity to ethanol in crosses derived from the C57BL/6 and DBA/2 mouse strains

BACKGROUND: Acute ethanol sensitivity is thought to be a predisposing factor toward the development of alcoholism. Accumulated evidence suggests that this characteristic may be at least partly heritable. A widely accepted approach for identifying genes thought to contribute to alcoholism is to map quantitative trait loci (QTLs) for various ethanol-related behaviors in rodent models. METHODS: Ethanol sensitivity QTLs were interval-mapped in a C57BL/6 (B6) X DBA/2 (D2) F2 intercross that contained 391 mice. Sensitivity was measured as the duration of loss of righting reflex (LORR) after 4.1 g/kg ip. LORR also was evaluated in a chromosome 1 marker-assisted congenic strain that had an approximately 30 centiMorgan (cM) portion of D2 DNA from the distal end of chromosome 1 introgressed onto a B6 background. RESULTS: A suggestive QTL was mapped on chromosome 1 (LOD = 3.3; approximately 80 cM) and a provisional QTL on chromosome 5 (LOD = 2.3; approximately 26 cM). The provisional chromosome 5 QTL was found to be sex-specific (LOD = 2.5 for males; LOD < 1 for females) with the D2 allele increasing LORR. The chromosome 1 D2 allele decreased LORR. Consistent with the F2 QTL mapping, congenic mice heterozygous for the chromosome 1 interval (B6/D2) had a significantly different mean (+/- SEM) LORR of 74.0 +/- 4.9 min (n = 36) compared with 90.8 +/- 6.2 min (n = 33) for their homozygous (B6/B6) littermates (p = 0.02). Blood ethanol concentration at regain of righting reflex was 377 +/- 10 mg% for the B6/D2 and 368 +/- 10 mg% (p = NS) for the B6/B6. CONCLUSIONS: LORR results in the chromosome 1 congenic mice were consistent with and very similar to what was predicted from the QTL analysis in the B6 X D2 F2 population. These results support a suggestive LORR QTL on the distal end of mouse chromosome 1. The results also indicate that there is a provisional sex-specific LORR QTL on chromosome 5.     

Evaluation of Patients under Investigation for MERS-CoV Infection,United States,January 2013–October 2014

Middle East respiratory syndrome (MERS) cases continue to be reported from the Middle East. Evaluation and testing of patients under investigation (PUIs) for MERS are recommended. In 2013–2014, two imported cases were detected among 490 US PUIs. Continued awareness is needed for early case detection and implementation of infection control measures.     

Depletion of total antioxidant capacity in type 2 diabetes

The purpose of the study was to examine the relationship between antioxidant depletion, glycemic control, and development of chronic complications in a controlled population of type 2 diabetic patients. Fifty age-matched type 2 diabetic patients receiving sulfonylureas but not insulin treatment were screened and assigned to two groups based on the presence or absence of proteinuria. A third group of normal subjects without diabetes were also enrolled in the study. All subjects in the three groups were Egyptians who were matched for body weight, and the two diabetic groups were also age-matched. Plasma glucose and fructosamine levels were higher in the two groups of diabetic patients versus the control group, but lipid peroxide levels were higher only in the patients with proteinuria. Compared with the control group, the total antioxidant capacity was depleted in the two diabetic groups, but the depletion was more severe in patients with proteinuria. Thus, the mean Trolox equivalent antioxidant capacity (TEAC) of the control group was 2.7+/-0.45, versus 1.7+/-0.5 (P < .001) in the patients without proteinuria. Furthermore, the TEAC measured in patients with proteinuria, who also had more diabetic complications, was lower (1.4+/-0.5, P < .001) than the TEAC in patients without urinary protein. In conclusion, a depletion of the total antioxidant capacity is associated with a higher incidence of diabetic complications.     

Prognostic value of beta-thromboglobulin in patients with transient cerebral ischaemia

Plasma levels of beta-thromboglobulin (BTG) and fibrinopeptide A (FPA), markers of platelet alpha-granule release and thrombin generation respectively, were measured in 27 subjects with transient cerebral ischaemic attacks (TIA), 43 age-matched controls, and 32 young controls. BTG and FPA were both higher in elderly controls than in young controls. BTG was higher in TIA subjects than in age-matched controls and higher in the 12 TIA subjects who had further vascular events in the next year than in those who had no further events. FPA was not significantly associated with TIA or with further events. These results support a relationship between platelet activation and TIA and suggest that BTG levels indicate a group at higher risk of further vascular events.