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Biomedical subjects

Jennifer White

Publications and source records attributed to Jennifer White.

16 recordsLinked to original sources
PubMed2005

Protection of erythrocytes from human complement-mediated lysis by membrane-targeted recombinant soluble CD59: a new approach to PNH therapy.

Paroxysmal nocturnal hemoglobinuria (PNH) results from the expansion of a hematopoietic clone that is deficient in glycosylphosphatidylinositol-anchored molecules. PNH is characterized by chronic hemolysis with acute exacerbations due to the uncontrolled activity of complement on PNH cells, which lack the inhibitor of homologous complement, CD59. Symptoms include severe fatigue, hemoglobinuria, esophageal spasm, erectile dysfunction, and thrombosis. We report the use of a novel synthetically modified recombinant human CD59, rhCD59-P, a soluble protein that attaches to cell membranes. In vitro treatment of PNH erythrocytes with rhCD59-P resulted in levels of CD59 equivalent to normal erythrocytes and effectively protected erythrocytes from complement-mediated hemolysis. The administration of rhCD59-P to CD1 mice resulted in levels of CD59 on erythrocytes, which protected them from complement-mediated lysis. Thus, rhCD59-P corrects the CD59 deficiency in vitro and can bind to erythrocytes in an in vivo murine model, protecting the cells from the activity of human complement, and represents a potential therapeutic strategy in PNH.

Animals↗
PubMed2005

The relation of renal function to ischemic and bleeding outcomes with 2 different glycoprotein IIb/IIIa inhibitors: the do Tirofiban and ReoPro Give Similar Efficacy Outcome (TARGET) trial.

BACKGROUND: Renal function significantly impacts morbidity and mortality after a percutaneous coronary intervention. Platelet glycoprotein (GP) IIb/IIIa inhibitors reduce ischemic complications during percutaneous coronary intervention; little is known of whether their safety and efficacy are influenced by renal function. In particular, whether outcome differences exist between agents that are renally excreted (tirofiban) or not (abciximab) in patients with mild renal impairment is not known. METHODS: The TARGET trial randomized 4623 patients to tirofiban or abciximab. In this analysis, patients were grouped in creatinine clearance quartiles (<70, 70-90, 90-114, >114 mL/min) and analyzed for efficacy and bleeding risk. Univariate and multivariate analyses were performed to identify interactions between GP IIb/IIIa inhibitor used and creatinine clearance with respect to ischemic outcomes and bleeding. RESULTS: Using unadjusted logistic regression tests for trend, 30-day death/myocardial infarction/urgent target vessel revascularization was greater in patients with lower creatinine clearances (7.3%, 8.5%, 5.1%, and 5.8%, P = .005), as were both major and minor bleeding. There was no interaction between assigned GP IIb/IIIa inhibitor, creatinine clearance and ischemic outcome, major bleeding or minor bleeding. CONCLUSIONS: Both ischemic and bleeding complications are highest in the lowest creatinine clearance quartile of patients treated with GP IIb/IIIa inhibitors. Although tirofiban is renally cleared and abciximab is not, there was no interaction between these GP IIb/IIIa inhibitors and creatinine clearance regarding ischemic or bleeding events.

Abciximab↗
PubMed2004

Cryopreservation of human embryos at the morula stage and outcomes after transfer.

OBJECTIVE: To evaluate the survival rate of human morula embryo freezing and the morphological alterations during freezing, during and after thawing, and their applications in embryo selection. DESIGN: Retrospective observational study. SETTING: Private infertility clinic. PATIENT(S): Consecutive patients under age 39 undergoing frozen morula embryo transfers from December 1999 to May 2003. INTERVENTION(S): Embryo freezing was performed at the morula stage. Embryo thaw and post-thaw ETs were conducted on the same day, which is equivalent to a day 4 ET. MAIN OUTCOME MEASURE(S): Morphological alterations during freezing and thawing and after thawing. Post-thaw embryo survival rates, transferable rates, pregnancy rates, and implantation rates. RESULT(S): Morula embryos showed reversed morphological alterations during the freezing process; these alterations were recovered during thawing or shortly after the thawing. Post-thaw survival rates showed no significant difference between any of the morula substages. However, embryos scored as grade 3, which represented good quality, had significantly higher post-thaw survival and transferable rates than grade 2 and 1 embryos. Patients who received at least one grade 3 embryo had significantly higher pregnancy rates, implantation rates, and ongoing/live birth rates than other groups. CONCLUSION(S): An acceptable survival rate can be achieved after cryopreservation of human morula embryos, and morphological alterations that occur during and shortly after an embryo thaw can be a feasible index for determining viable embryos.

Cryopreservation↗
PubMed2004

Biological activity, membrane-targeting modification, and crystallization of soluble human decay accelerating factor expressed in E. coli.

Decay-accelerating factor (DAF, CD55) is a glycophosphatidyl inositol-anchored glycoprotein that regulates the activity of C3 and C5 convertases. In addition to understanding the mechanism of complement inhibition by DAF through structural studies, there is also an interest in the possible therapeutic potential of the molecule. In this report we describe the cloning, expression in Escherichia coli, isolation and membrane-targeting modification of the four short consensus repeat domains of soluble human DAF with an additional C-terminal cysteine residue to permit site-specific modification. The purified refolded recombinant protein was active against both classical and alternative pathway assays of complement activation and had similar biological activity to soluble human DAF expressed in Pichia pastoris. Modification with a membrane-localizing peptide restored cell binding and gave a large increase in antihemolytic potency. These data suggested that the recombinant DAF was correctly folded and suitable for structural studies as well as being the basis for a DAF-derived therapeutic. Crystals of the E. coli-derived protein were obtained and diffracted to 2.2 A, thus permitting the first detailed X-ray crystallography studies on a functionally active human complement regulator protein with direct therapeutic potential.

Amino Acid Sequence↗
PubMed2003

Angiographic variables predict increased risk for adverse ischemic events after coronary stenting with glycoprotein IIb/IIIa inhibition: results from the TARGET trial.

OBJECTIVES: We sought to assess whether pre-procedural angiographic characteristics are associated with adverse clinical outcomes after coronary stenting with glycoprotein IIb/IIIa inhibition. BACKGROUND: Ischemic complications after balloon angioplasty are associated with pre- and post-procedural angiographic variables. However, in the current era of stenting with IIb/IIIa inhibition, it is unknown whether angiographic features assessed before intervention confer an increased risk of adverse procedural and subsequent clinical outcomes. METHODS: In the Do Tirofiban and ReoPro Give Similar Efficacy Outcomes? Trial (TARGET), 4,809 patients undergoing planned stenting were randomized to tirofiban or abciximab. Baseline demographic, clinical, and angiographic variables were obtained. Clinical end points were recorded at 30 days and six months. The relationship between angiographic variables and adverse clinical outcomes was assessed. RESULTS: Patients with the combination of thrombus, lesion eccentricity, and lesion length >20 mm had a 21.4% composite incidence of death, myocardial infarction, or urgent target vessel revascularization (TVR) at 30 days, compared with 4.2% in those patients without these high-risk features (hazard ratio [HR] 3.24, p < 0.001). After adjustment, the risk was independently associated with thrombus (HR 1.40, p = 0.034), eccentricity (HR 1.67, p < 0.001), and lesion length >20 mm (HR 1.89, p < 0.001). The risk of six-month TVR was independently associated with left anterior descending coronary artery lesions (HR 1.46, p < 0.001), restenotic lesions at baseline (HR 1.58, p = 0.006), and lesion length (HR 1.19, p = 0.03). CONCLUSIONS: Patients with thrombus, eccentric lesions, or lesion length >20 mm are at high risk for ischemic outcomes after coronary stenting, despite IIb/IIIa inhibition. Further research into novel anti-thrombotic therapies or procedural strategies is necessary for these patients.

Abciximab↗
PubMed2003

A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease.

OBJECTIVES: This study was designed to determine if aspirin resistance is associated with clinical events. BACKGROUND: Aspirin resistance, defined by platelet function testing and presumed clinical unresponsiveness to aspirin, has been previously reported by our group and others. However, little information exists linking the laboratory documentation of aspirin resistance and long-term clinical events. METHODS: We prospectively enrolled 326 stable cardiovascular patients from 1997 to 1999 on aspirin (325 mg/day for > or =7 days) and no other antiplatelet agents. We tested for aspirin sensitivity by optical platelet aggregation using adenosine diphosphate (ADP) and arachidonic acid (AA). The primary outcome was the composite of death, myocardial infarction (MI), or cerebrovascular accident (CVA). Mean follow-up was 679 +/- 185 days. Aspirin resistance was defined as a mean aggregation of > or =70% with 10 microM ADP and > or =20% with 0.5 mg/ml AA. RESULTS: Of the patients studied, 17 (5.2%) were aspirin resistant and 309 (94.8%) were not aspirin resistant. During follow-up, aspirin resistance was associated with an increased risk of death, MI, or CVA compared with patients who were aspirin sensitive (24% vs. 10%, hazard ratio [HR] 3.12, 95% confidence interval [CI] 1.10 to 8.90, p = 0.03). Stratified multivariate analyses identified platelet count, age, heart failure, and aspirin resistance to be independently associated with major adverse long-term outcomes (HR for aspirin resistance 4.14, 95% CI 1.42 to 12.06, p = 0.009). CONCLUSIONS: This study demonstrates the natural history of aspirin resistance in a stable population, documenting a greater than threefold increase in the risk of major adverse events associated with aspirin resistance.

Adult↗
PubMed2003

Mitral valve repair with aortic valve replacement is superior to double valve replacement.

OBJECTIVES: Double valve replacement has been advocated for patients with combined aortic and mitral valve disease. This study investigated the alternative that, when feasible, mitral valve repair with aortic valve replacement is superior. PATIENTS AND METHODS: From 1975 to 1998, 813 patients underwent aortic valve replacement with either mitral valve replacement (n = 518) or mitral valve repair (n = 295). Mitral valve disease was rheumatic in 71% and degenerative in 20%. Mitral valve replacement was more common in patients with severe mitral stenosis (P =.0009), atrial fibrillation (P =.0006), and in patients receiving a mechanical aortic prosthesis (P =.0002). These differences were used for propensity-matched multivariable comparisons. Follow-up extended reliably to 16 years, mean 6.9 +/- 5.9 years. RESULTS: Hospital mortality rate was 5.4% for mitral valve repair and 7.0% for replacement (P =.4). Survivals at 5, 10, and 15 years were 79%, 63%, and 46%, respectively, after mitral valve repair versus 72%, 52%, and 34%, respectively, after replacement (P =.01). Late survival was increased by mitral valve repair rather than replacement (P =.03) in all subsets of patients, including those with severe mitral valve stenosis. After repair of nonrheumatic mitral valves, 5-, 10-, and 15-year freedom from valve replacement was 91%, 88%, and 86%, respectively; in contrast, after repair of rheumatic valves, it was 97%, 89%, and 75% at these intervals. CONCLUSIONS: In patients with double valve disease, aortic valve replacement and mitral valve repair (1) are feasible in many, (2) improve late survival rates, and (3) are the preferred strategy when mitral valve repair is possible.

Adult↗
PubMed2003

Can particulate extraction from the ascending aorta reduce neurologic injury in cardiac surgery?

OBJECTIVE: This study examined whether extraction of particulate emboli using intra-aortic filtration could decrease neurologic outcomes. METHODS: Patients (N = 582) were enrolled in a prospective, controlled study and alternately assigned to the therapy arm (n = 304; intra-aortic filtration) or control arm (n = 278). Preoperative, procedural, and postoperative data were collected. Neurologic examinations included the National Institutes of Health Stroke Scale, Glasgow Coma Scale, and memory tests. Investigators administering neurologic tests were blinded to the study arm. By the use of logistic regression and propensity matching, composite neurologic outcomes (transient ischemic attack, stroke, delirium, coma, and memory deficit) were evaluated. RESULTS: Patients in the filter group experienced a lower incidence of adverse neurologic outcomes than patients in the control group (4.3% vs 11.9%) (P <.001). There were significantly less transient ischemic attacks (0% vs 1.4%), delirium (3.0% vs 6.5%), and memory deficit (1.3% vs 6.2%). There were fewer strokes in the filter group compared with the control group (0.7% vs 2.2%), although the sample size was too small for a significant finding. Both groups experienced 1 coma outcome. The use of a filter was associated with an adjusted odds ratio of 0.375, implying that a patient who does not receive a filter is 2.7 times more likely to experience an adverse neurologic event. Logistic modeling also demonstrated that there are increasing chances of poor neurologic outcome with increasing age. The model indicates that there may be an increasing protective benefit from the filter with increasing age, although the interaction was not significant. CONCLUSIONS: The extraction of particulate emboli using intra-aortic filtration resulted in decreased neurologic outcomes.

Aged↗
PubMed2003

Precision of single vs bilateral hip bone mineral density scans.

This study was performed to determine and compare the precision of single and bilateral hip bone mineral density (BMD) measurements and to determine the precision of spinal and total body measurements by dual-energy X-ray absorptiometry (DXA). Precision (group root-mean-square average coefficient of variation) was determined in 6 subjects scanned six times each at the spine, both hips, and total body, with repositioning after each scan. Mean percentage coefficients of variance (%CVs) in BMD for single and bilateral hip scans were, respectively: 0.65% and 0.67% for the total hip, 1.16% and 1.03% for the trochanter, and 1.66% and 1.31% for the femoral neck, respectively. Mean %CV was 1.04% for spine BMD (L2-L4), 0.67% for total body BMD, 1.12% for total body bone mineral content (BMC), 0.94% for total body fat tissue, and 0.77% for total body nonfat soft tissue. We conclude that precision overall is excellent and that femoral neck precision can be improved with bilateral compared with the traditional single hip scans.

Absorptiometry, Photon↗
PubMed2002

The LifeSite hemodialysis access system: implications for the nephrology nurse.

A new subcutaneous device--the LifeSite Hemodialysis Access System (Vasca, Inc., Tewksbury, MA)--was designed to overcome limitations of transcutaneous dialysis catheters and is now available for use in the United States. A fully implantable device, the LifeSite System provides immediate, reliable, high-flow vascular access. The durable stainless steel and titanium LifeSite valve is implanted in a subcutaneous tissue pocket, typically below the clavicle. It is connected to a biocompatible silicone cannula that is tunneled to a central vein. The device is cannulated using a virtually pain-free, buttonhole technique. The valve is designed to allow cleansing of the valve, valve pocket, and buttonhole site with 70% isopropyl alcohol before and after each use to minimize the risk of infection. One hundred fifty-day results from an ongoing multicenter trial designed to compare the LifeSite System to a Tesio Cath dialysis catheter are reviewed. These results demonstrate that the LifeSite System is associated with statistically significant higher blood flow rates (p < 0.001) and lower rates of adverse events (p < 0.0004), infection (p < 0.032), and thrombolytic infusions (p < 0.044) than a standard dialysis catheter. The positive clinical experience with the LifeSite System carries significant implications for the dialysis team, indicating that this subcutaneous, pain-free route to vascular access may offer a safer, more effective bridge to a permanent arteriovenous (AV) access than a tunneled dialysis catheter. Potential implications of these benefits include improved outcomes, greater convenience for patients, improved efficiency and time management for the nursing staff, along with reduced direct and indirect costs related to vascular access management.

Catheterization, Central Venous↗
PubMedDate not supplied

Potential benefits of physical activity for children with acute lymphoblastic leukaemia.

Acute lymphoblastic leukaemia (ALL) is the most common form of paediatric leukaemia. The survival rate in children with ALL has improved significantly over the past several years, which makes quality of life an important focus for researchers. Some of the side effects of treatment (i.e. osteoporosis and obesity) are not realized until years after conclusion of therapy. Few studies have addressed the impact of physical activity (PA) on the side effects that occur during treatment of children with ALL. This paper discusses the increased risk for both osteoporosis and obesity due to treatment for ALL and suggests ways that PA may attenuate bone loss and risk of obesity by discussing what is known about effects of PA in healthy children and children with other chronic diseases. Recommendations will be made for PA interventions and future research in children with ALL.

Body Composition↗