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F Van Lente

Publications and source records attributed to F Van Lente.

At least 19 recordsLinked to original sources

The impact of routine mycophenolate mofetil drug monitoring on the treatment of cardiac allograft rejection.

INTRODUCTION: Mycophenolate mofetil (MMF) is a unique immunosupressive agent that has been shown to be efficacious in the treatment of cardiac allograft rejection. The utility of therapeutic drug monitoring on rejection prophylaxis and treatment is inconclusive. This study was undertaken to evaluate the incidence of rejection in relation to MMF trough level following heart transplantation. METHODS: Between May 1998 and February 1999, we retrospectively analyzed the clinical outcome of 215 heart transplant patients who had routine monitoring of MMF trough level at the time of scheduled endomyocardial biopsy. Patients were divided into three groups according to the time interval post transplant, and were evaluated in relation to the MMF trough level. Group I, 104 patients within 6 months of transplant; Group II, 90 patients, 6-12 months post transplant; and Group III, 71 patients beyond one year of transplant. Fifty patients had samples in more than one group. Rejection was defined as Grade > or = 3A based on ISHLT criteria. Mean follow-up period was 179+/-52 days. RESULTS: A significantly decreased incidence of rejection was noted in the samples with MMF trough level > or = mg/l compared to those with less than 2 mg/l inpatients evaluated within the first year of transplant (Group I: 8.8% vs. 14.9%, Group II: 4.2% vs. 11.3%, both P=0.05). In the presence of therapeutic cyclosporine (CSA) or tacrolimus (FK) blood levels, the incidence of rejection decreased significantly when MMF trough level was > or = 2 mg/l compared to samples with MMF trough level <2 mg/l (3.6% vs. 14.4%, P=0.005). No significant difference was noted in the presence of subtherapeutic CSA or FK levels (15.4% vs. 13.9%, P=NS). CONCLUSIONS: Monitoring of MMF trough levels may play a role in the management of cardiac transplant recipients during the first year post transplant.

Adult↗

Markers of inflammation as predictors in cardiovascular disease.

Recent research suggests that inflammation in the coronary arteries may be intimately involved in the development of atherosclerosis and its associated acute coronary syndromes. Experimental and clinical studies based on the biochemical markers of inflammation and vascular perturbation in plasma as well as in atherosclerotic tissue have provided substantial evidence of ongoing inflammation in coronary heart disease. These studies have suggested a potential role for biochemical markers of inflammation in the prediction of risk for the development of coronary heart disease as well as in the prediction of adverse cardiac-related outcomes in patients with known coronary syndromes. Markers of inflammation appear to offer risk prediction information that is independent of, and possibly complementary to, traditional risk factors for the development of cardiovascular disease. There are numerous potential markers for these inflammatory processes and their interdependence remains somewhat unclear. Clinical studies have investigated some, but not all of these markers in a critical and comparative fashion. Therefore, further well-designed prospective studies should elucidate the role of markers of inflammation in the prediction, diagnosis, and management of cardiovascular disease.

Animals↗

Iron stores and coronary artery disease: a clinical application of a method to incorporate measurement error of the exposure in a logistic regression model.

Rates of coronary artery disease (CAD) increase sharply after menopause. We examined the hypotheses that high iron stores, as measured by plasma ferritin levels, are a risk factor for CAD and that the increase in iron stores after menopause is at least in part responsible for the rise in CAD in women. We also investigated measurement error of plasma ferritin using a Bayesian conditional independence model and incorporated it into the estimation of the odds ratio (OR) for males. Cases had >/=1 coronary artery stenosis >/=70%. Controls had no visible coronary lesions on angiography. The median plasma ferritin level was 48 mg/L (interquartile range: 28 to 86) among 244 cases and 45 mg/l (24 to 85) among 140 controls. The multivariate analyses among females, males, and females and males combined did not support an association between plasma ferritin levels and CAD (OR for one unit change in log ferritin 1.01, 95% CI 0.71-1.44, OR 0.95, 95% CI 0.66-1.37 and OR 0.95, 95% CI 0.75-1.21, respectively). Accounting for the measurement error of ferritin in males slightly improved the precision of the estimate of the OR but did not unmask an association (OR: 0.94, 95% CI 0.69-1.30). We conclude that high ferritin levels before or after menopause are not associated with CAD. Measurement error might be considered in situations where a one-time measurement is assumed to be representative of long-term exposure.

Aged↗

Ability of troponins to predict adverse outcomes in patients with renal insufficiency and suspected acute coronary syndromes: a case-matched study.

OBJECTIVES: The purpose of this study was to investigate the utility of cardiac troponin T and troponin I for predicting outcomes in patients presenting with suspected acute coronary syndromes and renal insufficiency relative to that observed in similar patients without renal disease. BACKGROUND: Cardiac troponin T and troponin I have shown promise as tools for risk stratification of patients with acute coronary syndromes. However, there is uncertainty regarding their cardiac specificity and utility in patients with renal disease. METHODS: We measured troponin T, troponin I and creatine kinase MB in 51 patients presenting with suspected acute coronary syndromes and renal insufficiency and in 102 patients without evidence of renal disease matched for the same peak troponin T or I value, selected from a larger patient cohort. Blood samples were obtained at presentation to an emergency room 4 hours, 8 hours and 16 hours later. The ability of biochemical markers to predict adverse outcomes in both groups including infarction, recurrent ischemia, bypass surgery, heart failure, stroke, death or positive angiography/angioplasty during hospitalization and at six months was assessed by receiver-operator curve analysis. The performance of both troponins was compared between groups. RESULTS: Thirty-five percent of patients in the renal group and 45% of patients in the nonrenal group experienced an adverse initial outcome; over 50% of patients in all groups had experienced an adverse outcome by 6 months, but these differences were not significant. The area under the curve (AUC) for the ROC curve for troponin T as predictor of initial outcomes was significantly lower in the renal group than in the nonrenal group: 0.56+/-0.07 and 0.75+/-0.07, respectively. The area under the curve was also significantly lower in the renal group compared with the nonrenal group for troponin T as predictor of six month outcomes: 0.59+/-0.07 and 0.74+/-0.07, respectively. The area under the curve was also significantly lower in the renal group compared to the nonrenal group for troponin I as predictor of both initial and six month outcomes: 0.54+/-0.06 vs. 0.71+/-0.07 and 0.53+/- 0.06 vs. 0.65+/-0.07, respectively. The sensitivity of troponin T for both initial and six month adverse outcomes was significantly lower in the renal group than in the nonrenal group at a similar level of specificity (0.87): 0.29 vs. 0.60 and 0.45 vs. 0.56, respectively. Troponin I also exhibited similar differences in sensitivity in the renal group (0.29 vs. 0.50 and 0.33 vs. 0.40, respectively). CONCLUSIONS: The ability of cardiac troponin T and troponin I to predict risk for subsequent adverse outcomes in patients presenting with suspected acute coronary syndromes is reduced in the presence of renal insufficiency.

Acute Disease↗

Serum prostate specific antigen, sex hormone binding globulin and free androgen index as markers of pubertal development in boys.

OBJECTIVE: Prostate specific antigen (PSA) expression in the prostate gland is regulated by androgens. Serum levels of PSA are undetectable by routine assays in normal boys. Measurable values could serve as a marker for pubertal development. In order to explore this question, we measured serum PSA levels in normal boys throughout puberty and examined the interrelationships with various hormonal and physical developmental changes. DESIGN: Sera from 77 normal boys in Tanner stages I to V (T-I to T-V) were analysed for PSA levels by a sensitive time-resolved fluoro-immunometric assay (sensitivity: 0.012 microgram/l). In addition, sex hormone binding globulin (SHBG), insulin like growth factor I (IGF-I), IGF binding protein 3(IGFBP-3) and testosterone were measured. RESULTS: PSA was detectable in 0% of Stage T-I (n = 16), 33% of T-II (n = 18), 65% of T-III (n = 17) and 100% of T-IV (n = 10) and T-V (n = 16) boys. PSA levels rose significantly according to stage (P < 0.05). Also, there were significant (P < 0.05) increments in serum testosterone, IGF-I and IGFBP-3 levels from stages T-I to T-IV. PSA showed a positive correlation with testosterone (r = 0.86, P < 0.001), IGF-I (r = 0.66, P < 0.001), and IGFBP-3 (r = 0.34, P = 0.004) levels. Both PSA and these analytes, however, showed significant overlap between stages T-I and T-II with only 6/18 (33%) and 12/18 (66%) of T-II subjects having PSA and testosterone levels, respectively, above the T-I range. In contrast, serum SHBG levels decreased markedly from stages I to II (P < 0.001). At the calculated best cut-off point for SHBG of 50 nmol/l, 16/18 T-II subjects had values below the T-I range (sensitivity = 89%). Because of this decrement of SHBG and the increasing testosterone secretion in early puberty, the Free Androgen Index (FAI = Testosterone/SHBG) could even better differentiate the onset of puberty with all except one of the T-II subjects having FAI levels above the T-I range (sensitivity = 94.4%). The decrease of SHBG in T-II subjects coincided with an increase in total body weight (P = 0.001) and body mass index (BMI, P = 0.0003). Despite the continuing pubertal rise in testosterone, SHBG levels showed a rebound increment from T-II-T-III subjects (P = 0.02) with a concomitant decrease in BMI (P = 0.0014). CONCLUSIONS: Prostate specific antigen closely reflects serum free androgen activity during puberty. However, it was unable to differentiate the earliest pubertal development. In comparison, SHBG levels and Free Androgen Index are more sensitive markers for the onset of puberty in boys. The inverse association between SHBG levels and BMI in pubertal stages Tanner stages, I to III suggests that body fatness, via its effect on insulin sensitivity, may play an important role in the regulation of SHBG production during early pubertal development.

Adolescent↗

Creatinine clearance as a measure of GFR in screenees for the African-American Study of Kidney Disease and Hypertension pilot study.

Serum creatinine and endogenous creatinine clearance (CrCl) are widely used measures of renal function. This study compares the precision, bias, and sources of error in using different CrCl measures to estimate the glomerular filtration rate (GFR) in 118 men and women screened for the African-American Study of Kidney Disease and Hypertension (AASK) pilot study. We measured serum creatinine, 24-hour CrCl, and CrCl during timed clearance periods conducted simultaneously with an 125I-iothalamate GFR study. Serum creatinine was measured using two different kinetic rate Jaffe methods (CX3 and Hitachi). After standardization for body surface area, the different measures of renal function available for each individual were compared with the 125I-iothalamate GFR simultaneous to the CrCl. In a subset of 50 participants, the CrCl measures were compared with a follow-up GFR (fGFR). The mean 125I-iothalamate GFR was 65.2 (SD, 26.4), with a range of 11 to 122 mL/min/1.73 m2. The mean +/- SD percentage differences from the GFR were -9%+/-22% for the Cockcroft-Gault estimated CrCl, 1%+/-29% for the 24-hour CrCl, and 8%+/-16% for the CX3 simultaneous CrCl. The Hitachi method overestimated serum creatinine and underestimated GFR. Compared with an fGFR, the mean +/- SD differences were 2%+/-19% for the first GFR, -6%+/-20% for the Cockcroft-Gault estimated CrCl, 10%+/-28% for the 24-hour CrCl, and 14%+/-29% for the CX3 simultaneous CrCl. Thus, the increased precision with which the timed CrCl predicted its simultaneous GFR did not extend to improved ability to predict a future GFR. The fractional excretion of creatinine, measured as the ratio of the CX3 simultaneous CrCl to 125I-iothalamate clearance, increased with decreasing GFR but was lower than expected (mean +/- SD of 1.21+/-0.16 for GFRs between 20 and 40 mL/min/1.73 m2). The lower fractional excretion explains why the 24-hour and Cockcroft-Gault CrCls did not overestimate GFR, but the reasons for this lower excretion are uncertain. Creatinine assay specificity and calibration are important sources of variability that must be examined in any CrCl measure of GFR. We conclude that despite requiring substantially more time and effort, neither the outpatient 24-hour urine nor the timed CrCl offered increased precision over a calculation based on serum creatinine, sex, age, and weight in predicting GFR.

Black People↗

Combined nested reverse transcription-PCR assay for prostate-specific antigen and prostate-specific membrane antigen in detecting circulating prostatic cells.

Accurate staging is an important issue in managing patients with prostate cancer. Current staging modalities are poor predictors for locally advanced disease. In the present study, we investigated the role of a peripheral blood-based, nested reverse transcription-PCR (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) in prostate cancer staging. Our nested RT-PCR could detect both PSA and PSM mRNA in one LNCaP cell diluted in 10(6) mononuclear cells. None of the controls, including patients with benign prostate hyperplasia, normal male subjects, and female subjects, were positive for either marker, confirming the assay's specificity for prostate cancer. In patients with bony metastases, 100% were positive by combined PSA/PSM assays (64% by PSA and 91% by PSM). In patients with clinically localized prostate cancer, 29% were positive by combined PSA/PSM assays (13% by PSA and 23% by PSM). The combined PSA/PSM assay is more sensitive than the PSA assay alone in detecting circulating prostatic cells (P = 0.0071). PSM is a more sensitive marker than PSA (P = 0.042). We also correlated preoperative nested RT-PCR results with pathological findings in prostatectomy patients. Nested RT-PCR for PSA/PSM has an odds ratio of 20 in predicting tumor extracapsular penetration (P = 0.017). These results indicate that a nested RT-PCR result may provide the staging information unavailable from other modalities, including the clinical stage, initial serum PSA, and Gleason score. Additional investigation is needed to determine the ultimate role of this assay in the management of patients with prostate cancer.

Antigens, Neoplasm↗

Inability of serum myocyte death markers to predict acute cardiac allograft rejection.

Acute cardiac rejection involves myocyte necrosis. Hence, markers of myocyte death may be useful in diagnosing rejection. Creatine kinase MB, MB isoforms, and troponins I and T were measured in 186 patients undergoing 365 endomyocardial biopsies. No differences were noted with rejection (rejectors vs. nonrejectors: CK=63.8 U/L and 86.6 U/L, P=0.0881; CK MB=2.04 ng/ml and 2.06 ng/ml, P=0.949; troponin T=0.134 ng/ml and 0.0881 ng/ml, P=0.374; troponin I=0.216 ng/ml and 0.707 ng/ml, P=0.357). The time course of troponins T and I levels in rejectors and nonrejectors do not differ with both groups having early elevations. Markers of myocyte death are inadequate predictors of acute rejection in cardiac allografts. The time course of troponins T and I suggests a possible role as prognostic indicators of outcome.

Acute Disease↗

Indirect ultraviolet detection of biologically relevant organic acids by capillary electrophoresis.

Indirect UV detection of fourteen short-chain organic acids (e.g., oxalic acid, citric acid, malonic acid, tartaric acid, methylmalonic acid, alpha-ketoglutaric acid, succinic acid, ethylmalonic acid, methylsuccinic acid, glutaric acid, apidic acid, methylglutaric acid, lactic acid and pyruvic acid) by capillary electrophoresis is described. The method used phthalate as the UV-absorbing additive in carbonate buffer and the non-absorbing analytes were detected indirectly at 230 nm. The influences of buffer pH, ionic strength, concentration of phthalate and organic modifier on indirect signal response and migration behavior of the organic acids were investigated. Comparisons of reproducibility on migration time, limit of detection and separation efficiency among three types of capillary (e.g., polyacrylamide-coated, myristyltrimethylammonium bromide-coated and uncoated capillaries) were conducted. The method developed was applied to detect succinic acid, methylmalonic acid, citric acid, glutaric acid and lactic acid in human body fluids, and preliminary results were provided.

Buffers↗

Immunoradiometric assay measurements of insulin-like growth factor-I (IGF-I): comparison with radioimmunoassays using native or des (1-3) IGF-I as radioligands.

Insulin-like growth-factor-binding proteins (BPs) in serum interfere with the measurement of insulin-like growth factor-I (IGF-I). Various assays have been developed to overcome this interference. We evaluated an immunoradiometric (IRMA) assay and compared it with the radioimmunoassay (RIA) using both native IGF-I and a truncated form of IGF-I [des (1-3) IGF-I] as radioligands. The IRMA was simpler (one step assay) and faster (3 hr incubation) than RIA(s) (overnight incubation). Sera were extracted with acid ethanol (AE) before all three assays. Analysis of serum samples (n = 78) performed by use of the two different radioligands in the RIA assays were highly correlated (r = 0.967, P < 0.0001). Measurements of serum IGF-I by IRMA in same samples were also highly correlated with those of the RIA assays (r = 0.952 for RIA and 0.947 for triGF-I RIA, P < 0.0001 for both). To assess the effect of binding protein-3 (BP-3) levels (after AE extraction) on these assays, BP-3 levels were measured in sera from 36 healthy women. The mean BP-3 level was 3.6 +/- 0.79 (S.D.) mg/L (range 1.3-5.0), and there was no significant difference in IGF-I levels measured by the three assays. Also, BP-3 levels were inversely correlated with IGF-I levels as measured by all three methods (r = 0.73 for IRMA, 0.71 for triGF-I, and 0.75 for IGF-I RIA). To assess the effect of binding protein-1 (BP-1) levels on these assays, IGF-I was also measured by IRMA and trlGF-I RIA in 19 women with advanced breast cancer. Women with breast cancer had significantly higher (P < 0.001) BP-1 levels than age matched healthy women. IGF-I levels measured by IGF-I IRMA were slightly lower than those measured by trlGF-I RIA in breast cancer patients. However, this difference was not statistically significant (P = 0.56). These findings suggest that variations in BP-3 or BP-1 levels after AE extraction have no significant effect in any of these assays. "We conclude that trlGF-I as a radioligand provides no added advantage over the standard IGF-I RIA. We also conclude that the IRMA assay is valid for measuring IGF-I and is faster and more convenient than RIA.

Adult↗

Decreased free radical scavengers with reperfusion after coronary angioplasty in patients with acute myocardial infarction.

Early reperfusion after myocardial infarction improves survival rate and is thought to preserve myocardial function, but the reperfusion of ischemic tissue may release oxygen free radicals, which could adversely affect left ventricular function and diminish the beneficial effects of reperfusion. Measurements related to free radical scavenging (plasma and erythrocyte enzyme systems, which are involved in free radical control, alpha-tocopherol, selenium, and manganese superoxide dismutase) may be indirect markers of free radical production. We evaluated 10 patients undergoing coronary angioplasty within 4 hours of myocardial infarction to measure the impact of abrupt reperfusion on free radical scavenger-related indexes. Pulmonary artery samples were taken before, immediately after, and 3 hours after angioplasty. During reperfusion, significant reductions occurred in alpha-tocopherol (1.1 +/- 0.3 mg/dl before, 0.9 +/- 0.2 mg/dl immediately after [p = 0.03], and 0.8 +/- 0.2 mg/dl 3 hours after percutaneous transluminal coronary angioplasty [p = 0.02]), and selenium levels (13.7 +/- 2.4 micrograms/dl before, 12.9 +/- 2.4 micrograms/dl immediately after, and 10.2 +/- 3.0 micrograms/dl 3 hours after angioplasty [p = 0.0006]). Erythrocyte markers (glutathione peroxidase and superoxide dismutase) were not altered by reperfusion, possibly reflecting the relatively long half-life of the erythrocyte. The erythrocyte glutathione peroxidase value before reperfusion in patients (30.8 +/- 5.1 IU/gm of hemoglobin) was lower than in a control group (36.1 +/- 6.5 IU/gm of hemoglobin; p = 0.01). Thus the decrease in plasma alpha-tocopherol and selenium after reperfusion in this group of patients may reflect a general alteration in plasma free radical scavenger levels, suggesting consumption of plasma free radical scavengers with reperfusion after acute myocardial infarction.

Angioplasty, Balloon, Coronary↗

Effect of measurement error on calculated variables of oxygen transport.

The effect of measurement error in pH, PCO2, and PO2 on mathematically derived variables of oxygen transport in patients was delineated by comparing calculated oxygen saturations from a blood-gas machine with measured saturations from a CO-oximeter and further by modeling the error in a computer simulation. Twenty-one critically ill patients aged 30-84 yr were studied. A total of 80 arterial and 80 mixed venous blood gas samples were collected. The intraclass correlation results between measured and calculated arterial (SaO2) and mixed venous (Sv-O2) oxygen saturations were 0.59 and 0.68, respectively. The product-moment correlation for SaO2 was 0.75 and for Sv-O2 was 0.77. The percent error in calculating and measuring oxygen saturation was found to be greater at low PO2 values, whereas percent error of calculating oxygen consumption increased as the PO2 increased. Measurement repeatability at high PO2 is better than at low PO2 for both measured and calculated methods. We conclude from this comparison that measured and calculated SaO2 and Sv-O2 values are not interchangeable. Each can introduce substantial error in calculating oxygen consumption through error propagation and error amplification.

Adult↗

Antioxidants in hereditary pancreatitis.

OBJECTIVE: The cause of hereditary pancreatitis (HP) remains unknown. This study evaluated the hypothesis that patients with HP have genetically determined low concentrations of antioxidants that may predispose them to repetitive pancreatic injury. METHODS: This cross-sectional analysis compared antioxidant levels in four groups of patients. Group 1 included 14 related people with chronic pancreatitis. Group 2 (11 individuals) belonged to the same kindred but did not have pancreatitis. Group 3 was a group of 65 unrelated control subjects, and Group 4 consisted of seven unrelated children with chronic pancreatitis from other causes. The antioxidant levels analyzed included glutathione peroxidase, superoxide dismutase, glutathione reductase, glutathione transferase, selenium, and vitamin E. Amylase levels were measured in all patients in groups 1, 2, and 4. RESULTS: People with chronic pancreatitis or relatives of people with hereditary pancreatitis (groups 1, 2, and 4) had significantly lower mean glutathione peroxidase values than controls (group 3, p < 0.001). Group 1 also had significantly lower selenium levels than groups 2 and 3 (p < 0.001) but greater levels than group 4 (p = 0.029). Vitamin E levels were lower in group 1 than in groups 2 and 4. The superoxide dismutase levels were significantly different between each group (p < 0.001), and group 1 had the highest level. The glutathione reductase, glutathione transferase, and amylase levels did not differ significantly between groups. However, group 1 had a significantly higher glutathione transferase level than group 4. CONCLUSION: We identified antioxidant deficiencies in a group of patients with hereditary pancreatitis. Higher selenium and vitamin E levels may have prevented their relatives in group 2 from having pancreatitis secondary to oxidant injury, despite low glutathione peroxidase levels. Supplementation with selenium or vitamin E or both may be a beneficial therapeutic option in these patients to decrease the frequency of pancreatitis.

Adolescent↗

Enzymatic markers of gallstone-induced pancreatitis identified by ROC curve analysis, discriminant analysis, logistic regression, likelihood ratios, and information theory.

We investigated the diagnostic utility of frequent serial determinations of aspartate aminotransferase, alanine aminotransferase (ALT), lipase, amylase, and the lipase/amylase (L/A) ratio for distinguishing patients with acute pancreatitis due to biliary obstruction from those with acute pancreatitis due to other pathogenesis. Analyzed were enzyme activities obtained at admission and peak enzyme activities identified retrospectively from serial measurements in 53 patients with acute pancreatitis due to various causes. We evaluated the data with multiple statistical tools. Discriminant analysis and logistic regression revealed the diagnostic significance of ALT at initial and peak values, and the maximum information provided by peak ALT was confirmed by both logistic regression and stratum-specific likelihood ratios. Stratum-specific likelihood ratios showed peak ALT > 150 U/L was highly diagnostic of biliary pancreatitis. The L/A ratio, either at admission or at peak, was the only other significant variable for identifying patients with acute pancreatitis due to biliary obstruction. A multivariate logistic discriminant function including ALT and the L/A ratio significantly discriminated biliary acute pancreatitis from pancreatitis due to other causes. Evaluation of initial and peak enzyme data by information theory revealed that the optimal test depended on disease prevalence. Initial ALT activities were the test of choice for identifying biliary pancreatitis, up to a disease prevalence of approximately 0.75. At disease prevalence > 0.75, the initial L/A ratio provided the greatest amount of diagnostic information.

Acute Disease↗