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Biomedical subjects

D C Wolf

Publications and source records attributed to D C Wolf.

At least 19 recordsLinked to original sources
PubMed2005

Effects of prenatal perfluorooctane sulfonate (PFOS) exposure on lung maturation in the perinatal rat.

BACKGROUND: Perfluorooctane sulfonate (PFOS), found widely in wildlife and humans, is environmentally and metabolically stable. Environmental PFOS may be from its use as a surfactant, hydrolysis of perfluorooctanesulfonyl fluoride, and degradation of N-alkyl-perfluorooctanesulfonamide compounds formerly used in numerous applications. Prenatal exposure to PFOS in rodents causes neonatal mortality; treatment on gestation days (GD) 19-20 is sufficient to induce neonatal death in rats. Affected pups are born alive but present with labored breathing. Their lungs are pale and often do not expand fully on perfusion. METHODS: Pregnant Sprague-Dawley rats received 0, 25, or 50 mg/kg/day PFOS/K+ orally on GD 19-20. Lungs from GD 21 fetuses and neonates were prepared for histology and morphometry. Rescue experiments included co-administration of dexamethasone or retinyl palmitate with PFOS. Pulmonary surfactant was investigated with mass spectrometry in GD 21 amniotic fluid and neonatal lungs. Microarray analysis was carried out on PND 0 lungs. RESULTS: Histologically, alveolar walls were thicker in lungs of PFOS-exposed newborns compared to controls. The ratio of solid tissue:small airway was increased, suggesting immaturity. Rescue studies were ineffective. Phospholipid concentrations and molecular speciation were unaffected by PFOS. No changes in markers of alveolar differentiation were detected by microarray analysis. CONCLUSIONS: Morphometric changes in lungs of PFOS exposed neonates were suggestive of immaturity, but the failure of rescue agents and normal pulmonary surfactant profile indicate that the labored respiration and mortality observed in PFOS-treated neonates was not due to lung immaturity.

Alkanesulfonic Acids↗
PubMed2005

Transcriptomic analysis of F344 rat nasal epithelium suggests that the lack of carcinogenic response to glutaraldehyde is due to its greater toxicity compared to formaldehyde.

Formaldehyde is cytotoxic and carcinogenic to the rat nasal respiratory epithelium inducing tumors after 12 months. Glutaraldehyde is also cytotoxic but is not carcinogenic to nasal epithelium even after 24 months. Both aldehydes induce similar acute and subchronic histopathology that is characterized by inflammation, hyperplasia, and squamous metaplasia. Because early aldehyde-induced lesions are microscopically similar, we investigated whether transcriptional patterns using cDNA technology could explain the different cancer outcomes. Treatments included 1-, 5-, or 28-day exposure by nasal instillation of formaldehyde solution (400 mM) or glutaraldehyde solution (20 mM). Animals were euthanized and the nasal respiratory epithelium removed for gene expression analysis and a subset of rats treated for 28 days was processed for microscopic examination. RNA was isolated and processed for expression assessment using Clontech Atlas Toxicology II Arrays. Both aldehydes induced hyperplasia, squamous metaplasia, and inflammatory infiltrates with scattered apoptotic bodies in the epithelium covering luminal surfaces of the nasoturbinate, maxilloturbinate, and nasal septum. A subset of 80 genes that were the most variant between the treated and control included the functional categories of DNA repair and apoptosis. Hierarchical clustering discriminated chemical treatment effects after 5 days of exposure, with 6 clusters of genes distinguishing formaldehyde from glutaraldehyde. These data suggest that although both aldehydes induced similar short-term cellular phenotypes, gene expression could distinguish glutaraldehyde from formaldehyde. The gene expression patterns suggest that glutaraldehyde's lack of carcinogenicity may be due to its greater toxicity from lack of DNA-repair, greater mitochondrial damage, and increased apoptosis.

Administration, Intranasal↗
PubMed2004

Changes in cecal microbial metabolism of rats induced by individual and a mixture of drinking water disinfection by-products.

Disinfection of drinking water has been one of the greatest public health successes. Numerous halogenated disinfection by-products (DBPs) occur and chronic ingestion has been associated with an increased risk for colorectal cancer in human populations. Because the intestinal microbiota can bioactivate xenobiotics, studies have been performed to examine the effects of individual DBPs on intestinal microbial metabolism. No studies have been conducted on a defined mixture of DBPs to determine if there is an enhancement of response to a mixture. Ten-week-old male Long-Evans rats were treated in their drinking water for 17 weeks with 0.4 g/l potassium bromate, 1.8 g/l chloroform, 0.7 g/l bromodichloromethane (BDCM), 0.07 g/l 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), or a mixture of the four chemicals or distilled water. Cecal nitroreductase (NR), azoreductase (AR), dechlorinase (DC), beta-glucuronidase (GLR), beta-galactosidase (GAL), and beta-glucosidase (GLU) were assayed. No change in GLU or GLR activity was detected after treatment. BDCM treatment reduced DC and GAL activities and elevated NR and AR activity. GAL, AR, and NR activities were significantly different after treatment with bromate, chloroform, BDCM, and MX, but not the mixture. DC activity after chloroform-, MX-, or BDCM-treatment was significantly below control levels. The present study shows that changes in intestinal microbial metabolism do occur after treatment with individual and a mixture of DBPs but the changes were not additive in the mixture group.

Animals↗
PubMed2003

Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: a randomized, double-blind, placebo-controlled, dose-escalation trial.

BACKGROUND: Repifermin (keratinocyte growth factor-2) has been shown to reduce inflammation in animal models of colitis. AIM: To evaluate repifermin for the treatment of active ulcerative colitis. METHODS: Eighty-eight patients with active ulcerative colitis were enrolled in a 6-week, double-blind trial. Patients were randomized to receive treatment for five consecutive days with intravenous repifermin at a dose of 1, 5, 10, 25 or 50 microg/kg, or placebo. The primary objective of the study was to evaluate the safety of repifermin. The primary efficacy outcome was clinical remission at week 4, defined as a score of zero on the endoscopic appearance and stool blood components of the Mayo score and a score of zero or unity on the stool frequency and physician's global assessment components. RESULTS: At week 4, the rates of clinical remission in the 1, 5, 10, 25 and 50 microg/kg repifermin groups were 19%, 9%, 0%, 0% and 0%, respectively, and 11% for the placebo group (P = 0.32 for repifermin vs. placebo). The frequencies of commonly occurring adverse events and severe adverse events were similar in both groups. CONCLUSIONS: Intravenous repifermin at a dose of 1-50 microg/kg was very well tolerated, but there was no evidence that repifermin was effective for the treatment of active ulcerative colitis at these doses. An additional study to determine the efficacy of repifermin at doses of > 50 microg/kg or for a longer treatment duration may be warranted, as the maximally tolerated dose was not reached in the present study.

Adult↗
PubMed2003

Prenatal window of susceptibility to perfluorooctane sulfonate-induced neonatal mortality in the Sprague-Dawley rat.

The critical period for increased neonatal mortality induced by perfluorooctane sulfonate (PFOS) exposure was evaluated in the rat. Timed-pregnant Sprague-Dawley rats were treated by oral gavage with 25 mg/kg/d PFOS/K(+) on four consecutive days (gestation days (GD) 2-5, 6-9, 10-13, 14-17, or 17-20) or with 0, 25, or 50 mg/kg/d PFOS/K(+) on GD 19-20. Controls received vehicle (10 ml/kg 0.5% Tween-20) on these days. Maternal weight gain was reduced in treated animals during dosing, as were food and water consumption. Following a 4-day treatment, litter size at birth was unaffected while pup weight was similarly reduced in the three earliest PFOS groups. All PFOS groups experienced decreases in survival while controls remained near 100%. Neonatal survival decreased in groups dosed later during gestation, approaching 100% with dosing on GD 17-20. Most deaths occurred before postnatal day (PND) 4, with the majority in the first 24 hours. Maternal serum PFOS levels on GD 21 were higher in groups exhibiting higher mortality. Following a 2-day treatment, PFOS groups experienced significant pup mortality by PND 1. Neonatal mortality continued through PND 5, when survival was 98, 66, and 3% for the 0, 25, and 50 mg/kg groups, respectively. Pup weight was reduced in treated groups with surviving litters. Gross dissection and histological examination of lungs revealed differences in maturation between control and treated animals on PND 0. We conclude that exposure to PFOS late in gestation is sufficient to induce 100% pup mortality and that inhibition of lung maturation may be involved.

Abnormalities, Drug-Induced↗
PubMed2003

Influence of organic and inorganic soil amendments on plant growth in crude oil-contaminated soil.

Phytoremediation can be a viable alternative to traditional, more costly remediation techniques. Three greenhouse studies were conducted to evaluate plant growth with different soil amendments in crude oil-contaminated soil. Growth of alfalfa (Medicago sativa L., cultivar: Riley), bermudagrass (Cynodon dactylon L., cultivar: Common), crabgrass (Digitaria sanguinalis, cultivar: Large), fescue (Lolium arundinaceum Schreb., cultivar: Kentucky 31), and ryegrass (Lolium multiflorum Lam., cultivar: Marshall) was determined in crude oil-contaminated soil amended with either inorganic fertilizer, hardwood sawdust, papermill sludge, broiler litter or unamended (control). In the first study, the addition of broiler litter reduced seed germination for ryegrass, fescue, and alfalfa. In the second study, bermudagrass grown in broiler litter-amended soil produced the most shoot biomass, bermudagrass produced the most root biomass, and crabgrass and bermudagrass produced the most root length. In the third study, soil amended with broiler litter resulted in the greatest reduction in gravimetric total petroleum hydrocarbon (TPH) levels across the six plant treatments following the 14-wk study. Ryegrass produced more root biomass than any other species when grown in inorganic fertilizer- or hardwood sawdust + inorganic fertilizer-amended soil. The studies demonstrated that soil amendments and plant species selection were important considerations for phytoremediation of crude oil-contaminated soil.

Cynodon↗
PubMed2003

Phytoremediation of pyrene in a Cecil soil under field conditions.

We evaluated the effects of annual ryegrass (Lolium multiflorum Lam.) and phosphorus (P) availability on the dissipation of pyrene added at a concentration of approximately 600 mg kg-1 dry soil in the top 7.5 cm of a Cecil loamy sand (fine, kaolinitic, thermic Typic Kanhapludults) in a 10-month experiment under field conditions in Clemson, South Carolina. Plastic canopies were installed to prevent flooding of plots and raindrop dispersion of pyrene. Treatment factors were pyrene, vegetation, and available P levels. Each of the eight treatments had four replicates. The soil was adjusted to low and high P concentrations (an average of 41 and 66 kg extractable P ha-1, respectively). After a 175-d lag period for all treatments, the rate of pyrene removal followed first-order kinetics. The first-order rate constant was significantly higher in nonvegetated (0.098 d-1) than vegetated treatments (0.034 d-1). These data suggest that the presence of easily biodegradable organic matter from plant roots slowed the removal rate of pyrene. The levels of available P did not affect the rate of pyrene dissipation. Pyrene decreased below the detection limit of 6.25 mg kg-1 dry soil in all treatments after 301 d.

Biodegradation, Environmental↗
PubMed2003

A mathematical model of phytoremediation for petroleum-contaminated soil: model development.

We present a simple model for root length density that combines the generally accepted spatial (exponential decrease with depth) and temporal (sinusoidal) variability of root length. Parameters in this model for root length density can be determined from assumed or measured information regarding the annual biomass turnover, maximum standing biomass, and maximum depth of root penetration. The root length density model, coupled with information regarding the average root lifespan, gives specific root growth and senescence functions that are the forcing functions for the phytoremediation model. We present a screening level mathematical model for phytoremediation that accounts for the growth and senescence of roots in the system. This is an important factor for recalcitrant, immobile compounds found in weathered crude oil contaminated soils. The phytoremediation model is based on variable volume compartments that have individual first-order degradation rate constants; as the roots move through the soil, the soil cycles through the rhizosphere zone, decaying root zone and bulk soil zone. Thus, although the oil is immobile, as the roots penetrate through the soil the oil is brought into contact with the rhizosphere.

Algorithms↗
PubMed2003

A mathematical model of phytoremediation for petroleum contaminated soil: sensitivity analysis.

Phytoremediation is an attractive treatment technology for many contaminated sites due to its cost effectiveness and public acceptance. We present a sensitivity analysis of important parameters from a screening level model for phytoremediation by grass species of weathered petroleum-contaminated sites. The conceptual framework is that root movement through contaminated soil will enhance contaminant biodegradation by providing a local environment more favorable for petroleum degrading microorganisms--the so-called rhizosphere effect. Common questions in phytoremediation are, "What species should be planted?" and "What management practices should be followed?" These choices may affect degradation kinetics, root biomass (and therefore rhizosphere volume), and the root turnover. Important model parameters are the rate constants, rhizosphere volume, and the rate of root turnover. We present a sensitivity analysis with the aim of identifying the most important factors for improving phytoremediation effectiveness. For simulations of the phytoremediation of weathered diesel range organics, our results indicate that annual species, with higher root turnover, are preferred over perennial species with the caveat of equal degradation rate constants, that is, no species-dependent effects. In addition, the results suggest that the management of nonrhizosphere soil could play an important role in the overall effectiveness of phytoremediation. Finally, the effect of increasing root biomass or increasing the rhizosphere thickness is approximately equivalent with respect to the ultimate removal of the contaminants.

Environmental Pollution↗
PubMed2002

Treatment of mildly to moderately active ulcerative colitis with a tryptase inhibitor (APC 2059): an open-label pilot study.

BACKGROUND: Mast cells isolated from the colonic mucosa in active ulcerative colitis appear to be partially degranulated, suggesting the release of tryptase. AIM: To investigate the safety and activity of APC 2059, a highly specific tryptase inhibitor, in the treatment of ulcerative colitis. METHODS: This was an open-label, Phase 2, multicentre pilot study in patients with mildly to moderately active ulcerative colitis, with a disease activity index of 6-9 on a 12-point scale. Fifty-six adults received 20 mg APC 2059 subcutaneously twice daily and 53 completed 28 days of treatment. The primary end-point was response, defined as a final disease activity index of < or = 3. Supplementary analyses were also performed. RESULTS: Sixteen (29%) of 56 patients responded. Five (9%) showed complete remission (disease activity index=0). Twenty-seven (49%) improved, with a final disease activity index of < or = 3 or a four-point reduction. Improvement or normalization in each category of the disease activity index was as follows: stool frequency, 64%; bleeding, 64%; endoscopy, 50%; physicians' rating, 63%. There were no significant relationships between outcome and pharmacokinetics. The most common adverse events were related to the injection site (32.1%). CONCLUSIONS: In this pilot study, the tryptase inhibitor APC 2059 was safe and there was evidence of activity in the treatment of ulcerative colitis.

Adult↗
PubMed2001

An engineered human antibody to TNF (CDP571) for active Crohn's disease: a randomized double-blind placebo-controlled trial.

BACKGROUND & AIMS: We evaluated CDP571, a humanized antibody to tumor necrosis factor, for the treatment of active Crohn's disease. METHODS: One hundred sixty-nine patients with moderate-to-severe Crohn's disease were enrolled in a 24-week placebo-controlled trial. Patients were initially randomized to a single dose of 10 or 20 mg/kg CDP571 or placebo to assess dose response. Patients were then retreated with 10 mg/kg CDP571 or placebo every 8 or 12 weeks to assess subsequent dosing intervals. The primary endpoint was clinical response at week 2, defined as a decrease in the Crohn's Disease Activity Index score > or = 70 points. RESULTS: At week 2, clinical response occurred in 45% of CDP571-treated patients compared with 27% of patients in the placebo group (P = 0.023). Patients appeared to benefit from retreatment with CDP571 over 24 weeks, but not all of the results for secondary endpoints were statistically significant. The frequency of severe or serious adverse events was similar among all groups. CONCLUSIONS: CDP571 at an initial dose of 10 or 20 mg/kg is safe and effective for treatment of patients with moderate-to-severe Crohn's disease. Preliminary evidence suggests that retreatment with 10 mg/kg CDP571 at dose intervals of 8 or 12 weeks may also be beneficial, but additional studies are needed.

Adolescent↗
PubMed2000

Re-evaluation of the 2-year chloroform drinking water carcinogenicity bioassay in Osborne-Mendel rats supports chronic renal tubule injury as the mode of action underlying the renal tumor response.

Chloroform, generally regarded as a non-genotoxic compound, is associated with the induction of liver and/or kidney tumors in laboratory mice and rats. In particular, chloroform produced renal tubule tumors in low incidence in male Osborne-Mendel rats when administered by corn-oil gavage or in the drinking water. There is a lack of data on intermediate endpoints that may be linked to renal cancer development in this strain of rat, in contrast to mice. Specifically, evidence linking chloroform-induced liver and kidney tumors in mice with cytotoxicity and regenerative cell proliferation is very strong, but weak in the rat. In the present study, kidney tissue from a carcinogenicity bioassay of chloroform in Osborne-Mendel rats was re-evaluated for histological evidence of compound-induced cytotoxicity and cell turnover. All rats treated with 1800 ppm (160 mg/kg/day, high-dose group) in the drinking water for 2 years and half the rats treated with 900 ppm (81 mg/kg/day) had mild to moderate changes in proximal convoluted tubules in the mid to deep cortex indicative of chronic cytotoxicity. Tubule alterations specifically associated with chronic chloroform exposure included cytoplasmic basophilia, cytoplasmic vacuolation, and nuclear crowding consistent with simple tubule hyperplasia. Occasional pyknotic cells, mitotic figures in proximal tubules, and prominent karyomegaly of the renal tubule epithelium were present. These alterations were not present in control groups or at the 200-ppm (19 mg/kg/day) or 400-ppm (38 mg/kg/day) dose levels. This new information adds substantially to the weight of evidence that the key events in chloroform-induced carcinogenicity in rat kidney include sustained cellular toxicity and chronic regenerative hyperplasia.

Adenoma↗
PubMed2000

Bioavailability of the genotoxic components in coal tar contaminated soils in Fischer 344 rats.

The effect of chemical aging on the bioavailability and subsequent genotoxicity of coal tar (CT)-contaminated soils was evaluated in a 17-day feeding study using Fischer 344 male rats. Rats consumed a control diet or diets amended with soil, 0.35% CT, or soil freshly prepared or aged for 9 months with 0.35% CT. Mild treatment-related microscopic lesions in liver tissue and elevated enzyme levels in serum were detected in all CT treatment groups. The (32)P-postlabeling assay was employed to determine DNA adduct formation in treated animals. All CT treatment groups induced DNA adducts in both the liver and lung. Adduct levels were 3-fold higher in lung DNA compared to hepatic DNA. After correcting adduct levels for total ingested polycyclic aromatic hydrocarbons (PAHs), a significant decrease (p < 0.05) in adduct levels was observed in both CT/soil treatment groups compared to CT control in liver and lung DNA. Adduct profiles of (32)P-postlabeled hepatic and lung DNA displayed several nonpolar DNA adducts that comigrated with PAH-adducted calf thymus DNA standards as determined through both thin-layer chromatography (TLC) and high-pressure liquid chromatography (HPLC). These results suggest that soil, but not aging of contaminants in soil, decreases the bioavailability of genotoxic components in CT, as evidenced by DNA adduct analysis.

Animals↗
PubMed2000

Sensitivity of commonly available screening tests in detecting hepatocellular carcinoma in cirrhotic patients undergoing liver transplantation.

OBJECTIVE: Recognition of hepatocellular carcinoma (HCC) is important in the management of patients awaiting liver transplantation. HCCs >5 cm in diameter are at high risk to recur after transplant. The goal of this study was to assess the sensitivity of the diagnostic tests employed in a pretransplant screening program. METHODS: The study is a retrospective analysis of charts of 106 consecutive adults transplanted over a 1-yr period. All patients had ultrasonography (US), computerized tomography (CT), and serum alpha fetoprotein (AFP) testing within 6 months of transplantation. Radiographic reports were subdivided into low-risk and high-risk groups, based upon level of suspicion for HCC. The results were compared to explant pathology. RESULTS: Pathological analysis of 106 explants revealed HCC in 19 patients. High-risk US exams had a positive predictive value (PPV) of 0.69 and a negative predictive value (NPV) of 0.91 in the diagnosis of HCC. High-risk CT exams had a PPV of 0.67 and an NPV of 0.90. When patients had either a high-risk US or a high-risk CT, there was a PPV of 0.59 and an NPV of 0.83. Of the 19 patients with HCC, three had high-risk US and low-risk CT; two had high-risk CT and low-risk US. Four patients, all with HCC <4 cm, had low-risk US, CT, and serum AFP. CONCLUSIONS: US, CT, and serum AFP, as single tests, are insensitive for detection of HCC in the cirrhotic liver. However, they are highly specific. Sensitivity and specificity for US are comparable to those for CT. Given its lower cost, US is preferable to CT for routine screening of HCC in patients with end-stage liver disease undergoing liver transplantation.

Adult↗
PubMed2000

Promotion by sodium barbital induces early development but does not increase the multiplicity of hereditary renal tumors in Eker rats.

Induced cell proliferation is important in the mode of action of many non-genotoxic renal carcinogens. Since Tsc2 mutant (Eker) rats are genetically predisposed to the development of renal cell tumors, they provide a useful animal model in which to study the action of renal carcinogens. Sodium barbital was used as a model non-genotoxic renal carcinogen to test whether a concentration that increased renal tubular proliferation without severe nephrotoxicity would enhance tumor induction in a hereditary tumor model. First, a subchronic concentration-response study was conducted in wild-type male Long-Evans rats to determine increased cell proliferation without severe nephrotoxicity. Rats were dosed with sodium barbital in the feed at 0, 50, 250, 500, 1000, 2000 or 4000 p.p.m. for 3 or 8 weeks. Cell proliferation within the cortex and nephrotoxicity were quantitated. Enhanced proliferation with minimal nephrotoxicity occurred at 500 p.p.m. A second study was conducted in male Tsc2 mutant rats given sodium barbital in the feed at 0, 100 or 500 p.p.m. from 9 weeks of age to either 6 or 12 months of age. An additional group of rats was treated with sodium barbital for 6 months and then provided control feed until 12 months of age. Rats necropsied at 6 months of age had a concentration-dependent increase in preneoplastic and total renal lesions. Sodium barbital-treated rats necropsied at 12 months of age had numbers of lesions that were not different from controls. Total combined preneoplastic and neoplastic lesions in the 6 month, high dose group was the same as the 12 month control group. These data show that sodium barbital caused progression to the stage of spontaneous renal lesions in Tsc2 mutant rats but did not increase their overall number. These data suggest that enhanced cell proliferation without significant cytotoxicity exerted a promotional influence in this hereditary model.

Animals↗
PubMed1999

Concomitant human immunodeficiency virus protease inhibitor therapy markedly reduces tacrolimus metabolism and increases blood levels.

We present the case of a patient with hepatitis C-induced cirrhosis and concomitant human immunodeficiency virus infection who underwent orthotopic liver transplantation. The patient developed severe, prolonged tacrolimus toxicity in the presence of human immunodeficiency virus protease inhibitors. At various times, the patient received saquinavir, ritonavir, and nelfinavir in conjunction with tacrolimus. In each instance, the tacrolimus concentration rose to toxic levels. We hypothesize that the protease inhibitors' competition for binding to cytochrome P450 isoenzyme system CYP3A induced extreme prolongation of tacrolimus metabolism. After stabilization of the patient, reinstitution of treatment with nelfinavir resulted in a >95% reduction in tacrolimus dosing from 4 mg twice per day to 0.5 mg once every 3-5 days.

Aryl Hydrocarbon Hydroxylases↗
PubMed1999

Lack of effect of intravenous administration on time to respond to azathioprine for steroid-treated Crohn's disease. North American Azathioprine Study Group.

BACKGROUND & AIMS: Azathioprine is effective for Crohn's disease but acts slowly. A loading dose may decrease the time to response. METHODS: A placebo-controlled study was conducted in patients with active Crohn's disease despite prednisone treatment. Patients were randomized to a 36-hour infusion of azathioprine, 40 mg/kg (51 patients), or placebo (45 patients) followed by oral azathioprine, 2 mg/kg, for 16 weeks. Prednisone was tapered over 5 weeks. The primary outcome measure was complete remission at week 8, defined by discontinuation of prednisone and a Crohn's Disease Activity Index of </=150 points. Erythrocyte concentrations of the azathioprine active metabolite, 6-thioguanine nucleotide, were measured. RESULTS: At week 8, 13 patients (25%) were in complete remission in the azathioprine-loaded group compared with 11 patients (24%) in the placebo group. The frequency of complete remission did not increase after 8 weeks in either group. Both groups achieved steady state of 6-thioguanine nucleotide by week 2, and no differences were found in mean concentrations between the groups. There were no significant differences in the frequency of adverse events between the groups. CONCLUSIONS: A loading dose does not decrease the time to response in patients with steroid-treated Crohn's disease beginning azathioprine therapy. Steady state of erythrocyte 6-thioguanine nucleotide and complete response occurred earlier than previously reported.

Administration, Oral↗