Cholesterol metabolism and non-cholesterol sterols in patients with ileal pouch anastomosis

Background: Previous studies suggest only minor changes in bile acid metabolism after panproctocolectomy with ileal pouch construction.Aims/Methods: To investigate these changes further, we studied cholesterol absorption and serum, biliary and fecal non-cholesterol sterols and lipids in 12 ileal pouch patients and 10 controls.Results: In patients, cholesterol absorption was markedly reduced and was associated with low serum total and LDL cholesterol and LDL triglyceride levels, but surprisingly, cholesterol synthesis, as indicated by sterol-balance data or serum cholesterol precursor levels, was within low normal limits. The high proportions of serum plant sterol to cholesterol, particularly that of campesterol, were not related to cholesterol absorption, but were attributable to a markedly reduced biliary cholesterol secretion. Interestingly, in these patients the fractional absorption of campesterol was normal, whereas that of sitosterol, like cholesterol, was reduced and was positively related to the intestinal influx of cholesterol. The patients' serum cholestanol proportion was normal, but the proportion of the cholestanol formed during intestinal passage was significantly reduced (17.9% vs 65.2% in controls).Conclusions: Thus ileal pouch patients are characterized by sterol malabsorption, lowered serum total and LDL-cholesterol levels, but unexpectedly without any increase in cholesterol synthesis. The lack of high serum cholestanol, shown earlier frequently in unoperated patients with ulcerative colitis, may indicate reversible cholestasis, a finding deserving further exploration.     

Novel parameters indicate significant differences in severity of obstructive sleep apnea with patients having similar apnea–hypopnea index

Sleep apnea–hypopnea syndrome (SAHS) causes impairment of daytime functions and increases risk of cardiovascular diseases. Apnea–hypopnea index (AHI), currently used for the estimation of the severity of SAHS, does not contain information on the morphology or duration aspects of the breathing cessations and related oxygen desaturations. Longer breathing cessations and deeper desaturations may have more severe consequences than shorter and shallower ones. To address these issues, novel parameters containing information on the duration and morphology of breathing cessations and oxygen desaturations were calculated and evaluated on 160 male patients (40 patients in normal, mild, moderate and severe AHI severity categories). Obstruction and desaturation duration parameters consist of sum of event durations normalized with the total analysed time. Desaturation severity is a sum of desaturation event areas normalized with total analysed time and obstruction severity parameter is a sum of the products of apnea and hypopnea durations and related desaturation areas normalized with total analysed time. The median follow-up time of the patients was 183 months (range 154–215 months). The 40 patients in each category were further divided into subgroups A and B with lowest and highest novel parameter values, respectively. AHI showed no differences between the subgroups. Mortality was increased in subgroups B compared to subgroups A. The correlation of the novel parameters with AHI was only moderate and the parameter values were partially overlapping between the AHI severity categories. This suggests that patients with similar AHI may in fact suffer from SAHS of very different severity. Thus, the present results suggest that the novel parameters could bring new insight to the individual estimation of the severity of SAHS.     

The severity of individual obstruction events is related to increased mortality rate in severe obstructive sleep apnea

Obstructive sleep apnea (OSA) is linked to an increased mortality rate. However, the severity of individual obstruction events is rarely considered quantitatively in clinical practice. We hypothesized that OSA with especially severe obstruction events would predispose a patient to greater health risks than OSA with a similar apnea–hypopnea index (AHI), but lower severity of individual events. This hypothesis was tested in a follow‐up (198.2 ± 24.7 months) of a population of 1068 men referred for ambulatory polygraphic recording due to suspected OSA. The recordings were analysed according to the guidelines of the American Academy of Sleep Medicine. Furthermore, a novel obstruction severity parameter was determined; this was defined as the product of duration of the individual obstruction event and area of the related desaturation event. Patients treated with continuous positive airway pressure (CPAP) were omitted. We identified 125 deceased patients from our original population and for 113 of these a matching alive patient with similar AHI, age, body mass index (BMI), smoking habits and follow‐up time could be found. The deceased patients with severe OSA (based on conventional AHI) showed higher obstruction severity values than their AHI‐matched alive controls. Based on the multivariate logistic regression analysis, obstruction severity was the only parameter which was related statistically significantly to mortality in the severe OSA category. Furthermore, 59% of all deceased patients and 83% of those who had severe OSA displayed higher obstruction severity than the AHI‐matched alive counterparts. To conclude, the obstruction severity parameter provided valuable prognostic information supplementing AHI. The obstruction severity parameter might improve recognition of the patients with the highest risk.     

Fatigue failure load of immature anterior teeth: influence of different fiber post-core systems

Odontology - The aim was to explore the fracture-behavior, survival and marginal-microgaps within the root-canal of immature anterior teeth restored with different fiber-reinforced post-core...     

Alcoholic Liver Damage is Provoked by 4-Methylpyrazole, which Prolongs the Influence of Ethanol but Reduces Acetaldehyde Levels

Rats chronically fed ethanol developed liver injury only if they also received low doses of the alcohol dehydrogenase inhibitor, 4-methylpyrazole, suggesting that the consistency of the influence of ethanol and its metabolism, rather than the level of acetaldehyde or the degree of the metabolic effects, contributes to the pathogenesis of alcoholic liver damage.     

Platelet membrane collagen receptor glycoprotein VI polymorphism is associated with coronary thrombosis and fatal myocardial infarction in middle-aged men

Glycoprotein VI is a platelet collagen receptor binding to subendothelial collagen after a rupture of an atherosclerotic plaque. The GPVI gene is polymorphic with several SNPs and the T13254C polymorphism predicting amino acid substitution (serine to proline) has been associated with the risk of MI in a preliminary study. We studied the association of the GPVI T13254C with fatal myocardial infarction (MI) and coronary artery disease among the 300 men of the Helsinki Sudden Death Study (HSDS). Genotype frequencies were 77.9% for TT, 20.7% for CT and 1.4% for CC. We found a significant association (P = 0.02) between the C-allele carriers (CT or CC) and coronary thrombosis (OR 2.5, 95% CI: 1.05-6.2). There was also a tendency (P = 0.07) for an association between the C-allele and acute myocardial infarction (AMI) (OR 2.2). The average area of complicated coronary lesions was also significantly (P = 0.01) larger in carriers compared to non-carriers of the C-allele. Our findings support previous results on the role of this GPVI polymorphism, or another linked polymorphism, as a possible predictor of the risk of coronary thrombosis.     

Circumspect descent prevails in solving random constraint satisfaction problems

We study the performance of stochastic local search algorithms for random instances of the K-satisfiability (K-SAT) problem. We present a stochastic local search algorithm, ChainSAT, which moves in the energy landscape of a problem instance by never going upwards in energy. ChainSAT is a focused algorithm in the sense that it focuses on variables occurring in unsatisfied clauses. We show by extensive numerical investigations that ChainSAT and other focused algorithms solve large K-SAT instances almost surely in linear time, up to high clause-to-variable ratios alpha; for example, for K = 4 we observe linear-time performance well beyond the recently postulated clustering and condensation transitions in the solution space. The performance of ChainSAT is a surprise given that by design the algorithm gets trapped into the first local energy minimum it encounters, yet no such minima are encountered. We also study the geometry of the solution space as accessed by stochastic local search algorithms.