Evaluation of oxidative stress markers and vascular risk factors in patients with diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is one of the most common diabetic chronic complications. The pathogenesis of DPN is complex and involves an intertwined array of mechanisms. The purposes of this study were to evaluate the association of oxidative stress and vascular risk factors with the prevalence of DPN and to determine the role of these biochemical parameters in the prognosis of DPN. One hundred patients with type 2 diabetes mellitus and 40 clinically healthy individuals were evaluated. The patients were divided into two groups. Group 1 included 40 diabetic patients without peripheral neuropathy, and group 2 consisted of 60 patients with DPN. Erythrocytes glutathione (GSH) level, plasma malondialdehyde (MDA), nitrite/nitrate (NOx) and homocysteine (Hcy) levels as well as serum ceruloplasmin (Cp), total antioxidants (TAO), endothelin-1 (ET-1) levels and γ-glutamyl transferase (GGT) activity were estimated. A significant decrease of erythrocyte GSH was observed in groups 1 and 2 relative to the controls. An increase in glycosylated haemoglobin (HbA1c), MDA, NOx, GGT, Cp, TAO, Hcy and ET-1 was noted in patients with DPN. In conclusion, oxidative stress biomarkers and vascular risk factors could be important in the pathogenesis of DPN. The measurement of serum GGT and Hcy in addition to HbA1c and disease duration could facilitate the early detection of neuropathy in diabetic patients.     

Plasma lipids and lipoprotein patterns in angiographically graded atherosclerosis of the legs and in coronary heart disease.

The prevalence and type of plasma lipoprotein abnormalities were determined in 114 French-Canadian patients with angiographically proven peripheral vascular disease (PVD). The severity of atherosclerosis was positively correlated with plasma triglyceride concentration, especially in the younger patients (r = 0.29, P less than 0.05), and (not significantly) with plasma cholesterol concentration. Of the risk factors believed to predispose individuals to atherosclerosis, cigarette smoking was the most frequently found in the PVD patients (72.8%), especially among the men. Combination of two or more risk factors was the rule. Findings were compared with those in 114 patients who had undergone coronary angiography for suspected coronary heart disease (CHD). The CHD patients were, on average, younger by 10 years. Hyperlipidemia was present in 58.8% of CHD patients, compared with 43.9% of PVD patients. A far higher proportion of CHD patients showed the type II plasma lipoprotein pattern (24.6% v. 7.9%), although the type IV pattern was more common in both groups (31.6% and 28.9%, respectively). A high proportion of all patients (56.1% with PVD and 41.2% with CHD) showed a normal lipoprotein pattern on paper electrophoresis.     

Predictors of new atherosclerotic carotid plaque development in patients with rheumatoid arthritis: a longitudinal study

Introduction

Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality attributed to both classical risk factors and chronic inflammation. We assessed longitudinally the factors associated with new carotid plaques in nondiabetic RA patients and apparently healthy individuals.

Methods

In our present prospective observational study, carotid plaques were identified by ultrasonography at baseline and follow-up end, separated by an average of 3.6 ± 0.2 years, in 64 patients (mean age 59.2 ± 12.0 and disease duration at baseline 7.8 ± 6.2 years, 83% women, clinical and laboratory evaluation every 3 to 6 months). In a substudy, 35 of the patients were matched 1:1 for traditional cardiovascular risk factors with 'healthy' controls and were studied in parallel.

Results

New atherosclerotic plaques formed in 30% of patients (first plaque in 9%) who were significantly older than the remaining patients. Tobacco use, blood pressure, body mass index, average cumulative low-density lipoprotein, high-sensitivity C-reactive protein, erythrocyte sedimentation rate level, RA stage, functional class, disease duration and treatment modalities during follow-up did not differ significantly between subgroups after application of the Bonferroni correction. RA was in clinical remission, on average, for approximately 70% of the follow-up time and was not different between subgroups. Multivariate analysis including all the above parameters revealed that age (P = 0.006), smoking (P = 0.009) and duration of low-dose corticosteroid use (P = 0.016) associated independently with new plaque formation. RA patients displayed similar numbers of newly formed carotid plaques to the tightly matched for traditional cardiovascular risk factors 'healthy' controls, although more patients than controls had carotid plaques at baseline.

Conclusions

Formation of new atherosclerotic plaques in this small cohort of patients with well-controlled RA depended mainly on traditional cardiovascular risk factors and corticosteroid use, whereas an adverse effect of residual systemic inflammation was not readily detectable.     

Lack of Association Between a Common Polymorphism Near the INSIG2 Gene and BMI,Myocardial Infarction,and Cardiovascular Risk Factors

Epidemiological studies revealed an increasing prevalence of and a steep increase in obesity, a risk factor for cardiovascular disease. Because significant influence of a polymorphism, rs7566605, near the INSIG2 gene on BMI has been shown in the general population and in obesity cohorts, we hypothesized that this polymorphism might also act through an elevated BMI on the development of coronary artery disease (CAD) or myocardial infarction (MI). We pursued two strategies: First, the polymorphism rs7566605 was investigated for association with BMI, CAD/MI, and cardiovascular risk factors in a large German cohort at high risk for CAD and MI (n = 1,460 MI patients) as compared to unrelated healthy controls (n = 1,215); second, we extended our analyses on the families of MI patients and performed family‐based association testing (n = 5,390 individuals). The polymorphism rs7566605 was analyzed using TaqMan technology. No deviation from Hardy–Weinberg equilibrium could be observed, and the call rate was 98.2%. No significant associations of rs7566605 with CAD/MI, BMI, and classical cardiovascular risk factors could be detected in the full sample size or in the subgroups. A total of 6,878 individuals were investigated in a population of German MI patients and their family members. Although the number of individuals was large enough, no influence of the rs7566605 INSIG2 polymorphism was detected on BMI and CAD/MI. We therefore conclude that in our sample the SNP rs7566605 near the INSIG2 gene does not influence BMI and is not associated directly with CAD/MI or indirectly through cardiovascular risk factors.     

Erythrocyte membrane fatty acids in ischemic heart disease

The erythrocyte ghosts fatty acid composition of 27 patients with coronary artery disease (CAD) and 6 healthy people were investigated. Patients suffering from CAD were divided in two groups. The first group was matched by 18 patients with CAD and essential hypertension (EH) and 9 patients with CAD without EH. Significant decrease of the levels of some saturated fatty acids such as palmitic, stearic and begenic acids in the erythrocyte ghosts of the patients with CAD without EH was established among the major changes of the erythrocyte ghosts fatty acid composition. At the same time the amount, of arachidonic acid increased by 74% and docosahexaenoic acid--by 5.7 times. The content of miristic, palmitic and stearic acids was also diminished in patients with CAD and EH. The percent of arachidonic acid was elevated by 51% and docosatrienic acid--by 94%. It is notable that the quantity of docosahexaenoic acid did not change markedly if copmare to healthy people but was fallen for 5 times if compare to patients with CAD without EH. It was suggested that the lack of adaptive changes in erythrocyte ghosts omega-3 fatty acids of patients with CAD and EH was an important factor which could rise the risk of heart attack development.     

Pro-antioxidant ratio in healthy men exposed to muscle-damaging resistance exercise

The purpose of this study was to compare the pro-antioxidant status in healthy men exposed to muscle-damaging resistance exercise, and to investigate the practical application of Loverro's coefficient (P/A ratio) to evaluate the presence of oxidative stress. Twenty-eight healthy men were assigned to two groups performed multi-joint (M) or single-joint (S) resistance exercise. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) as well as the concentration of lipid peroxidation products (TBARS) in blood were evaluated. The P/A ratio was calculated from the mean values of erythrocyte TBARS, SOD, CAT and GPx. Creatine kinase (CK) activity was used as a marker of muscle damage. The applied resistance exercises triggered off the changes in pro-antioxidant ratio towards peroxidation which was proved by significant increase in erythrocyte TBARS concentration in M (+25%) and S (+27%) groups. Plasma TBARS increased only after multi-joint resistance exercise and correlated with erythrocyte P/A ratio (r = 0.536, P < 0.01). The multi-joint exercise caused decrease in SOD activity by 28% whereas the single-joint resistance exercise elevated enzyme activity by 20%. Activities of the other antioxidant enzymes changed simultaneously i.e. CAT activity increased by 14%-16% immediately after exercise, and GPx activity declined by 18%-34% during recovery in M and S groups. Even though, all erythrocyte parameters significantly changed following multi-joint and single-joint resistance exercises, the assessment of pro-antioxidant ratio showed the considerable increase in P/A only in M group. In summary, an analysis of pro- and antioxidant parameters showed significant changes in response to muscle-damaging exercise and demonstrated the practical application of P/A ratio to evaluate the risk of oxidative stress in athletes.     

The estimation of microcirculation state in cerebrovascular disorders by data of laser Doppler flowmetry and hemorheological parameters

The study was aimed to evaluate microvascular blood flow and theological blood properties in healthy volunteers (n = 27) and patients with cerebral accident (n = 30). To study cutaneous blood flow we used the multifunctional laser analyzer of blood microcirculation LAKK (LAZMA, Moscow) with spectrophotometric channel and wavelet analysis of blood flow oscillations. Viscosity of the whole blood, plasma, RBC aggregability and deformability were assessed. Results: microcirculation index was by 25% (p < 0.05) lower in patients compared to the control group. Computing amplitude-frequency range of blood flow oscillations revealed notable changes in the blood flow regulation mechanisms under cerebrovascular accident: the amplitudes of all active rhythms (endothelial, neurogenic and myogenic ones) were increased. In spite of such activization of regulatory mechanisms, aimed to keep essential blood supply to tissue, index of specific oxygen consumption by tissue was decreased by 21% (p < 0.05) under cerebrovascular disorders. Blood rheological properties in patients group were impaired compared to the healthy group: blood viscosity was increased because of elevated plasma viscosity, increased RBS aggreagation and decreased erythrocyte deformability. Thus, our results demonstrated the decrease of tissue perfusion, activization of vasodilating mechanisms, impaired blood rheology and the decrease of oxygen supply to tissue in patients with cerebrovascular accident. Statistical analysis revealed a number of significant correlations between the hemorheological parameters and passive rhythms of microcirculation in norm. In patients blood viscosity correlated to the amplitude of active regulatory rhythms (endothelial, neurogenic and myogenic oscillations). Close interralations between rheological and microcirculation parameters testified the important role of hemorheological factors in maintenance of microvascular blood flow and oxygen delivery to tissue.     

Homocysteine in relation to C-reactive protein and low-density lipoprotein cholesterol in assessment of cardiovascular risk.

Coronary vascular disease (CVD) is a chronic, multifactorial disease that occurs often in individuals without known risk factors. We investigated the predictive value of homocysteine (Hcy) in relation to C-reactive protein (CRP) and low-density lipoprotein (LDL)-cholesterol in patients with confirmed coronary disease. The study included 87 German and 92 Syrian patients in addition to 87 German and 64 Syrian control individuals. Patients and controls were of comparable age, lifestyles and cultural background. Patients of both ethnic groups had significantly higher concentrations of Hcy and C-reactive protein compared to the controls. The lipids were higher only in Syrian patients compared to the controls. Elevated concentrations of Hcy or that of CRP (>75th percentiles) were associated with increased probability for CVD. In both population groups, the risk increased markedly in subjects who had elevated concentrations of Hcy and CRP or those who had elevated concentrations of Hcy and LDL-cholesterol. The results emphasize that detemination of Hcy may improve the predictive value of C-reactive protein and the LDL-cholesterol. Measurements of these markers are especially important for identification of patients at high risk for CVD.     

Is adrenomedullin a causal agent in some cases of type 2 diabetes?

The study of two populations with a recent onset of type 2 diabetes showed that a subset of the patients had higher levels of adrenomedullin (AM) than the rest of the diabetics. In this subset, physiological elevations of AM might have triggered the disease in predisposed individuals. Diabetics showed higher levels of AM than healthy controls. In addition, glycemia was measured in diabetic rats after injection of saline, AM, or antiAM antibody. AM elevated glycemia, whereas the antibody reduced circulating glucose to normal. These results suggest that manipulation of AM levels could represent a new approach in the management of diabetes for the appropriate individuals.     

Human leukocyte antigen (HLA) complex and anti-thyroidal antibodies in Graves' disease

The study aimed at: 1) assessing occurrence of HLA-A, HLA-B and HLA-C antigens in patients with Graves' disease in comparison with control group of healthy individuals; 2) determining relationship between circulating serum antimicrosomal and antithyroglobulin antibodies and selected HLA complex antigens. Human leukocyte antigens A, B, and C were detected with serological technique using cytotoxicity test. Thyroidal antimicrosomal and antithyroglobulin antibodies were titrated with radioimmunological solid phase technique while anti-membrane antibodies with immunoenzyme technique. The study involved 50 patients with Graves' disease and 50 healthy individuals. HLA-B8, HLA-B15, HLA-B35, and HLA-Cw3 antibodies were detected more frequently in patients with Graves' disease than in the healthy individuals. Antimicrosomal and antithyroglobulin antibodies were detected in the same group in 76% and 58% of patients, respectively whereas anti-membrane antibodies in 92% of patients. Comparison of the occurrence of thyroidal antimicrosomal and antithyroglobulin antibodies with the presence of HLA-B8, HLA-B35, HLA-B15, and HLA-Cw3 antigens did not show statistically significant correlation between these two parameters.     

An almond-enriched diet increases plasma α-tocopherol and improves vascular function but does not affect oxidative stress markers or lipid levels

Abstract

Vascular dysfunction is one of the major causes of cardiovascular (CV) mortality and increases with age. Epidemiological studies suggest that Mediterranean diets and high nut consumption reduce CV disease risk and mortality while increasing plasma α-tocopherol. Therefore, we have investigated whether almond supplementation can improve oxidative stress markers and CV risk factors over 4 weeks in young and middle-aged men.

Healthy middle-aged men (56 ± 5.8 years), healthy young men (22.1 ± 2.9 years) and young men with two or more CV risk factors (27.3 ± 5 years) consumed 50 g almond/day for 4 weeks. A control group maintained habitual diets over the same period.

Plasma α-tocopherol/cholesterol ratios were not different between groups at baseline and were significantly elevated by almond intervention with 50 g almond/day for 4 weeks (p < 0.05). Plasma protein oxidation and nitrite levels were not different between groups whereas, total-, HDL- and LDL-cholesterols and triglycerides were significantly higher in healthy middle-aged and young men with CV risk factors but were not affected by intake. In the almond-consuming groups, flow-mediated dilatation (FMD) improved and systolic blood pressure reduced significantly after 50 g almonds/day for 4 weeks, but diastolic blood pressure reduced only in healthy men.

In conclusion, a short-term almond-enriched diet can increase plasma α-tocopherol and improve vascular function in asymptomatic healthy men aged between 20 and 70 years without any effect on plasma lipids or markers of oxidative stress.     

Fenvalerate-induced chromosome aberrations and sister chromatid exchanges in the bone marrow cells of mice in vivo

To investigate whether subjects with low-acid states are exposed to increased genetic risk with respect to controls, we evaluated mutagenicity and presence of clastogenic factors (CF) in the gastric juice of chronic atrophic gastritis and omeprazole-treated patients. Mutagenic gastric juice was found in 8/15 (53%) chronic atrophic gastritis patients, 8/11 (73%) omeprazole-treated patients, and 2/13 (15%) healthy control subjects. The mean mutagenicity ratio of omeprazole-treated patients (1.52+/-0.48/0.1 ml gastric juice) was significantly higher than those of either controls (1.07+/-0.15; P<0.01) or chronic atrophic gastritis patients (1.16+/-0.21; P<0.05). Only chronic atrophic gastritis patients showed an increased clastogenic index with respect to healthy controls (2.67+/-2.13 versus 0.38+/-0.51; P<0.001). These findings expand our knowledge of gastric disease risk factors, and indicate that there may well be a risk of mucosal DNA damage arising from the presence of mutagenic and CF in the gastric juice.     

A critical evaluation of urinary immunoreactive thromboxane: feasibility of its determination as a potential vascular risk indicator

Urinary immunoreactive thromboxane (irTXB2) has been found helpful in acute settings with altered renal, but also extrarenal thromboxane formation. As only trace amounts of systemically formed thromboxane are excreted unmetabolized, the nature of urinary irTXB2 was explored. The two most abundant metabolites of systemic thromboxane, 2,3-dinor-TXB2 and 11-dehydro-TXB2, crossreacted about 70% and less than 1%, respectively, with a widely used thromboxane antiserum. After solid-phase extraction of urine samples and separation on reversed-phase HPLC, the bulk of immunoreactivity always eluted as one peak shown to correspond to 2,3-dinor-TXB2. Much less was found in fractions where TXB2 eluted. Therefore, urines were read against calibration curves constructed with 2,3-dinor-TXB2. This direct estimation gave good recoveries for standard 2,3-dinor-TXB2 and correlated well, both in healthy controls and in patients at increased risk or with overt vascular disease, to values obtained after solid phase extraction, purification on reversed-phase HPLC and quantitation by either gas-chromatography mass-spectrometry or radioimmunoassay. Patients with multiple cardiovascular risk factors but free from detectable vascular disease excreted significantly more irTXB2 than age-matched controls with non-vascular conditions or normals. Therefore, urinary irTXB2 measured with this antiserum represents 2,3-dinor-TXB2, reflecting the systemic formation of TXB2. This simple approach is feasible for screening thromboxane formation in large series of patients. Its acumen in detecting the early development of vascular disease and its relation to established risk factors deserves large-scale prospective testing.     

Vascular effects of non-esterified fatty acids: implications for the cardiovascular risk factor cluster.

Insulin resistance emerges as a central component of the risk factor cluster and is a likely contributor to vascular disease independently of traditional risk factors such as hypertension and diabetes mellitus. However, the intermediary mechanisms by which atherosclerosis is accelerated among patients with the insulin resistance syndrome remain inadequately defined. Most of the attention has centered on hyperinsulinemia and defects of insulin-mediated glucose disposal. However, we observed that obese hypertensive patients have elevated plasma concentrations of non-esterified fatty acids (NEFAs), including oleic acid, which are highly resistant to suppression by insulin. Resistance to insulin's fatty acid lowering action correlate with blood pressure in obese subjects independently of defects in glucose disposal. This observation raises the possibility that NEFAs have biologically significant effects on the cardiovascular system. In fact, oleic acid impairs nitric oxide synthase activity and endothelium-dependent vasorelaxation in vitro. Moreover, raising NEFAs in normal human volunteers to levels observed in obese hypertensive patients impairs lower extremity endothelium-dependent vasodilation and augments local and systemic vascular alpha1-adrenoceptor reactivity in normal volunteers. Thus, raising NEFAs replicates in healthy subjects important functional vascular changes implicated in the hypertension and atherosclerosis observed in patients with the risk factor cluster. At a molecular level, experiments in cultured vascular smooth muscle cells demonstrate that oleic acid activates a mitogenic signaling cascade which includes protein kinase C, reactive oxygen species and extracellular signal-regulated kinases. Each of these signaling events has been implicated in the structural and functional vascular changes which accompany the risk factor cluster. Collectively, these observations raise the possibility that fatty acids contribute to functional and structural vascular changes among insulin-resistant individuals. A better understanding of the signaling mechanisms by which NEFAs exert their vascular effects may facilitate novel and more effective therapeutic approaches to managing the cardiovascular risk factor cluster.     

Apolipoprotein polymorphism is associated with pro-thrombotic profile in non-demented dyslipidemic subjects

Apolipoprotein gene polymorphism has an important role in lipid metabolism and in the development of cerebro- and cardio-vascular disease (CCVD), including dementia. Dyslipidemia and hemostatic abnormalities are key risk factors associated with athero-sclerotic events preceding CCVD. The aim of this study was to evaluate the possible relationships of various apolipoprotein-species with hemostatic parameters and cognitive function. Lipid profile, gene polymorphism, coagulation markers, and mini-mental state examination (MMSE) scores were assessed in 109 dys-lipidemic subjects and in 107 healthy control volunteers. Thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels were significantly higher in apolipoprotein-E2 (apoE2) patients when compared to other apoE forms. The apoA5 -1131T>C polymorphism was associated with elevated D-dimer concentration in dyslipidemic TT homozygous individuals. MMSE did not correlate with lipid or coagulation profile. These data suggest that apoE and apoA5 variants have an effect on hemostatic parameters, but they neither influence nor predict cognitive performance in non-demented individuals.     

Angiogenic and angiostatic factors in systemic sclerosis: increased levels of vascular endothelial growth factor are a feature of the earliest disease stages and are associated with the absence of fingertip ulcers

To examine whether the lack of sufficient neoangiogenesis in systemic sclerosis (SSc) is caused by a decrease in angiogenic factors and/or an increase in angiostatic factors, the potent proangiogenic molecules vascular endothelial growth factor (VEGF) and basic fibroblast growth factor, and the angiostatic factor endostatin were determined in patients with SSc and in healthy controls. Forty-three patients with established SSc and nine patients with pre-SSc were included in the study. Serum levels of VEGF, basic fibroblast growth factor and endostatin were measured by ELISA. Age-matched and sex-matched healthy volunteers were used as controls. Highly significant differences were found in serum levels of VEGF between SSc patients and healthy controls, whereas no differences could be detected for endostatin and basic fibroblast growth factor. Significantly higher levels of VEGF were detected in patients with Scl-70 autoantibodies and in patients with diffuse SSc. Patients with pre-SSc and short disease duration showed significant higher levels of VEGF than healthy controls, indicating that elevated serum levels of VEGF are a feature of the earliest disease stages. Patients without fingertip ulcers were found to have higher levels of VEGF than patients with fingertip ulcers. Levels of endostatin were associated with the presence of giant capillaries in nailfold capillaroscopy, but not with any other clinical parameter. The results show that the concentration of VEGF is already increased in the serum of SSc patients at the earliest stages of the disease. VEGF appears to be protective against ischemic manifestations when concentrations of VEGF exceed a certain threshold level.     

Evaluation of various hemorheological parameters in nonagenarians: evidence of an increase of fibrinogen

Cardiovascular disease is the most frequent cause of mortality in the elderly. A reduced microvascular blood flow associated with an increase in atherosclerosis might contribute to age related increases in the incidence of ischemic vascular disease. In order to evaluate the effect of age on some haemorheological parameters, blood and plasma viscosity and fibrinogen have been measured in 10 healthy elderly subjects, aged between 88 and 96 years, compared with 15 healthy young subjects (mean age 37 years). Elderly subjects showed a significant increase in plasma fibrinogen (p less than 0.0005) and a trend to an increase in plasma viscosity, whereas no difference was present in blood viscosity. These data confirm that aging is associated with a greater deal of thrombotic risk factors, the most important of which seems to be fibrinogen.     

Multiple cardiovascular disease risk factors in Canadian adults. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To estimate the prevalence and distribution of the coexistence of major cardiovascular disease (CVD) risk factors among Canadian adults. DESIGN: Population-based cross-sectional surveys. SETTING: Nine Canadian provinces, from 1986 to 1990. PARTICIPANTS: A probability sample of 26,293 men and women, aged 18 to 74 years, was selected from provincial health insurance registries. For 20,582 of these participants, at least two blood pressure (BP) measurements were taken using a standardized technique. At a subsequent visit to a clinic, two additional BP readings, anthropometric measurements and a blood specimen for plasma lipid analysis were obtained. OUTCOME MEASURES: The percentage distribution of subjects by number of major risk factors (smoking, high BP and elevated blood cholesterol level) and by concomitant factors (body mass index [BMI], ratio of waist to hip circumference [WHR], physical activity, diabetes, awareness of CVD risk factors and education). MAIN RESULTS: Sixty-four percent of men and 63% of women had one or more of the major risk factors. Prevalence increased with age to reach 80% in men and 89% in women aged 65 to 74 years. Prevalence of two or three risk factors was highest among men in the 45-54 age group (34%) and in women in the 65-74 age group (37%). The most common associations were between smoking and high blood cholesterol level (10%) and between high BP and high blood cholesterol level (8%). Prevalence of high BP and elevated blood cholesterol, alone or in combination, increased with BMI and WHR. Smoking, elevated blood cholesterol, BMI and prevalence of one or more risk factors increased with lower level of education. Less than 48% of participants mentioned any single major risk factor as a cause of heart disease. Awareness was lowest in the group with fewest years of education. CONCLUSION: The findings of this study call for an approach to reduce CVD that stresses collaboration of the different health sectors to reach both the population as a whole and the individuals at high risk.     

Genetic and environmental explanations for the distribution of sodium-lithium countertransport in pedigrees from Rochester, MN.

An elevated level of erythrocyte sodium-lithium (Na-Li) countertransport has been suggested as a predictor of predisposition to essential hypertension. In order to evaluate whether a single genetic or environmental factor with large effects explains the mixture of distributions in Na-Li countertransport in the general population, complex segregation analyses were conducted by using 1,273 individuals more than age 20 years from 276 pedigrees selected without respect to disease risk factors or health status. Either a single genetic locus or a single environmental factor with large gender-specific effects explained the mixture of distributions for Na-Li countertransport in this sample equally well. In the subsample of pedigrees supporting a single-locus etiology, the single genetic locus explained 29.0% of the variability in adjusted Na-Li countertransport in males and 16.6% of that in females. In a subsample of pedigrees supporting an environmental factor etiology, the environmental factor explained 35.2% of the adjusted Na-Li countertransport in males and 20.5% of that in females. These results suggest that there are at least two different explanations for the mixture of distributions in Na-Li countertransport in the general population. Attempts to relate genetic variation in Na-Li countertransport to risk of essential hypertension must consider that the factor with large phenotypic effects on this trait is gender specific and may not be a single major locus in all pedigrees.     

Attitudes about Tuberculosis Prevention in the Elimination Phase: A Survey among Physicians in Germany

Background

Targeted and stringent measures of tuberculosis prevention are necessary to achieve the goal of tuberculosis elimination in countries of low tuberculosis incidence.

Methods

We ascertained the knowledge about tuberculosis risk factors and stringency of tuberculosis prevention measures by a standardized questionnaire among physicians in Germany involved in the care of individuals from classical risk groups for tuberculosis.

Results

510 physicians responded to the online survey. Among 16 risk factors immunosuppressive therapy, HIV-infection and treatment with TNF-antagonist were thought to be the most important risk factors for the development of tuberculosis in Germany. Exposure to a patient with tuberculosis ranked on the 10^th position. In the event of a positive tuberculin-skin-test or interferon-γ release assay only 50%, 40%, 36% and 25% of physicians found that preventive chemotherapy was indicated for individuals undergoing tumor necrosis factor-antagonist therapy, close contacts of tuberculosis patients, HIV-infected individuals and migrants, respectively.

Conclusions

A remarkably low proportion of individuals with latent infection with Mycobacterium tuberculosis belonging to classical risk groups for tuberculosis are considered candidates for preventive chemotherapy in Germany. Better knowledge about the risk for tuberculosis in different groups and more stringent and targeted preventive interventions will probably be necessary to achieve tuberculosis elimination in Germany.