Progression to multifactorial diseases is determined jointly by genes and environment. A valid approach for the prediction and prevention of such diseases might be to define at birth, or at an early age, the population at increased genetic risk by analysing the risk genes or risk alleles, the subsequent follow-up of those at risk, and the appropriate implementation of preventive measures at optimum time, if available. The feasibility and acceptance of population-wide genetic tests aimed at an early recognition of the risk of common multifactorial diseases with clinical presentation later in life is not known.The Type I Diabetes Prediction and Prevention project (DIPP) is an effort to predict and search for means to delay or prevent the disease in a large population-based cohort of children in Finland. The case of Type I diabetes is probably a useful model for the prediction and prevention of chronic, multifactorial Diabetologia (2001)
AbstractAims/hypothesis. Population-wide genetic screening of susceptibility to multifactorial diseases will become relevant as knowledge of the pathogenesis of these diseases increases and preventive interventions are identified. Methods. Feasibility and acceptance of neonatal genetic screening for Type I (insulin-dependent) diabetes mellitus susceptibility and adherence of the atrisk children to frequent autoantibody follow-up were studied. Screening was offered to all families. The infants with HLA-DQB1 genotypes *02/*0302 and *0302/x (x¹*02, *0301, *0602) were invited to autoantibody follow-up. The children who developed signs of b-cell autoimmunity were invited to a separate prevention trial. Results. The parents of 31 526 babies born between November 1994 and April 1999 (94.4 % of those eligible) agreed to genetic screening. We found that 4651 infants (14.8 %) had increased genetic risk (2.5 to 15 times that of the general population) for Type I (insulin-dependent) diabetes mellitus, and 80 % of them joined the autoantibody surveillance. At the age of 1, 2, 3 and 4 years, 74, 69, 68 and 76 % of the at-risk children, respectively, attended the follow-up. A total of 17 of the 22 children (77 %) who were born during the study period and have developed diabetes carry the risk genotypes we currently use for screening. Conclusions/interpretation. Population-based screening of genetic susceptibility for Type I diabetes, linked with a possibility to participate later in a prevention trial, is highly accepted in Finland and identifies about 75 % of those developing diabetes at an early age. Families adhere well to the frequent measurement of signs of b-cell autoimmunity in the children at-risk. [Diabetologia (2001) 44: 290±297]
Muscle pain and weakness are frequent complaints in patients receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many patients with myalgia have creatine kinase levels that are either normal or only marginally elevated, and no obvious structural defects have been reported in patients with myalgia only. To investigate further the mechanism that mediates statin-induced skeletal muscle damage, skeletal muscle biopsies from statin-treated and non-statin-treated patients were examined using both electron microscopy and biochemical approaches. The present paper reports clear evidence of skeletal muscle damage in statin-treated patients, despite their being asymptomatic. Though the degree of overall damage is slight, it has a characteristic pattern that includes breakdown of the T-tubular system and subsarcolemmal rupture. These characteristic structural abnormalities observed in the statin-treated patients were reproduced by extraction of cholesterol from skeletal muscle fibres in vitro. These findings support the hypothesis that statin-induced cholesterol lowering per se contributes to myocyte damage and suggest further that it is the specific lipid/protein organization of the skeletal muscle cell itself that renders it particularly vulnerable.
These preliminary data suggest an acceptable safety of the procedure with a low rate of adverse events and support further clinical development of baroreflex activation as a new concept to treat resistant hypertension.
Falsely high ankle-brachial index (ABI) values are associated with an adverse clinical outcome in diabetes mellitus. The aim of the present study was to verify whether such an association also exists in patients with chronic critical limb ischemia (CLI) with and without diabetes. A total of 229 patients (74 ± 11 years, 136 males, 244 limbs with CLI) were followed for 262 ± 136 days. Incompressibility of lower limb arteries (ABI > 1.3) was found in 45 patients, and was associated with diabetes mellitus ( p = 0.01) and renal insufficiency ( p = 0.035). Limbs with incompressible ankle arteries had a higher rate of major amputation ( p = 0.002 by log-rank). This association was confirmed by multivariate Cox regression analysis (relative risk [RR] 2.67; 95% CI 1.27-5.64, p = 0.01). The relationship between ABI > 1.3 and amputation rate persisted after subjects with diabetes and renal insufficiency had been removed from the analysis (RR 3.85; 95% CI 1.25-11.79, p = 0.018). Dividing limbs with measurable ankle pressure according to tertiles of ABI, the group in the second tertile (0.323 ≤ ABI ≤ 0.469) had the lowest amputation rate (4/64, 6.2%), and a U-shaped association between the occurrence of major amputation and ABI was evident. No association was found between ABI and mortality. In conclusion, this study demonstrates that falsely high ABI is an independent predictor of major amputation in patients with CLI.
The aim of this study was to evaluate the reliability of distal pulse palpation. The dorsalis pedis and the tibialis posterior arteries of 25 patients with suspected lower limb arterial disease were independently palpated by three vascular surgeons and three medical students in the outpatient clinic and by two vascular nurses and one physician in the vascular laboratory. The palpation findings were compared to the ankle/brachial index (ABI). Palpable and unpalpable pulses were best separated with ABI 0.76 as the cutoff point. The degree of misdiagnosis was unacceptably high, with an underdiagnosis of more than 30%. The agreement was highest (kappa 0. 68, good) among the vascular laboratory personnel in the peaceful vascular laboratory and lowest (kappa 0.38, fair) among the vascular surgeons in the busy outpatient clinic. The poor agreement and the high proportion of misdiagnosis obtained in the outpatient clinic argue against the use of pulse palpation as a single diagnostic method. Palpable pulses with low ABIs clearly state the need for more objective measurements whenever ischemia is suspected. Yet, by carefully palpating both pedal arteries under good, nonhurried conditions the reproducibility and accuracy of pulse palpation can be tolerable.
These data suggest increased procoagulant activity in EVAR compared with open surgery. A procoagulant state may favor possible morbidity derived from micro- and macrovascular thrombosis, such as in myocardial infarction, multiple organ dysfunction, venous thrombosis and thromboembolism, or disseminated intravascular coagulation.
Regional thrombolysis combined with surgical thrombectomy is relatively easy to perform and seems safe. Vein patency and valve function were restored, and post-thrombotic syndrome was prevented. Additional procedures to overcome pelvic vein obstructions were required in 11 of 33 patients (33%). The procedure should be tested against standard anticoagulation therapy in patients with acute iliofemoral thrombosis.
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