Biomedical subjects

Diane E Grill

Publications and source records attributed to Diane E Grill.

15 recordsLinked to original sources

PubMed2006

Global transcriptional effects of PEG-IFN-alpha and ribavirin on peripheral blood cells obtained from patients with chronic hepatitis C.

The global transcriptional profile during the first 4 weeks of treatment with pegylated interferon alfa (PEG-IFN-alpha) therapy for chronic hepatitis C (CHC) was evaluated. cDNA array technology was used to assess expression of 10,918 human genes in peripheral blood cells obtained from 17 CHC patients at days 0, 7, and 28 following treatment with PEG-IFN-alpha and ribavirin. Hierarchical average linkage clustering identified seven temporal profiles of differential expression comprising 148 genes. Gene expression profiles were comparable between the PEG-IFN-alpha-2a and PEG-IFN-alpha-2b therapy. Genes representing a broad range of molecular functions were differentially regulated with distinct temporal patterns of expression. The initial global response to interferon treatment appears to be a net up-regulation of genes, consistent with gene responses identified previously in vitro, though by 4 weeks an overall down-regulation of genes was observed. Novel transcription factors potentially involved in secondary gene regulation cascades, a potential dsRNA receptor and members of the ubiquitin signaling, including a novel predicted deubiquitinating peptidase were all identified as being up-regulated upon treatment with IFN. The overall findings provide new light on possible physiological effects of IFN-alpha and open new lines of investigations on the mode of action of PEG-IFN-alpha combination therapy.

Journal Article↗

PubMed2006

Impact of prosthesis-patient mismatch on long-term survival in patients with small St Jude Medical mechanical prostheses in the aortic position.

BACKGROUND: The impact of aortic prosthesis-patient mismatch (P-PtM) on long-term survival is unclear. METHODS AND RESULTS: Between 1985 and 2000, 388 patients at Mayo Clinic in Rochester, Minn, underwent aortic valve replacement (AVR) with 19- or 21-mm St Jude Medical prostheses and had transthoracic echocardiography within 1 year after AVR. Mean age of patients was 62+/-13 years; 69% were female. Prosthesis effective orifice area (EOA) was derived from the continuity equation. P-PtM was classified as severe (indexed EOA < or =0.60 cm2/m2), moderate (0.60 cm2/m2 0.85 cm2/m2). P-PtM was severe in 66 patients (17%), moderate in 168 (43%), and not hemodynamically significant in 154 (40%). Patients with severe P-PtM had a significantly larger body surface area (P<0.0001), higher mean gradient (P<0.0001), lower preoperative (P<0.0001) and postoperative (P<0.0001) ejection fractions, and lower stroke volume (P<0.0001) and more often received a 19-mm prosthesis (P=0.0008) than patients with moderate or no hemodynamically significant mismatch. For patients with severe mismatch, 5-year survival rates (72+/-6%) and 8-year survival rates (41+/-8%) were significantly less than for patients with moderate mismatch (80+/-3% and 65+/-5%; P=0.026) or no hemodynamically significant mismatch (85+/-3% and 74+/-5%; P=0.002). On multivariate analysis after adjustment for other predictors of outcome, severe mismatch was associated with higher mortality (hazard ratio 2.18; 95% confidence interval 1.24 to 3.85; P=0.007) and higher incidence of congestive heart failure (hazard ratio 3.1; 95% confidence interval 1.3 to 7.4; P=0.009) than no hemodynamically significant mismatch. CONCLUSIONS: Severe P-PtM is an independent predictor of higher long-term mortality and congestive heart failure in patients with small St Jude Medical aortic valve prostheses. For patients undergoing AVR who are at risk of severe mismatch, every effort should be made to use a larger prosthesis or to consider a prosthesis with a larger EOA.

Aged↗

PubMed2006

Immune activation at effector and gene expression levels after measles vaccination in healthy individuals: a pilot study.

Cellular immunity to measles vaccination is not fully understood at the effector response and gene expression levels. We enrolled 15 healthy individuals (15-25 years old) previously vaccinated with two doses of measles-mumps-rubella-II vaccine to characterize their cellular immunity. We detected a spectrum of lymphoproliferative response (median stimulation indices of 3.4), low precursor frequencies of interferon-gamma (median 0.11%) and interleukin-4 (median 0.05%) by Elispot, and cosecretion of Th1 and Th2 cytokines after measles virus stimulation. Further, global gene expression was examined in five subjects from this cohort after vaccination with an additional dose of measles vaccine (Attenuax, Merck) to identify the genes involved in measles immunity. Linear mixed effect models were used to identify genes significantly up or downregulated in vivo between baseline and Days 7 and 14 after measles vaccination. Measles vaccination induced upregulation of a set of 80 genes, which play a role in measles immunity, signal transduction, apoptosis, cell proliferation, and metabolic pathways. Among the 34 genes that were downregulated, only interferon-alpha is known to have a direct role in measles immunity. This study suggests that measles vaccination leads to activation of multiple cellular mechanisms that can override the immunosuppressant effects of the measles virus and induce immunity.

Adolescent↗

PubMed2006

The impact of observer and patient factors on the occurrence of digit preference for zero in blood pressure measurement in a hypertension specialty clinic: evidence for the need of continued observation.

BACKGROUND: Many investigators have reported unconscious over-reporting of the terminal digit zero but little literature exists on observer or patient-related factors that may predict the occurrence. This study analyzes the occurrence of zero preference in 52,827 blood pressure (BP) measurements in 8513 patients by 11 hypertension nurse specialists in the Hypertension Division at Mayo Clinic, Rochester, Minnesota. METHODS: Data from the electronic database of the Hypertension Division from April 1997 to September 2001 were analyzed for the occurrence of zero preference. Nurse-specific zero preference was stratified on four variables: number of BPs performed, years as hypertension nurse specialist, time of day BP performed (fatigue), and nursing degree. Three patient-specific factors were analyzed: age at visit (stratified by decade), type of care (continuing versus short-term), and hypertension status. RESULTS: We found significantly increased frequency of zero preference for all BPs with mean frequency of 31% v 20% expected (P < .0001). Individual nurse zero preference varied widely, 22.0% to 53.6% for systolic BP and 22.2% to 40.8% for diastolic BP). Continuing care patients had a higher zero preference than did short-term care patients for both systolic BP (34.5% v 30.2%; P < .0001) and diastolic BP (34.7% v 33.3%; P = .006). Zero preference was also more common at higher categories of hypertension (P < .001). Time of day, nursing degree, patient age, the number of BPs performed, years of service did not affect the occurrence of digit preference. CONCLUSIONS: Digit preference was demonstrated and varied significantly among well-trained hypertension nurse specialists. Further studies in a larger number of observers are required.

Adult↗

PubMed2005

Direct thrombin inhibitors are not equally effective in vivo against arterial thrombosis: in vivo evaluation of DuP714 and argatroban in a porcine angioplasty model and comparison to r-hirudin.

BACKGROUND: Qualitative differences in antithrombotic efficacy between thrombin inhibitors may be explained by the affinity for which they bind thrombin. This affinity is inversely proportional to the inhibitory constant for the agent (Ki). Thrombin inhibitors, DuP714 (Ki=10(-11)) and argatroban (Ki=10(-8)), were compared to our previous studies with r-hirudin (Ki=10(-13)). METHODS AND RESULTS: Prior to balloon angioplasty, thirty pigs randomly received DuP714 (0.1 mg/kg bolus and 0.6 mg/kg/h infusion; n=8), argatroban (0.2 mg/kg/min. continuous infusion; n=9), or saline (n=17). Injured arterial segments were measured for (111)In-platelet and 125I-fibrin(ogen) deposition and the incidence of macroscopic thrombus. In DuP714-treated animals, platelet and fibrin(ogen) deposition were significantly lower than controls in both carotid (10+/-2 vs. 62+/-18 and 20+/-4 vs. 74+/-6) and coronary (10+/-4 vs. 160+/-63 and 17+/-3 vs. 86+/-22) arteries (p<0.005). In contrast, platelet and fibrin(ogen) deposition were similar when comparing argatroban to saline in carotid (41+/-20 vs. 40+/-9 and 71+/-5 vs. 49+/-7) and coronary (92+/-33 vs. 151+/-45 and 114+/-37 vs. 89+/-38) arteries (p=0.82 and 0.38, respectively). Compared to argatroban, fibrin(ogen) (p<0.001) and coronary platelet deposition (p<0.05) were significantly reduced in animals treated with DuP714 with no significant difference in carotid platelet deposition (p=0.10). Neither inhibitor prevented macroscopic thrombosis. In previous studies with r-hirudin in this model, platelet deposition was limited to a monolayer with complete inhibition of macroscopic thrombus. CONCLUSIONS: Direct thrombin inhibitors do not equally prevent arterial thrombosis. Qualitative differences may be explained in part by the affinity for which they bind thrombin.

Angioplasty, Balloon↗

PubMed2005

Limited (6-h) ambulatory blood pressure monitoring is a valid replacement for the office blood pressure by trained nurse clinician in the diagnosis of hypertension.

OBJECTIVE: To assess the ability of limited ambulatory blood pressure monitoring as a valid replacement for office blood pressure measurement done to American Heart Association criteria in diagnosing hypertension. METHODS: In all, 105 adults, who had been referred for limited ambulatory blood pressure monitoring, participated in the study. Limited ambulatory blood pressure monitoring consisted of 6 h of blood pressure measurement while ambulatory at the Mayo Clinic, using a SpaceLabs 90207 (SpaceLabs Medical, Issaquah, Washington, USA) collecting six readings per hour for the period of observation. The study participants gave consent for three additional consecutive office blood pressure measurements, using a validated aneroid device, done to American Heart Association criteria, by a single hypertension nurse specialist. RESULTS: Mean systolic blood pressure by limited ambulatory blood pressure monitoring was 137.9+/-14.2 mmHg and for the nurse, 137.9+/-20.1 mmHg. Mean diastolic blood pressure by limited ambulatory blood pressure monitoring was 81.5+/-9.7 mmHg and for the nurse, 74.3+/-11.9 mmHg. The intermethod difference for systolic blood pressure was 0.03+/-12.5 mmHg and diastolic blood pressure, -7.2+/-8.0 mmHg. Using <140/90 as criteria factor, limited ambulatory blood pressure monitoring and the trained nurse agreed 77% of the time on whether the patient was hypertensive. This agreement increased to 81% if the participant's referral blood pressure was >or=140/90. CONCLUSIONS: Limited ambulatory blood pressure monitoring is an excellent replacement for office blood pressure, done to American Heart Association criteria, in diagnosing hypertension. This avoids issues of variability introduced by the observers, such as digit preference and bias, and increases reproducibility of blood pressure measurements. The appropriate normal value for limited ambulatory blood pressure monitoring is <140/90 mmHg compared with <135/85 mmHg used in 24-h ambulatory blood pressure monitoring.

Adolescent↗

PubMed2005

Association of heparin-dependent antibodies and adverse outcomes in hemodialysis patients: a population-based study.

OBJECTIVE: To determine whether some adverse outcomes of hemodialysis could be explained by subclinical heparin-induced thrombocytopenia (HIT). PATIENTS AND METHODS: Platelet factor 4 (PF4)-heparin antibodies were measured by enzyme-linked immunosorbent assay In a population-based cohort of hemodlalysis patients. Participants were then followed up prospectively for thromboembollc events, cardiovascular events, or death. RESULTS: Of the 59 hemodialysis patients residing In Olmsted County, Minnesota, 57 (97%) agreed to study participation. The mean +/- SD age of the patients was 64 +/- 17 years (median hemodialysis duration, 23 months), and 27 (47%) were women. The enzyme-linked Immunosorbent assay was positive for PF4-heparin antibodies in 2 patients (3.5%). The PF4-heparin antibody content varied over a 10-fold range and was not associated with the duration of hemodialysis (P = .99). During a median follow-up of 798 days, 16 thrombotic events, 37 cardiovascular events, and 23 deaths (Including 13 cardiovascular deaths) occurred. After adjusting for the Framingham risk score, the all-cause mortality rate was significantly higher for patients with the highest tertile of PF4-heparln antibody content compared with patients in the lower tertilles (hazard ratio, 2.47; P = .03). Furthermore, 8 (73%) of deaths in this tertile were due to cardiovascular causes (hazard ratio, 4.14; P = .02). CONCLUSIONS: Despite repetitive heparin exposure, the prevalence of HIT In patients undergoing maintenance hemodialysis is no greater than that anticipated for other patient populations. However, to our knowledge, this is the first study to show an association between elevated PF4-heparin antibodies and Increased mortality rates in hemodlalysis patients.

Aged↗

PubMed2004

Functional gene expression analysis of clonal plasma cells identifies a unique molecular profile for light chain amyloidosis.

Immunoglobulin light chain amyloidosis (AL) is characterized by a clonal expansion of plasma cells within the bone marrow. Gene expression analysis was used to identify a unique molecular profile for AL using enriched plasma cells (CD138+) from the bone marrow of 24 patients with AL and 28 patients with multiple myeloma (MM) and 6 healthy controls. Class prediction analysis (PAM) revealed a subset of 12 genes, which included TNFRSF7 (CD27), SDF-1, and PSMA2, that distinguished between these 2 groups with an estimated and observed accuracy of classification of 92%. This model was validated with an independent dataset of 11 patients with AL and 12 patients with MM with 87% accuracy. Differential expression for the most discriminant genes in the 12-gene subset was validated using quantitative real-time polymerase chain reaction and protein expression analysis, which upheld the observations from the micro-array expression data. Functional analyses using a novel network mapping software revealed a number of potentially significant pathways that were dysregulated in patients with AL, with those regulating proliferation, apoptosis, cell signaling, chemotaxis, and migration being substantially represented. This study provides new insight into the molecular profile of clonal plasma cells and its functional relevance in the pathogenesis of light chain amyloidosis.

Aged↗

PubMed2004

Faster cyclic loess: normalizing RNA arrays via linear models.

MOTIVATION: Our goal was to develop a normalization technique that yields results similar to cyclic loess normalization and with speed comparable to quantile normalization. RESULTS: Fastlo yields normalized values similar to cyclic loess and quantile normalization and is fast; it is at least an order of magnitude faster than cyclic loess and approaches the speed of quantile normalization. Furthermore, fastlo is more versatile than both cyclic loess and quantile normalization because it is model-based. AVAILABILITY: The Splus/R function for fastlo normalization is available from the authors.

Algorithms↗

PubMed2003

Opportunities to prevent sudden out-of-hospital death due to coronary heart disease in a community.

BACKGROUND: Intervening successfully to reduce the burden of sudden out-of-hospital death due to coronary heart disease (OHCD) requires knowledge of where these deaths occur and whether they are observed by bystanders. METHODS: To establish the proportion of OHCDs that were witnessed and where they occurred, we reviewed the coroner's notes and medical records of a previously-described sample of OHCD cases among residents of Olmsted County, Minnesota. This cohort (n=113) consisted of a 10% random sample of all Olmsted County residents who died out-of-hospital between 1981 and 1994 and whose deaths were attributed to coronary heart disease. RESULTS: Excluding deaths in nursing homes (n=27), 71 (83%) of the deaths occurred in private homes and 15 (17%) occurred in public places. The event was not witnessed in 59% of deaths occurring in private homes and in 20% of deaths occurring in public places. The presence or absence of a bystander could not be established for 10% of deaths in private homes and 7% of deaths in public areas. CONCLUSIONS: A significant proportion of OHCDs occur in private homes and are not witnessed. Prevention of unwitnessed deaths will require programs that result in primary prevention and/or calls to first responders at the time of impending cardiac arrest.

Cause of Death↗

PubMed2003

Platelet hyperactivity after statin treatment discontinuation.

Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as by non-lipid related actions. Among them, the modulation of platelet activity could play a relevant role in vascular protection. Furthermore withdrawal of statins has been associated with increased cardiovascular event rate. The aim of our study was to evaluate platelet activity after cerivastatin discontinuation in eighteen subjects that did not accept other drugs and in sixteen subjects continuing treatment with simvastatin. Fourteen subjects at the end of the discontinuation period decided to receive other drugs (simvastatin) and they were evaluted six weeks later. We measured complete lipid profile by the chromogenic method (LDL-C was calculated); oxidized-LDL (ox-LDL; ELISA), platelet P-selectin (P-sel) expression (flow cytometry detection), platelet aggregation (% change of transmitted light), intracellular citrullin production (iCit; HPLC) as an indicator of intracellular NO synthase activity at baseline and 7, 14, 28, 60 days after statin discontinuation. P-sel expression and platelet aggregation were increased at 14 days (p < 0.001 and p < 0.05) in association with raised ox-LDL (r = 0.30, p < 0.05) and decreased iCit (r = 0.53, p < 0.01). Increased LDL-C was related to P-sel and platelet aggregation at 28 days (r = 0.30, p < 0.05). Subjects continuing statin treatment had no significant changes of P-sel at 28 (p = 0.221) and 60 days (p = 0.238). Subjects treated with simvastatin after 60 days of diet showed a significant reduction of P-sel and platelet aggregation after six weeks of treatment (p < 0.01). Our data suggest a platelet hyperactivation state in the second week after statin discontinuation which is partially related to raised LDL-C. Such a finding could participate in the increased cardiovascular event rate after statin discontinuation.

Adult↗

PubMed2002

Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention.

BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI) in the modern era, the incidence and prognostic implications of acute renal failure (ARF) are unknown. METHODS AND RESULTS: With a retrospective analysis of the Mayo Clinic PCI registry, we determined the incidence of, risk factors for, and prognostic implications of ARF (defined as an increase in serum creatinine [Cr] >0.5 mg/dL from baseline) after PCI. Of 7586 patients, 254 (3.3%) experienced ARF. Among patients with baseline Cr <2.0, the risk of ARF was higher among diabetic than nondiabetic patients, whereas among those with a baseline Cr >2.0, all had a significant risk of ARF. In multivariate analysis, ARF was associated with baseline serum Cr, acute myocardial infarction, shock, and volume of contrast medium administered. Twenty-two percent of patients with ARF died during the index hospitalization compared with only 1.4% of patients without ARF (P<0.0001). After adjustment, ARF remained strongly associated with death. Among hospital survivors with ARF, 1- and 5-year estimated mortality rates were 12.1% and 44.6%, respectively, much greater than the 3.7% and 14.5% mortality rates in patients without ARF (P<0.0001). CONCLUSIONS: The overall incidence of ARF after PCI is low. Diabetic patients with baseline Cr values <2.0 mg/dL are at higher risk than nondiabetic patients, whereas all patients with a serum Cr >2.0 are at high risk for ARF. ARF was highly correlated with death during the index hospitalization and after dismissal.

Acute Kidney Injury↗

PubMed2002

Unrestricted availability of intracoronary stents is associated with decreased abrupt vascular closure rates and improved early clinical outcomes.

The purpose of this study was to determine whether the unrestricted availability of intracoronary stents is affecting abrupt vascular closure rates and early clinical outcomes. Intracoronary stents have improved procedural outcome despite their application in more complex lesions, but the impact of unrestricted availability of stents on abrupt closure and early clinical outcomes is unknown. Two cohorts were identified retrospectively from a coronary intervention registry: patients treated between 1988 and 1992 (n = 3,617) when stents were not generally available, and patients treated between 1994 and 1997 (n = 4,518) when stents were freely available. The late cohort patients consisted of more females; it also had greater comorbidity and more complex presentation. However, there was a significant reduction in the abrupt closure rates between the two time periods (7% vs. 4%, P < 0.0001). After adjusting for female gender, thrombus, and lesion angulation, the late cohort remained significantly associated with decreased odds of abrupt closure (odds ratio [OR] = 0.62, 95% upper and lower confidence intervals [CI] = 0.52-0.75, P = 0.0001). The late cohort also had decreased in-hospital mortality (OR = 0.91, CI = 0.86-0.95, P = 0.0002) and major adverse clinical event (OR = 0.93, CI = 0.91-0.96, P = 0.0001). Unrestricted availability of intracoronary stents is associated with reduced abrupt closure rates and improved early clinical outcomes among patients undergoing coronary intervention despite treatment of high-risk patients.

Acute Disease↗

PubMed2002

Implantable cardioverter defibrillator implantation rates in the Olmsted County, Minnesota, population: 1989-1999.

Although the efficacy of implantable cardioverter defibrillators (ICDs) has been demonstrated in randomized clinical trials, implantation and survival rates have not been reported for a defined population. We performed a retrospective cohort analysis of Olmsted County, Minnesota residents (n = 70) who received their first ICD between 1 January 1989 and 31 December 1999. The ICD implantation rate increased from approximately 2.5/100,000 (95% confidence interval [CI], 0.9-4.1) in the first 4 years to 11.5/100,000 (95% CI, 6.7-16.2) in the last 2 years. Twenty-three patients (33%) received an appropriate ICD shock during the observation period. Based on these data, ICDs are estimated to reduce total mortality rates in this population by 0.3%. We conclude that, in patients drawn from a community setting with AHA/ACC class I indications for ICD implantation, implantation of ICDs appears to be highly efficacious in aborting potentially fatal events.

Death, Sudden, Cardiac↗

PubMed2002

Incidental renal artery stenosis among a prospective cohort of hypertensive patients undergoing coronary angiography.

OBJECTIVE: To determine the feasibility, safety, and clinical yield of angiographic screening among hypertensive patients undergoing coronary angiography. PATIENTS AND METHODS: This study was a prospective cohort analysis of hypertensive patients who underwent cardiac catheterization at a tertiary care referral center from July 1998 to March 1999. Abdominal aortography was performed to screen for renal artery stenosis, the percentage of which was measured. RESULTS: The mean +/- SD age of the 297 study patients was 64.9+/-10.2 years; 58.6% were male, and 98.0% were white. Mean +/- SD systolic/diastolic blood pressure was 142.8+/-22.5/79.6+/-11.4 mm Hg. Aortography required a mean incremental dose of 62+/-9 mL of nonionic contrast agent. No complications were attributable to aortography. Of 680 renal arteries, 611 (90%) were visualized adequately. Also, 53% of patients had normal renal arteries, 28% had stenoses less than 50%, and 19.2% had stenoses of 50% or more. Renal artery stenosis was bilateral in 3.7% of patients and high grade (>70% stenosis) in 7%. Patients with renal artery stenosis were more likely to have had a previous coronary intervention. In multivariate analysis, systolic blood pressure (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.03-138; P=.02), history of stroke or transient ischemic attack (OR, 2.7; 95% CI, 1.27-5.78; P=.01), and cancer (OR, 2.0; 95% CI, 1.02-3.82; P=.04) independently correlated with renal artery stenosis of 50% or more. CONCLUSION: The prevalence of incidental renal artery stenosis among hypertensive patients undergoing coronary catheterization is significant. Therefore, screening abdominal aortography should be considered in these patients to better define their risk of cardiovascular complications.

Aortography↗