bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of Academic Emergency Medicine over a Decade (1991‐2001)
Authors: Gallagher E. John 
Published: October 2002

Abstract Objective: To test the hypothesis that emergency medicine (EM) has made significant, quantifiable progress within U.S. academic medicine over the past ten years, 1991‐2001. Methods: Baseline (7/1/1991) and comparison (7/1/2001) data sets contained all Liaison Committee on Medical Education (LCME)‐accredited schools, Association of Academic Chairs of Emergency Medicine (AACEM)‐recognized academic departments of EM, Residency Review Committee (RRC)‐accredited EM residencies, and Association of American Medical Colleges (AAMC)‐designated academic medical centers. The increase over ten years in the two primary variables of academic departmental status, and EM residencies located at academic medical centers, was examined in the aggregate, then stratified by medical schools grouped by academic rank. Differences over time are expressed as simple proportions, bounded by 95% confidence intervals (95% CIs). Results: Between 1991 and 2001, the proportion of academic departments of EM at medical schools increased from 18% to 48% (95% CI for difference of 30%= 19% to 41%). The proportion of EM residencies at academic medical centers increased from 42% to 66% (95% CI for a difference of 24%= 11% to 36%). The largest increment of 37% (95% CI = 22% to 52%) in academic departments of EM, and of 36% (95% CI = 20% to 52%) in EM residencies located at academic medical centers, occurred within medical schools whose academic rank was above the median. Conclusions: A quantitatively and statistically significant increase in academic departments of EM within medical schools and EM residency programs at academic medical centers has occurred over the past decade. Half of all medical schools now have academic departments of EM, and two‐thirds of academic medical centers house EM residency programs. This has taken place largely within institutions whose academic ranking places them among the top half of all U.S. medical schools.
Comparison of the Efficacy of Local Therapies for Localized Prostate Cancer in the Prostate-Specific Antigen Era: A Large Single-Institution Experience With Radical Prostatectomy and External-Beam Radiotherapy
Authors: Kupelian Patrick A. , Elshaikh Mohamed , Reddy Chandana A. , Zippe Craig , Klein Eric A. 
Published: October 2002

PURPOSE: To review biochemical relapse-free survival (bRFS) rates after either external-beam radiotherapy (RT) or radical prostatectomy (RP) for localized prostate cancer. PATIENTS AND METHODS: All 1,682 patients had pretreatment prostate-specific antigen (PSA) levels and biopsy Gleason scores (bGS) assigned. No adjuvant therapy was administered after local treatment. RP was the treatment in 1,054 patients (63%) and RT in 628 patients (37%). Median follow-up was 51 months (range, 1 to 134). The median follow-up for RP versus RT patients was 50.5 v 51.0 months. Biochemical relapse was considered detectable PSA levels (> 0.2 ng/mL) in RP patients and three consecutive rising PSA levels in RT patients. The analysis was repeated with a more stringent definition of biochemical control after either RP or RT—namely, reaching and maintaining a PSA level ≤ 0.5 ng/mL—and excluding patients receiving any androgen deprivation (AD). RESULTS: Eight-year bRFS rates for RP versus RT were 72% and 70%, respectively (P = .010). Multivariate analysis indicated T stage (P < .001), pretreatment PSA (P < .001), bGS (P < .001), year of therapy (P < .001), and neoadjuvant AD (P = .019) to be the only independent predictors of relapse. Age (P = .78), race (P = .29), prior transurethral resection of prostate (P = .81), and treatment modality (P = .96) were not independent predictors of treatment failure. Fifty-one percent of RP patients had favorable tumors (T1 to T2A, pretreatment PSA ≤ 10 ng/mL, bGS ≤ 7), compared with only 34% of RT patients (P < .001). Repeat analysis with a stringent definition of biochemical failure and excluding patients receiving AD indicated no impact of treatment modality on outcome. CONCLUSION: Eight-year biochemical failure rates were identical between RT and RP in any subgroup. Outcome is determined mainly by pretreatment PSA levels, bGS, clinical T stage, and, for RT patients, radiation dose.
Nutrition and Survival After the Diagnosis of Breast Cancer: A Review of the Evidence
Authors: Rock Cheryl L. , Demark-Wahnefried Wendy 
Published: October 2002

PURPOSE: To review and summarize evidence from clinical and epidemiologic studies that have examined the relationship between nutritional factors, survival, and recurrence after the diagnosis of breast cancer. MATERIALS AND METHODS: Relevant clinical and epidemiologic studies were identified through a MEDLINE search. References of identified reports also were used to identify additional published articles for critical review. RESULTS: Several nutritional factors modify the progression of disease and prognosis after the diagnosis of breast cancer. Overweight or obesity is associated with poorer prognosis in the majority of the studies that have examined this relationship. Treatment-related weight gain also may influence disease-free survival, reduce quality of life, and increase risk for comorbid conditions. Five of 12 studies that examined the relationship between dietary fat and survival found an inverse association, which was not evident on energy adjustment in most of these studies. The majority of the studies that examined intakes of vegetables or nutrients provided by vegetables and fruit found an inverse relationship with survival. Alcohol intake was not associated with survival in the majority of the studies that examined this relationship. CONCLUSION: Much remains to be learned about the role of nutritional factors in survival after the diagnosis of breast cancer. Healthy weight control with an emphasis on exercise to preserve or increase lean muscle mass and a diet that includes nutrient-rich vegetables can be recommended. Diets that have adequate vegetables, fruit, whole grains, and low-fat dairy foods and that are low in saturated fat may help to lower overall disease risk in this population.
Clinical Features and Outcome of Initially Unresected Nonmetastatic Pediatric Nonrhabdomyosarcoma Soft Tissue Sarcoma
Authors: Spunt Sheri L. , Hill D. Ashley , Motosue Alison M. , Billups Catherine A. , Cain Alvida M. , Rao Bhaskar N. , Pratt Charles B. , Merchant Thomas E. , Pappo Alberto S. 
Published: October 2002

PURPOSE: To describe the clinical features, response to therapy, and outcome of pediatric patients with initially unresected nonmetastatic nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). PATIENTS AND METHODS: We retrospectively reviewed the presenting clinical features and tumor characteristics of all 40 pediatric patients with initially unresected nonmetastatic NRSTS who were seen at our institution between March 1962 and December 1996. A subset of 27 patients for whom complete treatment information was available was analyzed to determine whether response to therapy was associated with local disease control and event-free and overall survival. RESULTS: More than 70% of the 40 patients had tumors with high-risk features (tumor size > 5 cm, high grade, invasiveness). For the 27 patients included in the outcome analysis, 5-year event-free survival and survival estimates were 33% ± 9% and 56% ± 10%, respectively. Ten (37%) of these patients had a complete or partial response to neoadjuvant chemotherapy and/or radiotherapy, and only two of the 10 had residual tumor after surgery. Combined chemotherapy and radiotherapy seemed more effective than either modality alone in inducing a response, but the response to neoadjuvant therapy did not predict outcome. Most treatment failures were local, and postrelapse survival was poor (19% ± 10%). CONCLUSION: Initially unresected NRSTS constitutes a unique subgroup of pediatric sarcomas that commonly present with high-risk features and respond poorly to neoadjuvant therapy. Only about one third of patients treated with multimodal therapy remain disease-free, and local control is the major limiting factor in achieving cure. More effective risk-directed treatments are needed for this unique subgroup of patients.
Phase I and Pharmacokinetic Study of E7070, a Novel Chloroindolyl Sulfonamide Cell-Cycle Inhibitor, Administered as a One-Hour Infusion Every Three Weeks in Patients With Advanced Cancer
Authors: Raymond E. , ten Bokkel Huinink W.W. , Taïeb J. , Beijnen J.H. , Faivre S. , Wanders J. , Ravic M. , Fumoleau P. , Armand J.P. , Schellens J.H.M. 
Published: October 2002

PURPOSE: The objectives were to determine the maximum-tolerated dose, the recommended dose, the dose-limiting toxicity, the pharmacokinetics, and the activity of E7070, a novel cell-cycle inhibitor. PATIENTS AND METHODS: E7070 was given as a 1-hour intravenous infusion every 3 weeks in two groups of patients with advanced solid tumors who met prespecified eligibility criteria (group A) or who met the same eligibility criteria but in addition were less heavily pretreated and had more favorable liver functions (group B). RESULTS: Forty patients (31 patients in group A and nine patients in group B) were entered. Dose escalation proceeded through eight levels (range, 50 to 1,000 mg/m2). In group A, neutropenia and thrombocytopenia were dose-limiting toxicities occurring during the first cycle in two of seven patients treated at the doses of 700 mg/m2 and two of four patients treated at 800 mg/m2. Identical dose-limiting toxicities were observed in zero of six and two of three patients from group B at doses of 800 and 1,000 mg/m2, respectively. Other toxicities included acne-like skin eruption, mucositis, conjunctivitis, nausea, fatigue, and alopecia. At doses greater than 400 mg/m2, the area under the concentration-time curve increased disproportionately to the administered dose. Tumor stabilization lasting ≥ 6 months was observed in six assessable patients. CONCLUSION: The recommended doses of E7070 in this schedule were 700 mg/m2 (group A) and 800 mg/m2 in patients who were less heavily pretreated (group B) with a moderate tumor burden. Prolonged disease stabilization observed in this study might warrant further investigation of E7070 in selected tumor types.
Randomized Study of Three Different Doses of Suramin Administered With a Fixed Dosing Schedule in Patients With Advanced Prostate Cancer: Results of Intergroup 0159, Cancer and Leukemia Group B 9480
Authors: Small Eric J. , Halabi Susan , Ratain Mark J. , Rosner Gary , Stadler Walter , Palchak David , Marshall Ernest , Rago Randall , Hars Vera , Wilding George , Petrylak Daniel , Vogelzang Nicholas J. 
Published: October 2002

PURPOSE: To test the hypothesis that the efficacy and toxicity of suramin in the treatment of patients with hormone-refractory prostate cancer was dose dependent. PATIENTS AND METHODS: Patients were randomized with equal probability to receive low-, intermediate-, or high-dose suramin (total doses 3.192, 5.320, and 7.661 g/m2, respectively). Overall survival, time to progression, and response rate (prostate-specific antigen [PSA] and objective) for each treatment arm were compared. Relationships between plasma suramin concentrations and response, toxicity, and survival were also evaluated. RESULTS: Three hundred ninety patients were randomized. For the low-, intermediate-, and high-dose arms, the median survival time was 16, 14, and 13 months, respectively (P = .49). The objective response rate was 9%, 7%, and 15%, respectively (P = .10). PSA response rates were 24%, 28%, and 34%, respectively (P = .082). Landmark analyses of a 50% decline in PSA at 20 weeks showed a significant correlation with survival. There was a dose-response relationship between dose and toxicity. After adjusting for treatment arm, the measured suramin concentration was not associated with clinical response, PSA response, survival, or toxicity. CONCLUSION: Although high-dose suramin was associated with higher objective and PSA response rates, these were not statistically significant. Overall, no dose-response relationship was observed for survival or progression-free survival, but toxicity was increased with the higher dose. Patients treated with the low-dose level experienced modest toxicity, making it the preferred arm on this study. The lack of a dose-response relationship and the toxicity profile observed raise questions regarding the utility of suramin, particularly high-dose suramin, as administered on this schedule.
Preoperative Combined Nested Reverse Transcriptase Polymerase Chain Reaction for Prostate-Specific Antigen and Prostate-Specific Membrane Antigen Does Not Correlate With Pathologic Stage or Biochemical Failure in Patients With Localized Prostate Cancer Undergoing Radical Prostatectomy
Authors: Thomas John , Gupta Manjula , Grasso Ying , Reddy Chandana A. , Heston Warren D. , Zippe Craig , Dreicer Robert , Kupelian Patrick A. , Brainard Jennifer , Levin Howard S. , Klein Eric A. 
Published: October 2002

PURPOSE: We report a prospective study examining the ability of preoperative nested reverse transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) to predict pathologic stage and biochemical recurrence in patients with clinically localized prostate cancer treated with radical prostatectomy. PATIENTS AND METHODS: One hundred forty-one patients were entered onto the study. Preoperative evaluation included clinical T stage, serum PSA, biopsy Gleason score, and serum RT-PCR for PSA/PSM. Univariate and multivariate logistic regression models, Kaplan-Meier estimates, and Cox proportional hazards modeling were used to identify predictors of pathologic stage and biochemical failure. RESULTS: Seventy-three patients (51.8%) were RT-PCR positive for PSA, PSM, or both. In the multivariate logistic regression model, only initial PSA was an independent predictor of pathologic stage as defined by organ-confined disease (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00 to 1.13; P = .026) or organ-/specimen-confined disease (OR, 1.09; 95% CI, 1.02 to 1.16; P = .009). Overall Kaplan-Meier biochemical relapse-free survival (bRFS) was 85% at 59 months. Multivariate analysis of predictors for bRFS with the Cox proportional hazards model indicated that only initial PSA (OR, 1.05; 95% CI, 1.02 to 1.09; P = .004) and biopsy Gleason score (OR, 3.57; 95% CI, 1.37 to 9.58; P = .009) were independent predictors of biochemical failure. RT-PCR status did not predict pathologic stage or biochemical failure. Repeat analysis excluding 27 patients who received preoperative androgen-deprivation therapy did not change the results. CONCLUSION: Combined nested RT-PCR for PSA and PSM is not an independent predictor of pathologic stage or biochemical failure in patients with localized prostate cancer undergoing radical prostatectomy. This assay has no clinical utility in this patient population.
Reproductive Cycle Regulation of Nuclear Import, Euchromatic Localization, and Association with Components of Pol II Mediator of a Mammalian Double-Bromodomain Protein
Authors: Crowley Thomas E. , Kaine Emily M. , Yoshida Manabu , Nandi Anindita , Wolgemuth Debra J. 
Published: October 2002

AbstractFsrg1 (female sterile homeotic-related gene 1) is the mouse homolog of the human RING3 protein, which has been shown to associate with the E2 promoter binding factor (E2F) transcription factor and to have a possible role in cell cycle-linked transcriptional regulation. The Fsrg1 protein is 60% identical in sequence to the RNA polymerase II mediator subunit Fsrg4, another member of this subfamily of double bromodomain-containing proteins that are homologs of Drosophila female sterile homeotic. Antibodies against murine Fsrg1 were generated and used in immunoblot and immunoprecipitation experiments to identify proteins interacting with Fsrg1 and RING3. In the presence of acetylated but not nonacetylated histone H3 and H4 peptides, RING3 was shown to interact with E2F, mediator components cyclin-dependent kinase 8 and thyroid receptor-associated protein 220, and the RNA polymerase II large subunit. Fsrg1 mRNA had been previously shown to be expressed at high levels in the epithelium of the adult mouse mammary gland. To determine the physiological relevance of these potential associations, we examined the patterns of expression of Fsrg1 mRNA and protein in the adult mammary epithelia during the reproductive cycle as the tissue is responding to estrogen, progesterone, and prolactin. Changes in the nuclear vs. cytoplasmic localization of Fsrg1 were observed and correlated with physiological changes in mammary gland function. The observations suggested that Fsrg1 may be involved in the transcriptional activities of genes involved in proliferation of the mammary epithelia during pregnancy and in orchestrating postlactation involution and apoptosis. Localization of Fsrg1 on euchromatin, the transcribed portion of the chromosomes, is consistent with its hypothesized function as a transcription regulator.
Evaluation of the Pharmacological Actions and Pharmacokinetics of BOF-4272, a Xanthine Oxidase Inhibitor, in Mouse Liver
Authors: Naito Shinsaku , Nishimura Masuhiro , Tamao Yumi 
Published: October 2002

Abstract
BOF-4272 (±)-8-(3-methoxy-4-phenylsulphinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4-(1H)-one, a new synthetic anti-hyperuricaemic drug, which has a chiral centre and exists as racemates, is a potent inhibitor of xanthine oxidase/dehydrogenase in the purine catabolism pathways. The present studies using mice demonstrated that BOF-4272 was specifically distributed in the liver, which is the main organ of uric acid production. Therefore, a decrease in uric acid concentration in the liver, rather than the plasma, was identified as a pharmacological action of BOF-4272.
The ratio of liver to plasma concentrations of BOF-4272 increased from 2.5 to 6.3 over time, up to 8 h after oral administration. The elimination half-life of BOF-4272 in the liver was 5.1-fold longer than that in the plasma. High concentrations of BOF-4272 were observed in the liver up to 8 h after oral administration. Furthermore, the influx of BOF-4272 into hepatocytes occurred in a temperature-dependent manner.
The liver concentrations of uric acid from 1 h to 8 h after the oral administration of BOF-4272 (0.34–0.75 μg (g tissue)−1) were significantly lower than those in control animals (5.03–10.96 μg (g tissue)−1). BOF-4269 (the sulphide metabolite of BOF-4272) was the only metabolite detected in plasma or faeces after intravenous or oral administration. BOF-4269, which has no inhibitory action on the uric acid biosynthesis system, is generated by the metabolism of BOF-4272 in the intestinal tract.
In conclusion, this work using the liver as the target organ has allowed us to identify the pharmacological actions of BOF-4272 in mice. The long-lasting effect of BOF-4272 in reducing levels of hepatic uric acid was consistent with the prolonged high BOF-4272 concentrations in the liver. These results also demonstrate that the mouse is a suitable animal species for evaluating the clinical pharmacology and pharmacokinetics of BOF-4272.
Rapid Detection of CYP2C18 Genotypes by Real-time Fluorescence Polymerase Chain Reaction
Authors: Mizugaki Michinao , Hiratsuka Masahiro , Agatsuma Yasuyuki , Matsubara Yoichi , Fujii Kunihiro , Kure Shigeo , Narisawa Kuniaki 
Published: October 2002

Abstract
In man, CYP2C19, a liver enzyme, plays an important role in the metabolism of several drugs. Mutation of the CYP2C19 gene results in a poor metaboliser phenotype. S-Mephenytoin hydroxylation genetic polymorphism is due to two mutations of the CYP2C19 gene, namely CYP2C19*2, located in exon 5, and CYP2C19*3, located in exon 4. CYP2C18 is also polymorphically expressed. The mutant alleles of this enzyme are CYP2C18m1, located in exon 2 and CYP2C18m2, located in the 5′-flanking region. We have developed an allele-specific TaqMan polymerase chain reaction (PCR) assay with which to detect CYP2C18 mutant alleles. This assay combines hybridization of the TaqMan probe and allele-specific amplification primers to the target DNA. The TaqMan probe is labelled with 6-carboxyfluorescein at the 5′ end and 6-carboxytetramethylrhodamine together with a phosphate at the 3′ end. Genotypes are separated according to the different threshold cycles of the wild type and mutant primers.
We applied this procedure to DNA extracted from the blood or saliva of 144 healthy Japanese volunteers. The wt/wt, wt/m1, wt/m2, m1/m1, m1/m2 and m2/m2 genotypes of the CYP2C18 alleles detected by the assay were consistent with the results obtained from restriction enzyme cleavage. In accordance with a previous report, the genotypes of CYP2C18m1 and CYP2C18m2 coincided with those of CYP2C19*3 and CYP2C19*2, respectively. Therefore, detection of CYP2C18 mutant alleles also allows that of CYP2C19 mutant alleles. Among 19 poor metabolisers, eight showed the homozygous CYP2C19*2/CYP2C19*2, two the homozygous CYP2C19*3/CYP2C19*3 and nine the compound heterozygous CYP2C19*2/CYP2C19*3 genotype.
We found the allele-specific TaqMan PCR assay rapid, simple and cost-effective, as well as suitable for high-throughput applications in a routine laboratory. This assay allows the fast and reliable detection of inherited disorders that might influence diagnosis and treatment.
Antiplatelet Effect of Marchantinquinone, Isolated from Reboulia hemisphaerica, in Rabbit Washed Platelets
Authors: Liao Chang-Hui , Ko Feng-Nien , Wu Chia-Li , Teng Che-Ming 
Published: October 2002

Abstract
Platelet activation is involved in serious pathological situations, including atherosclerosis and restenosis. It is important to find efficient antiplatelet medicines to prevent fatal thrombous formation during the course of these diseases.
Marchantinquinone, a natural compound isolated from Reboulia hemisphaerica, inhibited platelet aggregation and ATP release stimulated by thrombin (0.1 units mL−1), platelet-activating factor (PAF; 2 ng mL−1), collagen (10 μg mL−1), arachidonic acid (100 μm), or U46619 (1 μm) in rabbit washed platelets. The IC50 values of marchantinquinone on the inhibition of platelet aggregation induced by these five agonists were 62.0 ± 9.0, 86.0 ± 7.8, 13.6 ± 4.7, 20.9 ± 3.1 and 13.4 ± 5.3 μm, respectively. Marchantinquinone inhibited thromboxane B2 (TxB2) formation induced by thrombin, PAF or collagen. However, marchantinquinone did not inhibit TxB2 formation induced by arachidonic acid, indicating that marchantinquinone did not affect the activity of cyclooxygenase and thromboxane synthase. Marchantinquinone did inhibit the rising intracellular Ca2+ concentration stimulated by the five platelet-aggregation inducers. The formation of inositol monophosphate induced by thrombin was inhibited by marchantinquinone. Platelet cAMP and cGMP levels were unchanged by marchantinquinone.
The results indicate that marchantinquinone exerts antiplatelet effects by inhibiting phosphoinositide turnover.