bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diastereotopic analysis of mesoridazine besylate (serentil)
Authors: Morrow Ryan J. , Millership Jeff S. , Collier Paul S. 
Published: July 2004

AbstractNMR studies were conducted with the aim of determining the diastereoisomeric ratio of a commercially supplied sample of mesoridazine (MES) and to compare the results with a freshly synthesised sample of MES. The results indicated that the commercially supplied MES consisted almost entirely of one diastereoisomeric pair, which was in agreement with previous findings reported by Eap et al. (J Chromatogr 669:271–279, 1995). The synthesised sample of MES was analysed by NMR in two stages: 1) as the initial product isolated as the free base from the direct synthesis, and 2) as the free base isolated from the crystallised besylate salt of the synthetic product. The NMR results show that the initial synthetic product consisted of two equal pairs of diastereoisomers. The diastereoisomeric pairs were further separated by the addition of the chiral shift reagent (R)‐(–)‐N‐(3,5 dinitrobenzoyl)‐α‐benzylamine to reveal equal quantities of all four enantiomers, clearly observed at the methyl sulfoxide proton peak of the NMR scan. The sample obtained from the crystallisation of MES besylate, however, indicated a significant difference, with a diastereoisomeric ratio of 75:25. The results suggest that MES besylate undergoes preferential crystallisation of one pair of diastereoisomers, with the other pair remaining in solution. Chirality 16:534–540, 2004. © 2004 Wiley‐Liss, Inc.
Determination of the absolute configuration of Anisotome irregular diterpenes: Application of CD and NMR methods
Authors: van Klink John W. , Baek Seung‐Hwa , Barlow Anna J. , Ishii Hideki , Nakanishi Koji , Berova Nina , Perry Nigel B. , Weavers Rex T. 
Published: July 2004

AbstractSeveral Anisotome diterpene derivatives were synthesized in an attempt to obtain a crystalline compound for X‐ray analysis. Although we were unable to obtain a suitable crystal, the absolute configuration of the irregular diterpene skeleton was determined using two other techniques: a circular dichroism (CD) protocol based on a tetraarylporphyrin molecular tweezer that allowed prediction of the absolute stereochemistry on a microscale level, and a method employing differences in NMR shifts from derivatization of the naturally occurring acid 1 with enantiomers of a phenylglycine methyl ester (PGME) chiral anisotropic reagent. The excellent agreement between the CD and NMR methods led to the assignment of a 2S‐absolute configuration for anisotomenoic acid 1. Chirality 16:549–558, 2004. © 2004 Wiley‐Liss, Inc.
Physicochemical properties, binary and ternary phase diagrams of ketoprofen
Authors: Hong Lu Ying , Bun Ching Chi 
Published: July 2004

AbstractCompared to simulated moving bed (SMB) chromatography, fractional crystallization is a simple and economical method for enantioseparation. Therefore, the coupling of SMB chromatography and fractional crystallization is suggested for enantioseparation of racemic compounds. In this work, a nonsteroidal antiinflammatory drug, ketoprofen (Kp), was chosen to be studied. Kp was verified as a racemic compound by FTIR, PXRD, and thermodynamic calculations. To derive the condition where pure (S)‐Kp could be crystallized from a solution, which was previously enantiomerically enriched, the binary melting phase diagram and the ternary solubility phase diagram in the mixed solvent of ethanol and water over a temperature range of 15–30°C were obtained. From these phase diagrams the eutectic point was determined as 91.6% mole percent (S)‐Kp from the binary phase diagram and 91% from the ternary phase diagram. The results may provide valuable experiment data for the possibility of coupling fractional crystallization with SMB for Kp separation. Chirality 16:541–548, 2004. © 2004 Wiley‐Liss, Inc.
Prospective randomized Phase II trial of pegylated doxorubicin in the management of symptomatic hormone‐refractory prostate carcinoma
Authors: Heidenreich Axel , Sommer Frank , Ohlmann Carsten H. , Schrader Andres J. , Olbert Peter , Goecke Joachim , Engelmann Udo H. 
Published: July 2004

AbstractBACKGROUNDLiposomal encapsulation of doxorubicin has been shown to reduce nonspecific delivery of this agent to normal tissue and to increase specific delivery to malignant cells. On the basis of doxorubicin's demonstrated clinical efficacy against hormone‐refractory prostate carcinoma (HRPCA), the authors conducted a prospective, randomized Phase II clinical trial to evaluate the feasibility, toxicity, and therapeutic efficacy associated with the pegylated form of this agent.METHODSForty‐eight patients with symptomatic HRPCA were randomized to receive pegylated liposomal doxorubicin at either 25 mg/m2 every 2 weeks for 12 cycles (Group A) or 50 mg/m2 every 4 weeks for 6 cycles (Group B). Thirty‐eight of these 48 patients (79%) presented with severe pain (corresponding to a pain score of 7.5 on a visual analog scale [VAS] ranging from 0 to 10) due to osseous metastases. Therapeutic efficacy was assessed by serial evaluation of serum prostate‐specific antigen (PSA) concentrations and by serial measurement of pain levels (using a VAS ranging from 0 to 10). Toxicity data were obtained using the National Cancer Institute of Canada/Cancer and Leukemia Group B criteria and the 30‐item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire.RESULTSThe median patient age was 68.9 years (range, 58–79 years), and the mean follow‐up duration was 42 months. The mean pretreatment PSA level was 660.4 ng/mL (mean, 8–6340 ng/mL); an objective decrease in PSA levels (i.e., a decrease of > 50%) was observed in 8 of 31 patients (25.8%) in Group B, whereas no other patient in either group experienced such a decrease. The mean time to disease progression was 6.5 months, and the mean survival duration was 13.4 months. Patients in Group B had a significantly higher rate of response with respect to pain (52.6% vs. 28.6%; P = 0.04), and the mean 1‐year survival rate also was significantly higher in Group B (42% vs. 15%; P = 0.02). Severe side effects were observed, with 24 patients (50%) experiencing World Health Organization Grade 3/4 toxicity. Toxicity types differed significantly between Group A and Group B; palmar‐plantar erythrodysesthesia developed in 60% of patients in the former group (P < 0.0005), whereas tachycardia was more common in the latter group (39% of patients; P < 0.0005). No dose‐limiting cardiotoxicities or hematotoxicities were documented.CONCLUSIONSPegylated liposomal doxorubicin yielded a noteworthy objective palliative response rate and a mean survival of 13 months for patients with symptomatic HRPCA. The dosage tested in the current study should be used in future Phase II and Phase III trials of pegylated liposomal doxorubicin–containing combination regimens for patients with HRPCA. Cancer 2004. © 2004 American Cancer Society.
Squamous cell carcinoma in situ at oropharyngeal and hypopharyngeal mucosal sites
Authors: Muto Manabu , Nakane Mari , Katada Chikatoshi , Sano Yasushi , Ohtsu Atsushi , Esumi Hiroyasu , Ebihara Satoshi , Yoshida Shigeaki 
Published: July 2004

AbstractBACKGROUNDHead and neck squamous cell carcinoma typically is diagnosed at an advanced stage, and the prognosis for patients with this type of malignancy is poor. Detection of these lesions at an earlier stage (e.g., as carcinoma in situ) would be of clear benefit to patients. However, it has been extremely difficult to detect carcinoma in situ at head and neck mucosal sites during routine endoscopy, even after numerous passes of the endoscope through the oral cavity and the pharynx.METHODSThe current clinical investigation was performed during routine endoscopic screening or surveillance procedures. The authors used a novel optical technique, known as narrowband imaging (NBI) that allows noninvasive visualization of the microvascular structure of an organ's surface using reflected light.RESULTSBetween April 2002 and August 2003, 34 consecutive superficial lesions were found in 18 patients. Multifocal carcinoma was found in 5 patients (28%). The median age of the patients examined was 59.5 years (range, 43–71 years), and 83% of all patients were male. All lesions exhibited a microvascular proliferation pattern on magnified NBI. Thirteen patients with a combined total of 29 lesions underwent endoscopic resection under general anesthesia. The pyriform sinus was the most frequent primary site (66%; 19 of 29 lesions). The median tumor diameter was 20 mm (range, 1.3–40 mm). Twenty‐one lesions (72%) were histologically confirmed to be carcinoma in situ, and the remaining lesions showed evidence of microinvasion (0.05–1 mm) beneath the epithelium. Vascular invasion was observed in only one lesion. The median hospital stay was 10 days (range, 4–18 days). All patients were discharged without severe complications. After a median follow‐up period of 8 months (range, 1–16 months), there were no cases of local disease recurrence.CONCLUSIONThe authors stress the importance of endoscopic detection of superficial carcinoma at oropharyngeal and hypopharyngeal mucosal sites. NBI is a promising and potentially powerful tool for identifying carcinomas at an earlier stage during routine endoscopic examination. Cancer 2004. © 2004 American Cancer Society.
The role of fludarabine in the treatment of follicular and mantle cell lymphoma
Authors: Lenz Georg , Hiddemann Wolfgang , Dreyling Martin 
Published: July 2004

AbstractAdvanced‐stage follicular lymphoma (FL) and mantle cell lymphoma (MCL) cannot be cured using conventional chemotherapy. Fludarabine, the most widely used purine analog, exhibits a particularly high level of activity against small lymphocytic lymphoma and chronic lymphocytic leukemia (CLL). Numerous studies have investigated the efficacy of fludarabine as a single agent or in combination with other cytostatic compounds in the treatment of FL and MCL. Hematologic toxicity is the most commonly observed adverse event in patients treated with fludarabine, but serious infectious complications are relatively rare. Fludarabine monotherapy has proven to be particularly effective in the treatment of FL; however, complete responses (CRs) are observed in only approximately 20–40% of all cases. In contrast, combinations containing fludarabine and anthracyclines or alkylating agents have yielded superior response rates and longer periods of progression‐free survival (PFS), and the addition of the anti‐CD20 antibody rituximab appears to yield even better results. In a randomized trial, an immunochemotherapy regimen consisting of a fludarabine‐containing combination and rituximab resulted in superior remission and survival rates compared with the fludarabine‐containing combination alone. In summary, fludarabine has proven to be a safe and effective agent in the treatment of indolent lymphoma. In particular, combinations containing fludarabine, anthracyclines and/or alkylating agents, and rituximab have yielded remarkable CR and PFS rates. Consequently, current research efforts have focused on the use of fludarabine‐containing combinations in the first‐line treatment of FL and MCL. Cancer 2004. © 2004 American Cancer Society.
Patterns of high‐dose morphine use in a home‐care hospice service
Authors: Bercovitch Michaela , Adunsky Abraham 
Published: July 2004

AbstractBACKGROUNDManagement of cancer pain is one of the most important goals of palliative care. Relieving pain is often problematic. High doses of morphine at home may be required to relieve patients' pain, and is therefore feared. The goals of the current study were to assess the feasibility of high‐dose morphine use at home, to characterize the patients, and to examine whether the use of high‐dose morphine might affect their survival.METHODSThe authors retrospectively studied the medical charts of 661 outpatients, which were completed by a home‐care hospice team. The authors collected data regarding demographic parameters, medical diagnosis, pain type, morphine dosage, use of rescue doses in addition to regular doses, use of coanalgesics and adjuvant treatments, and survival time as associated with morphine dosage. The authors also compared the data of patients receiving high‐dose morphine with those of a group of patients receiving regular doses.RESULTSThe authors identified 435 patients (65.8%) who received morphine for pain relief. Of these, 396 patients (91%) received a dose of 5–299 mg of morphine per day), 32 patients (7.4%) received 300–599 mg of morphine per day), and 7 patients (1.6%) received very high doses (≥ 600 mg of morphine per day). Overall, 39 patients (9%) received > 299 mg per day. Morphine dosage was found to be inversely correlated (r) with age (r = −0.254; P < 0.001). Male patients required slightly higher dosages than female patients (62.5% of high‐dose and 71% of very high‐morphine groups, respectively). Primary gastrointestinal (P = 0.015) and lung (P = 0.027) carcinomas, as well as metastatic bone disease (P = 0.001), ovarian carcinoma (P = 0.037), and brain tumors (P = 0.0053) were associated with higher and very higher morphine dosages. Adverse effects were similar in the groups receiving regular, high, and very high doses of morphine. The median survival of patients treated with high doses of morphine was 27 days and was 37 days for those treated with very high doses. Patients treated with low doses of morphine survived for 18 days. Patients not treated with morphine survived for 22 days (P = 0.001 by Mantel–Cox analysis; P = 0.029 by Breslow analysis).CONCLUSIONSThe use of high and very high morphine doses at home proved safe and did not appear to affect the patients' life expectancy adversely. The use of high or very high‐dose morphine should not be a barrier to providing palliative terminal care for home‐care hospice patients. Cancer 2004. © 2004 American Cancer Society.
Idarubicin and standard‐dose cytosine arabinoside in adults with recurrent and refractory acute lymphocytic leukemia
Authors: Karbasian‐Esfahani Merat , Wiernik Peter H. , Novik Yelena , Paietta Elisabeth , Dutcher Janice P. 
Published: July 2004

AbstractBACKGROUNDDrug resistance and early disease recurrence were major contributing factors in the limited survival of patients with acute lymphocytic leukemia (ALL). New chemotherapeutic agents and drug combinations were employed in refractory patients to overcome drug resistance.METHODSThe current study evaluated the efficacy of a regimen comprising intravenous bolus injections of idarubicin, 12 mg/m2 daily × 3, and a continuous 7‐day infusion of cytosine arabinoside (ara‐C), 100 mg/m2 daily, in adults with refractory or recurrent ALL. Twenty patients aged 14–75 years were treated.RESULTSSix patients (30%) achieved complete remission (CR), 5 (25%) had a partial response (PR), and 9 (45%) did not respond. Recovery of blood counts occurred at a median of 20 days. One patient who achieved CR and one who achieved PR survived 1.5 and 2 years, respectively, after receiving this treatment. The median response and overall survival periods were 2.75 and 6.3 months, respectively. There was no relation between remission duration and previous chemotherapy. Neither leukocyte count at study entry nor patient karyotype was associated with attainment of CR. All patients experienced profound myelosuppression. Gastrointestinal toxicity was mild to moderate, with the exception of one case of World Health Organization Grade 3 mucositis.CONCLUSIONSThe regimen of idarubicin and ara‐C achieved a 55% overall response rate in patients with recurrent or refractory ALL. This response rate compared favorably with other regimens and was achieved with acceptable toxicity. Response duration was disappointing, however. Cancer 2004. © 2004 American Cancer Society.
Tissue microarray immunohistochemical expression of estrogen, progesterone, and androgen receptors in uterine leiomyomata and leiomyosarcoma
Authors: Leitao Mario M. , Soslow Robert A. , Nonaka Daisuke , Olshen Adam B. , Aghajanian Carol , Sabbatini Paul , Dupont Jakob , Hensley Martee , Sonoda Yukio , Barakat Richard R. , Anderson Sibyl 
Published: July 2004

AbstractBACKGROUNDBenign uterine leiomyomata (LMA) are hormonally responsive neoplasms. To the authors' knowledge, little is known regarding the hormonal expression patterns of leiomyosarcomas (LMSs) of the uterus. The objective of the current study was to assess the immunohistochemical (IHC) patterns of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR) expression in LMA and LMS of the uterus using a tissue microarray. The authors also sought to assess the prognostic value of ER, PR, and AR expression in LMS.METHODSBetween January 1991 and March 2001, 25 patients were identified with primary uterine LMS for whom tissue was available. A tissue microarray was created with 3 representative cores from each of the LMS cases, as well as from 19 cases with benign uterine LMA. IHC staining was scored as follows: negative (0–1) and positive (2–3). Outcome analyses were performed for LMS only. First recurrence was determined from the time of the initial diagnosis. Survival was determined from the time of the initial diagnosis to last follow‐up.RESULTSER, PR, and AR positivity in LMA compared with LMS was as follows: ER, 78% versus 40% (P = 0.03); PR, 88% versus 38% (P = 0.001); and AR, 32% versus 40% (P = 0.75). There was no difference noted with regard to IHC expression based on stage of LMS. The median overall survival for patients with LMS was 23.5 months (95% confidence interval, 19.5, NR). When adjusted for stage, PR and AR were found to be predictive of a lower risk of recurrence (P = 0.01 and P = 0.035, respectively). ER, PR, and AR were not found to be associated with overall survival after adjustment for stage. Tumor stage was found to be associated with survival (P = 0.005).CONCLUSIONSThe rate of ER and PR expression was found to be significantly less in uterine LMS compared with LMA. ER, PR, and AR expression was observed in approximately 30–40% of uterine LMS cases. In the current series, PR and AR expression appeared to be associated with disease‐free survival but were not found to correlate with overall survival. Cancer 2004. © 2004 American Cancer Society.
B‐cell subsets in blood and lymphoid organs in Macaca fascicularis
Authors: Vugmeyster Y. , Howell K. , Bakshi A. , Flores C. , Hwang O. , McKeever K. 
Published: July 2004

AbstractBackgroundCynomolgus monkeys (Macaca fascicularis) are widely used animal models in biomedical research. However, the phenotypic characteristics of cynomolgus monkey (CM) B cells in peripheral blood (PB) and lymphoid organs are poorly understood.MethodsFACS analyses of PB‐, spleen‐, lymph node (LN)‐, and bone marrow (BM)‐derived B cells were performed.ResultsCM peripheral blood B cells have a smaller fraction of CD27− (naive) cells (∼40%), as compared to human blood samples (∼70%). Similar to humans, an early activation marker, CD23, is expressed more on CD27− CM naive B cells, as compared to CD27+ B cells. The mean fraction of B cells exhibiting a memory phenotype is similar to that seen in human blood. Unlike humans, CM blood contains a subset of CD20++CD80+CD21−IgM+/−CD27+CD19+FSC++BAFF‐Rlow B cells that are likely of germinal center origin. Thus, CM blood contains (i) a higher percentage of B cells that express the co‐stimulatory molecule CD80, and (ii) a lower fraction of B cells that are CD21+, as compared to human blood. Due to the relative paucity of information on B‐cell subsets in organs of healthy humans, a direct comparison between human and CM lymphoid organ data is limited. The fraction of CD27+ and CD23+ B cells appears to be similar, while the fraction of CD80+ B cells appears to be higher than that seen in human lymphoid organs. CM spleens and to some extent lymph nodes have a distinct subset of CD21++ cells that are also CD80+/−CD23lowIgM++CD27+/−FSC++. This subset is phenotypically similar to the marginal zone B cells present in human spleen and LN samples. We also provide detailed analyses on the fraction of lymphoid organ B cells that express CD21, CD23, CD32, and/or CD80 B‐cell markers.ConclusionsIn general, cynomolgus monkey B‐cell subsets are similar to those seen in humans, as well as to those seen in other nonhuman primates. However, there are some clear differences between human and cynomolgus monkey B‐cell subsets. These findings have direct implications for a variety of in vivo studies in cynomolgus monkeys, ranging from basic research on primate B‐cell differentiation to models of infectious diseases and trials of new B‐cell targeting therapeutic agents. © 2004 Wiley‐Liss, Inc.
Comparison of CD4 and CD8 lymphocyte counts in HIV‐negative pulmonary TB patients with those in normal blood donors and the effect of antitubercular treatment: Hospital‐based flow cytometric study
Authors: Uppal S. S. , Tewari S. C. , Verma Shashi , Dhot P. S. 
Published: July 2004

AbstractBackgroundThis study was designed to flow cytometrically determine baseline and sequential values of CD4 and CD8 lymphocyte subsets in patients without the human immunodeficiency virus and with pulmonary tuberculosis (TB) and to correlate these values with those obtained from normal male blood donors and with the radiologic extent of disease and response to therapy.MethodsWe studied 39 male patients without the human immunodeficiency virus and with sputum positive for pulmonary TB who had been admitted to Military Hospital (Cardiothoracic Center) in Pune, India. Clinical, laboratory, and radiologic evaluations of these patients were done. Hematologic parameters were assessed by an automated hematology cell counter (AcT*Diff, Coulter), and T‐cell subsets (CD4 and CD8) were determined flow cytometrically (EPICS‐XL, Coulter).ResultsCD4 counts and percentages of CD4 were significantly lower, but CD8 values were normal, in patients with pulmonary TB when compared with values obtained in normal blood donors. The CD4/CD8 ratio was significantly lower in patients with TB. The CD4 counts normalized with antitubercular treatment. The radiologic extent of disease did not correlate well with the immune parameters studied.ConclusionsTB is a reversible cause of CD4 lymphocytopenia and is associated with normal numbers of CD8 cells. The radiologic extent of disease does not seem to determine the immune response. © 2004 Wiley‐Liss, Inc.