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Biomedical subjects

Andrea Schmitt

Publications and source records attributed to Andrea Schmitt.

At least 19 recordsLinked to original sources
PubMed2026

Effects of quetiapine on cognitive functioning in schizophrenia: evidence for the remyelination hypothesis?

Postmortem findings, neuroimaging data, and in-vitro models suggest a decrease in number and density of oligodendrocytes is driving cognitive deficits in schizophrenia (SCZ). Second-generation antipsychotics are discussed to improve oligodendrocyte dysfunction with most conclusive evidence available for quetiapine (QET). We postulate that sustained QET treatment leads to cognitive improvement in SCZ, particularly, in tests with high demands for working memory function. We further hypothesize that these effects are moderated by polygenic factors associated with hippocampus-related brain volumes, general white matter integrity, and/or oligodendroglia-related SCZ risk. Using data of the prospective PsyCourse study, we identified 166 patients with SCZ spectrum disorder receiving QET at one or two consecutive visits plus 166 matched patients without QET. Polygenic scores were calculated for subcortical brain volumes, measures of white matter integrity, and for cell type-specific genetic SCZ risks. QET treatment was consistently associated with improved cognitive function independent of time, specifically, in tests with high, but not with low to medium working memory load. Polygenic analyses did not reveal significant moderation effects. In contrary, low genetic SCZ risk specific for genes related to human oligodendrocyte function was associated with higher cognitive performance independent from QET. While we observed improved cognitive performance under QET in high working memory tests, we did not find evidence that polygenic factors associated with hippocampus-related brain volumes, white matter integrity, or oligodendroglia-related SCZ risk moderate this association. Thus, our tentative findings do not provide evidence for the hypothesis that polygenic estimates of hippocampal remyelination capacities influence the association between QET and cognitive performance in SCZ.

Humans↗
PubMed2006

Neural correlates of working memory dysfunction in first-episode schizophrenia patients: an fMRI multi-center study.

Working memory dysfunction is a prominent impairment in patients with schizophrenia. Our aim was to determine cerebral dysfunctions by means of functional magnetic resonance imaging (fMRI) in a large sample of first-episode schizophrenia patients during a working memory task. 75 first-episode schizophrenia patients and 81 control subjects, recruited within a multi-center study, performed 2- and 0-back tasks while brain activation was measured with fMRI. In order to guarantee comparability between data quality from different scanners, we developed and adopted a standardized, fully automated quality assurance of scanner hard- and software as well as a measure for in vivo data quality. After these quality-control measures had been implemented, 48 patients and 57 controls were included in the final analysis. During attention-related processes, even when the performance between patients and controls was comparable, there was a recognizable emergence of cerebral dysfunctions with hypoactivations in the ventrolateral prefrontal cortex (VLPFC), in the superior temporal cortex and in the thalamus. During working memory performance, parietal hypoactivations, especially in the precuneus, were prominent and were accompanied by poorer performance in patients. A hyperfrontality emerged in the ventrolateral prefrontal cortex. Hence, results point to a dysfunctional ventrolateral prefrontal-parietal network during working memory in patients, suggesting impairments in basic functions such as retrieval, storage and maintenance. The brain activation pattern of this large and significant sample of first-episode schizophrenia patients indicates an imbalanced system failing to adjust the amount of brain activity required in the cerebral network involved in attention and working memory.

Adolescent↗
PubMed2006

D2 antidopaminergic modulation of frontal lobe function in healthy human subjects.

BACKGROUND: Although the major principles of dopamine (DA) signaling have been well described previously, its precise modulatory impact on the prefrontal cortex (PFC) in humans is poorly understood. Two major neurophysiological models propose segregated functional circuits on the systems level as well as D(1) and D(2) receptor-dependent processing states on the cellular level (two-state model). METHODS: We examined the predictive validity of these models in 10 healthy male volunteers with a haloperidol challenge (HLP). Cortico-striatal-thalamo-cortical (CSTC) motor loop functions were examined during functional magnetic resonance imaging (fMRI) with a sequential finger opposition task. Neuropsychological implications of the two-state model were evaluated with a test battery of D(1)- or D(2)-sensitive prefrontal measures. RESULTS: Analysis of fMRI data revealed a significant HLP-induced blood oxygen level dependent-signal decrease in the sensorimotor striatum and a lateralized activation loss of ipsilateral higher order motor cortices and contralateral cerebellum. Neuropsychological evaluation demonstrated a preferential impairment of D(2)-sensitive functions, whereas D(1) or non-dopaminergic domains were unaffected. CONCLUSIONS: Our data support the hypothesis that mesocortical D(1) and D(2) receptors exert differential influences in the PFC for cognitive function, but the nigrostriatal CSTC network model for the motor domain could not be confirmed.

Adult↗
PubMed2005

Disturbance in the neural circuitry underlying positive emotional processing in post-traumatic stress disorder (PTSD). An fMRI study.

This study was designed to investigate the circuitry underlying movie-induced positive emotional processing in subjects with chronic PTSD. Ten male subjects with chronic PTSD and ten matched controls were studied. In an fMRI-paradigm a sequence of a wellknown Walt Disney cartoon with positive emotional valence was shown. PTSD subjects showed an increased activation in the right posterior temporal, precentral and superior frontal cortex. Controls recruited more emotion-related regions bilateral in the temporal pole and areas of the left fusiform and parahippocampal gyrus. This pilot study is the first to reveal alterations in the processing of positive emotions in PTSD possibly reflecting a neuronal correlate of the symptom of emotional numbness in PTSD.

Adult↗
PubMed2005

Increased serum S100B in elderly, chronic schizophrenic patients: negative correlation with deficit symptoms.

In schizophrenia, elevations of serum and CSF S100B levels have been reported and related to state of the disease and negative symptoms. In elderly chronic schizophrenic inpatients with stable medication, S100B may be increased and correlated to psychopathology and neuropsychological deficits. We have measured serum levels of S100B in 41 elderly, chronic schizophrenic patients and 23 age- and gender-matched controls using an immunoluminometric assay. In patients, we assessed detailed psychopathology and neuropsychological performance and determined serum levels of haloperidol, clozapine and its two main metabolites desmethylclozapine and clozapine metabolite N-oxid by HPLC. S100B levels were increased in elderly chronic schizophrenic patients compared to healthy controls. In patients, levels were negatively correlated with deficit symptoms and positively with age. There were no significant differences of S100B between medication groups and no correlation with serum levels of antipsychotics or neuropsychological scores. Elevations of S100B in elderly chronic schizophrenic patients may be related to an active disease process lasting until old-age. Correlations point to the impact of S100B in neuroplasticity and ageing. Post-mortem studies should clarify the presence of altered S100B function in the brain and its relationship to neuroplastic or neurodegenerative processes.

Aged↗
PubMed2005

Helicobacter pylori vaccine development: facing the challenge.

An effective vaccine would be a desirable way to control Helicobacter pylori-induced gastric disease. Initial studies in animal models demonstrated the feasibility of immunization and led to high hopes for a human vaccine. In the mouse model immunological approaches have to date not brought a satisfactory explanation for the mechanisms of protection against this largely luminal pathogen. Recently, transcriptome studies have identified new factors. It is now proposed that non-classical immune mediators may be the key to vaccine-induced protection. Human trials of H. pylori vaccines are going ahead but although at least some formulations are clearly immunogenic, their effectiveness remains untested. The recent development of a human challenge model has now opened up new prospects for testing candidate vaccines and this will undoubtedly have a great impact in the near future. Future priorities for H. pylori vaccine development must be a better understanding of the protective mechanisms and the identification of biomarkers which can be used as reliable predictors of efficacy in humans. Despite some important advances in recent years, important issues must be resolved before an H. pylori vaccine will become a reality.

Adjuvants, Immunologic↗
PubMed2005

Protective drugs in acute large-dose exposure to organophosphates: a comparison of metoclopramide and tiapride with pralidoxime in rats.

Weak and reversible inhibitors of cholinesterase(s), when coadministered in excess with a more potent inhibitor such as organophosphates, can act in a protective manner. The benzamide compound, metoclopramide, confers some protection (putatively via this mechanism) for cholinesterases against inhibition by paraoxon both in vitro and in vivo, after chronic small-dose exposure. Tiapride is a related benzamide. In this study, we compared the protection by metoclopramide and tiapride in rats acutely exposed to large doses of paraoxon with the therapeutic "gold standard," pralidoxime. Group 1 received 1 micromol paraoxon (approximately 75% lethal dose), Group 2 received 50 micromol metoclopramide, Group 3 received 50 micromol tiapride, Group 4 received 50 micromol pralidoxime, Group 5 received 1 micromol paraoxon + 50 micromol metoclopramide, Group 6 1 micromol paraoxon + 50 micromol tiapride, and Group 7 1 micromol paraoxon + 50 micromol pralidoxime. All substances were administered intraperitoneally. The animals were monitored for 48 h and mortality was recorded at 30 min, 1, 2, 3, 4, 24, and 48 h. Blood was taken for red blood cell acetylcholinesterase measurements at baseline, 30 min, 24, and 48 h. With the exception of Group 7, in which some late mortality was observed, mortality occurred mainly in the first 30 min after paraoxon administration with minimal changes occurring thereafter. Mortality at 30 min was 0% in the metoclopramide, tiapride, and pralidoxime groups and 73 +/- 20 (paraoxon), 65 +/- 15 (paraoxon + metoclopramide), 38 +/- 14 (paraoxon + tiapride), and 13 +/- 19 (paraoxon + pralidoxime). Mortality at 48 h was 75 +/- 18 (paraoxon), 67 +/- 17 (paraoxon + metoclopramide), 42 +/- 16 (paraoxon + tiapride), and 27 +/- 24 (paraoxon + pralidoxime). Metoclopramide does not significantly influence mortality after acute large-dose paraoxon exposure. Both tiapride and pralidoxime significantly decreased mortality in our model. The protection conferred by tiapride was significantly less than that conferred by pralidoxime at 30 min, but was not significantly different at 24 and 48 h.

Acetylcholinesterase↗
PubMed2004

Transcription profiling analysis of the mechanisms of vaccine-induced protection against H. pylori.

Development of a vaccine against H. pylori is regarded as desirable alternative to the current antibiotic therapy regimens. Mice immunized with an attenuated recombinant Salmonella typhimurium expressing H. pylori urease subunits A&B have dramatically reduced bacterial loads after a single dose. The mechanism(s) of protection against this largely extra-cellular pathogen are not fully understood. The aim of this study was to identify genes that were regulated specifically in response to immunization, in order to gain a broader picture of the immune response in the immunized gastric epithelium. Gene expression in RNA isolated from the gastric mucosa of immunized and infected Balb/c mice was compared with that in infected only mice at 1, 3, and 14 days after challenge with a mouse-adapted strain of H. pylori. We show that infection with H. pylori causes an immediate reaction in vivo, which was clearly divided into acute and chronic phases, and further that the transcriptional response in the H. pylori infected and immunized gastric mucosa is unique. Analysis of gene expression patterns at day 14 post-infection suggested not only the beginning of a lymphocytic infiltrate, but of an integrated epithelial response characterized by increased expression of genes controlling cell cycle and turnover. This observation was confirmed in independent experiments. The global approach has brought new insights to the effect of immunization on the gastric epithelium and has led us to propose a new multi-factorial model for the mechanisms underlying vaccine-induced protection.

Animals↗
PubMed2004

Enzymatic modification of low-density lipoprotein in the arterial wall: a new role for plasmin and matrix metalloproteinases in atherogenesis.

OBJECTIVE: Functionally interactive proteases of the plasminogen/plasmin and the matrix metalloproteinase (MMP) system degrade and reorganize the extracellular matrix of the vessel wall in atherosclerosis. Here we investigated whether such proteases are able to confer atherogenic properties onto low density lipoprotein by nonoxidative modification. METHODS AND RESULTS: Similar to the recently described enzymatically-modified low-density lipoprotein (E-LDL), native LDL exposed to plasmin or matrix MMP-2 or MMP-9 and cholesterylester-hydrolase (CEH) showed extensive deesterification, with ratios of free cholesterol to total cholesterol rising to 0.8 compared with 0.2 in native LDL. When the ratio exceeded 0.6, both plasmin/CEH-LDL and MMP/CEH-LDL fused into larger particles. In parallel, they gained C-reactive protein-dependent complement-activating capacity. E-LDL produced with any protease/CEH combination was efficiently taken up by human macrophages, whereby marked induction of MMP-2 expression by E-LDL was observed. These in vitro findings had their in vivo correlates: urokinase-type plasminogen activator, MMP-2, and MMP-9 were detectable in both early and advanced human atherosclerotic lesions in colocalization with E-LDL. CONCLUSIONS: Plasmin and MMP-2/MMP-9 may not only be involved in remodeling of the extracellular matrix in progressing plaques, but they may also be involved in lipoprotein modification during genesis and progression of atherosclerotic lesions.

Adolescent↗
PubMed2004

Altered thalamic membrane phospholipids in schizophrenia: a postmortem study.

BACKGROUND: Membrane lipids are important mediators of neuronal function. In a postmortem study, we measured membrane lipid components in the left thalamus of schizophrenic patients. This region might play an important role in the pathophysiology of schizophrenia and has not been studied thus far with respect to its membrane lipid composition. METHODS: The study included 18 chronic schizophrenic patients and 23 healthy control subjects. Using lipid extraction and thin-layer chromatography, we measured membrane phospholipids, galactocerebrosides 1 and 2, and sulfatides in thalamus homogenate. RESULTS: The main membrane phospholipid phosphatidylcholine and the major myelin membrane components sphingomyelin and galactocerebrosides 1 and 2 were found to be decreased in schizophrenic patients. In contrast, phosphatidylserine was increased. These lipid contents did not correlate with postmortem intervals and medication doses. There was no difference in the membrane phospholipids lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylglycerol or in sulfatides. CONCLUSIONS: Our results confirm findings of magnetic resonance imaging, postmortem, and gene expression studies. They support the notion of an increased phospholipid breakdown in schizophrenia as a sign for decreased myelination and oligodendrocyte dysfunction.

Aged↗
PubMed2004

In vitro antibacterial activity of fluoroquinolones against Porphyromonas gingivalis strains.

OBJECTIVES: The objective of the study was to evaluate the in vitro activity of ciprofloxacin, gatifloxacin and moxifloxacin against 16 Porphyromonas gingivalis strains. METHODS: MICs of the quinolones were established by Etest and the agar dilution technique. Experiments focused on determination of the spontaneous mutation rate and the induction of resistant strains, using 0.25-fold MIC of antibiotic. Fragments of gyrA and gyrB as well as of parC were sequenced. RESULTS: Moxifloxacin and gatifloxacin had very low MIC values. Subinhibitory concentrations of the fluoroquinolones rapidly induced mutations. The spontaneous mutation rate was strain- and quinolone-dependent; the lowest rate was encountered after moxifloxacin. The predicted serum concentrations of the quinolones were bactericidal to wild-type strains, but 100 mg/L of each tested quinolone was insufficient to kill a mutant exhibiting moderate resistance. Often the mutants exhibited high resistance to >/=32 mg/L. All these mutants bore a Ser-83-->Phe substitution in GyrA. CONCLUSIONS: DNA gyrase is the primary target of fluoroquinolones in P. gingivalis. In terms of the achievable level in the gingival fluid and the MICs, moxifloxacin might prevent the development of resistance and may be an alternative in the antibiotic treatment of P. gingivalis-associated periodontitis.

Anti-Bacterial Agents↗
PubMed2004

Differential effects of long-term treatment with clozapine or haloperidol on GABAA receptor binding and GAD67 expression.

One of the most consistent findings in postmortem studies of schizophrenia is increased GABAA receptor binding and reduced glutamic acid decarboxylase (GAD67) expression. Due to long-term antipsychotic treatment before death, these findings may reflect not only the consequences of schizophrenia but also medication effects. To differentiate between these options, we used an animal model and evaluated long-term effects of typical (haloperidol) and atypical (clozapine) antipsychotic drugs on the GABAergic system. A total of 33 adult male rats were treated in three cohorts over a period of 6 months. One cohort of 11 animals received clozapine (45 mg/kg/day), another one received haloperidol (1.5 mg/kg/day) and a third one received pH-adapted minimal concentrations of HCl in the drinking water. Receptor autoradiography of the GABAA receptor ([3H]-muscimol binding) and in situ hybridization in adjacent sections with 35S-labeled cRNA probes of the y-aminobutyric acid (GABA)-producing enzyme, GAD67, was performed. While haloperidol increased GABAA receptor binding in striatum and nucleus accumbens (NA), it suppressed GABAA receptor binding in temporal (TEMPC) and parietal (PARC) cortex. Clozapine induced GABAA receptor binding in infralimbic cortex (ILC) and similar like haloperidol in anterior cingulate cortex (ACC), two regions of the limbic cortex. In addition, either drug increased gene expression of GAD67. It is concluded that antipsychotic drugs differentially alter the GABAergic system, strongly suggesting that drug effects are partially responsible for the up-regulation of GABAA receptor binding in certain brain regions as observed in postmortem brains of schizophrenic patients. However, the reduced GAD67 expression seen in postmortem brains does not appear to reflect drug effects, since our animal model demonstrated increased gene expression.

Animals↗
PubMed2004

Pedophilia: neuropsychological evidence encouraging a brain network perspective.

Although the vast majority of current pathogenetic theories support a neurobiological understanding of psychiatric disorders, the brain functional correlates of pedophilia are largely unknown. Based on prior behavior genetics research on human sexual orientation and phenomenology as well as the phenotypical intersection of pedophilia with other psychiatric spectrum disorders, we hypothesize the involvement of striato-thalamo-cortical processing loops in the formation of pedophilic urges and behaviors. Data from a current neuropsychological pilot study in four pedophiles encourage our brain functional perspective. As deduced from the network model, all four patients exhibited pronounced and circumscribed deficits in cognitive domains mediated by striato-thalamically controlled areas of the frontal cortex. All patients were especially impaired in neuropsychological functions associated with the prefrontal and motor processing loops (e.g., response inhibition, working memory and cognitive flexibility), with a performance level located up to five standard deviations below the normative data. Contrary to this, neuropsychological performances in cognitive domains without a comparable high frontal loading were in all participants unobtrusive. In future, studying gene by environment interactions in combination with functional neuroimaging and neuropsychological assessment is promising to elucidate the pathophysiological relationship of psychiatric disorders that are characterized by inadequate urges and poor behavioral inhibition.

Adult↗
PubMed2004

Ethanol induces expression of the glutamate transporters EAAT1 and EAAT2 in organotypic cortical slice cultures.

BACKGROUND: Exposure of the developing brain to ethanol disposes the fetus to fetal alcohol syndrome and causes a number of changes in several neurochemical systems. In particular, the glutamatergic system is affected by ethanol. Thus, increased sensitivity of glutamate receptors and enhanced transmembrane transport of glutamate were found in primary astrocyte cultures. However, in these in vitro studies, changes in the expression of glutamate transporters were not detected. To further characterize the influence of chronic ethanol exposure on the developing brain, we assessed the transcriptional and translational regulation of glutamate transporters in a less artificial in vitro system. METHODS: We exposed postnatal rat cortical organotypic slice cultures to ethanol (100 mM) for 4 and 8 days. Expression of the excitatory amino acid transporters EAAT1 and EAAT2 was analyzed in comparison to untreated controls with semiquantitative reverse transcriptase-polymerase chain reaction. In addition, changes in protein expression were detected by Western blotting. RESULTS: In ethanol-exposed cortical slices, we observed more prominent fiber outgrowth and significantly increased gene expression (EAAT1: +35%, p = 0.029; EAAT2: +251%, p = 0.015). These findings could be verified on the protein level, because Western blot analysis revealed significantly higher levels of EAAT1 (+76%; p = 0.008) and EAAT2 (+104%; p = 0.018) in ethanol-treated slices compared with controls. CONCLUSIONS: Our results are in concert with earlier studies describing the induction of glutamate transport by ethanol. Enhanced expression of EAAT1 and EAAT2 after ethanol exposure can be viewed as a maladaptive process that disposes the developing brain to fetal alcohol syndrome.

Amino Acid Transport System X-AG↗
PubMed2003

Decreased gene expression of glial and neuronal glutamate transporters after chronic antipsychotic treatment in rat brain.

Post-mortem studies in schizophrenic patients revealed alterations in glutamate transporter gene expression. The question concerning a possible influence of chronic antipsychotic treatment on these gene expressions, however, remained open. In this study, 11 rats per group were treated with either haloperidol (1.5 mg/kg per day) or clozapine (45 mg/kg per day) over a period of 6 months in doses comparable to clinic application. Gene expression of glial glutamate transporter EAAT2 and the predominantly neuronal glutamate transporter EAAT3 were examined by in situ hybridization. Clozapine significantly downregulated EAAT2 in hippocampal CA1 and parietal cortex and EAAT3 in the cingulate cortex compared to the expression upon haloperidol treatment and controls. Additionally, clozapine decreased EAAT2 in temporal, cingulate and frontal cortex and downregulated EAAT3 in cingulate and infralimbic cortex, striatum and hippocampal CA1 and CA2 compared to controls. Haloperidol downregulated EAAT2 in cingulate and frontal cortex and reduced EAAT3 in nucleus accumbens, infralimbic cortex and hippocampal CA2. We hypothesize that glutamate transporter downregulation by neuroleptics increases glutamatergic action at the postsynaptic neuron and thereby may be related to beneficial antipsychotic effects and side effects.

Amino Acid Transport System X-AG↗
PubMed2003

Effects of long-term antipsychotic treatment on NMDA receptor binding and gene expression of subunits.

Postmortem studies in schizophrenic patients revealed alterations in NMDA receptor binding and gene expression of specific subunits. Because most of the patients had been treated with antipsychotics over long periods, medication effects might have influenced those findings. We treated animals with haloperidol and clozapine in clinical doses to investigate the effects of long-term antipsychotic treatment on NMDA receptor binding and gene expression of subunits. Rats were treated with either haloperidol (1.5 mg/kg/day) or clozapine (45 mg/kg/day) given in drinking water over a period of 6 months. Quantitative receptor autoradiography with [3H]-MK-801 was used to examine NMDA receptor binding. In situ hybridization was performed for additional gene expression studies of the NR1, NR2A, NR2B, NR2C, and NR2D subunits. [3H]-MK-801 binding was found to be increased after haloperidol treatment in the striatum and nucleus accumbens. Clozapine was shown to up-regulate NMDA receptor binding only in the nucleus accumbens. There were no alterations in gene expression of NMDA subunits in any of the three regions. However, the NR2A subunit was down-regulated in the hippocampus and prefrontal cortex by both drugs, whereas only clozapine induced a down-regulation of NR1 in the dorsolateral prefrontal cortex. NR2B, 2C, and 2D subunits did not differ between treatment groups and controls. Both altered NMDA receptor binding and subunit expression strengthen a hyperglutamatergic function after haloperidol treatment and may contribute to some of our postmortem findings in antipsychotically treated schizophrenic patients. Because the effects seen in different brain areas clearly vary between haloperidol and clozapine, they may also be responsible for some of the differences in efficacy and side effects.

Animals↗
PubMed2003

Effect of in vitro hemodilution with hydroxyethyl starch and dextran on the activity of plasma clotting factors.

OBJECTIVE: A recent thrombelastography study indicated a compromised in vitro blood coagulation after 10:10 (equal parts of blood and infusion) and 10:4 (10 parts blood to four parts infusion) hemodilution with several plasma substitutes. Oncovertin N (Oncovertin) (a 10% dextran 40 solution) had the strongest anticoagulant effect of all solutions tested, and HAES-sterile 10% (HAES) (a 10% hydroxyethyl starch 200/0.5 solution) showed the strongest effect of five different hydroxyethyl starch preparations. The aim of this study was to determine how in vitro hemodilution with HAES and Oncovertin affects the activity of coagulation factors. DESIGN: HAES and Oncovertin were tested to determine the intrinsic effect of colloid molecules, as opposed to hemodilution. Normal saline (NaCl) and nonlactated Ringer solution were used as noncolloidal controls. SETTING: University research institute. PATIENTS: Six healthy volunteers. INTERVENTIONS: Twenty milliliters of blood was obtained from each subject. MEASUREMENTS AND MAIN RESULTS: Prothrombin index, activated partial prothrombin time, soluble fibrin monomers, and the activity of coagulation factors I, II, V, VII, VIII, IX, X, XI, and XII were measured with the Behring Chromotimer according to the manufacturer's instructions. Two dilution ratios of citrated blood to infusion were used: 10:10 (equal parts of blood and infusion) and 10:4 (10 parts blood to four parts infusion). Baseline was undiluted. Hemodilution with NaCl at both 10:4 and 10:10 influenced the coagulation variables measured. The activities of factors I, VII, and soluble fibrin monomers were less influenced than expected by hemodilution alone. The activities of factors II, V, IX, and XI were significantly (p <.04) lower with both 10:4 and 10:10 dilution with NaCl. In the assays for factors IX, XI, and XII, clots formed immediately after adding the appropriate reagents in the presence of Ringer solution at 10:10 hemodilution, so that the activities of those factors could not be measured. For the other factors and for 10:4 dilution, the outcome after Ringer solution was similar to that of NaCl. The activities were less influenced after 10:4 hemodilution with both HAES and Oncovertin than after dilution with NaCl and Ringer solution, with no significant differences from baseline. At 10:10 hemodilution with both HAES and Oncovertin, several factor activities were significantly (p <.04) lower than baseline. CONCLUSIONS: Both NaCl and Ringer solution cause measurable effects on coagulation factors at 10:4 hemodilution that can be explained by hemodilution alone. The effects on clotting factors of 10:4 hemodilution with HAES and Oncovertin were not significant. Even at 10:10 hemodilution with HAES or Oncovertin, the reduction in factor activities, although significantly (p <.04) different from baseline, was less than what was expected by dilution alone.

Blood Coagulation Factors↗