Biomedical subjects

John W Wilson

Publications and source records attributed to John W Wilson.

At least 37 records · Page 2Linked to original sources

PubMed2005

A procedure for benchmarking laboratory exposures with 1 A GeV iron ions.

A new version of the HZETRN code capable of simulating HZE ions with either laboratory or space boundary conditions is under development. The computational model consists of combinations of physical perturbation expansions based on the scales of atomic interaction, multiple scattering, and nuclear reactive processes with use of asymptotic/Neumann expansions with non-perturbative corrections. The code contains energy loss with straggling, nuclear attenuation, nuclear fragmentation with energy dispersion and downshifts, and off-axis dispersion with multiple scattering under preparation. The present benchmark is for a broad directed beam for 1 A GeV iron ion beams with 2 A MeV width and four targets of polyethylene, polymethyl metachrylate, aluminum, and lead of varying thickness from 5 to 30 g/cm2. The benchmark quantities will be dose, track averaged LET, dose averaged LET, fraction of iron ion remaining, and fragment energy spectra after 23 g/cm2 of polymethyl metachrylate.

Aluminum↗

PubMed2005

Gastroesophageal reflux (symptomatic and silent): a potentially significant problem in patients with cystic fibrosis before and after lung transplantation.

BACKGROUND: The significance of gastroesophageal reflux (GER) and aspiration are unclear in cystic fibrosis (CF) and may contribute to declining lung function before and after lung transplantation (LTx). METHODS: We sought to establish whether GER occurs in patients with CF on the LTx waiting list and after LTx. We then investigated whether GER correlates with patients' symptoms. Adults with CF on the waiting list and after LTx were prospectively recruited. Completion of a valid, structured symptom questionnaire was followed by ambulatory, dual-probe, 24-hour esophageal pH monitoring. RESULTS: Twenty-four patients were studied, including 11 (6 males) in the pre-LTx group and 13 (9 males) in the post-LTx group. The pre-LTx group was 29.3 +/- 8.2 years of age, and the post-LTx group was 32.7 +/- 8.2 years of age. DeMeester score (normal value <14.7) was 36.6 +/- 22.3 for the pre-LTx group and 40.0 +/- 37.3 for the post-LTx group. Proximal esophageal acid exposure was significantly higher in both CF groups compared with normal. Symptom scores (normal <4, range -2 to 18) were: pre-LTx group, 5.8 +/- 6.5; post-LTx group, 7.7 +/- 5.4. Percent forced expiratory volume in 1 second (FEV1%) predicted was: pre-LTx group, 31.3 +/- 7.8; post-LTx group, 65.2 +/- 29.3. In the pre-LTx group, 10 of 11 (90.9%) patients had significant GER on monitoring, including 4 (40%) with symptomatic GER and 6 (60%) with silent GER. In the post-LTx group, 11 of 13 (84.6%) had significant GER on monitoring, including 9 (82%) with symptomatic GER and 2 (18%) with silent GER. CONCLUSIONS: GER, symptomatic and silent, is a significant problem in CF. This condition should be aggressively treated and surgery should be considered if GER persists on re-testing.

Adolescent↗

PubMed2005

Does androgen excess contribute to the cardiovascular risk profile in postmenopausal women with type 2 diabetes?

The purpose of this study was to determine if postmenopausal women with type 2 diabetes have clinical and biochemical evidence of androgen excess as a potential contributor to an increase in risk for coronary heart disease when compared with women without diabetes. Fasting glucose, insulin, lipids, sex hormone-binding globulin (SHBG), and sex steroids (from pooled samples) (total testosterone and free testosterone [non-SHBG-T], androstenedione [A-dione], total estrogens) were measured at baseline in 16 postmenopausal women with type 2 diabetes treated with diet or a sulfonylurea and 17 age-matched controls. Measurements of glucose, insulin, and sex steroids were repeated at hourly intervals for 3 hours after oral glucose administration. Hirsutism scores and insulin sensitivity (homeotasis model assessment [HOMA] insulin [SI]) were obtained. Women with type 2 diabetes were more hyperglycemic, hyperinsulinemic, and insulin-resistant (HOMA SI, 46.7 +/- 7.0 vs 12.9 +/- 2.0, P < .001), and had higher total to high-density lipoprotein cholesterol (TC/HDL) ratios, lower SHBG (20.8 +/- 3.5 vs 59.3 +/- 14.4 nmol/L, P < .05), higher non-SHBG-T (0.225 +/- 0.025 vs 0.135 +/- 0.021 nmol/L, P < .05), and higher hirsutism scores (1.1 +/- 0.3 vs 0.3 +/- 0.2, P = .004) than those without diabetes. No changes in sex steroids occurred after the oral glucose challenge. HOMA SI and area under the curve for glucose correlated significantly with SHBG (r = -0.42), non-SHBG-T (r = 0.40), and TC/HDL (r = 0.41) (all P < .05) in the combined groups. Postmenopausal women with type 2 diabetes have both clinical and biochemical evidence of androgen excess that may contribute to more adverse cardiovascular risk profiles.

Aged↗

PubMed2004

P-glycoprotein activity is decreased in CD4+ but not CD8+ lung allograft-infiltrating T cells during acute cellular rejection.

BACKGROUND: Modulation of P-glycoprotein (P-gp) activity in graft-infiltrating T cells may alter their susceptibility to immunosuppression. METHODS: P-gp activity was measured by rhodamine efflux in T-cell subsets from bronchoalveolar lavage (BAL) of five healthy volunteers and 27 lung allograft recipients. The effect of T-cell activation on P-gp activity was modeled by stimulation of peripheral blood mononuclear cells with staphylococcal enterotoxin B. RESULTS: Most BAL T cells expressed memory-effector markers. Patients had a lower proportion of CD4 T cells (P = 0.005), whereas control subjects had CD4-to-CD8 ratios similar to peripheral blood. In controls, basal P-gp activity was greatly increased in both CD4 (35% P-gp active) and CD8 (63%) lung T cells compared with peripheral T cells. Basal P-gp activity was elevated in patient BAL T cells but was lower than control BAL activity (CD4, P = 0.07; CD8, P = 0.03). Lung T cells from transplant patients had modest (CD4) or marked (CD8) increases in substrate-induced P-gp activity compared with normal lung, indicating that P-gp was not irreversibly inhibited. Patients with acute cellular rejection (ACR) had reduced P-gp activity in CD4, but not CD8, BAL T cells compared with patients without ACR (P = 0.004). To determine the relationship between T-cell activation on P-gp modulation, P-gp activity was measured in staphylococcal enterotoxin B-stimulated peripheral blood mononuclear cells. P-gp activity was abrogated in CD71 cycling cells but remained high in a persistent but minor population of resting naive T cells. CONCLUSIONS: Lung T cells have increased in vivo P-gp activity and therefore may eliminate substrate drugs, resulting in local resistance to immunosuppressive therapy. However, P-gp function is reduced during T-cell activation, providing a window of susceptibility to treatment during ACR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Estrogen receptor status of primary breast cancer is predictive of estrogen receptor status of contralateral breast cancer.

BACKGROUND: Tamoxifen reduces the risk for contralateral breast cancer by approximately 30%-50%, with benefits probably limited to women with estrogen receptor (ER)-positive primary disease. In a retrospective analysis of data from National Surgical and Adjuvant Breast and Bowel Project trials B-18, B-22, and B-25, we determined whether the ER status of primary breast cancer predicts the ER status of a subsequent contralateral breast cancer and whether tamoxifen treatment affects this relationship. In these trials, tamoxifen at 20 mg/day had been administered only to women aged 50 years or older, rather than to those determined by the ER status of their primary tumor, allowing an assessment of the treatment's effects in ER-negative disease. METHODS: Among the 5513 eligible patients, 176 patients developed a contralateral breast cancer. The ER status of the primary and contralateral tumor was determined and cross-classified for women who did not receive tamoxifen (i.e., those aged 49 years or younger) and for women who did (i.e., those aged 50 years or older). ER data were available for 110 evaluable invasive contralateral breast cancers. RESULTS: Among patients who did not receive tamoxifen (n = 62), 89% with an ER-positive primary cancer had an ER-positive contralateral breast cancer and 70% with an ER-negative primary breast cancer had an ER-negative contralateral breast cancer (odds ratio for the association between primary and contralateral ER status = 14.8, 95% confidence interval = 3.8 to 74.3; P<.001). Among patients who received tamoxifen (n = 48), 56% with an ER-positive primary cancer had an ER-positive contralateral breast cancer and 78% with an ER-negative primary cancer had an ER-negative contralateral breast cancer (odds ratio = 3.4, 95% confidence interval = 0.53 to 39.2; P =.25). CONCLUSION: The ER status of the primary breast cancer was associated with that of the contralateral breast for patients not receiving tamoxifen. Patients with an ER-positive primary cancer who received tamoxifen had a lower concordance rate with fewer ER-positive contralateral breast cancers, which may be a result of tamoxifen treatment.

Age Factors↗

PubMed2004

De novo breast cancer in patients with liver transplantation: University of Pittsburgh's experience and review of the literature.

De novo malignancies are one of the current problems in patients with organ transplantation. The incidence has been considered to be higher as a result of increases of oncogenic viruses in immunosuppressed organ recipients. Published reports have shown increased incidence of de novo tumors such as malignant lymphomas and cutaneous neoplasms but decreased incidence of breast cancer. A variety of factors affect de novo breast cancer development in organ recipients, including immunosuppression, viruses, and underlying disease. The aims of this review are to evaluate the incidence and management of patients with de novo breast cancer by giving the University of Pittsburgh's data, and to evaluate the incidence of de novo breast cancer in published reports in light of an age-adjusted rate. According to age-adjusted rates presented by the National Cancer Institute's Surveillance, Epidemiology and End Results data, we found increased incidence rate of de novo breast cancer in the previously published series. The University of Pittsburgh's incidence rate of de novo breast cancer was determined in a fashion similar to that for the Surveillance, Epidemiology and End Results data. Eighty-three percent of all patients were diagnosed at early stages, and it appeared to take longer for de novo breast cancer to develop in patients treated with tacrolimus than in patients treated with cyclosporine. In conclusion, surgical treatment of breast cancer in liver recipients is the same as treatment of breast cancer in patients without transplantation. However, the effects of chemotherapy, radiotherapy, and/or tamoxifen remain unclear in transplanted patients and need to be evaluated in larger studies.

Breast Neoplasms↗

PubMed2004

Bioequivalence revisited: influence of age and sex on CYP enzymes.

BACKGROUND AND OBJECTIVE: The activity of cytochrome P450 (CYP) enzymes, which determine the rate of elimination of lipid-soluble drugs, demonstrates considerable interindividual variability. The extent to which age and sex influence CYP activity remains unclear in humans. Our objectives were to determine whether in vivo activity of selected CYP enzymes is affected by age or sex and to evaluate sex bioequivalence in a large sample size. METHODS: We have assessed in vivo activity of the CYP1A2, 2C19, 2D6, 2E1, and 3A4 enzymes in 161 normal subjects (51% female subjects and 40% aged >50 years). After simultaneous administration of a cocktail of selective probes (caffeine, mephenytoin, debrisoquin [INN, debrisoquine], chlorzoxazone, and dapsone, respectively), phenotypic indices for metabolism of these drugs were used as measures of individual CYP activity. Sex bioequivalence analysis used the bootstrap method. RESULTS: There were no sex differences associated with CYP1A2 activity. A significant negative correlation (r = -0.572, P < .01) between enzyme activity and age was observed for CYP2C19, but there were no sex differences. CYP2D6 activity showed no dependence on age or sex. In contrast, CYP2E1 activity showed an age-associated increase (r = 0.393, P < .01), which developed earlier in life in male subjects compared with female subjects. These results were further supported by the sex bioequivalence analysis of CYP phenotypic activity, which revealed that sexes were equivalent with respect to CYP2C19 (90% confidence interval [CI], 0.874-1.04), CYP3A4 (90% CI, 0.95-1.176), and CYP2D6 (90% CI, 0.928-1.09) phenotype and just exceeded the 0.8 to 1.25 limits to be equivalent with respect to CYP2E1 (90% CI, 0.785-1.08) and CYP1A2 (90% CI, 0.736-1.03) phenotype. CONCLUSION: These observations suggest that the presence of selective mechanisms of regulation for individual CYP enzymes can be influenced by age and sex. However, we suggest that sex has a limited ability to explain intersubject variation of activity for these phenotypic measures of CYP enzyme activity.

Adolescent↗

PubMed2004

Crohn's disease: a two-year prospective study of the association between psychological distress and disease activity.

Our objective was to explore the relationship between psychological distress and subsequent Crohn's disease (CD) activity. Eighteen CD patients were followed prospectively for 2 years at 8- to 12-week intervals. Disease activity was assessed using the Crohn's Disease Activity Index (CDAI). Psychological distress was assessed using the following self-administered questionnaires: Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Beck Hopelessness Scale (BHS), and multiple Holmes Recent Life Changes (RLC) Questionnaires. The effects of psychological distress on current and subsequent CDAI (approximately 8-12 weeks later) were assessed using generalized estimating equations (GEE). The mean CDAI score during follow-up was 138 +/- 86, with a median of 121 (range, 0 to 394). BDI scores (possible range of 0 to 63) were independently associated with CDAI scores simultaneously (beta = 5.64, P = 0.004) and 8-12 weeks later (beta = 6.08, P = 0.004). Higher levels of anxiety, hopelessness, and recent life changes were also suggestive of higher CDAI scores, however, their effects were generally of lesser magnitude and not independent of the influence of depressive symptoms. Levels of depressive symptoms are positively associated with future changes in CDAI. Routine psychological assessment may help to identify patients at higher risk for exacerbation.

Adult↗

PubMed2004

Nodular glomerulosclerosis in cystic fibrosis mimics diabetic nephropathy.

BACKGROUND/AIMS: Despite the cystic fibrosis gene product, the cystic fibrosis transmembrane conductance regulator, being widely expressed throughout the kidney, there is no clearly defined renal phenotype in patients with cystic fibrosis. As patients with cystic fibrosis survive longer progressive pancreatic destruction may lead to abnormal glucose tolerance and diabetes mellitus, which in the kidney may be associated with the characteristic changes of nodular glomerulosclerosis. METHODS: The adult cystic fibrosis service at the Alfred hospital consists of a cohort of 200 patients. We describe 3 cystic fibrosis patients with impaired renal function who had renal biopsies performed as part of their diagnostic work-up. All patients had fasting plasma glucose levels, oral glucose tolerance tests and measurements of HbA1c performed to assess for the presence of cystic fibrosis-related diabetes mellitus. RESULTS: The renal biopsies of all 3 patients showed histological changes characteristic of diabetic nephropathy. In all cases described characteristic Kimmelstiel-Wilson nodules were present. However, in all 3 patients the presence of impaired glucose tolerance and diabetes mellitus was excluded using standard biochemical diagnostic criteria. CONCLUSION: We describe 3 adult CF patients, who on renal biopsy had histological evidence of nodular glomerulosclerosis in the absence of abnormal glucose metabolism. We speculate that the pro-inflammatory cytokine profile, typical of cystic fibrosis, predisposes to the lesions described.

Adult↗

PubMed2004

Astronaut EVA exposure estimates from CAD model spacesuit geometry.

Ongoing assembly and maintenance activities at the International Space Station (ISS) require much more extravehicular activity (EVA) than did the earlier U.S. Space Shuttle missions. It is thus desirable to determine and analyze, and possibly foresee, as accurately as possible what radiation exposures crew members involved in EVAs will experience in order to minimize risks and to establish exposure limits that must not to be exceeded. A detailed CAD model of the U.S. Space Shuttle EVA Spacesuit, developed at NASA Langley Research Center (LaRC), is used to represent the directional shielding of an astronaut; it has detailed helmet and backpack structures, hard upper torso, and multilayer space suit fabric material. The NASA Computerized Anatomical Male and Female (CAM and CAF) models are used in conjunction with the space suit CAD model for dose evaluation within the human body. The particle environments are taken from the orbit-averaged NASA AP8 and AE8 models at solar cycle maxima and minima. The transport of energetic particles through space suit materials and body tissue is calculated by using the NASA LaRC HZETRN code for hadrons and a recently developed deterministic transport code, ELTRN, for electrons. The doses within the CAM and CAF models are determined from energy deposition at given target points along 968 directional rays convergent on the points and are evaluated for several points on the skin and within the body. Dosimetric quantities include contributions from primary protons, light ions, and electrons, as well as from secondary brehmsstrahlung and target fragments. Directional dose patterns are displayed as rays and on spherical surfaces by the use of a color relative intensity representation.

Astronauts↗

PubMed2004

Incidence of tuberculosis in Olmsted County, Minnesota, 1990-2001.

OBJECTIVE: To describe and compare the incidence and clinical characteristics of tuberculosis in Olmsted County, Minnesota, among US-born and foreign-born persons. PATIENTS AND METHODS: We performed a retrospective cohort study at the Mayo Clinic in Rochester, Minn, of all residents of Olmsted County (2000 population: 124,277) diagnosed as having tuberculosis between January 1, 1990, and December 31, 2001. Potential cases were identified with use of a computerized diagnostic coding database and microbiological laboratory data; all identified medical records were abstracted. Definite cases were those in which Mycobacterium tuberculosis was recovered in culture. Probable cases were those that met predefined clinical or radiographic evidence of tuberculosis and other criteria. Age-specific, sex-specific, and country of origin-specific incidence rates were calculated with use of Olmsted County census data. Variables were compared among risk groups using the Fisher exact test. RESULTS: During a 12-year period, 71 cases of tuberculosis (53 definite, 18 probable) were identified, for an incidence of 5.3 per 100,000 person-years. Of these cases, 54 (76%) occurred during the second half of the study (incidence: 7.7 per 100,000 person-years). The incidence among US-born persons was similar throughout the study period; however, the Incidence among foreign-born persons increased more than 3-fold during the second half of the study period. Twenty-five patients (35%) were former refugees. All isoniazid-resistant infections (12% of isolates) and multidrug-resistant infections (6% of isolates) occurred among foreign-born persons. CONCLUSION: The incidence of tuberculosis increased substantially in Olmsted County between 1990 and 2001, primarily because of an increase in the number of cases among foreign-born persons.

Adult↗

PubMed2003

Airway vascular remodeling in asthma.

Several characteristic changes occur in the bronchial wall in asthma, including specific changes to the vasculature. These result in an increase in vessel numbers per unit area, as well as increased vessel activity suggested by vasodilatation, vessel leakage, and cellular margination with transmigration to target tissues. This combined action in asthma leads to airway-wall thickening and reduced airflow. Each component of the vascular response has been shown to be controlled by a range of inflammatory mediators and growth factors. These factors are themselves regulated by a complex process initially involving gene expression, transcription, and translation at the molecular level, then subsequent protein release, binding to matrix elements, endothelial cell activation, and a proliferative endothelial response. Many commonly used airway medications are capable of modulating the vascular response to inflammatory stimuli. New therapies might improve airflow through better regulation of vessel growth, dilatation, and leakage in the airway wall.

Airway Resistance↗

PubMed2003

Coordinated intrahepatic and extrahepatic regulation of cytochrome p4502D6 in healthy subjects and in patients after liver transplantation.

Cytochrome p450 (CYP) 2D6 activity exhibits wide intersubject variation even among individuals with similar genotypes in whom the active enzyme is expressed. There is, therefore, a need to understand the mechanisms involved in determining its activity. The relationship of messenger ribonucleic acid (mRNA) expression to CYP2D6 activity has been evaluated in hepatic and extrahepatic tissues to test the hypothesis of coordinated regulation. In human liver microsomes, there was a greater than 25-fold variation in both bufuralol hydroxylation and concentration of mRNA for CYP2D6, with a significant association between variables (n = 20; Spearman correlation coefficient [r(s)] = 0.85, P <.001). In normal subjects, there was a similar extent of interindividual variation in in vivo activity of CYP2D6, measured as the debrisoquin (INN, debrisoquine) recovery ratio, and in mRNA for CYP2D6 in peripheral blood mononuclear cells, with a significant association between variables (n = 78; r(s) = 0.56 [95% confidence interval, 0.35 to 0.73], P <.001), whereas no association was found between mRNA for CYP2D6 and CYP2E1 activity. Recipients of liver transplants, at a time of stable liver function, had a similar relationship between debrisoquin recovery ratio and concentration of mRNA for CYP2D6 in peripheral blood mononuclear cells (n = 27; r(s) = 0.74 [95% confidence interval, -0.16 to 0.44], P <.001). Three recipients, who had CYP2D6*4/*4 genotypes, remained phenotypically poor metabolizers for CYP2D6 after liver transplantation. Collectively, these results imply that transcriptional regulation of mRNA for CYP is a major determinant of in vivo activity and that regulation of intrahepatic and extrahepatic enzymes is coordinated, possibly through a mechanism that is predominantly extrahepatic.

Actins↗

PubMed2003

Preliminary validation of computational procedures for a new atmospheric ionizing radiation (AIR) model.

A new computational procedure to determine particle fluxes in the Earth's atmosphere is presented. The primary cosmic ray spectrum has been modeled through an analysis of simultaneous proton and helium measurements made on high altitude balloon flights and spacecraft. An improved global fit to the data was achieved through applying a unique technique utilizing the Fokker-Plank equation with a non-linear rigidity-dependent diffusion coefficient. The propagation of primary particles through the Earth's atmosphere is calculated with a three-dimensional Monte Carlo transport program called FLUKA. Primary protons and helium nuclei (alphas) are generated within the rigidity range of 0.5 GV-20 TV uniform in cos2 theta. For a given location, primaries above the effective cutoff rigidity are transported through the atmosphere. Alpha particles are initially transported with a separate package called HEAVY to simulate fragmentation. This package interfaces with FLUKA to provide interaction starting points for each nucleon originating from a helium nucleus. Results from this calculation are presented and compared to measurements.

Alpha Particles↗

PubMed2003

Differential inhibition of thrombin- and EGF-stimulated human cultured airway smooth muscle proliferation by glucocorticoids.

The present study compared the effects of glucocorticoids on thrombin- and EGF-stimulated proliferation in human cultured airway smooth muscle (ASM) to identify pathways that may be differentially regulated by glucocorticoids. Mitogenic responses to thrombin were inhibited by extracellular-regulated kinase (ERK 1/2) and phosphoinositide 3-kinase (PI3K) inhibitors, whereas mitogenic responses to EGF were inhibited by ERK 1/2 and PI3K inhibitors as well as by the p38 mitogen activated protein kinase inhibitor, SB203580 (10 microM). Mitogenic responses to thrombin were more sensitive to inhibition by dexamethasone (Dex) or fluticasone propionate (FP) than were those to EGF. Elevated cyclin D1 protein and mRNA levels induced by thrombin and EGF were attenuated equally by glucocorticoids. The protein or mRNA levels of the cyclin-dependent kinase inhibitors (cdki) p21(Cip1), p27(Kip1) were unaffected by Dex treatment of ASM cells treated with mitogens. The resistance of EGF-induced proliferation to inhibition by glucocorticoids is not associated with a failure to regulate cyclin D1 induction, nor does it appear to be explained by differential regulation of the levels of the cdki's, p21(Cip1) and p27(Kip1).

Bronchi↗

PubMed2003

Collagen-induced resistance to glucocorticoid anti-mitogenic actions: a potential explanation of smooth muscle hyperplasia in the asthmatic remodelled airway.

Glucocorticoids (GCS) inhibit mitogenesis of airway smooth muscle (ASM) cells grown on plastic. We have now evaluated the effects of GCS on proliferation of ASM grown on extracellular matrix proteins (ECM) abundant in noninflamed airways (laminin) and in fibrotic asthmatic airways (collagen type I). Dexamethasone inhibited basic fibroblast growth factor (bFGF)-induced proliferation in cells maintained on laminin, but not collagen. Cells grown on collagen were resistant to the anti-mitogenic actions of fluticasone propionate. In addition, dexamethasone did not inhibit thrombin-induced proliferation. Thus, resistance induced by collagen is not dependent on the mitogen and appears to be a class effect on GCS. The inhibition of bFGF-induced granulocyte-macrophage colony-stimulating factor production was unaffected by the ECM type on which cells were grown. The impaired anti-mitogenic activity of GCS in cells maintained on collagen may be due to a lack of efficacy against the collagen-amplified mitogenesis, rather than any defect in responsiveness that is specific to glucocorticoid receptor mechanisms.

Asthma↗

PubMed2003

Smoking during pregnancy is associated with alterations in markers of endothelial function.

OBJECTIVE: Alterations in endothelial function may explain the reduced risk of preeclampsia that is associated with smoking. We hypothesized that markers of endothelial function increase over pregnancy but decrease with smoking. STUDY DESIGN: Plasma samples were obtained throughout pregnancy from 63 primiparous women with normal pregnancies. The samples were assayed for cellular fibronectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1. Smoking status was determined by urinary cotinine concentrations. RESULTS: Mean cellular fibronectin concentrations were different by time (P<.001) and smoking status (P=.01); the lowest concentrations were found in smokers. In contrast, intracellular adhesion molecule-1 was different by smoking status (P=.046); the highest concentrations were found in smokers. Vascular cell adhesion molecule-1 was different over time (P<.001), but not by smoking status. CONCLUSION: Smoking during pregnancy is associated with reduced cellular fibronectin and increased intracellular adhesion molecule-1. These differences may be the result of different aspects of endothelial function or the source of the marker. The explanation for reduced preeclampsia in smokers remains elusive.

Biomarkers↗

PubMed2003

A limited sampling method for the estimation of serum calcitriol area under the curve in cancer patients.

Pharmacokinetic (PK) data from 34 cancer patients receiving 2 to 10 micrograms of calcitriol subcutaneously (s.c.) were used to develop a limited sampling method for predicting serum calcitriol area under curve (AUC) based on three samples instead of the full complement of 12 to 16 samples. Serum calcitriol levels were measured by 1, 25-dihydroxyvitamin D3-[I125] radioimmunoassay. Individual patient-corrected serum calcitriol AUC0-12 h was calculated by the trapezoidal rule after subtracting the pretreatment serum calcitriol level. PK data were split into "training" and "evaluation" sets based on calcitriol dose and chronological order of enrollment. Linear regression models of log-corrected AUC0-12 h versus individual log calcitriol serum levels in the hour 1, 2, 3, 4, 6, and 8 samples were established using the training data set of 17 patients. The fit was tested on the evaluation data set of 17 patients using mean squared error (MSE) as the fit criterion. The best single time point predictor of log AUC0-12 h was the log serum (calcitriol) at hour 6 (MSE = 0.0061). The best prediction of log AUC0-12 h using two time points was found to involve hour 6 and hour 2 (MSE = 0.0018). The prediction equation for the latter model was as follows: Log AUC = 1.125 + 0.3756.log (calcitriol) at hour 2 + 0.5859.log (calcitriol) at hour 6. This limited sampling method was further evaluated in 83 cancer patients treated with 4 to 38 micrograms of oral (p.o.) calcitriol; observed and predicted calcitriol AUC0-12 h were highly correlated (r > or = 0.90, p = 0.0001). These results show that serum calcitriol AUC0-12 h after s.c. and p.o. calcitriol administration is accurately estimated using pretreatment and 2- and 6-hour blood samples.

Area Under Curve↗