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Biomedical subjects

M Donner

Publications and source records attributed to M Donner.

At least 37 records · Page 2Linked to original sources
PubMed1994

Increased erythrocyte aggregation in insulin-dependent diabetes mellitus and its relationship to plasma factors: a multivariate analysis.

Red blood cell aggregation in vitro (kinetics and shear resistance) was studied in 13 healthy controls and 13 type I (insulin-dependent) diabetic patients free of severe degenerative complications who were matched for age, sex, and body mass index. Measurements were performed with a device that analyzes the laser light backscattered by a blood suspension. Both the velocity of rouleau formation and the cohesion of the rouleau network were significantly increased in diabetic patients. Plasma viscosity and whole-blood viscosity measured at low shear rate (0.95 s-1) were also significantly elevated in the diabetic group. Multivariate analyses of the whole population sample and the diabetic patients confirmed the influence of plasma proteins on the kinetics of aggregation. Fibrinogen levels, which were close to normal, affected mainly the shear resistance of the aggregates. Triglyceride and apolipoprotein (apo) B levels and indexes of metabolic control or protein glycation (fasting blood glucose and fructosamine) also appeared to influence markedly both the kinetics of rouleau formation and the cohesion of the rouleau networks. These rheological abnormalities occurred in diabetic patients before the appearance of any severe degenerative complications. We suggest that these rheological abnormalities are linked to plasma or erythrocyte factors, and are not due to angiopathy.

Adult↗
PubMed1994

Rheologic effects of plasma substitutes used for preoperative hemodilution.

This study was designed to compare the influence of various plasma substitutes, administered for preoperative hemodilution, on blood rheology. We studied 40 patients, ASA grade I, who underwent elective facial reconstructive surgery and received 4% albumin (n = 10), 3.5% dextran 40 (n = 10), gelatin (n = 10), or hydroxyethyl starch (HES) (n = 10). Ten patients, undergoing the same surgical procedure without hemodilution, were chosen as controls. After hemodilution, hematocrit was decreased approximately 30%. Fibrinogen decreased in all tested groups except in the gelatin group. Plasma viscosity decreased with albumin (1.13 +/- 0.05 to 1.06 +/- 0.03 mPa.s; P < 0.01) and increased with HES (1.15 +/- 0.04 to 1.22 +/- 0.05 mPa.s; P < 0.01). At a high shear rate, the blood viscosity decreased in all groups. In contrast, at a low shear rate and at 40% corrected hematocrit, the blood viscosity decreased in the albumin (15.9 +/- 1.9 to 13.1 +/- 2.1 mPa.s; P < 0.01) and the dextran 40 (16.9 +/- 2.9 to 12.8 +/- 2.5 mPa.s; P < 0.01) groups and was unchanged in the gelatin and the HES groups. Erythrocyte aggregation (measured with primary aggregation time) was markedly decreased in the albumin (3.27 +/- 1.74 to 7.03 +/- 2.95 s; P < 0.01) and in the dextran 40 (2.72 +/- 0.58 to 6.24 +/- 2.55 s; P < 0.001) groups, unchanged with HES, and increased with gelatin (2.41 +/- 0.90 to 1.55 +/- 0.33 s). These findings suggest that albumin and dextran 40 may be the plasma substitutes of choice for preoperative hemodilution when this technique aims to improve rheologic conditions.

Adolescent↗
PubMed1993

Effects of lisinopril and hydrochlorothiazide on platelet function and blood rheology in essential hypertension: a randomly allocated double-blind study.

AIM: To compare the effects of an angiotensin converting enzyme (ACE) inhibitor and a thiazide diuretic on platelet function and haemorrheological variables, since these factors may contribute to the atherosclerotic and thrombotic complications associated with hypertension. METHODS: Following a 2-week placebo period, 80 male and female patients with mild to moderate hypertension, aged 50 +/- 10 (mean +/- SD) years, were randomly allocated in a double-blind study to 4 weeks of treatment with the ACE inhibitor lisinopril at 20 mg once a day or the diuretic hydrochlorothiazide at 25 mg once a day. Venous blood was sampled before and at the end of the 4-week treatment period to assess platelet function and haemorrheological variables. RESULTS: Both treatments lowered systolic and diastolic blood pressure equally and had no significant effect on platelet counts and platelet aggregation in response to ADP and to arachidonic acid. Haematocrit plasma viscosity and blood filterability were not altered by either drug. Hydrochlorothiazide tended to increase and lisinopril tended to decrease whole blood viscosity at all shear rates but these changes did not reach statistical significance. Lisinopril increased the erythrocyte aggregation time (from 1.98 +/- 0.50 to 2.08 +/- 0.52 s) and decreased the disaggregation shear rate (from 159 +/- 46 to 153 +/- 40 s-1) and the disaggregation shear stress (from 705 +/- 257 to 659 +/- 204 mPa). Hydrochlorothiazide induced the opposite effects (2.00 +/- 0.47 to 1.92 +/- 0.39 s, 181 +/- 531 to 196 +/- 82 s-1 and 813 +/- 268 to 868 +/- 392 mPa, respectively) with a statistically significant (P < 0.05) intergroup difference. CONCLUSIONS: These findings suggest that chronic treatment with the ACE inhibitor lisinopril, but not the diuretic hydrochlorothiazide, may produce favourable effects on blood rheology, but the clinical relevance requires further investigation.

Adult↗
PubMed1993

[In vivo effects of plasma substitutes on the rheologic properties of blood].

The objective was to investigate in vivo the rheological effects of plasma substitutes (fluid gelatin, dextran 40, dextran 60, hydroxyethylstarch). The study was performed during a hypervolemic hemodilution in 60 adult volunteers who underwent an odontological surgery. Two control groups were infused with Ringer-Lactate or 4% human albumin. Each patient was infused with 500 ml of plasma substitute or control fluid. Blood samples were obtained at four different times: prior to (t0) and immediately after (t1) the infusion, then 3 hours (t2) and 24 hours (t3) after the hemodilution. At t1 and t2, plasma viscosity did not present important variations, except for the group infused with dextran 60 where a significant increase in plasma viscosity was observed. Blood viscosity and erythrocyte aggregation measurements were performed at hematocrit 40% to determine the intrinsic properties of substitute and eliminate the effects of hemodilution. Blood viscosity at high shear rates underwent minor variations in all groups. In contrast, blood viscosity at low shear rate and aggregation parameters exhibited important variations which markedly depended on the used substitute. The infusion of Ringer-Lactate, albumin and dextran 40 induced a significant decrease in blood viscosity and in erythrocyte aggregation. With dextran 60 and gelatin, blood viscosity and erythrocyte aggregation increased. Finally, the infusion with hydroxyethylstarch did not present important differences as compared to the results recorded at t0. Twenty for hours after the infusion, it should be noted an increase in plasma fibrinogen, probably due to surgery, which caused an increase in erythrocyte aggregation in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

[In vitro effects of ionic and non-ionic contrast media on erythrocyte aggregation].

An in vitro model was designed to examine the effect of three contrast media (CM): two non ionic (Iohexol, Iopamidol) and one ionic (Ioxaglate) molecules on erythrocyte aggregation. Red blood cells were suspended in a chemically defined medium (Albumin: 10 g/l), Immunoglobulins: 12 g/l, Fibrinogen: 1.5 g/l) supplemented with various proportions of CM (10-25% V/V). Control samples contained NaCl or Saccharose solutions with a nearly similar osmolality. Erythrocyte aggregation at constant hematocrit (HT = 40%) was determined by the analysis of the light backscattered by blood suspension during the aggregation process. As compared to control samples, non ionic CM induced a weak decrease in erythrocyte aggregation, when the ionic molecule caused a marked increase in the aggregation, which was related to CM concentration. A different interaction of ionic and non ionic CM with erythrocyte membranes has been shown by fluorescence studies. After addition of CM, it was noted a fluorescence quenching of lipophilic probes (TMA-DPH and DPH) embedded in erythrocyte membranes. This quenching probably due to benzene ring and iodine atoms of contrast media markedly varied according to the used fluorescent probe and the CM. In the presence of ionic CM, the fluorescence quenching is more important than that induced by non ionic CM. Thus, besides osmolality and viscosity of CM which play a role in erythrocyte aggregation, some intrinsic properties of CM such as the ionic or non ionic nature could influence erythrocyte membrane-contrast medium interactions and consequently erythrocyte aggregation.

Diphenylhexatriene↗
PubMed1992

Use of fluorescence anisotropy determinations for indicating the physiological status of hybridoma cell cultures.

The evolution of lipid compartment fluidity during culture of hybridoma cells was studied by fluorescence polarization measurements. The probe partition between the plasma membrane and intracytoplasmic compartments was determined by a quenching fluorescence method. A progressive decrease of the plasma membrane fluidity was observed during the growth phase with an increase during stationary and degeneration phases of the culture. These data suggest that fluidity parameters could be used to follow the behaviour of hybridoma cell cultures.

Cell Membrane↗
PubMed1992

Linkage analysis of spinal muscular atrophy.

Linkage data between four markers on chromosome 5 confirm and extend our previous studies that localized the mutation in spinal muscular atrophy to 5q11.2-q13.3. Localization of D5S6 by in situ hybridization refines the mapping of the defective gene to the region 5q12.2-q13. We also report the use of a highly informative PCR-based polymorphism with five alleles. This RFLP will be particularly useful for prenatal diagnosis where only old tissue samples from affected individuals are available. The high heterozygosity of this locus should also assist in identifying recombinants that will refine the genetic mapping of the mutation.

Chromosome Mapping↗
PubMed1992

[In vivo rheologic studies of plasma substitutes].

The aim of this study was to compare in 60 ASA1 patients, the rheological effects of a 500 ml plasma substitute infusion at induction of general anaesthesia. The 60 patients were allocated into 6 groups of 10. Each group received either albumin 4%, or dextran 40 3.5%, or dextran 60 6%, or hydroxyethylstarch (HES) 200 6%, or modified fluid gelatin or Ringer lactate. The infusion extended over 30 minutes. In blood samples obtained before infusion, immediately after the end, three and 24 hours after the end of infusion, osmotic pressure, oncotic pressure, proteins and fibrinogen concentration were measured. Following rheological parameters were also assessed: plasma viscosity, blood viscosity at two shear rates (0.5 and 128 s-1), erythrocyte aggregation by primary and final aggregation times as well as total and partial dissociation thresholds. The determinations were carried out at haematocrit corrected to 40%. At intergroup analysis of the different substitutes compared to albumin 4%, with the exception of Ringer lactate, there was no significant modification of osmotic and oncotic pressures or fibrinogen concentrations. Only gelatin and dextran 60 modified the rheological parameters. The intragroup comparison did not demonstrate significant variations of osmotic and oncotic pressures. Fibrinogen concentrations remained unchanged up to the 24th hours, where they increased as a reaction to surgery. Similar changes of rheological parameters occurred for Ringer lactate, albumin 4% and dextran 40: decrease of plasma viscosity (< 10%) and blood viscosity (< 20% at shear rate of 0.5 s-1), increase of primary aggregation time (30-50%) with decrease of total dissociation threshold (10-20%). These changes ended 24 hours after infusion. Dextran 60 and gelatin elicited a modification of blood rheology until the 24th hour after the end of infusion. Such modifications did not occur with HES. It is concluded that when a rheological effect is required albumin 4% or dextran 40 3.5% should be used.

Albumins↗
PubMed1992

CNS in congenital muscular dystrophy without mental retardation.

We have evaluated the CNS findings of 30 patients with congenital muscular dystrophy and normal mental development. The intelligence was estimated by psychological testing or school performance. There were more children of above average intelligence than expected. Neuroradiological examination was done to 15/17 patients still alive. White matter changes were seen in five and cerebral atrophy in four patients. Three patients had epilepsy, two mild, one drug resistant. The EEG did not reveal any common pattern, though there were various abnormalities in several children.

Achievement↗
PubMed1991

[Hemorrheology in clinical practice. Applications in an in vitro study of troxerutin].

It is now well established that blood behaves like a non Newtonian fluid varying with the shear rate. Blood viscosity pattern relative to various shear rates shows a high viscosity at low shear rate (due to rouleau formation or erythrocyte aggregation) with a decrease at high shear rate. This high blood viscosity will be of a great importance only while pathological blood flowing with low output or stasis. Pathological variations of one factor determining blood viscosity and clinical signs define hyperviscosity syndrome. From an hemodynamical point of view, the appearance of an hyperviscosity syndrome, may, as a result of feedback mechanism, aggravate the disorders leading to a slowing down and even to a stop in local blood flow, subsequently encouraging ischemia. Moreover hyperviscosity also leads to a theoretical lowering capacity of oxygen transport by blood approximatively in proportion with the haematocrit/blood viscosity ratio. With regard to therapeutic aspect, the pharmacology of rheological influence drugs must be displaced into the wider outline proposed by Virchow. So we could distinguish between therapeutic action of drugs upon haematocrit, plasmatic proteins level, red blood cell deformability and erythrocyte aggregation. Among this last category disaggregating effect of rutosides has been first pointed out by Schmid-Schöenbein and Col. Our results of an in vitro study of troxerutine effect with ranging concentrations from 10(-5) to 10(-2) M upon blood viscosity and erythrocyte aggregation are reported.

Anticoagulants↗
PubMed1991

Clinical and electroretinographic comparison between Aland Island eye disease and a newly found related disease with X-chromosomal inheritance.

Two subjects representing AIED (Aland Island Eye Disease) and a family with 5 males affected with an AIED related X-linked hereditary eye disease were studied clinically and electrophysiologically. The clinical picture of AIED includes myopia and astigmatism, reduced visual acuity, nystagmus, ocular albinism, hemeralopia and dyschromatopsia (No. 300600, McKusick 1990). The subjects with the related disease showed astigmatism with or without myopia, reduced visual acuity, slight hemeralopia, normal color vision in 3/5 subjects, no ocular albinism and nystagmus only in one case. In both diseases the ERG was abnormal showing defective a- and b-waves, but there were also differences. The most notable was the greater reduction of the b-wave amplitude in the mixed (rod and cone) responses for the white stimulus in the ERG of the AIED related disease. With regard to the pathogenesis we propose that in both diseases rod and cone functions are defective but in an AIED related disease a defective cone function inhibits the transmission of the rod signals to the rod bipolars, causing greatly reduced mixed responses. The clinical and ERG findings of this study suggest that the 5 subjects of our family do not represent AIED but another X-linked hereditary eye disease. The investigation to find out the gene locus of this disease is going on.

Adolescent↗
PubMed1991

New trends in clinical hemorheology: an introduction to the concept of the hemorheological profile.

It has now been clearly established that blood behaves like a non-Newtonian fluid exhibiting specific features with the probable existence of a plasticity threshold, a viscosity that varies as a function of shear rate and a non-homogeneous nature of the medium during flow. When apparent blood viscosity is represented as a function of shear rate, a high viscosity is observed at low shear rates, mainly due to rouleaux formation or red cell aggregates. At high shear rates, viscosity decreases. Apparent blood viscosity is mainly dependent on the following parameters: cell volume concentration (hematocrit); plasma viscosity (which is itself dependent on the type and concentration of the proteins); mechanical properties of the red cells, the main determinants being the cell membrane and internal viscosity; red blood cell aggregation; shear stress applied. Pathological changes in one of the factors controlling blood viscosity and the resulting clinical symptoms constitute the hyperviscosity syndromes. The field of hyperviscosity syndromes concern the situations where the increased blood viscosity and the accompanying modifications in flow resistance must be considered as being the result of the overall rheological behaviour of blood. In this general context, hyperviscosity syndromes can be divided into 4 main groups: 1. Increase in the number of blood cells (mainly red cells) 2. Increase in the plasma protein concentrations or the appearance of high amounts of a monoclonal protein 3. Increase in internal red cell viscosity or a change in the mechanical properties of the erythrocyte membrane 4. Increase in erythrocyte aggregation (formation of barely or in no way dissociable aggregates). Considered from a hemodynamic viewpoint, the appearance of a hyperviscosity syndrome could (by 'feed back' mechanisms) enhance the phenomenon and slow down blood flow or even stop flow completely, thus making ischemia and thrombosis easier. Further, the appearance of the syndrome also results in a decrease in the blood's overall oxygen transport capacity, which, at a primary approach, is proportional to the ratio hematocrit/blood viscosity.

Animals↗
PubMed1991

[Hemorheology in clinical practice. Introduction to the notion of hemorheologic profile].

Although the non-Newtonian characteristics of blood have now been accurately defined, the influence and effect of a hyperviscosity syndrome at the onset of ischemia and in oxygen transport to the tissues remains within the realm of assumptions. Using a simple theoretical approach it can be shown that oxygen transport capacity to the tissues is proportional to the radio H/eta s (where H = hematocrit, eta s = blood viscosity), as long as vascular bed geometry remains constant (with no sign of compensatory vasodilation). With the help of examples, the authors show the changes in oxygen transport as a function of various rheological parameters (red cell aggregation ans deformability). Further, the authors introduce the concept of a hemorheological profile for taking all the hemorheological parameters into consideration and for standardising the presentation of the results for hyperviscosity syndromes.

Blood Viscosity↗
PubMed1991

[Erythrocyte aggregation in patients with monoclonal gammopathies: effect of plasma exchange treatment].

Analyses of erythrocyte aggregation have been carried out in 15 patients with multiple myeloma or Waldenström's macroglobulinemia before and after plasma exchange. The volume of exchanged plasma was about 1.2-1.5 plasmatic mass. It was replaced by the same volume of a 4% solution of human albumin. Each treatment included at least 3 plasma exchanges at 48 hours intervals. The kinetic (aggregation times) and rheological (dissociation threshold) parameters of erythrocyte aggregation were determined before and immediately after each plasma exchange using a device based on the analysis of the backscattered light by a blood suspension. Before the first plasma exchange, erythrocyte aggregation measurements revealed a pronounced reduction in time aggregation and high values of dissociation thresholds indicating an hyperaggregation of red cells. The successive plasma exchanges produced very different changes in erythrocyte aggregation. For some patients, the aggregation parameters presented normal values from the first plasma exchange when similar changes were only noted after the second plasma exchange in other patients. Finally, in some cases, an hyperaggregation state was maintained after a series of three plasma exchanges. The influence of the nature and the concentration of monoclonal immunoglobulin as well as plasmatic fibrinogen are discussed.

Blood Viscosity↗
PubMed1990

Erythrocyte membranes alteration in a shear stress measured by fluorescence anisotropy.

An experimental setup has been designed to allow fluorescence anisotropy measurements on labeled cell membranes under shear stress. An important change is observed when increasing the shear stress and varying the experimental parameters indicates that a decrease in membrane cohesion leads to a subsequent increase in the membrane alteration under shear stress. A model has been developed that shows, in agreement with experiment, that the effect observed is mainly the result of the alteration of the membrane, elongation, and orientation with respect to the fluid flow, which can be estimated.

Cholesterol↗
PubMed1990

Rheological properties and membrane fluidity of red blood cells and platelets in primary hyperlipoproteinemia.

Lipid fluidity of the erythrocyte membrane and intact platelets was examined in 32 male patients affected by types IIA, IIB and IV primary hyperlipoproteinemia and 15 control subjects. Lipid fluidity was determined by fluorescence polarization using two probes: DPH and TMA-DPH which are localized in different lipid areas of the cell membrane. Classical haemorheological tests were also performed including plasma viscosity, whole blood viscosity and erythrocyte aggregation. As compared to a control group, plasma viscosity and whole blood viscosity at low shear rate was significantly increased in types IIB and IV, but not in type IIA patients. In contrast, the increase in erythrocyte aggregation was significant in all HLP types. Concerning lipid fluidity, the results recorded with red cells and platelets were not significantly different for type IIA HLP compared to the control group. In contrast, erythrocyte membranes from patients with types IIB and IV HLP had a significantly higher level of fluidity in lipid regions characterized by TMA-DPH. Using DPH as a fluorescent probe, identical results were only noted in type IIB patients. Regarding intact platelets of IIB and IV patients, an increase in lipid fluidity was noted for two fluorescent probes. These findings suggest that HLP associated erythrocyte and platelet fluidity alterations are not related to hypercholesterolemia but to the triglyceride level.

Adult↗
PubMed1990

Genetics of congenital nemaline myopathy: a study of 10 families.

In order to investigate the inheritance in congenital nemaline myopathy (CNM), we studied the family histories and pedigrees of 13 patients with CNM from 10 families, and the 20 patients, by physical examination, single fibre electromyography, ultrasonography of muscles, measurement of serum creatine kinase, muscle biopsy, and electrophoresis of muscle proteins. None of the parents was affected. In three families there were two affected children. Of the parents, 15 showed deficiency of type 2B muscle fibres, and all except one father showed some other minor neuromuscular abnormality. These may represent heterozygous manifestations of recessive gene. Most of the ancestors came from sparsely populated rural communities in the west of Finland. We conclude that in the Finnish CNM patients, the mode of inheritance appears to be recessive. Apart from a few instances of dominant inheritance, most cases published also seem compatible with recessive inheritance.

Adolescent↗