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Biomedical subjects

T Haas

Publications and source records attributed to T Haas.

At least 73 records · Page 4Linked to original sources
PubMed1998

Static and dynamic information in metabolic medicine.

Several computer models and dynamic parameters were used to describe metabolic state of patients. We have used models to explain the process of glycation of hemoglobin and albumin, to identify insulin sensitivity, to describe individual insulin therapy needs and to predict outcome of metabolic diseases. We also compared static and dynamic description of patients with metabolic X syndrome. We can conclude that static and dynamic parameters bring different quality of information in metabolic care.

Computer Simulation↗
PubMed1998

Heterozygosity for the C282Y mutation in the hemochromatosis gene is associated with increased serum iron, transferrin saturation, and hemoglobin in young women: a protective role against iron deficiency?

Genetic hemochromatosis (GH) is the most common autosomal-recessive disorder (1 in 300 in populations of Celtic origin). Homozygosity for a C282Y mutation in the hemochromatosis (HFE) gene is the underlying defect in approximately 80% of patients with GH, and 3. 2-13% of Caucasians are heterozygous for this gene alteration. Because the high frequency of this mutation may result from a selection advantage, the hypothesis was tested that the C282Y mutation confers protection against iron deficiency in young women. To address this question the genotype of codon 282 was determined in a cohort of 468 unrelated female healthcare workers, ages 18-40 years. In all study participants, a complete blood count was obtained, and erythrocyte distribution width, serum iron, transferrin, transferrin saturation, and ferritin were measured. Two individuals were homozygous for the C282Y mutation, 44 were heterozygous, and 416 were homozygous for the wild-type allele. Heterozygous women had significantly higher values for hemoglobin (P = 0.006), serum iron (P = 0.013), and transferrin saturation (P = 0. 006) than women homozygous for the wild-type allele. Our data provide evidence for a protective role of the C282Y mutation in the HFE gene against iron deficiency in young women and suggest that a more efficient utilization of nutritional iron may have contributed to the high prevalence of the mutation in Caucasian populations.

Adolescent↗
PubMed1998

The interrelationship of alpha4 integrin and matrix metalloproteinase-2 in the pathogenesis of experimental autoimmune encephalomyelitis.

Previous studies have suggested that surface expression of alpha4 integrin by autoreactive T-cell clones is necessary for the clones to induce experimental autoimmune encephalomyelitis (EAE), a mouse model for human multiple sclerosis. To provide direct evidence for this phenomenon, we have transfected alpha4 integrin into C19alpha4-LO, a myelin basic protein-reactive T-cell clone that does not express alpha4 integrin and does not induce EAE when adoptively transferred into a susceptible mouse strain. Transfection of alpha4 integrin converted this clone to an alpha4 integrin-expressing clone that induced EAE. We then examined potential mechanisms by which alpha4 integrin may facilitate the disease process. C19 T-cell clones adhered equally to a monolayer of microvascular endothelial cells, regardless of level of alpha4 integrin expression. However, in contrast to T-cell clones that do not express alpha4 integrin, T-cell clones that express alpha4 integrin (endogenously or by transfection) transmigrated through an endothelial cell layer and subendothelial matrix at an enhanced rate and adhered to recombinant vascular cell adhesion molecule-1 (rVCAM-1) and the CS1 fragment of fibronectin, and after adhesion to these ligands, a matrix-degrading metalloproteinase (MMP-2) was induced and activated. The clones were also shown to constitutively express the membrane-type matrix metalloproteinase (MT1-MMP), an enzyme that activates MMP-2. GM6001 and UK-221,316, inhibitors of metalloproteinases, reduced alpha4 integrin-mediated transmigration and EAE induction by C19 T-cell clones. In addition, we studied a second EAE-inducing T-cell clone, MM4, which constitutively expresses alpha4 integrin and MMP-2. Engagement of alpha4 integrin on the MM4 clone up-regulated the expression and activation of MMP-2, without changing the expression of MT1-MMP. MMP inhibitors also reduced transmigration of and EAE induction by the MM4 T-cell clone. These studies demonstrate directly that expression of alpha4 integrin by autoreactive T-cell clones is required for adoptive transfer of EAE in this model. We also define a role for alpha4 integrin in the disease process in mediating the induction and coordinate activation of a matrix metalloproteinase (MMP-2), which facilitates T-cell transmigration.

Animals↗
PubMed1997

[Urinary incontinence in patients in long-term institutional care. Results of an international study in 8 countries].

BACKGROUND: Urinary incontinence (UI) represents a prevalent nursing problem in geriatric facilities. Yet, comparison of the Czech Republic with countries using different chronic care system has not been conducted. METHODS AND RESULTS: Data from INTERRAI international database from 8 countries: Czech Republic, Denmark, France, Iceland, Italy, Japan, Sweden and USA have been evaluated in the sample of 280,271 nursing home residents. Prevalence of bladder and bowel incontinence and correlates with selected clinical factors have been determined and national samples compared with the results of 1080 patients in the Czech Republic. Prevalence of UI reached from 42.9% in Japan to 65.2% in France. France and CR belong to countries with the highest prevalence of both bladder and bowel incontinence. Cognitive impairment and dependency in ambulation are factors significantly associated with UI in all countries (p < 0.001). Immobility, age, gender and urinary tract infection reached the statistical significance only in some countries. CONCLUSIONS: High prevalence of bladder and bowel incontinence has been demonstrated in an extended sample of nursing home residents. Common protocol Resident Assessment Instrument-Minimum Data Set (RAI-MDS) and creation of a large cross-national database are opening up possibilities for a new level of clinical research in geriatrics.

Aged↗
PubMed1997

[Urinary and fecal incontinence in geriatric facilities in the Czech Republic].

BACKGROUND: Incontinence represents one of the common problems in long-term care geriatric facilities and nursing homes. However, in the Czech Republic data on prevalence, severity and incontinence-associated factors for nursing home residents are not available. The aim of the study was to report the prevalence of urinary (UI) and bowel incontinence (BI) in different geriatric facilities and to identify factors positively associated with incontinence. METHODS AND RESULTS: In a sample of 1162 residents of 18 long-term care facilities UI has been found in 684 residents (63.3%). Health and social care facilities did not differ significantly (60.7 vs 65.6%). Of the incontinent 294 residents (27.2%) suffered from permanent/daily incontinence, 390 (36.1%) from occasional transitory UI. Prevalence of BI reached 54.4%, as well as double incontinence (45.9%). Cognitive impairment, self-care ADL and/or mobility dependency and bed rest are factors significantly associated with UI (for all P < 0.001). However, age, gender and urinary tract infection did not reach the statistical significance (P = 0.280-0.069). Risk adjustment/stratification for UI revealed the prevalence of 33.0% in the low risk group. In the high risk group (high ADL dependency and severe cognitive impairment) the prevalence came up to 96.0%. CONCLUSIONS: Our study presents the first results focused on incontinence problem in long-term care geriatric institutions in the Czech Republic. High prevalence of this condition makes incontinence an important medical, nursing and economical yet neglected problem.

Aged↗
PubMed1997

[Insulin, steroids and steroidogenesis].

Presented survey summarises insulin-steroid interactions. Beside the well known resistance to insulin induced by steroid hormones, also the central effect of insulin, its influence on the system hypophysis-adrenals, and its stimulatory effect on the generation of steroids in adrenals and ovaries are reviewed. Insulin-steroid interactions are further illustrated by pathogenesis of the polycystic ovary syndrome and by our study on dehydroepiandrosterone regulation. Insulin induced changes in the dehydroepiandrosterone level during the intravenous glucose tolerance test were described.

Adrenal Cortex Hormones↗
PubMed1997

[DHEA: another hormonal modulator of bone blood flow in rats].

Dehydroepiandrosterone (DHEA) is a steroid with important effects on the bone tissue. We tried to check up if it influenced also the bone blood flow (similarly as estradiol and testosterone). We administered DHEA (Sigma) dissolved in dimethylsulphoxide s.c. three times weekly for four weeks in the doses of 15-20 mg per rat on 125 mg/kg body weight to female rats--sham-operated or oophorectomized (OOX). In two experiments (A and B) we ascertained the uptake of 85Sr-microspheres, local blood flow, cardiac output, density and ash weight of the burned tibia, in the third experiment (C) 24 hour incorporation of 45Ca and 3H-proline into the bone. The 85Sr-microsphere uptake in the tibia was elevated after OOX in both experiments A and B; this increase was inhibited completely (and statistically significantly versus the OOX group) by the administration of DHEA. Similar and also significant reactions were found in the microsphere uptake values in the distal end of femur. No significant changes could be demonstrated in the diaphysis of femur and calvaria as well as in the cardiac output, output, blood pressure and heart rate. The incorporation of 45Ca and 3H-proline into the tibia (experiment C) was significantly increased after OOX. The administration of DHEA inhibited this increase significantly in the values of 3H-proline. The density of tibia in both experiments A and B and ash weight of tibia in experiment A, suppressed after OOX, were significantly increased after the administration of DHEA to OOX females. The results show that also DHEA--in the experimental conditions used--has similar effect on the bone blood flow as estradiol and testosterone.

Animals↗
PubMed1997

Possible participation of EDRF-NO in the hormonal regulation of bone blood flow in rats.

An increase in bone blood flow (BBF) was observed in rats after castration whereas a decrease in BBF occurred after oestradiol or testosterone. The possible participation of prostaglandins in these changes was demonstrated. The present results show that the endothelium-derived relaxing factor, i. e. nitric oxide (EDRF-NO), might play a role in these hormonal actions on BBF. Until now, almost nothing is known about the possible action of NO on bone circulation. Methylene blue (MB) as a substance blocking EDRF-NO was administered to sham-operated or oophorectomized (OOX) female rats. We determined local blood flow (85Sr-microsphere uptake), cardiac output, blood pressure, heart rate, density of the tibia and ash weight, as well as 24-h incorporation of 45Ca and 3H-proline into the tibia. The administration of MB (0.5% in the food for 4 weeks) significantly lowered both 85Sr-microsphere uptake and blood flow values in the tibia and distal femur of sham-operated and OOX rats. MB lowered cardiac output and blood pressure to the same extent, indicating no change in the vascular resistance. After the administration of MB (0.1% in the food), 85Sr-microsphere uptake decreased significantly in the tibia of OOX females while no significant change was found in soft tissues. Bone density and ash weight were significantly lower in OOX rats and in sham-operated rats after MB treatment. Finally, the 24-h incorporation of both 45Ca and 3H-proline decreased significantly in OOX females after MB administration (0.04% in the food). It can be concluded that 1) MB lowers BBF, suggesting the participation of EDRF-NO in BBF regulation, 2) MB does not influence or may even suppress cardiac output and blood pressure in high dosage, 3) MB lowers 24-hour incorporation of 45Ca and 3H-proline into the tibia of OOX rats, which is in agreement with the circulatory effect, 4) MB lowers bone density and ash weight of the tibia in non-castrated female rats. The effects of MB observed in our experiments partially differ from those of arginine-derived blocking agents. This requires further elucidation.

Animals↗
PubMed1996

[The effect of micronized fenofibrate on lipid parameters and fibrinogen in heterozygous familial hypercholesterolemia and familial combined hyperlipidemia].

BACKGROUND: The aim of the study was to approve the hypolipidemic potency of the new drug from the group of fibrate derivates Lipanthyl 200 M(R) (micronized fenofibrate, cps a 200 mg, Laboratoires Fournier, France) in patients with familial hyperlipoproteinemias. The drug has been administered in constant dose of 200 mg daily with the evening meal for three months. Clinical examinations and monitoring of safety laboratory have been performed in addition to complete analysis of lipids, lipoproteins and apolipoproteins during the study. METHODS AND RESULTS: The group of 30 patients consisted from 14 heterozygotes of familial hypercholesterolemia and 16 patients affected by familial combined hyperlipidemia. Levels of total, HDL- and LDL-cholesterol, triglycerides, apolipoproteins A-I and B and Lp(a) have been measured and concentrations of fibrinogen in plasma as well. Concentration of total cholesterol 8.29 +/- 1.3 mmol/l on the beginning of the study decreased after one and three months of the treatment to 6.94 +/- 1.19 resp. 6.98 +/- 1.21 mmol/l, concentration of triglycerides has been reduced from 2.86 +/- 1.29 mmol/l to 1.70 +/- 0.86 and 1.74 +/- 0.99 mmol/l respectively HDL-cholesterol raised from 1.14 +/- 0.32 mmol/l to 1.27 +/- 0.36 and to 1.34 +/- 0.37 mmol/l in contrast to decrease of LDL-cholesterol 5.88 +/- 1.53 mmol/l on the beginning of the study to 4.87 +/- 1.49 and 4.79 +/- 1.60. Apo B in plasma fall after three month period of the treatment from 1.83 +/- 0.43 g/l to 1.46 +/- 0.47 g/l. On the other hand the concentration of apolipoprotein apo A-I1.20 +/- 0.35 g/l increased to 1.40 +/- 0.32 g/l. Fibrinogen in plasma was reduced from 3.63 +/- 0.69 g/l to 2.77 +/- 0.50 g/l. Also this decrease was statistically significant. CONCLUSIONS: Micronized fenofibrate is a potent hypolipidemic drug with only rare side effects. It is very good tolerated by the patients. Micronized fenofibrate is particularly prescribed for combined hyperlipidemia, however we can use it also in some patients with familial hypercholesterolemia. For to the treatment very resistant hyperlipoproteinemias we should consider combined drug therapy.

Adult↗
PubMed1996

Comparison of insulin sensitivity in patients with insulinoma and obese Type 2 diabetes mellitus.

Insulin sensitivity was evaluated in 16 insulinoma patients and in 15 obese persons with Type 2 diabetes mellitus by using hyperinsulinaemic clamps and analysis of insulin receptor characteristics on erythrocytes. Significantly decreased insulin sensitivity index (M/l) was found in both insulinoma and obese Type 2 diabetic patients as compared with healthy non-obese controls (21.2 +/- 2.2 and 19.5 +/- 2.6 vs 40.3 +/- 3.7 mumol.kg-1.min-1 per mU.l-1 x 100, p < 0.001). No difference was observed between both groups of patients. Metabolic clearance rate of glucose was strongly reduced in obese diabetic patients but it was normal in insulinoma patients in comparison with healthy persons (2.7 +/- 0.4 vs 8.7 +/- 0.6 or 7.9 +/- 0.7 ml.kg-1.min-1, p < 0.001). A decreased insulin binding on specific receptors caused by reduced binding capacity was observed only in insulinoma patients but not in obese Type 2 diabetic patients. A significant negative correlation was proved between body mass index (BMI) and insulin sensitivity index (r = -0.82, p < 0.001) indicating that BMI is the main determining factor of insulin resistance in the total cohort of examined patients. We conclude that insulin resistance was caused by postreceptor changes in obese Type 2 diabetes, whereas a decreased insulin binding capacity together with post-receptor defect was present in insulinoma patients.

Adult↗
PubMed1996

The roles of adhesion molecules and proteinases in lymphocyte transendothelial migration.

T cell extravasation into perivascular tissue during inflammation involves transmigration through the endothelial cell (EC) layer and basement membrane. We have demonstrated that matrix metalloxproteinase-2 (MMP-2) is induced in T cells upon adhesion to endothelial cells and that the induction of MMP-2 is mediated by binding of T cell VLA-4 to VCAM-1. Cloned murine Th1 cells antigenic to myelin basic protein, either expressing VLA-4 on their cell surface and causing experimental autoimmune encephalomyelitis (EAE) or not expressing VLA-4 and not causing EAE, were used. VLA-4 positive (+) T cells that adhered to VCAM-1 positive (+) endothelial cells exhibited an induction in MMP-2 mRNA, protein, and activity, whereas MMP-2 was not induced in the T cells that adhered to the VCAM-1 negative (-) endothelial cells or VLA-4 negative (-) T cells that adhered to VCAM-1+ endothelial cells. Incubating T cells with rVCAM-1-coated dishes showed that VLA-4+ T cells adhered to the molecule and that adhesion to rVCAM-1 was sufficient to induce MMP-2. VLA-4+ T cells that had transmigrated through a VCAM-1+ endothelial cell monolayer exhibited MMP-2 activity. TIMP-2 was shown to reduce T cell transmigration in vitro. Transmigrated T cells exhibited downregulation of VLA-4 and LFA-1 integrin surface expression and decreased binding to rVCAM-1 and rICAM-1 and increased binding to collagens I and IV, fibronectin, and laminin. Brain sections of mice demonstrated that as T cells migrated farther into the tissue, VLA-4 expression was lost, although CD4 expression remained unchanged. These results demonstrate that binding to VCAM-1 on endothelial cells induces MMP-2 in T cells, which, in turn, may facilitate T cell migration into perivascular tissue. The significance of these findings in the modulation of the inflammatory response is discussed.

Animals↗
PubMed1996

[Further evidence of the role of prostaglandin on the effects of hormones on blood circulation in bones].

In a short communication we demonstrated the inhibitory affect of acetylosalicylic acid (ASA) on the increased bone blood flow and 45Ca and 3H-proline incorporation in oophorectomized (OOX) female rats. This finding suggested probable participation of prostaglandin. The aim of the present work was to confirm and extend the initial observation and to find out, whether the administration of ASA did not affect also the decrease in the bone blood flow after the administration of estradiol benzoate (EB). Local blood flow was determined by means of the uptake of 85Sr-microspheres. In experiment A (females) the local circulatory values were increased after OOX significantly in tibia and distal femur, insignificantly in diaphysis of the femur and calvaria; this increase after OOX was suppressed by simultaneous administration of ASA completely in tibia, partially (and statistically insignificantly) in distal femur and diaphysis of the femur; no effect of ASA could be demonstrated in the calvaria. The blood flow through the kidneys of OOX female rats was decreased after ASA, while no change occurred in muscle and skin. The bone mineral content was significantly lower in both groups of OOX females. In experiment B (males), we observed an increase in local circulatory values after ORX in tibia, distal femur and diaphysis of the femur and suppression of this increase by the administration of ASA. These changes were not demonstrable in the calvaria and soft tissues studied. In experiment C (females), we found that significant decrease in the local circulatory values in the tibia after 4 weeks of administration of EB was not altered by simultaneous administration of ASA. Experiment D (females) proved again that 24 hour incorporation of 45Ca and 3H-proline was markedly suppressed by the administration of ASA not only in OOX females but also in sham operated control rats. Thus, the present results confirm the inhibitory effect of ASA on the increase in bone blood flow after castration, indicating with high probability participation of prostaglandin (PGE2?) (while no effect of ASA could be demonstrated on the decrease in bone blood flow after EB). The described blood flow changes are induced by local vascular reactions and occur in the bones of both female and male rats. Marked suppression by ASA of 45Ca and 3H-proline incorporation supports the circulatory results and indicates an important interconnection between metabolic processes and local circulation in the bone. We conclude that prostaglandin may be one of the factors regulating bone blood flow.

Animals↗
PubMed1996

[The role of EDRF-NO in the regulation of bone blood flow in rats: inhibition with L-NAME].

EDRF-NO probably participates-besides the prostaglandins [3, 4]-in local circulatory changes in the bones of female rats with modified level of sex hormones; we could demonstrate it indirectly using methylene blue as a blocking agent [5]. In this paper, we present corresponding results of two experiments with NG-nitro-arginine methyl ester (L-NAME) as a substance blocking the production of endothelium derived relaxing factor, i.e. nitric oxide (EDRF-NO). Circulatory values were estimated by means of 85Sr-microspheres. In experiment A we ascertained whether the duration of L-NAME administration (0.025% in the food) influenced the effect. It could be demonstrated that the effect of one week's, two weeks', or four weeks' administration of L-NAME was the same: 85Sr-microsphere uptake and blood flow throught the tibia of female rats, increased after oophorectomy (OOX, performed four weeks prior to the experiment), was significantly suppressed to the level in sham-operated animals. In the experiment B, L-NAME was administered in the food in concentration of 0.05% for two weeks prior to the experiment. 85Sr-microsphere uptake was decreased significantly after L-NAME in the tibia of sham-operated females, in the tibia and distal femur of OOX animals; no significant changes were found in the diaphysis of femur and in calvaria. Blood flow values were significantly decreased in all bone samples of OOX females and in tibia of sham-operated rats (besides the local reaction also due to the decrease in the cardiac output). In both experiments the cardiac output was decreased and blood pressure elevated after L-NAME. It can be concluded, from the results of both experiments, that the blockade of EDRF-NO production by L-NAME decreases local circulatory values in the bones of female rats-particularly OOX-in a similar way as methylene blue; however, in contrast to methylene blue, L-NAME induces marked increase in the blood pressure and partially decrease in the cardiac output. Thus, as in the case of methylene blue, the effect of L-NAME on the circulation of blood in the rat bones supports the hypothesis of the participation of EDRF-NO in bone blood flow regulations.

Animals↗
PubMed1995

Pre-/postdilution hemofiltration.

Hemofiltration creates the best conditions for toxin removal and cardiovascular stability in the treatment of chronic renal failure patients. The increase in hematocrit due to erythropoietin, the blood flow rate and the necessary volume of substitution fluid limit the post- or the predilution hemofiltration. The technical progress made now offers the possibility to routinely and safely treat patients with pre-/postdilution hemofiltration. When adjusting the substitution flow rate to the blood flow rate, small-molecule clearances are higher than those in hemodialysis and are close to those in hemodiafiltration.

Hemodilution↗
PubMed1995

Dehydroepiandrosterone and insulinaemia.

Low dehydroepiandrosterone (DHEA) and hyperinsulinaemia are assumed to be risk factors of atherosclerosis. Exogenous hyperinsulinaemia during hyperinsulinaemic clamp decreases DHEA. We have evaluated interaction of these hormones during 2 weeks of therapeutic starvation in 11 obese patients (mean BMI 41.2 kg/m2), 5 nondiabetics and 6 diabetics with diet only therapy. Comparing diabetics with normals we have found no differences in BMI and blood DHEA, DHEAS and insulin levels. We have found a light implication of negative correlation of insulin to DHEA and DHEAS level in diabetics (r = -0.71, -0.73, p = 0.16, 0.18). During starvation insulinaemia is declining, DHEA initial increase is followed by a decrease (r = 0.93, p = 0.01). We conclude that insulin decrease during starvation could be a cause of DHEA decrease. This finding is unexpected according to the potential of exogenous insulin to suppress DHEA. Further investigation of endogenous DHEA and insulin relation is necessary.

Arteriosclerosis↗
PubMed1995

Retrospective testing of an insulin advisory system.

A retrospective analysis of the function of adaptive model based consultation system for insulin therapy was performed. The program proved good adaptation ability with improving blood glucose level prediction. In a group of 12 brittle type 1 diabetic patients individual analysis showed problems resulting from retrospective testing of dynamic systems, when treatment is determined only by the physician.

Blood Glucose↗