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T Haas

Publications and source records attributed to T Haas.

At least 19 recordsLinked to original sources

Relation of cholesterol metabolism and non-cholesterol sterols to insulin resistance.

Using non-cholesterol sterols investigation several authors postulated a hypothesis that in the metabolic syndrome cholesterol endogenous synthesis is increased and its absorption decreased. Our study is the first attempt to evaluate the direct relation of cholesterol metabolism to the principal pathogenetic phenomenon of the metabolic syndrome--namely to insulin resistance. We have measured insulin sensitivity by two methods--Quicki (Quantitative Sensitivity Check Index) and intravenous insulin tolerance test (Kitt) and 3 indirect markers--fasting insulin level, fasting C-peptide level and SHBG (sex hormone binding globulin). The investigation was performed in three groups of subjects with a different prevalence of insulin resistance: 72 non-diabetics with ischemic heart disease, 117 young blood donors and 63 type 2 diabetics on diet therapy only. Analyzing altogether 60 relationships--between four sterols (lathosterol, squalene, sitosterol and campesterol) and five markers of insulin resistance in three groups of subjects--we have found only six significant relations between cholesterol synthesis and absorption and insulin resistance in all groups of patients. Our results indicate that there exists a significant relationship between insulin sensitivity and indices of either increased cholesterol synthesis or decreased cholesterol absorption. Insulin resistance explains only a part of both abnormalities mentioned above.

Adult↗

Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy--a porcine model.

BACKGROUND: This study was conducted to assess whether the combined administration of fibrinogen and prothrombin complex concentrate (PCC) enables the reversal of dilutional coagulopathy resulting from intended blood loss and fluid replacement, and whether this treatment reduces further blood loss and mortality. METHODS: In 20 anaesthetized pigs, approximately 65% of the estimated blood volume was withdrawn and replaced with the same amount of hydroxyethyl starch (6% HES 130/0.4) to mimic blood loss and to develop a dilutional coagulopathy. Pigs (randomized) received either fibrinogen (200 mg kg(-1)) and PCC (35 IU kg(-1)) (n=10), or placebo (n=10). Thereafter, a standard liver laceration was performed to induce uncontrolled haemorrhage. The subsequent blood loss and survival time were determined as primary outcome variables. Throughout the experiment serial blood samples were obtained to assess the competence of the haemostatic system using standard coagulation tests, modified Thrombelastograph measurements (ROTEM) and electron microscopy clot imaging. RESULTS: As compared with baseline, after haemodilution both groups showed statistically significant impairment of haemostasis as measured with standard coagulation tests and thrombelastography. These parameters significantly improved after administration of the study drugs while aPPT measurements remained unchanged. Blood loss after liver injury was significantly less in the treatment group as compared with placebo: 240 ml (50-830) vs 1800 ml (1500-2500) (P<0.0001). All treated animals survived, whereas 80% of the placebo group died (P<0.0001). CONCLUSION: During haemodilution, substitution of fibrinogen and PCC causes an enhancement of coagulation and final clot strength. This reversal of dilutional coagulopathy may reduce blood loss and mortality when large amounts of colloids are needed to maintain normovolaemia during huge blood losses.

Animals↗

[Aminosalicylates and steroids in the treatment ot chronic inflammatory bowel diseases--consensus paper of the Working Group for Chronic Inflammatory Bowel Diseases of the OGGH].

5-aminosalicylates (5-ASA) and steroids constitute a cornerstone of medical therapy in patients with inflammatory bowel diseases (IBD). Whereas the efficacy of 5-ASA in Crohn's disease (CD) is equivocal, ulcerative colitis (UC) is the main indication for this drug. In UC, 5-ASA is effective in the treatment of mild to moderate acute disease and in maintenance of remission. Furthermore, 5-ASA topical therapy is an important treatment option in patients with mild to moderate proctitis and/or left-sided UC and shows additive efficacy to oral therapy. From retrospective data a chemo-preventative activity of long-term 5-ASA therapy in UC is delineated. Steroids are treatment of first choice for moderate to severe cases of CD and UC. Budesonide, a modified steroid with less side effects, plays a major role in the treatment of ileocolonic CD +/- involvement of the right colon and is used as treatment of choice in mild-to-moderate cases. In case of acute, severe disease conventional steroids are superior compared to budesonide and therefore budesonide should only be used after considerable improvement of disease activity. The necessity to apply steroids in a given patient represents a negative prognostic indicator for the course of disease and should incite the early introduction of immunosuppressive therapy in this case. Steroids are only effective as short term therapy of IBD and are to be avoided for maintenance treatment. In all cases of steroid therapy an osteoporosis prophylaxis with calcium and vitamin D is recommended. Topical steroid treatment is less effective in left-sided UC compared to 5-ASA.

Aminosalicylic Acids↗

Plasma levels of active and total ghrelin in renal failure: a relationship with GH/IGF-I axis.

Ghrelin was originally isolated from the rat stomach and significant amounts were found also in the kidney. Present study was designed to examine changes in ghrelin levels in renal failure and their relationship to the GH/IGF-I axis. Fourty patients with mild-to-severe CRF (19 men, 21 women, aged 62.5 +/- 2.2 years, BMI 27.57 +/- 0.73 kg/m(2)) and 34 healthy control subjects (17 men, 17 women, aged 60 +/- 2.6 years, BMI 27.55 +/- 0.79 kg/m(2)) were included in the study. Total ghrelin levels were significantly increased in patients with chronic renal failure (CRF) (p < 0.0001). Total ghrelin in CRF correlated positively with active ghrelin (p < 0.001), GH (p < 0.05), IGF-I (p < 0.05), free IGF-I (p = 0.0001), IGFBP-3 (p < 0.01), IGFBP-2 and -6 (p < 0.05). Active ghrelin in CRF correlated positively with IGF-I (p < 0.001), free-IGF-I (p < 0.005), IGFBP-2 (p < 0.05) and IGFBP-3 (p < 0.05). However, most of the correlation were markedly reduced and the significance disappeared after adjustment for different creatinine levels. Hemodialysis in patients with end stage renal disease (ESRD) resulted in a significant reduction of plasma total and active ghrelin (p < 0.01 and p < 0.001 respectively). In conclusion we demonstrated elevated plasma levels of total ghrelin in CRF, and a reduction of total and active ghrelin after a single course of hemodialysis in ESRD. The elevation of ghrelin levels could be caused by impaired clearance and/or metabolism of ghrelin in the kidney. We did not prove clearly significant relationship between ghrelin serum levels and parameters of GH/IGF-I axis in study subjects.

Animals↗

Effect of fibrinogen on reversal of dilutional coagulopathy: a porcine model.

BACKGROUND: This study was conducted to determine whether replacement of fibrinogen is useful in reversing dilutional coagulopathy following severe haemorrhage and administration of colloids. METHODS: In 14 anaesthetized pigs, approximately 65% of the estimated blood volume was withdrawn and replaced with the same amount of gelatin solution to achieve dilutional coagulopathy. Animals were randomized to receive either 250 mg kg(-1) fibrinogen (n=7) or normal saline (n=7). A standardized liver injury was then inflicted to induce uncontrolled haemorrhage. Modified thrombelastography and standard coagulation tests were performed at baseline, after blood withdrawal, after dilution, after injection of the study drugs, and on conclusion of the protocol. Further, electron microscopy imaging of the blood clots was performed and blood loss after liver injury was determined. RESULTS: Severely impaired haemostasis was observed after haemodilution with gelatin substitution. With administration of fibrinogen, clot firmness and dynamics of clot formation reached baseline values. Median blood loss following liver injury was significantly less (P=0.018) in the fibrinogen-treated animals (1100 ml; 800-1400 ml) than in the placebo group (2010 ml; 1800-2200 ml). CONCLUSIONS: Replacing 65% of the estimated blood volume with gelatin in swine resulted in dilutional coagulopathy; subsequent fibrinogen administration improved clot formation and reduced blood loss significantly.

Animals↗

[Management of coagulation after multiple trauma].

Hemorrhage after traumatic injury results in coagulopathy which only worsens the situation. This coagulopathy is caused by depletion and dilution of clotting factors and platelets, increased fibrinolytic activity, hypothermia, metabolic changes and anemia. The effect of synthetic colloids used for compensating the blood loss, further aggravates the situation through their specific action on the hemostatic system. Bedside coagulation monitoring permits relevant impairment of the coagulation system to be detected very early and the efficacy of the hemostatic therapy to be controlled directly. Administration of fresh frozen plasma (FFP), platelet concentrates and antifibrinolytic agents is essential for restoring the impaired coagulation system in trauma patients. Clotting factor concentrates should be administered if coagulopathy is based on diagnosed depletion of clotting factors, if FFP is not available and if transfusion of FFP is insufficient to treat the coagulopathy. Recombined FVIIa is frequently employed during severe bleeding which could not be treated by conventional methods but the results of on-going clinical trials are not yet available.

Anticoagulants↗

Employing vasopressin as an adjunct vasopressor in uncontrolled traumatic hemorrhagic shock. Three cases and a brief analysis of the literature.

Resuscitation of patients in hemorrhagic shock remains one of the most challenging aspects of trauma care. We showed in experimental studies that vasopressin, but not fluid resuscitation, enabled short-term and long-term survival in a porcine model of uncontrolled hemorrhagic shock after penetrating liver trauma. In this case report, we present two cases with temporarily successful cardiopulmonary resuscitation (CPR) using vasopressin and catecholamines in uncontrolled hemorrhagic shock with subsequent cardiac arrest that was refractory to catecholamines and fluid replacement. In a third patient, an infusion of vasopressin was started before cardiac arrest occurred; in this case, we were able to stabilize blood pressure thus allowing further therapy. The patient underwent multiple surgical procedures, developed multi-organ failure, but was finally discharged from the critical care unit without neurological damage.

Abdominal Injuries↗

The risk of Colles' fracture is associated with the collagen I alpha1 Sp1 polymorphism and ultrasound transmission velocity in the calcaneus only in heavier postmenopausal women.

To compare the ability of the bone mineral density (BMD) at the distal forearm, collagen I alpha 1 (COLIA1) polymorphism, and ultrasound stiffness to identify individuals with increased risk of wrist fracture, we studied 183 postmenopausal Czech women with a wrist fracture and 178 postmenopausal controls, ages 45-70 years. The genotypes "Ss" and "ss" were significantly overrepresented among fracture cases. The BMD measurements at the femoral neck, total femur, and distal forearm as well as ultrasound stiffness of the heel, broadband ultrasound attenuation (BUA), and speed of sound (SOS) were significantly lower in the fracture cohort. BMD of the distal forearm was the main determinant of susceptibility to the wrist fracture. Weight, the COLIA1 genotype, and ultrasound SOS further strengthened the predictive value of BMD. However, we found interaction between weight and both the COLIA1 Sp1 polymorphism and ultrasound parameters. Presence of the "s" allele as well as low SOS acted as significant predictors of wrist fracture only in heavier women, (> or =62 kg) but not in women with a body weight of less than 62 kg. In heavier women, both the COLIA1 Sp1 polymorphism and ultrasound parameters acted as independent markers that contributed to BMD to enhance fracture prediction. However, the COLIA1 enabled a higher specificity (specificity 72.4%, sensitivity 44.2%), whereas SOS enabled a higher sensitivity (sensitivity 73.9%, specificity, 45.7%). We conclude that BMD at total forearm, the COLIA1 polymorphism, and ultrasound SOS are independent predictors of wrist fracture in postmenopausal women. The effect of the COLIA1 Sp1 polymorphism and SOS on wrist fracture risk is more pronounced in patients with a higher body weight.

Aged↗

[Dilutional coagulopathy, an underestimated problem?].

When no fresh frozen plasma is available, acute major blood loss is compensated above all with crystalloids, colloids and erythrocyte concentrates, meaning that all plasma clotting factors are diluted. Consumption coagulopathy is almost always accompanied by dilutional coagulopathy. Formulas for calculating critical blood loss and standard coagulation tests are often not helpful in the case of massive transfusion. On the other hand, systems suitable for point of care, such as thrombelastography, have important advantages. In the case of consumption and dilutional coagulopathy plasma coagulation is disturbed and critical values are first seen for fibrinogen. Not only is fibrin polymerization impaired by the bleeding-induced loss and dilution of fibrinogen, but also by interaction with artificial colloids, particularly hydroxyethyl starch preparations. Therapy of consumption and dilutional coagulopathy calls for fresh frozen plasma. If this is not available in sufficient quantity or within a reasonable time, coagulation factor concentrates must be used. Neither fresh frozen plasma therapy nor treatment with coagulation factor concentrates has been the subject of detailed clinical study. Further studies are needed to work out guidelines for coagulation management in the case of massive blood loss.

Blood Coagulation↗

[Significance of plant sterols in diabetes].

Plant sterols occur naturally in plants and vegetable oils. Sitosterol and campesterol are markers of cholesterol absorption. The ratio of cholesterol endogenous synthesis to its absorption may be assessed by sitosterol, campesterol and other non-cholesterol sterols (lathosterol and squalen) serum concentration measurements. In 38 Type 2 diabetics (59.9 years, BMI 29.8 kg/m2, HbA1c 7.6%, C-peptid 0.82 nmol/l) and in 40 non-diabetics (37.2 years, BMI 25.4 kg/m2, HbA1c 5.2%, C-peptid 0.85 nmol/l) plant sterols serum concentration were measured: lathosterol (diabetics 10.64, non-diabetics 6.04 mumol/l, p = 0.09), squalen (diabetics 3.42, non-diabetics 1.78 mumol/l, p < 0.01), sitosterol (diabetics 3.91, non-diabetics 3.80 mumol/l, p = 0.60) and campesterol (diabetics 7.91, non-diabetics 8.85 mmol/l, p = 0.09). In non-diabetics squalen positive correlates with C-peptid, lathosterol with triacylglycerols and campesterol with HbA1c. In diabetics correlates diabetes compensation with plant sterols value negative. It seems that plant sterols and probably also cholesterol absorption can be influenced negative by higher value HbA1c.

Adult↗

[Rosiglitazon in treatment of Type II diabetes mellitus--experience of diabetologists in the Czech Republic. Part I: compensation of diabetes, sugar metabolism].

UNLABELLED: Thiazolidindione derivates (glitazones) make a very promising group of peroral antidiabetic drugs. They are represented by rosiglitazon which is available on our market to type II diabetics. As far as sugar metabolism is concerned, rosiglitazon can reduce glycaemia and insulin level both when fasting and postprandially. GOAL: The goal of the authors' work was to gain their own experience with rosiglitazon treatment in type II diabetics in the Czech Republic. SAMPLE: The monitored sample consisted of 388 patients with insufficiently compensated type II diabetes when treated by sulphonylurea compounds or metformine. METHODS: 95 diabetologists from diabetology medical offices started a 6-month-long treatment with rosiglitazon (Avandia) dose of 4 mg a day as stated in European recommendations. In order to assess changes in sugar metabolism (compensation of diabetes) glycaemia and C peptide were monitored when fasting and postpradially and HbA1c was monitored in 2-month-long intervals. RESULTS: Weight, waist-hip ratio (WHR) and C-peptide levels remained unchanged. Statistically significant (p < 0.0001) was a HbA1c decrease over 6 month from 9.61% to 8.48%. Fasting glycaemia decreased by 2.49 and postprandial glycaemia by 2.71 mmol/l. No significant side effects were identified. CONCLUSION: Rosiglitazon administration combined with administration of sulphonylurea compounds or metformine significantly improved compensation of diabetes compared to initial therapy.

Adult↗

[Ethical problems in randomized clinical studies from the aspect of statistics. Part II: when should patient randomization be stopped of modified?].

The ethical responsibility to the randomized study participants demands that the results be monitored during the course of the trial. The interim evaluation of the trial results may lead to the premature stopping. However, the repeated statistical testing inflates the probability of false positive error. Hence statistical adjustments are necessary. The probabilistic rules for the random allocation of patients may be changed during the course of the trial according to the observed responses.

Humans↗

Indications of neutralising anti-idiotypic antibodies and selective proteolytic fragmentation in polyclonal anti-D IgG preparations.

Proteolytic fragmentation is the only suggested cause of potency losses during storage of liquid human polyclonal anti-D Ig. Besides the effect of fragmentation, we have investigated the potential contribution of neutralising anti-idiotypic antibodies (anti-Ids). Potency changes during storage and/or upon pH reduction in anti-D IgG batches with or without addition of plasminogen and urokinase were quantitatively analysed by the autoanalyser (AA) method or by a special procedure of flow cytometry (FC). Moreover, simultaneous changes of the molecular size distribution pattern have been determined by size exclusion chromatography. In contrast to the AA procedure, the particular FC methodology was found to be almost insensitive to proteolysis comprising up to 30% of total IgG. Data interpretation was based on the assumption that both assays cannot detect Ids with neutralised paratopes. In the absence of detectable neutralisation (functional absence of anti-Ids), it could be demonstrated that the anti-D IgG subpopulation is more sensitive to fragmentation by endogenous protease as compared to the unrelated bulk. However, both methods detected batch- and assay-dependently variable potency losses during storage. Moreover, the increase of potency induced by pH reduction correlated with the increase of monomeric IgG, essentially on the expense of dimers. This finding was interpreted to indirectly indicate the neutralising action of anti-Ids known to be the major driving force of dimer formation in polyclonal IgG. A more or less pronounced pH-dependent potency increase was also detectable in three arbitrarily selected batches of two other manufacturers. The data allows to assume that anti-Id-mediated neutralisation can significantly contribute to losses of anti-D potency. In addition, it turned out that anti-D plasma itself can be the source of anti-Ids.

Antibodies, Anti-Idiotypic↗

[Microvascular reactivity in type 2 diabetes mellitus and its relation to IGF-I and its binding proteins].

BACKGROUND AND AIM: System of insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBP) may be involved in the pathogenesis of vascular damage in Type 2 diabetes. Aim of the study was to analyse the relationship between this system and microvascular reactivity in Type 2 diabetes as measured by laser-Doppler flowmetry. METHODS AND RESULTS: Thirteen Type 2 diabetic patients (8 women and 5 men) with microangiopathy and fifteen healthy subjects (8 women and 7 men) were examined clinically, underwent laser-Doppler flowmetry and intima-media thickness measurements. Fasting serum levels of IGF-I, IGFBP and lipids were examined. Percentage perfusion increase in the test with postocclusive reactive hyperaemia (PORH) as well as in that with thermal hyperaemia (TH) were significantly decreased in Type 2 diabetic patients (p < 0.05). Maximal perfusion after heating (THmax) was lower in Type 2 diabetic patients. Reaction of microcirculation after heating (THmax/t) was slower in Type 2 diabetic patients (p < 0.001). The changes in microvascular reactivity didn't significantly correlate with any of measured parameters of IGF-I/IGFBP system. CONCLUSIONS: Microvascular reactivity is impaired in Type 2 diabetic patients. The function of microcirculation is not significantly related to the particular parameters of the IGF-I/IGFBP system.

Diabetes Mellitus, Type 2↗

[Indirect relation between intimo-medial thickness of the carotid artery and vasodilation of the popliteal artery].

BACKGROUND: Intima-media thickness of the common carotid artery (IMT ACC) and flow-mediated vasodilatation (FMD) of the brachial artery is considered an early marker of atherosclerosis. This study was undertaken to elucidate whether endothelial dysfunction in the popliteal artery, pronoun to atherosclerosis, is related to IMT ACC. METHODS AND RESULTS: Twenty-nine control subjects, 29 asymptomatic patients with hyperlipoproteinemia (without therapy) and 26 patients with coronary artery disease were examined. Using ultrasound with a linear-array probe (7.5 MHz), we measured IMT ACC and diameter of the popliteal artery (PA) at rest and during reactive hyperaemia after release of 5-minute arterial occlusion. In control subjects we found thicker IMT ACC and greater FMD than did the patients (p<0.001, ANOVA test). A significant negative correlation between the IMT ACC and percent FMD was found in all of the subjects (p<0.001). On multiple regression analysis, percent FMD showed a significant negative correlation with the IMT ACC, total cholesterol, triacylglyceroles, body mass index, age, and diastolic blood pressure. CONCLUSION: We found significant negative correlation between IMT common carotid artery and FMD popliteal artery.

Adult↗

Association of obesity, diabetes, serum lipids and blood pressure regulates insulin action.

Insulin resistance is present in patients with Type 2 diabetes mellitus as well as in obese patients without diabetes. The aim of our study was to compare insulin action in diabetic and control persons with or without obesity and to evaluate the influence of serum cholesterol, serum triglyceride and blood pressure on metabolic variables of insulin action. We examined 42 Type 2 diabetic patients and 41 control persons with body mass index (BMI) from 21.1 to 64.5 kg x m(-2), and 33 to 71 years old. The isoglycemic hyperinsulinemic clamp technique was performed at an insulin infusion rate of 1 mU x kg(-1) x min(-1) during 120 min. We evaluated the metabolic clearance rate of glucose (MCR(G), ml x kg(-1) x min(-1)) as the most important indicator of insulin action by isoglycemic clamp. The Pearson's correlation and multiple regression models were used to compare studied factors with the insulin action. We found following predictors of insulin resistance expressed in the relationship with MCR(G): BMI (r = -0.68, p<0.001), plasma glucose concentration (r = -0.66, p<0.001), cholesterol (r=-0.55, p<0.001), triglycerides (r = -0.54, p<0.001) and mean blood pressure (r = -0.38, p<0.01). From the multiple regression analysis we conclude that obesity may have even greater influence on the insulin action than diabetes mellitus itself.

Adult↗