Publications by authors named "Yvonne H Datta"

19 Publications

  • Page 1 of 1

A microfluidic platform for simultaneous quantification of oxygen-dependent viscosity and shear thinning in sickle cell blood.

APL Bioeng 2019 Dec 15;3(4):046102. Epub 2019 Nov 15.

Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA.

The pathology of sickle cell disease begins with the polymerization of intracellular hemoglobin under low oxygen tension, which leads to increased blood effective viscosity and vaso-occlusion. However, it has remained unclear how single-cell changes propagate up to the scale of bulk blood effective viscosity. Here, we use a custom microfluidic system to investigate how the increase in the stiffness of individual cells leads to an increase in the shear stress required for the same fluid strain in a suspension of softer cells. We characterize both the shear-rate dependence and the oxygen-tension dependence of the effective viscosity of sickle cell blood, and we assess the effect of the addition of increasing fractions of normal cells whose material properties are independent of oxygen tension, a scenario relevant to the treatment of sickle patients with blood transfusion. For untransfused sickle cell blood, we find an overall increase in effective viscosity at all oxygen tensions and shear rates along with an attenuation in the degree of shear-thinning achieved at the lowest oxygen tensions. We also find that in some cases, even a small fraction of transfused blood cells restores the shape of the shear-thinning relationship, though not the overall baseline effective viscosity. These results suggest that untransfused sickle cell blood will show the most extreme relative rheologic impairment in regions of high shear and that introducing even small fractions of normal blood cells may help retain some shear-thinning capability though without addressing a baseline relative increase in effective viscosity independent of shear.
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http://dx.doi.org/10.1063/1.5118212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881198PMC
December 2019

Serum magnesium level and hematoma expansion in patients with intracerebral hemorrhage.

J Neurol Sci 2019 Mar 16;398:39-44. Epub 2019 Jan 16.

Department of Neurology, University of Minnesota, Minneapolis, MN, United States; Department of Neurosurgery, University of Minnesota, Minneapolis, MN, United States. Electronic address:

Spontaneous intracerebral hemorrhage (ICH) is a devastating subtype of stroke that results in significant rates of mortality and morbidities. The initial hematoma volume, hematoma expansion (HE), blood pressure (BP), and coagulopathy are considered strong predictors of clinical outcomes and mortality. Low serum magnesium (Mg) levels have been shown to be associated with larger initial hematoma and greater HE. Coagulopathy, platelet dysfunction, high BP, and increased inflammatory response might form the mechanistic link between low serum Mg levels, larger hematoma size and greater HE. However, randomized clinical trials administering intravenous Mg have shown no benefit over placebo in ICH patients. The confounding effect of hypocalcemia and a delay in Mg trafficking across the blood-brain barrier might explain the futile results for intravenous Mg therapy. In the current review, we will discuss the evidence regarding the possible role of low serum Mg level on HE in acute ICH.
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http://dx.doi.org/10.1016/j.jns.2019.01.027DOI Listing
March 2019

Oral anticoagulation therapy and subsequent risk of venous thromboembolism in atrial fibrillation patients.

Curr Med Res Opin 2019 05 3;35(5):837-845. Epub 2018 Dec 3.

e Department of Epidemiology , Rollins School of Public Health, Emory University , Atlanta , GA , USA.

Objective: Oral anticoagulation (OAC) prescribed to AF patients for the prevention of cardioembolic complications likely has the added benefit of preventing venous thromboembolism (VTE). This study evaluated, among AF patients who are anticoagulated, whether type of OAC was associated with subsequent VTE risk.

Methods: Non-valvular AF patients prescribed OACs between 2010 and September 2015 were identified via the MarketScan administrative claims databases. OACs included warfarin and direct OACs (DOACs: dabigatran, rivaroxaban, and apixaban). Incident VTE was defined by ICD-9-CM codes. Patients were matched on age, sex, CHADS-VASc, and high-dimensional propensity scores. The final analysis included 117,912 AF patients.

Results: In total, 1357 VTE events accrued over a mean follow-up of 484 days. In multivariable-adjusted, propensity score-matched Cox models, relative to new users of warfarin, risk of incident VTE was lower among new users of dabigatran [hazard ratio (95% confidence interval) = 0.55 (0.47-0.66)] and apixaban [0.51 (0.39-0.68)], but similar among new users of rivaroxaban [1.01 (0.87-1.19)]. In head-to-head DOAC comparisons, VTE risk was lower among users of dabigatran [0.48 (0.36-0.64)] and apixaban [0.61 (0.47-0.78)] vs rivaroxaban. Findings were mostly similar across patient sub-groups.

Conclusions: In this large practice-based population of AF patients prescribed OACs for primary prevention of stroke and systemic embolization, subsequent risk of VTE was lowest among those prescribed apixaban and dabigatran, while risk was similar with prescriptions for warfarin and rivaroxaban. Among AF patients prescribed OACs, lowering the risk of VTE may be an additional benefit of apixaban and dabigatran, beyond the reduced bleeding risk observed in randomized clinical trials.
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http://dx.doi.org/10.1080/03007995.2018.1541445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449182PMC
May 2019

The Role of Serum Calcium Level in Intracerebral Hemorrhage Hematoma Expansion: Is There Any?

Neurocrit Care 2019 08;31(1):188-195

Department of Neurology, University of Minnesota, MMC 295, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA.

Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke, with a high rate of mortality and morbidity. Even with the best current medical or surgical interventions, outcomes remain poor. The location and initial hematoma volume are strong predictors of mortality. Hematoma expansion (HE) is a further marker of poor prognosis that may be at least partly preventable. Several risk factors for HE have been identified, including baseline ICH volume, anticoagulation, and computed tomography angiography spot signs. Recent studies have shown the correlation of serum calcium (Ca) levels on admission with HE. Low serum Ca level has been associated with larger hematoma volume at the time of presentation, HE, and worse outcome. Although the causal and mechanistic links between low serum Ca level and HE are not well understood, several mechanisms have been proposed including coagulopathy, platelet dysfunction, and higher blood pressure (BP) in the context of low serum Ca level. However, low serum Ca level might be only a biomarker of the adaptive response due to acute inflammatory response following acute ICH. The purpose of the current review is to discuss the evidence regarding the possible role of low serum Ca level on HE in acute ICH.
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http://dx.doi.org/10.1007/s12028-018-0564-2DOI Listing
August 2019

Comparative effectiveness of direct oral anticoagulants and warfarin in patients with cancer and atrial fibrillation.

Blood Adv 2018 02;2(3):200-209

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA.

Randomized clinical trials comparing direct oral anticoagulants (DOACs) to warfarin in cancer patients have not been performed. We evaluated the effectiveness and associated risk of DOACs vs warfarin, as well as comparisons of DOACs, in a large population of cancer patients with nonvalvular atrial fibrillation (AF). Using the MarketScan databases, we identified 16 096 AF patients (mean age, 74 years) initiating oral anticoagulant and being actively treated for cancer between 2010 and 2014. Anticoagulant users were matched by age, sex, enrollment date, and drug initiation date. Study end points were identified with diagnostic codes and included ischemic stroke, severe bleeding, other bleeding, and venous thromboembolism (VTE). Cox regression was used to estimate associations of anticoagulants with study end points. Compared with warfarin, rates of bleeding (hazard ratio [95% confidence interval]) were similar in rivaroxaban (1.09 [0.79, 1.39]) and dabigatran (0.96 [0.72, 1.27]) users, whereas apixaban users experienced lower rates (0.37 [0.17, 0.79]). Rates of ischemic stroke did not differ among anticoagulant users. Compared with warfarin, rate of VTE (hazard ratio [95% confidence interval]) was lower among rivaroxaban (0.51 [0.41, 0.63]), dabigatran (0.28 [0.21, 0.38]), and apixaban (0.14 [0.07, 0.32]) users. In head-to-head comparisons among DOACs, dabigatran users had lower rates of VTE than rivaroxaban users; apixaban users had lower rates of VTE and severe bleeding than rivaroxaban users. In this population of patients with AF and cancer, DOAC users experienced lower or similar rates of bleeding and stroke compared with warfarin users, and a lower rate of incident VTE.
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http://dx.doi.org/10.1182/bloodadvances.2017010694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812321PMC
February 2018

Increased theta band EEG power in sickle cell disease patients.

J Pain Res 2018 27;11:67-76. Epub 2017 Dec 27.

Department of Biomedical Engineering.

Objective: Pain is a major issue in the care of patients with sickle cell disease (SCD). The mechanisms behind pain and the best way to treat it are not well understood. We studied how electroencephalography (EEG) is altered in SCD patients.

Methods: We recruited 20 SCD patients and compared their resting state EEG to that of 14 healthy controls. EEG power was found across frequency bands using Welch's method. Electrophysiological source imaging was assessed for each frequency band using the eLORETA algorithm.

Results: SCD patients had increased theta power and decreased beta2 power compared to controls. Source localization revealed that areas of greater theta band activity were in areas related to pain processing. Imaging parameters were significantly correlated to emergency department visits, which indicate disease severity and chronic pain intensity.

Conclusion: The present results support the pain mechanism referred to as thalamocortical dysrhythmia. This mechanism causes increased theta power in patients.

Significance: Our findings show that EEG can be used to quantitatively evaluate differences between controls and SCD patients. Our results show the potential of EEG to differentiate between different levels of pain in an unbiased setting, where specific frequency bands could be used as biomarkers for chronic pain.
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http://dx.doi.org/10.2147/JPR.S145581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749555PMC
December 2017

Direct oral anticoagulant use and the incidence of bleeding in the very elderly with atrial fibrillation.

J Thromb Thrombolysis 2016 Nov;42(4):573-8

Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, 420 Delaware St SE, MMC 480, Minneapolis, MN, 55455, USA.

Atrial fibrillation (AF) is a major risk factor for stroke in the elderly population. The use of anticoagulation in patients with AF greatly reduces the risk for stroke, but results in an increased risk of bleeding. Over the past several years, direct oral anticoagulants (DOACs, dabigatran, rivaroxaban, and apixaban) have been used in place of warfarin for stroke prevention in AF. We conducted a retrospective cohort study to assess the safety of DOACs in very elderly patients (75+) managed in a health care system encompassing both community and academic settings. We found that 36 % of patients had moderate to severe renal failure (estimated glomerular filtration rate <59 ml/min/1.73 m(2)) at the time of DOAC initiation. 142 patients were followed for a mean of 2.56 years, and five experienced a major bleeding episode while on anticoagulation, for a rate of 1.37 per 100 person years. All major bleeding episodes were associated with a decline in GFR compared to baseline. There were 12 non-major bleeding episodes reported. HAS-BLED scores were similar for those patients who experienced bleeding complications compared to those who did not. 21 % of patients were prescribed an inappropriately low dose of DOAC based on approved recommendations. DOACs appear to be a safe form of anticoagulation in very elderly patients with AF. However, the decline in GFR among patients with major bleeding highlights the importance of routine renal function monitoring.
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http://dx.doi.org/10.1007/s11239-016-1410-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042846PMC
November 2016

Antiplatelet and Anticoagulant Therapies for Prevention of Ischemic Stroke.

Clin Appl Thromb Hemost 2017 May 26;23(4):301-318. Epub 2016 Jul 26.

1 Department of Neurology, University of Minnesota, Minneapolis, MN, USA.

Ischemic stroke represents one of the leading causes of death and disability in both the United States and abroad, particularly for patients with prior ischemic stroke or transient ischemic attack (TIA). A quintessential aspect of secondary stroke prevention is the use of different pharmacological agents, mainly antiplatelets and anticoagulants. Antiplatelets and anticoagulants exhibit their effect by blocking the activation pathways of platelets and the coagulation cascade, respectively. Clinical trials have demonstrated the safety and efficacy of antiplatelets for noncardioembolic stroke prevention, while anticoagulants are more often used for cardioembolic stroke prevention. Commonly used antiplatelets include aspirin, clopidogrel, and aggrenox (aspirin plus extended-release dipyridamole). Furthermore, commonly used anticoagulants include warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban. Each of these drugs has a unique mechanism of action, and they share some common adverse events such as gastrointestinal bleeding and intracranial hemorrhage in more serious cases. Consequently, physicians should carefully assess the benefits and risks of using different antiplatelet or anticoagulant therapies when managing patients with previous ischemic stroke or TIA. This review discuses the published literature on major clinical trials assessing the efficacy of different antiplatelet and anticoagulant drugs under varying circumstances and the subsequent guidelines that have been developed by the American Heart Association/American Stroke Association. Additionally, the role of imaging in stroke prevention is discussed.
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http://dx.doi.org/10.1177/1076029616660762DOI Listing
May 2017

Effect of oral and vaginal hormonal contraceptives on inflammatory blood biomarkers.

Mediators Inflamm 2015 16;2015:379501. Epub 2015 Mar 16.

Blood and Marrow Transplantation Division, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.

The use of combined hormonal contraceptives has been reported to increase the level of C-reactive protein (CRP). We assessed the effect of hormonal contraceptive use on inflammatory cytokines including CRP, monocyte chemotactic protein-1, soluble tumor necrosis factor (sTNF), interleukin-6 (IL-6), and soluble CD40 ligand. We used 79 female subjects (19 to 30 years old) who were combined oral contraceptives users (n = 29), combined vaginal contraceptive users (n = 20), and nonusers (n = 30) with CRP values of ≤1 (n = 46) or ≥3 (n = 33). Information on medical history, physical activities, and dietary and sleeping habits were collected. Both oral and vaginal contraceptive users had higher levels of CRP (P < 0.0001), compared to nonusers. Only oral contraceptive users exhibited elevated sCD40L (P < 0.01). When comparing the groups with CRP ≤ 1 and CRP ≥ 3, levels of IL-6 and sTNF-RI were positively correlated with CRP among oral contraceptive users. We did not observe the same elevation for other inflammatory biomarkers for the CRP ≥ 3 group among vaginal contraceptive users. The clear cause of elevation in CRP level due to the use of different hormonal contraceptive formulations and methods is not well understood. Longitudinal studies with larger sample size are required to better assess the true cause of CRP elevation among hormonal contraceptive users.
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http://dx.doi.org/10.1155/2015/379501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378601PMC
April 2016

Risk of bleeding during long-term anticoagulation with warfarin: a tertiary care center experience.

Blood Coagul Fibrinolysis 2015 Jan;26(1):110-2

Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.

The risk of recurrent venous thromboembolism (VTE) must be weighed against the risk of bleeding in deciding to keep patients on extended anticoagulation with vitamin K antagonists (VKAs). Most of the studies of risk of bleeding on VKAs are randomized controlled trials of highly selected patients followed for less than 1 year. We sought to determine the rate of bleeding in 'real world' patients on long-term anticoagulation with VKAs for VTE. We conducted a retrospective cohort study of patients monitored at our anticoagulation clinic who were treated with prolonged anticoagulation (>1 year) for secondary VTE prevention to assess the incidence of significant bleeding in this population. We found that most of our patients had serious comorbidities, including diabetes, cancer and solid-organ transplantation. The overall rate of bleeding was 10 episodes per 100 person-years, with major bleeding 5.2 episodes per 100 person-years. The rate of significant bleeding while on long-term warfarin may be higher than what is anticipated based on outcomes from closely controlled trials.
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http://dx.doi.org/10.1097/MBC.0000000000000186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452012PMC
January 2015

Monitoring anticoagulation in patients with an unreliable prothrombin time/international normalized ratio: factor II versus chromogenic factor X testing.

Blood Coagul Fibrinolysis 2014 Apr;25(3):232-6

aDivision of Hematology, Oncology, and Transplantation, University of Minnesota bDepartment of Laboratory Medicine and Pathology, University of Minnesota cCTSI Biostatstics, University of Minnesota, Minneapolis, Minnesota, USA.

The international normalized ratio (INR) can be unreliable in patients with lupus anticoagulants (LACs) or other conditions affecting baseline testing. Alternative methods to assess anticoagulation on warfarin through measures of vitamin K-dependent factor activity by clot based or chromogenic assays may be necessary. In this patient population, the ideal method is unknown. Thirty-six patients stable on warfarin with LAC or unreliable INR testing had an INR, a prothrombin time-based clotting assay for factor II (FII) activity, and a chromogenic assay for factor X (CFX) activity were performed simultaneously. Eighty-nine sets of measurements were obtained of which 83 sets included all three assays. CFX and FII levels were well correlated (r = 0.92) in all patients and in 26 patients with a documented antiphospholipid antibody (r = 0.93). Parallel testing was seen in 99% of FII assays. Sixty-one percent of CFX and 57% of FII were within the therapeutic range. In 32 CFX and FII pairs wherein assessment of anticoagulation was discordant, 16 CFX agreed with INR and 13 FII agreed with INR (McNemar's, χ = 0.14, P = 0.7). The number of times tests were discrepant was not statistically different between CFX and FII (P = 0.36). CFX and FII activity are well correlated in patients that require alternative monitoring of warfarin. Either test can be used in this population.
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http://dx.doi.org/10.1097/MBC.0000000000000030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350672PMC
April 2014

Intracerebral hemorrhage: a review of coagulation function.

Clin Appl Thromb Hemost 2013 Nov-Dec;19(6):652-62. Epub 2012 Aug 16.

1Department of Neurology, University of Minnesota, Minneapolis, MN, USA.

Intracerebral hemorrhage (ICH) is associated with a higher mortality rate among stroke subtypes. The amount of hematoma at baseline and subsequent expansion are considered strong independent markers for determining poor clinical outcome. Even though reduction in blood pressure to prevent and control the amount of bleeding in ICH has received considerable amount of attention, the impact of coagulopathy and platelet dysfunction, on the bleeding diathesis has not been extensively investigated. With the increasing use of antiplatelets and/or anticoagulants, given the aging population, a deeper understanding of the interactions between ICH and hemostatic mechanisms is essential to help minimize the risk of a catastrophic coagulopathy-related ICH. In this review article, etiology and risk factors associated with coagulopathy-related ICH are discussed. An overview of coagulation abnormalities, hemostatic agents, and blood biomarkers pertaining to ICH is included.
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http://dx.doi.org/10.1177/1076029612454938DOI Listing
August 2014

Oral versus vaginal combined hormonal contraceptives' effect on coagulation and inflammatory biomarkers among young adult women.

Clin Appl Thromb Hemost 2012 Sep 19;18(5):487-94. Epub 2012 Mar 19.

Department of Neurology, University of Minnesota, 420 Delaware Street S.E., MMC 295, Minneapolis, MN 55455, USA.

In order to compare the effect of combined oral contraceptive (COC) and combined vaginal contraceptive (CVC) methods on the inflammation and procoagulation, we recruited female participants in 3 groups: control participants, COC users, and CVC users. We measured different blood biomarkers. The users of both COC and CVC had higher levels of C-reactive protein (P < .0001) and factor VII (P < .0001). However, CD40 ligand was only higher for COC users (P < .0001) and not the CVC users. Even though the levels of thrombin/antithrombin III were not higher for COC and CVC users, as compared to the controls, CVC users had higher levels as compared to COC users (P = .0327). As compared to the control group, we observed higher levels von Willebrand factor among CVC users but not the COC users. Longitudinal studies with larger sample size are needed to better assess the inflammatory and procoagulation response due to CVC use.
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http://dx.doi.org/10.1177/1076029612440036DOI Listing
September 2012

Evaluation of the coagulation profile among oral and vaginal combined hormonal contraceptive users using sonoclot coagulation analyzer.

Clin Appl Thromb Hemost 2012 Nov 23;18(6):576-81. Epub 2012 Jan 23.

Department of Neurology, University of Minnesota, Minneapolis, MN, USA.

Combined hormonal contraceptives possess an inherent risk of thrombus-related events. The purpose of this study is to elucidate alterations in the coagulation profile among young women using combined oral contraceptive (COC) or combined vaginal contraceptive (CVC) compared to a normal, healthy, female control group using the Sonoclot coagulation analyzer. We enrolled 159 participants (64 control individuals, 51 COC users, and 44 CVC users). Each participant completed a survey of medical history, family medical history, and lifestyle choices. Citrated venous whole blood was collected and analyzed using the Sonoclot coagulation analyzer. After adjusting for age, race, alcohol consumption, sleeping habits, and family history of cardiovascular disease, and stroke, we observed COC and CVC users had mostly similar coagulation profiles except when compared to the control, and COC and CVC users had an elevated glass bead peak signal while COC users had a shorter peak time.
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http://dx.doi.org/10.1177/1076029611434526DOI Listing
November 2012

Post-transplant lymphoproliferative disorder presenting as multiple myeloma.

Am J Hematol 2010 Aug;85(8):635-7

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http://dx.doi.org/10.1002/ajh.21762DOI Listing
August 2010

Risk factors for heart attack, stroke, and venous thrombosis associated with hormonal contraceptive use.

Clin Appl Thromb Hemost 2011 Aug 7;17(4):323-31. Epub 2010 Jun 7.

Minnesota Stroke Initiative, Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA.

The search for a safe and effective method of contraception has been ongoing for centuries. During the last century, a variety of hormonal contraceptives, including combined hormonal oral contraceptives (COCs), have been introduced into the market. COCs have evolved through modifications of different hormonal components to minimize the risk of thrombotic events including stroke, myocardial infarction, and venous thrombosis. The evolution of COC development led to the reduction in the estrogen dose, in an attempt to lower the risk of vascular diseases. Although the risk of thrombotic events due to COC use has been substantially reduced since their inception, the quest for developing safer methods of birth control continues. It is of great interest to study coagulation effects of newer COCs, as well as progestin only, as rigorously as older COCs.
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http://dx.doi.org/10.1177/1076029610368670DOI Listing
August 2011

RF-2 gene modulates proteinuria and albuminuria independently of changes in glomerular permeability in the fawn-hooded hypertensive rat.

J Am Soc Nephrol 2005 Apr 9;16(4):852-6. Epub 2005 Mar 9.

Human and Molecular Genetics Center, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.

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http://dx.doi.org/10.1681/ASN.2005010029DOI Listing
April 2005

Rituximab-induced remission of a gastric MALT lymphoma.

Leuk Lymphoma 2004 Jun;45(6):1297-9

Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.

Gastric MALT lymphoma is usually associated with H. pylori infection, and responds to treatment with antibiotics and a proton pump inhibitor. We report a case of H. pylori negative gastric MALT lymphoma. The patient was followed conservatively for 2 years until she developed gastrointestinal bleeding with significant anemia. She was treated with rituximab 375 mg/m2 weekly for four doses, which resulted in a biopsy proven complete remission. Rituximab therapy is a reasonable, well tolerated treatment alternative for MALT lymphomas not associated with H. pylori.
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http://dx.doi.org/10.1080/1042819032000159889DOI Listing
June 2004

Genetic mapping and characterization of the bleeding disorder in the fawn-hooded hypertensive rat.

Thromb Haemost 2003 Jun;89(6):1031-42

Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Release of platelet dense granule contents occurs in response to vascular injury, playing an important role in platelet aggregation and primary hemostasis. Abnormalities of the platelet dense granules results in a bleeding disorder of variable severity termed "storage pool defect" (SPD). We have examined the fawn-hooded hypertensive (FHH) rat as a model of SPD in order to genetically map the locus (Bd) responsible for prolonged bleeding. Platelet function assays of the FHH rat confirmed the presence of a platelet dense granule SPD. However electron microscopy and lysosomal enzyme assays indicated differences between the FHH rat and other rodent models of SPD. Genetic mapping through the use of congenic FHH rats localized the Bd locus to an approximately 1 cM region on rat chromosome 1. Through the use of comparative mapping between species and analysis of the initial draft of the rat genome assembly, six known and thirty-four putative genes were identified in the Bd locus. None of these genes have been previously implicated in platelet function. Therefore positional cloning of the gene responsible for the bleeding disorder in the FHH rat will lead to new insights in platelet physiology, with implications for diagnosis and management of hemostatic and thrombotic disorders.
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June 2003