Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 28
Filter
1.
J R Army Med Corps ; 163(5): 342-346, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28385926

ABSTRACT

INTRODUCTION: Our understanding of the expertise and equipment required to air transport injured soldiers with severe traumatic brain injuries (TBIs) continue to evolve. METHODS: We conducted a retrospective chart review of characteristics, interventions required and short-term outcomes of patients with severe TBI managed by the US Air Force Critical Care Air Transport Teams (CCATTs) deployed in support of Operation Iraqi Freedom and Operation Enduring Freedom between 1 June 2007 and 31 August 2010. Patients were cared for based on guidelines given by the Brain Trauma Foundation and the Joint Theater Trauma System by non-neurosurgeon physicians with dedicated neurocritical care training. We report basic characteristics, injuries, interventions required and complications during transport. RESULTS: Intracranial haemorrhage was the most common diagnosis in this cohort. Most injuries were weapon related. During this study, there were no reported in-flight deaths. The majority of patients were mechanically ventilated. There were 45 patients who required at least one vasopressor to maintain adequate tissue perfusion, including four patients who required three or more. Some patients required intracranial pressure (ICP) management, treatment of diabetes insipidus and/or seizure prophylaxis medications. CONCLUSIONS: Air transport personnel must be prepared to provide standard critical care but also care specific to TBIs, including ICP control and management of diabetes insipidus. Although these patients and their potential complications are traditionally managed by neurosurgeons, those providers without neurosurgical backgrounds can be provided this training to help fill a wartime need. This study provides data for the future development of air transport guidelines for validating and clearing flight surgeons.


Subject(s)
Air Ambulances/statistics & numerical data , Brain Injuries, Traumatic , Critical Care/statistics & numerical data , Military Medicine/statistics & numerical data , Transportation of Patients/statistics & numerical data , Afghan Campaign 2001- , Brain Injuries, Traumatic/epidemiology , Brain Injuries, Traumatic/therapy , Female , Humans , Iraq War, 2003-2011 , Male , Retrospective Studies , Treatment Outcome
2.
Med Hypotheses ; 79(4): 544-8, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22874451

ABSTRACT

Xerostomia resulting mostly from hyposalivation and alkaline salivary pH is a frequent but often underappreciated symptom in the diseased population of maintenance hemodialysis (HD) patients. We reviewed also other xerostomia-predisposing factors, its specific dental and oral clinical signs and features, as well as plausibly detrimental dialysis-specific pro-atherosclerotic and cardiovascular consequences. In view of increasing multidisciplinary importance of xerostomia, its general, pharmacological and emerging treatment methods were presented. Special attention was paid to the untoward and often neglected pro-xerostomic effects of multiple common medications and substances; they were listed and described in more detail. The combined therapeutic approach of dentists and nephrologists may effectively alleviate xerostomia and support general health condition of maintenance hemodialysis patients.


Subject(s)
Cardiovascular Diseases/etiology , Renal Dialysis/adverse effects , Xerostomia/etiology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/mortality , Dental Caries/etiology , Humans , Morbidity , Periodontal Diseases/etiology , Risk Factors , Xerostomia/complications , Xerostomia/therapy
3.
Antimicrob Agents Chemother ; 56(10): 5149-56, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22825118

ABSTRACT

Type III phosphatidylinositol-4-kinase beta (PI4KIIIß) was previously implicated in hepatitis C virus (HCV) replication by small interfering RNA (siRNA) depletion and was therefore proposed as a novel cellular target for the treatment of hepatitis C. Medicinal chemistry efforts identified highly selective PI4KIIIß inhibitors that potently inhibited the replication of genotype 1a and 1b HCV replicons and genotype 2a virus in vitro. Replicon cells required more than 5 weeks to reach low levels of 3- to 5-fold resistance, suggesting a high resistance barrier to these cellular targets. Extensive in vitro profiling of the compounds revealed a role of PI4KIIIß in lymphocyte proliferation. Previously proposed functions of PI4KIIIß in insulin secretion and the regulation of several ion channels were not perturbed with these inhibitors. Moreover, PI4KIIIß inhibitors were not generally cytotoxic as demonstrated across hundreds of cell lines and primary cells. However, an unexpected antiproliferative effect in lymphocytes precluded their further development for the treatment of hepatitis C.


Subject(s)
1-Phosphatidylinositol 4-Kinase/antagonists & inhibitors , Antiviral Agents/pharmacology , Hepacivirus/drug effects , Animals , Antiviral Agents/adverse effects , Bone Marrow Cells/cytology , Bone Marrow Cells/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Humans , Male , Mice , Rats , Rats, Sprague-Dawley
4.
Adv Med Sci ; 54(1): 32-6, 2009.
Article in English | MEDLINE | ID: mdl-19731406

ABSTRACT

PURPOSE: Anticoagulant tissue factor pathway inhibitor (TFPI) is released from its endothelial stores by heparin, which may lead to its untoward depletion. We investigated the effects of sulodexide--a commercially available mixture of heparan and dermatan sulfate, on plasma TFPI release and depletion. MATERIAL AND METHODS: An open-label pilot trial of intravenous and/or oral sulodexide effects on plasma immunoreactive total TFPI antigen level was performed in 11 healthy men. The drug was initially administered i.v. at a single dose of 120 mg, thenorally for 12 days (50 mg b.i.d), and again by i.v route after 2 weeks. RESULTS: Sulodexide injections induced marked increases in plasma TFPI; they were more pronounced on day 14 than on study initiation (3-fold vs. 2-fold after 10 min) and still evident after 120 min. TFPI levels did not change when measured at 120 min after oral sulodexide administration. The percentage increment in plasma TFPI after 10 min from initial sulodexide injection inversely correlated with baseline TFPI levels (r = - 0.664, P = 0.026). On day 14, the association became strong (r = - 0.970, P < 0.0001) and evident also after 120 min (r = - 0.810, P < 0.002). Baseline TFPI levels decreased over the trial; on day 14 they were lower by 34% than on study initiation (P = 0.001). CONCLUSIONS: TFPI release by i.v. sulodexide and its depletion during oral administration of this heparinoid compound constitute novel and likely important hemostatic effects of the drug.


Subject(s)
Anticoagulants/pharmacology , Glycosaminoglycans/pharmacology , Lipoproteins/metabolism , Adult , Analysis of Variance , Anticoagulants/administration & dosage , Blood Coagulation Tests , Glycosaminoglycans/administration & dosage , Humans , Lipoproteins/blood , Lipoproteins/deficiency , Male , Pilot Projects , Regression Analysis , Time Factors
5.
Adv Med Sci ; 54(2): 199-202, 2009.
Article in English | MEDLINE | ID: mdl-19758969

ABSTRACT

PURPOSE: Endostatin (ES) is a potent inhibitor of angiogenesis and neoangiogenesis, and interestingly its activity is modified by heparin. To understand if low-molecular weight heparins have different clinical profiles regarding this cytokine, we studied the effects of enoxaparin, nadroparin and dalteparin administered for hemodialysis (HD) anticoagulation on plasma ES levels. MATERIAL AND METHODS: Seventeen chronic HD patients completed this prospective, crossover trial. They were randomized into 6 groups - each patient was administered enoxaparin (effective dose of 0.75 mg/kg), nadroparin (70.4 IU/kg) and dalteparin (78.6 IU/kg) in 3 time periods of 2 months each. At the end of each period plasma levels of ES were measured at the start and at 10 min and 180 min of the HD procedure. RESULTS: Mean predialysis plasma ES levels in HD patients were extremely high for all three heparins used. We observed no changes in ES levels during dialysis, there were also no differences in ES profiles for each of the low-molecular weight heparins used. CONCLUSIONS: Plasma ES levels are unusually high in chronic HD patients and the significance of this fact needs future research. ES levels do not change after heparin administration and at least in that aspect enoxaparin, nadroparin and dalteparin are equal.


Subject(s)
Angiogenesis Inhibitors/blood , Anticoagulants/therapeutic use , Endostatins/blood , Heparin, Low-Molecular-Weight/therapeutic use , Renal Dialysis , Aged , Anticoagulants/administration & dosage , Cross-Over Studies , Dalteparin/administration & dosage , Dalteparin/therapeutic use , Enoxaparin/administration & dosage , Enoxaparin/therapeutic use , Female , Heparin, Low-Molecular-Weight/administration & dosage , Humans , Male , Nadroparin/administration & dosage , Nadroparin/therapeutic use , Prospective Studies , Time Factors
6.
Mucosal Immunol ; 1(1): 59-67, 2008 Jan.
Article in English | MEDLINE | ID: mdl-19079161

ABSTRACT

The follicle-associated epithelium (FAE) of Peyer's patches (PPs) transports antigens and microorganisms into mucosal lymphoid tissues where they are captured by subepithelial dendritic cells (DCs). Feeding of cholera toxin (CT) induced migration of subepithelial DCs to interfollicular T-cell areas within 24 h. This study investigated short-term effects of CT, Escherichia coli heat-labile toxin, and non-toxic derivatives on DC migration. CT or CTB injected into ligated intestinal loops induced significant increase in CD11c+ DCs within the FAE within 90 min. In mice fed CT intragastrically, DC numbers in the FAE increased by 1 h, were maximal by 2 h, declined between 8 and 12 h, and were reversed by 24 h. Feeding of native LT, recombinant CTB, dibutyryl cyclic AMP, and to a lesser extent mutated CT(E29H) or mutated LT(R192G) had the same effect. Thus, both A and B subunits of enterotoxins, presumably acting through distinct signaling pathways, may promote capture of incoming antigens and pathogens by PP DCs.


Subject(s)
Adjuvants, Immunologic/pharmacology , Bacterial Toxins/pharmacology , Cell Movement/drug effects , Cholera Toxin/pharmacology , Dendritic Cells/immunology , Enterotoxins/pharmacology , Escherichia coli Proteins/pharmacology , Intestinal Mucosa/immunology , Peyer's Patches/immunology , Amino Acid Substitution , Animals , Bacterial Toxins/genetics , Bacterial Toxins/immunology , Biological Transport/drug effects , Biological Transport/immunology , CD11c Antigen/immunology , Cell Movement/immunology , Cholera Toxin/genetics , Cholera Toxin/immunology , Dendritic Cells/cytology , Enterotoxins/genetics , Enterotoxins/immunology , Escherichia coli/genetics , Escherichia coli/immunology , Escherichia coli Proteins/genetics , Escherichia coli Proteins/immunology , Female , Intestinal Mucosa/cytology , Mice , Mice, Inbred BALB C , Mutation, Missense , Peyer's Patches/cytology , Signal Transduction/drug effects , Signal Transduction/immunology , Time Factors
7.
Rocz Akad Med Bialymst ; 49: 151-6, 2004.
Article in English | MEDLINE | ID: mdl-15631332

ABSTRACT

Chronic renal failure is a state of prominent endothelial dysfunction, accelerated atherosclerosis, high incidence of thromboembolic complications and excess cardiovascular mortality. We reviewed up-to-date experimental and clinical data showing close and deleterious links between these entities. Emerging therapeutic interventions aimed at improvement of endothelial function and better clinical outcomes in chronic kidney disease patients were also discussed.


Subject(s)
Arteriosclerosis/etiology , Endothelium, Vascular/physiopathology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Thrombosis/etiology , Animals , Arteriosclerosis/physiopathology , Humans , Kidney Failure, Chronic/physiopathology , Thrombosis/physiopathology
8.
Clin Appl Thromb Hemost ; 7(4): 296-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11697712

ABSTRACT

The euglobulin clot lysis time (ECLT), a traditional measure of plasminogen activation, directly depends on plasma fibrinogen (FBG) level. This fact was neglected in studies concluding that prolonged ECLT in chronic hemodialysis (HD) patients pointed exclusively to impaired fibrinolysis. We studied the relations between ECLT and plasma FBG levels in HD patients in relation to certain hepatic and inflammatory markers. Median ECLT of 320 minutes (range, 150 to 620 minutes) and plasma FBG of 306 mg/dL (range, 171 to 553 mg/dL) were higher in 75 HD patients than in 60 healthy controls (Mann-Whitney p < 0.0001). There were positive associations between these parameters both in the patients (Spearman p = 0.273, p = 0.018) and the controls (p = 0.672, p < 0.0001). The FBG-corrected ECLT (plasma FBG/ECLT) (in mg/[min x dL]) in the patients (0.92 [range, 0.47 to 2.43]) was not different (p = 0.065) from that in the controls (1.08 [0.58 to 1.67]). In the patients, serum alanine aminotransferase inversely correlated with ECLT (p = -0.306, p = 0.008) and FBG (p = -0.310, p = 0.007), whereas serum C-reactive protein was associated positively with these variables (p = 0.383, p = 0.0007; p = 0.477, p < 0.0001, respectively). The FBG-corrected ECLT was not related to either marker. In conclusion, increased plasma FBG level, a continuum between liver dysfunction and stimulation by chronic inflammation, is an important determinant of prolonged ECLT in HD patients. The FBG-corrected ECLT value suggests that baseline activation of fibrinolysis is normal in these patients, and that this simple index could be useful in its laboratory assessment.


Subject(s)
Fibrinogen/analysis , Fibrinolysis/drug effects , Renal Dialysis , Serum Globulins/pharmacology , Adolescent , Adult , Aged , Alanine Transaminase/blood , Alanine Transaminase/physiology , Blood Coagulation Tests/standards , C-Reactive Protein/analysis , C-Reactive Protein/physiology , Case-Control Studies , Diagnostic Errors , Female , Fibrinogen/pharmacology , Fibrinolysis/physiology , Humans , Inflammation/blood , Liver Diseases/blood , Male , Middle Aged , Time Factors
9.
Nephron ; 89(4): 381-3, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11721153

ABSTRACT

BACKGROUND/AIMS: We aimed to determine predictors of erythrocyte sedimentation rate (ESR), and the ESR level pointing to the presence of inflammation in 60 chronic hemodialysis (HD) patients. METHODS/RESULTS: On bivariate analysis, increased Westergren ESR of 62 (4-160) mm/h correlated inversely with hematocrit (Hct) and serum albumin, and positively with age, plasma fibrinogen, serum C-reactive protein (CRP), immunoglobulins A and G, alpha(1)-acid-glycoprotein and alpha(1)-antitrypsin. On multivariable analysis, independent predictors of the ESR were raised CRP (p < 0.0001), low Hct (p < 0.0001), increased fibrinogen (p < 0.0001) and immunoglobulin A (p = 0.009), and older age (p = 0.015). The Hct-corrected ESR level [ESR x (Hct/45)] of 38 (4-91) mm/h was independently predicted by CRP (p < 0.0001), fibrinogen (p < 0.0001), and age (p = 0.001). In the patients with normal CRP and albumin, the Hct-corrected ESR value was normal (23 mm/h) and lower than that of 59 mm/h in the subjects with elevated CRP and hypoalbuminemia. Using these cut-off points, the positive and negative predictive values of the Hct-corrected ESR on the presence of inflammation were 1.0, and its sensitivity and specificity were 100%. CONCLUSION: Increased Westergren ESR in HD patients is associated with activated acute-phase response, anemia, and aging. The Hct-corrected ESR values of 23 and 59 mm/h precisely select the HD patients with severe inflammation from those without.


Subject(s)
Acute-Phase Reaction/diagnosis , Blood Sedimentation , Hematocrit , Kidney Failure, Chronic/immunology , Renal Dialysis , Adolescent , Adult , Aged , C-Reactive Protein/analysis , Female , Fibrinogen/analysis , Humans , Kidney Failure, Chronic/therapy , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Sensitivity and Specificity
11.
Nephrol Dial Transplant ; 16(7): 1442-7, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11427638

ABSTRACT

BACKGROUND: Increased plasma soluble von Willebrand factor antigen (vWF : Ag) level, a marker of vascular endothelial cell dysfunction, is a strong predictor of atherosclerotic cardiovascular disease (CVD) in the general population. We studied cross-sectional associations between vWF : Ag level, prevalence of CVD, and related factors including pre-dialysis arterial blood pressure (BP) and some markers of inflammation in maintenance haemodialysis (HD) patients. Methods and results. Plasma vWF : Ag level measured by an enzyme-linked immunosorbent assay (ELISA) was higher in 110 HD patients than in 20 controls. On bivariate regression analysis, vWF : Ag level was directly associated with the presence of CVD, age, fibrinogen and the use of enoxaparin (vs unfractionated heparin) during HD procedures, and inversely with albumin and pre-dialysis BP. The patients with prevalent CVD were older, had higher vWF : Ag, white blood cell and platelet counts, fibrinogen and triglycerides, lower albumin levels, and were less frequently on combination antihypertensive therapy. Multivariable analyses identified low pre-dialysis BP, hypoalbuminaemia and hyperfibrinogenaemia (in descending order of significance) as independent predictors of high vWF : Ag level. There were no associations between vWF : Ag levels and gender, ABO blood type, smoking, body mass index, renal failure cause, duration of HD therapy, K(t)/V, normalized protein catabolic rate, dialysate buffers, dialysers, viral hepatitis, erythropoietin treatment, specific antihypertensive drugs, haemoglobin, white blood cell and platelet counts, liver enzymes, phosphorous, total cholesterol, and triglycerides. CONCLUSION: Elevated plasma levels of endothelial dysfunction marker vWF : Ag in maintenance HD patients are associated with established cardiovascular mortality risk factors such as low pre-dialysis blood pressure and the activated acute phase response.


Subject(s)
Arteriosclerosis/epidemiology , Blood Pressure/physiology , Cardiovascular Diseases/epidemiology , Endothelium, Vascular/physiopathology , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Renal Dialysis , von Willebrand Factor/analysis , Adult , Aged , Arteriosclerosis/blood , Arteriosclerosis/diagnosis , Biomarkers/blood , Cardiovascular Diseases/blood , Cardiovascular Diseases/diagnosis , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Kidney Failure, Chronic/physiopathology , Male , Middle Aged , Reference Values , Regression Analysis
12.
Nephrol Dial Transplant ; 16(4): 787-92, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11274275

ABSTRACT

BACKGROUND: The level of soluble thrombomodulin (sTM), a traditional marker of endothelial injury, is also dependent on renal excretory function. We studied serum sTM in chronic haemodialysis (HD) patients to determine which factors are predictive of its levels in this population. METHODS AND RESULTS: sTM levels of 10.7 (5.72-30.7) ng/ml in 100 HD patients were higher than in 30 controls (P<0.0001). In a bivariate regression analysis, immunoreactive sTM was positively associated with the presence of hepatitis B virus surface antigen and/or anti-hepatitis C virus antibodies measured by third generation ELISAs (P<0.0001), and was related to certain markers of liver injury and biosynthetic dysfunction. sTM was also directly associated with time on dialysis (P=0.001), or use of unfractionated heparin (UFH) (vs enoxaparin) (P=0.0007), erythropoietin (P=0.008), ACE-inhibitors (P=0.034), acetate-buffered dialysate (vs bicarbonate) (P=0.040), pre-dialysis systolic (P=0.012), and diastolic blood pressure (P=0.043). It was negatively associated with lipoprotein(a) (P=0.029). sTM was not related to age, sex, smoking, cause of renal failure, prevalence of cardiovascular disease, amount of HD delivered, preserved residual renal function, ferritin, C-reactive protein, and other vasoactive medications used. In a multivariable analysis, a positive hepatitis marker (P=0.0002), the use of UFH (P=0.030) and erythropoietin (P=0.019), and raised pre-dialysis blood pressure (P=0.024) were positive independent predictors of high sTM level. CONCLUSION: These data indicate that, in addition to endothelial activation, elevated sTM levels in HD patients may be related to viral infection and/or liver dysfunction, and influenced by modifiable factors such as increased blood pressure, and the type of heparin and erythropoietin treatment used.


Subject(s)
Kidney Diseases/blood , Kidney Diseases/therapy , Renal Dialysis , Thrombomodulin/blood , Adult , Age Factors , Aged , Biomarkers , Blood Pressure , Cross-Sectional Studies , Female , Hepatitis, Viral, Human/blood , Hepatitis, Viral, Human/physiopathology , Humans , Male , Middle Aged , Sex Factors
13.
Haemostasis ; 30(6): 308-15, 2000.
Article in English | MEDLINE | ID: mdl-11356999

ABSTRACT

Von Willebrand factor (vWF) abnormalities are involved in the hemostatic disturbances of uremia. Studies of vWF in both anemic and recombinant erythropoietin (EPO)-treated maintenance hemodialysis (HD) patients have given inconsistent results that could be partially dependent on the methodology. Therefore, the reciprocal relationships between four different vWF assays were studied in HD patients in relation to EPO therapy. Plasma vWF activity measured by ELISA using monoclonal antibodies against platelet glycoprotein (GP) Ibalpha (vWF:Act), plasma vWF antigen concentration by ELISA employing polyclonal antihuman vWF antibodies (vWF:Ag), and functional vWF activity by ristocetin-induced platelet aggregation (RIPA) in both platelet-rich plasma (PRP) and whole blood were studied in 70 HD patients. In the whole group, no correlations between these assays were found. In the non-EPO patients (n = 32), vWF:Act was correlated with vWF:Ag (r = 0.504, p = 0.003) but not with vWF activity by RIPA in PRP. In the EPO-treated patients (n = 38), vWF:Act was higher than in the untreated ones (p = 0.001), and vWF:Ag was related to the whole-blood RIPA (r = 0.386, p = 0.016). In conclusion, the platelet GP Ibalpha-binding epitope of the vWF molecule assessed by vWF:Act ELISA is intact in HD patients. However, this assay does not reflect the functional vWF activity as measured by RIPA in PRP. In EPO-treated patients, the GP Ibalpha-binding domains of vWF are more available but the plasmatic vWF monomers are neither more numerous by vWF:Ag ELISA nor more hemostatically active by RIPA PRP. The whole blood RIPA test has some potential for the quantification of vWF monomers in EPO-treated HD patients.


Subject(s)
Clinical Chemistry Tests/standards , Renal Dialysis , Renal Insufficiency/blood , Renal Insufficiency/therapy , von Willebrand Factor/metabolism , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Epitopes , Erythropoietin/administration & dosage , Erythropoietin/pharmacology , Female , Humans , Male , Middle Aged , Platelet Aggregation/drug effects , Platelet Function Tests , Platelet Glycoprotein GPIb-IX Complex/metabolism , Recombinant Proteins , von Willebrand Factor/drug effects , von Willebrand Factor/immunology
14.
Thromb Res ; 90(4): 171-80, 1998 May 15.
Article in English | MEDLINE | ID: mdl-9692616

ABSTRACT

Correction of uremic platelet serotonin (5-HT) storage pool deficiency is one of the very early hemostatic effects of erythropoietin (Epo) therapy. In this work, platelet 5-HT with relation to primary hemostasis was studied in 15 hemodialysis patients treated with Epo for 8 months. Moreover, effects of ketanserin, a blocker of platelet and vascular smooth muscle cell 5-HT2A receptors, in these patients were followed. The parameters studied were compared with relevant values in healthy controls and in hemodialysis patients not treated with Epo, and remeasured in the long-term Epo patients after a 14-day oral ketanserin trial. Platelet 5-HT content in the eighth month of Epo therapy was not different from the one in untreated patients. Ristocetin- and collagen-induced platelet aggregation were enhanced in comparison with both control groups, as opposed to unaltered response to ADP and arachidonic acid. Fibrinogen concentration was lower than in the untreated group. An inverse correlation between ADP-induced platelet aggregation and the skin bleeding time (r=-0.536, p<0.05) and a positive one between the former and platelet 5-HT (r=0.644, p<0.01) were found. Platelet count correlated positively with both platelet 5-HT (r=0.823, p<0.0002) and ADP-induced platelet aggregation (r=0.596, p<0.02). Ketanserin produced a decrease in ristocetin-induced platelet aggregation, fibrinogen, and prolongation of the bleeding time. The first two of the changes correlated positively with their pre-ketanserin values (r=0.923, p<0.00001 and r=0.839, p< 0.0001, respectively). Post-ketanserin, positive correlations between depressed ristocetin- and arachidonic acid-induced platelet aggregation (r=0.760, p<0.005), and between collagen- and corresponding values of arachidonic acid- (r=0.622, p<0.02), ADP-induced platelet aggregation (r=0.396, p<0.01), and platelet 5-HT (r=0.654, p<0.05) were found. Efficient hemostasis in hemodialysis patients on protracted Epo therapy is, in part, dependent on enhanced platelet aggregability. Correction of platelet 5-HT storage pool deficiency is not evident in this stage but 5-HT still influences complex mechanisms of primary hemostasis. Ketanserin is of anticoagulant value in these patients but its effects must be weighted against possible exacerbation of the anemia.


Subject(s)
Blood Platelets/drug effects , Blood Platelets/physiology , Erythropoietin/pharmacology , Erythropoietin/therapeutic use , Ketanserin/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation/drug effects , Renal Dialysis , Serotonin/metabolism , Adolescent , Adult , Bleeding Time , Child , Female , Fibrinogen/analysis , Hemostasis/physiology , Humans , Ketanserin/pharmacology , Male , Platelet Aggregation Inhibitors/pharmacology , Platelet Count , Platelet Storage Pool Deficiency/therapy , Serotonin/blood , Thrombosis/therapy , Time Factors
15.
Platelets ; 9(1): 31-5, 1998.
Article in English | MEDLINE | ID: mdl-16793742

ABSTRACT

Recombinant human erythropoietin (EPO) not only ameliorates the anemia of renal failure but also modulates platelet function and corrects uremic platelet serotonin (5-hydroxytryptamine, 5-HT) storage pool deficiency. We studied if ketanserin, a blocker of platelet and vascular smooth muscle receptors for 5-HT, could reverse any EPO-induced changes in hemostasis. A complete blood count, immunoreactive serum EPO concentration, skin bleeding time (BT) and whole blood platelet aggregation (electric impedance method) induced by ristocetin and ADP, and intraplatelet and whole blood 5-HT, were determined in seven chronic hemodialysis (HD) patients before and after 1, 2, 4 and 8 weeks of EPO therapy, and repeated after a 4-week co-treatment with oral ketanserin. Stimulation of erythropoiesis was accompanied by a rise in the platelet count ( P < 0.05), shortening of the BT ( P < 0.02), an increase in platelet aggregability, and by replenished intraplatelet 5-HT store. Ketanserin co-treatment produced an unexpected 33% fall in serum EPO level ( P < 0.02), a decrease in the platelet count ( P < 0.05), prolongation of the BT ( P < 0.05) and depressed platelet aggregation in response to both agonists. There was no change in the amount of intraplatelet 5-HT while whole blood 5-HT concentration decreased significantly ( P < 0.02). Strong positive correlations between the decrease in whole blood 5-HT and the prolongation of the BT ( r = 0.786, P < 0.05), and between the former parameter and the fall in the platelet count ( r = 0.820, P < 0.05) were found. In conclusion, we report dual erythro- and thrombocytopoietic effects of EPO combined with correction of a platelet defect in the storage of 5-HT and enhanced platelet aggregability. The ketanserin-induced falls in serum EPO concentration and the platelet count provide new evidence of the dependency of thrombocytopoiesis on EPO in the initial weeks of the therapy. The 'antiplatelet' effects of ketanserin observed in this study seem to be due to reduction in circulating thrombocyte number rather than from any inhibitory effect on their aggregation.

18.
Przegl Lek ; 54(3): 167-70, 1997.
Article in Polish | MEDLINE | ID: mdl-9297192

ABSTRACT

Chronic uremia is associated with a bleeding tendency, and paradoxically with propensity for thrombotic complications. Several physiological systems are subject to circadian rhythm, including among others hemostasis, platelet aggregability and fibrinolysis. Alterations in these rhythms were suggested to be involved in the pathogenesis of sudden cardiac and cardiovascular complications of diabetes mellitus. As cardiovascular events are the most frequent cause of death in dialyzed patients, we studied circadian rhythm of platelet function in chronically hemodialyzed patients in relation to blood and plasma serotonin. We investigated 16 patients (mean age 49.7 +/- 12.2 years, 10 females, 6 males) who had been maintained on chronic hemodialysis. Control group consisted of 8 age matched healthy volunteers. Blood was collected after 15 min. rest at 8:00, 11:00, 17:30, and 23:00 from antecubital veins. Platelet aggregation was measured according to the method of Born. Following concentrations of aggregating agents were used: ADP 5 microM; collagen, 2 micrograms/ml; arachidonic acid 0.75 microM, serotonin 1 microM; and ristocetin 1.5 micrograms/ml. Serotonin was measured in whole blood and plasma by HPLC method. In PRP from healthy subjects aggregatory responses to ADP and arachidonic acid were significantly higher at 17:30 than at 8:00. In uremic patients aggregatory response to ADP and ristocetin was more intensive at 11:30 and 23:00 in comparison to 8:00. Whole blood 5-HT did not change during the day, while plasma 5-HT concentration increased significantly in uremics at 11:30 in comparison to initial value. In conclusion, our study demonstrates that in chronically dialyzed patients circadian changes in platelet aggregation are different from normal persons.


Subject(s)
Circadian Rhythm/physiology , Platelet Aggregation/physiology , Renal Dialysis , Uremia/physiopathology , Uremia/therapy , Adult , Aged , Female , Humans , Male , Middle Aged , Serotonin/blood
19.
Nephrol Dial Transplant ; 11(12): 2444-8, 1996 Dec.
Article in English | MEDLINE | ID: mdl-9017620

ABSTRACT

BACKGROUND: Amelioration of the anaemia of chronic renal failure and subsequent improved haemorheology result in correction of bleeding diathesis as evidenced by shortening of the skin bleeding time (BT). However, the relationship between the haematocrit and platelet-vessel wall interactions in haemodialysis (HD) patients under recombinant human erythropoietin (rHuEpo) therapy, assessed by platelet aggregation in response to ristocetin is more complex and somewhat inconsistent. METHODS: We investigated the relationship between haemoglobin (Hb) levels and whole blood ristocetin-induced platelet aggregation (electric impedance method) in 28 HD patients treated with rHuEpo, and with normal BT. The measurements were repeated in 16 subjects after having reduced platelet aggregability with orally administered ketanserin. RESULTS: Ristocetin-induced platelet aggregation in the whole group was comparable to those found in 21 age-matched healthy subjects (normals) and in 25 HD patients not treated with rHuEpo (uraemics). Interestingly, a significant inverse correlation between this aggregation and Hb concentration was found (r = -0.392, P < 0.05). In the group of 16 patients, the pre-ketanserin aggregation was more intensive than in the normals and uraemics (P < 0.05). Ketanserin produced a fall in ristocetin-induced platelet aggregation (P < 0.02), prolongation of the BT (P < 0.02) and, unexpectedly, a decrease in serum Epo concentration (P < 0.0002) and the Hb level (P < 0.001). Again, an inverse correlation between depressed ristocetin-induced platelet aggregation and lowered Hb concentration was found (r = -0.590, P < 0.02). Moreover, a strong positive correlation between the extent of preketanserin platelet aggregation and the decrease in the intensity of this process that followed the trial was observed (r = 0.919, P < 0.000005). There were no changes in other haematological parameters or arterial blood pressure. CONCLUSIONS: Considering the role of von Willebrand factor and fibrinogen in mediating ristocetin-induced platelet aggregation, and enhanced synthesis and/or release of these macromolecules in response to uraemia or inflammation, we suggest that exaggerated whole-blood platelet aggregability to ristocetin points to blunted erythropoiesis in HD patients on rHuEpo therapy.


Subject(s)
Erythropoietin/therapeutic use , Hemoglobins/pharmacology , Platelet Aggregation/drug effects , Renal Dialysis , Ristocetin/pharmacology , Adult , Bleeding Time , Female , Hemoglobins/analysis , Humans , Ketanserin/pharmacology , Linear Models , Male , Middle Aged , Platelet Aggregation Inhibitors/pharmacology , Platelet Count , Recombinant Proteins/therapeutic use , Ristocetin/antagonists & inhibitors , Ristocetin/blood
20.
Clin Transplant ; 10(1 Pt 1): 63-6, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8652901

ABSTRACT

We have recently shown that ketanserin, an antagonist of peripheral serotonin 5-HT2 receptors lowers blood erythropoietin (Epo) levels in some chronic hemodialysis patients. Based on this finding, a preliminary study was undertaken to investigate the effect of a 3-week oral ketanserin administration on serum Epo concentration and relevant hematological parameters in 4 renal allograft recipients with posttransplant erythrocytosis (PTE). We found a marked decrease in Epo concentrations following ketanserin administration, from 48% to 76% of the abnormally elevated pretreatment values with subsequent increases at 3 weeks after discontinuation of the drug in all patients studied. In 3 of them a corresponding decrease or no rise in the erythrocyte count were noted. During the 6-week study period, the need for monthly phlebotomies was eliminated in these patients. It is hypothesized that ketanserin diminishes erythropoietin synthesis and may become a new drug in the treatment of posttransplant erythrocytosis.


Subject(s)
Erythropoietin/blood , Ketanserin/therapeutic use , Kidney Transplantation , Polycythemia/drug therapy , Serotonin Antagonists/therapeutic use , Adult , Humans , Ketanserin/administration & dosage , Male , Middle Aged , Postoperative Complications , Serotonin Antagonists/administration & dosage , Transplantation, Homologous
SELECTION OF CITATIONS
SEARCH DETAIL
...