bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opportunistic observations of interactions between sperm whales and deep‐water trawlers based on sightings from fisheries observers in the northwest Atlantic
Authors: Karpouzli Evanthia , Leaper Russell 
Published: January 2004

AbstractCetacean observations were made by fisheries observers on trawlers targeting Greenland halibut (Reinhardtius hippoglossoides) in the area around the Flemish Cap, northwest Atlantic.Data from four observers amounted to a total of 291 observer days at sea aboard fishing vessels. This effort was mainly concentrated in the periods July to September 1996 and February to April 1997.Sperm whales (Physeter macrocephalus) were the most frequently sighted cetacean, with 82 encounters on 64 different days. Pilot whales were encountered on nine occasions.Sighting rates of sperm whales during net hauling were significantly (approximately 30 times) greater than during shooting or steaming. Sperm whales were observed in aggregations of up to six animals close to the vessel and net during hauling. It is suggested that the sperm whales were attracted by the potential food source within the net, and possibly were feeding on fish escaping from the net. This represents rarely reported behaviour for this species.Copyright © 2003 John Wiley & Sons, Ltd.
Ecological and genetic evidence of the vulnerability of shallow‐water populations of the stylasterid hydrocoral Errina novaezelandiae in New Zealand's fiords
Authors: J. Miller Karen , Mundy Craig N. , Lindsay Chadderton W. 
Published: January 2004

Abstract
Some of the key life history characteristics that make modular marine invertebrates such as corals vulnerable to disturbance and stress are susceptibility to damage, slow growth, longevity, and philopatry. This may be particularly so for marginal populations at the limits of their range and, for instance, that are attractive to scuba divers.
In this study we examined the population structure and incidence of damage, quantified growth rates and estimated gene flow to assess the effects of divers on the deep‐water emergent populations of the fragile red coral Errina novaezelandiae in the Te Awaatu Marine Reserve in Fiordland, New Zealand.
We found that population structure in red corals is skewed, with small colonies the most abundant. Damage was up to eight times higher in dived than in non‐dived populations of red coral, and large colonies were more likely to be damaged. Growth in red corals can be high (up to 7 cm −1), although net growth is much lower (0.7 cm yr−1) due to the effects of partial mortality. On the basis of the slow growth rate, we estimate that large corals (>20 cm diameter) will be in excess of 30 yr old. We also found high genetic subdivision among red coral populations and evidence of inbreeding, indicative of limited larval dispersal among neighbouring populations.
Overall, our results indicate the shallow‐water populations of red coral in Fiordland will be susceptible to impacts from scuba diving, and the development of a management strategy to ensure ecologically sustainable tourism and to minimize the effects of divers will be essential for their conservation.
Copyright © 2003 John Wiley & Sons, Ltd.
Comparative pharmacokinetics of acetyl salicylic acid and its metabolites in children suffering from autoimmune diseases
Authors: Juárez Olguín Hugo , Flores Pérez Janett , Lares Asseff Ismael , Loredo Abdalá Arturo , Carbajal Rodríguez Luis 
Published: January 2004

AbstractThe aim of the present study was to compare the effect produced by juvenile rheumatoid arthritis (JRA) or rheumatic fever (RF) on the pharmacokinetics of acetyl salicylic acid (ASA) and its metabolites in children with autoimmune diseases (AD). Methods—A prospective, open labelled study was performed in 17 children with JRA and 17 with RF who received a single dose of 25 mg ASA/kg orally. The pharmacokinetics of ASA and its metabolites were determined. The blood and urine levels of each salicylate collected during 24 h were measured by HPLC. A group of 15 healthy teenage volunteers was included as a control group. Results—The maximum plasma concentration, half‐life time, area under the curve and the amount of salicylates excreted were statistically different between the JRA and the RF groups, as well as between the RF group and the controls, however, there were no significant differences between the JRA group and the controls. Conclusions—Dosage schemes must be adjusted for JRA patients, since the half life in these patients is longer than in RF patients. However, due to ample variability of pharmacokinetic parameters it is recommended that dose schemes are individualized on the type of autoimmune disease considered. Copyright © 2004 John Wiley & Sons, Ltd.
Disposition of WR‐1065 in the liver of tumor‐bearing rats following regional vs systemic administration of amifostine
Authors: Levi Micha , DeRemer Susan J. , Dou Chunzhi , Ensminger William D. , Smith David E. 
Published: January 2004

AbstractPurpose—Amifostine is a prodrug in which selectivity is largely determined by the preferential formation and uptake of its cytoprotective metabolite, WR‐1065, in normal tissues as a result of differences in membrane‐bound alkaline phosphatase activity. It was hypothesized that amifostine may be a good candidate for regional drug delivery to the liver because of its large hepatic extraction and total body clearance. Methods—Rat livers were implanted with Walker‐256 tumors. The tumor‐bearing rats received 15 min infusions of amifostine (200 mg/kg) via the portal vein or the femoral vein. WR‐1065 concentrations in the blood, liver and tumor were measured at various times. Results—The WR‐1065 tumor portal dosing AUC15−60 was 40% of systemic dosing, and tumor concentrations following portal dosing were one‐fifth of that following systemic dosing. The portal dosing WR‐1065 liver AUC15−60 was 60% higher than the values for systemic dosing. The liver/tumor concentration ratios of WR‐1065 following portal dosing were up to 8‐fold higher than the ratio following systemic administration. Unfortunately, systemic exposure to WR‐1065 was greater following portal vs systemic amifostine. Conclusions—Amifostine may provide increased liver protection and decreased tumor protection from radio‐ or chemotherapy when administered by the portal vein. However, portal dosing also increases systemic exposure to WR‐1065, which is associated with hypotension. Copyright © 2004 John Wiley & Sons, Ltd.
Transdermal delivery system for zidovudine: in vitro, ex vivo and in vivo evaluation
Authors: Narishetty Sunil Thomas Kumar , Panchagnula Ramesh 
Published: January 2004

AbstractThe objective of this study was to prepare a transdermal delivery system (TDS) for zidovudine (AZT) with a combination of menthol and oleic acid as penetration enhancers incorporated in hydroxypropyl methylcellulose, and to evaluate ex vivo as well as in vivo permeation across rat skin. It was found that AZT in gel formulation was stable in both refrigerated as well as accelerated stability conditions for 3 months and further, the gel did not significantly retard the permeability of AZT across the skin in comparison with solution formulation. Ex vivo steady state flux of AZT across rat skin from gel was 2.26 mg cm−2 h−1, which is sufficient to achieve therapeutic plasma concentrations. Intravenous pharmacokinetic parameters of AZT in rats were determined and used together with ex vivo flux data to generate theoretical plasma profiles of AZT and compared with plasma concentrations achieved after application of TDS. Further, steady state plasma concentrations of drug following multiple applications of TDS were determined and good correlations between ex vivo and in vivo data were observed. In addition, the combination of penetration enhancers used at 2.5% w/w in this study proved efficient in achieving sufficient enhancement in the transdermal permeability of AZT across rat skin with reduced skin irritation potential when compared with individual penetration enhancers at higher concentrations. Copyright © 2004 John Wiley & Sons, Ltd.
Comparative evaluation of digoxin concentrations determined by three assay systems: TDx, IMx and OPUS
Authors: Kagawa Yoshiyuki , Iwamoto Takuya , Matsuda Hiroaki , Mukohara Rika , Sawada Jun‐ichi , Kojima Michio 
Published: January 2004

AbstractDigoxin concentrations measured by three automated immunoassay systems, i.e. OPUS, TDx and IMx assays, were compared in order to evaluate precision and accuracy performance, and data compatibility. Coefficients of variation for all methods in within‐run and between‐run precision were less than 10% at weighed‐in concentrations of 0.545, 1.090 and 2.180 ng/ml. The accuracy relative to the three weighed‐in concentrations ranged from 97% to 123% for all methods. One hundred and three plasma samples from 60 patients receiving digoxin were used to evaluate the data compatibility. Digoxin concentrations measured by the three immunoassay systems correlated well with one another. These results suggest that there are few problems when switching between digoxin assay methods, and that IMx and OPUS are more useful than TDx because they do not require sample pretreatment. The digoxin concentrations of the plasma samples from one patient receiving both digoxin and potassium canrenoate were investigated as a case report. The digoxin concentrations measured by TDx and IMx became higher than those measured by OPUS after starting the combination treatment. In another patient suffering from bilirubinaemia, the digoxin concentrations measured by TDx or IMx were higher than those measured by OPUS. These results suggest that OPUS has a higher specificity for measuring the plasma digoxin concentrations compared with TDx or IMx. Copyright © 2003 John Wiley & Sons, Ltd.
In vitro investigation on the impact of the surface‐active excipients Cremophor EL, Tween 80 and Solutol HS 15 on the metabolism of midazolam
Authors: Bravo González Roberto C. , Huwyler Jörg , Boess Franziska , Walter Isabelle , Bittner Beate 
Published: January 2004

AbstractThe impact of the surface‐active formulation ingredients Cremophor EL, Tween 80 and Solutol HS 15 on the intrinsic clearance (Clint) of midazolam (MDZ) was investigated in rat hepatocytes and microsomes. In rat hepatocytes with 0.003%, 0.03% and 0.3% (w/v) Solutol HS 15 already present in the incubation medium, the Clint was significantly reduced in a dose‐dependent manner by about 25%, 30% and 50%, respectively. In the presence of Cremophor EL and Tween 80 a significant reduction in Clint by about 30% and 25%, respectively, was observed at 0.03% surfactant concentration. At 0.3% of Cremophor EL and Tween 80, Clint was reduced by about 50% and 20%, respectively. A reduction in Clint was also observed in experiments with rat liver microsomes. At surfactant concentrations up to 0.03%, cytotoxicity assays (lactate dehydrogenase release, adenosine triphosphate content) as well as light microscope investigations did not reveal any cytotoxic impact of the surfactants on the hepatocyte monolayer. A potential interaction of the surfactants with biological membranes was determined using phosphatidylcholine‐cholesterol liposomes loaded with self‐quenching concentrations of carboxyfluorescein. No marked release of carboxyfluorescein from the liposomes (that would be an indication for a surfactant‐dependent disruption of membrane integrity) was observed up to concentrations of 0.03% of the different surfactants. It is concluded that cytochrome P450 3A mediated metabolism of MDZ seems to be prevented by all surfactants at concentrations above 0.03%. In our experiments the surfactants did not show toxic effects at concentrations that resulted in a decreased Clint of MDZ. Thus, a direct inhibition of the metabolizing enzymes, a molecular interaction with the microsomes as well as an alteration of membrane properties that did not yet result in a release of LDH have to be taken into consideration as reasons for the observed changes in the metabolism of MDZ. Copyright © 2004 John Wiley & Sons, Ltd.
Chemotherapy‐induced neutropenia
Authors: Crawford Jeffrey , Dale David C. , Lyman Gary H. 
Published: January 2004

AbstractCytotoxic chemotherapy suppresses the hematopoietic system, impairing host protective mechanisms and limiting the doses of chemotherapy that can be tolerated. Neutropenia, the most serious hematologic toxicity, is associated with the risk of life‐threatening infections as well as chemotherapy dose reductions and delays that may compromise treatment outcomes. The authors reviewed the recent literature to provide an update on research in chemotherapy‐induced neutropenia and its complications and impact, and they discuss the implications of this work for improving the management of patients with cancer who are treated with myelosuppressive chemotherapy. Despite its importance as the primary dose‐limiting toxicity of chemotherapy, much concerning neutropenia and its consequences and impact remains unknown. Recent surveys indicate that neutropenia remains a prevalent problem associated with substantial morbidity, mortality, and costs. Much research has sought to identify risk factors that may predispose patients to neutropenic complications, including febrile neutropenia, in an effort to predict better which patients are at risk and to use preventive strategies, such as prophylactic colony‐stimulating factors, more cost‐effectively. Neutropenic complications associated with myelosuppressive chemotherapy are a significant cause of morbidity and mortality, possibly compromised treatment outcomes, and excess healthcare costs. Research in quantifying the risk of neutropenic complications may make it possible in the near future to target patients at greater risk with appropriate preventive strategies, thereby maximizing the benefits and minimizing the costs. Cancer 2004;100:228–37. © 2003 American Cancer Society.
Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project
Authors: Fisher Edwin R. , Land Stephanie R. , Fisher Bernard , Mamounas Eleftherios , Gilarski Linda , Wolmark Norman 
Published: January 2004

AbstractBACKGROUNDThe current report represents a 12‐year clinicopathologic update of an earlier 5‐year analysis of 180 patients with lobular carcinoma in situ (LCIS) who were treated with local excision and subsequent surveillance only.METHODSNineteen pathologic characteristics of LCIS were assessed as potential predictors of invasive and noninvasive ipsilateral breast tumor recurrence (IBTR) and contralateral breast tumor recurrence (CBTR) as well as mortality.RESULTSOverall, only 26 IBTRs (14.4%) and 14 CBTRs (7.8%) were observed. Nine IBTRs (5.0% of the total cohort) and 10 CBTRs (5.6% of the total cohort) were invasive carcinomas. Eight of 9 IBTRs (88.9%) and 6 of 8 invasive CBTRs (75%) that had histologic sections available for review were of the lobular invasive type. Ninety‐six percent of all IBTRs and 100% of invasive IBTRs occurred within the same site as the index LCIS. The numbers of invasive IBTRs were comparable within and after 5 years (5 invasive IBTRs vs. 4 IBTRs). Recurrences of invasive CBTR occurred later than recurrences of invasive IBTR, with 70% of invasive CBTRs recognized after 5 years compared with 44% of invasive IBTRs. It was found that Grade 2–3 LCIS was significantly predictive for invasive IBTR when combined with the number of recurrences of ductal carcinoma in situ (DCIS) alone or with LCIS. Only 2 patients in the cohort (1.1%) succumbed to breast carcinoma; 1 patient had a prior invasive IBTR, and the other patient had an invasive CBTR. The reasons for the lower frequency of invasive recurrences and the higher proportions of the lobular invasive phenotype than noted by others are discussed along with the impact of the findings on the nomenclature, precursor nature, and treatment of LCIS.CONCLUSIONSLCIS is a more indolent form of in situ breast carcinoma than DCIS, with which it shares other features of its natural history, particularly very low mortality rates. There is no compelling reason to surgically treat LCIS other than conservatively. The values of other adjuvant modalities in the management of LCIS are discussed. The authors acknowledge that their findings are based on relatively few events and, even at 12 years, may be regarded as ‘preliminary’. Nonetheless, their findings may reflect the true biologic nature of LCIS. Cancer 2004;100:238–44. © 2003 American Cancer Society.
Phase II study of alpha‐tocopherol in improving the cognitive function of patients with temporal lobe radionecrosis
Authors: Chan Agnes S. , Cheung Mei‐Chun , Law Stephen C. , Chan John H. 
Published: January 2004

AbstractBACKGROUNDRadiotherapy is an important treatment modality for brain tumors and is the standard radical treatment for nasopharyngeal carcinoma (NPC). However, the treatment is not free of side effects, and one possible neurologic sequela is the occurrence of temporal lobe radionecrosis (TLN) associated with cognitive dysfunction. Currently, there is no effective intervention to improve patients' cognitive performance.METHODSTwenty‐nine patients with TLN after radiotherapy for NPC were recruited on a voluntary basis. Among them, 19 patients (15 males and 4 females) received a megadose of alpha‐tocopherol (vitamin E) (2000 international units per day) for 1 year, whereas the other 10 (5 males and 5 females) served as control patients. Their cognitive function (i.e., global cognitive ability, attention, memory, language, and executive function) was evaluated by a battery of neuropsychological tests before and after treatment.RESULTSSignificant improvement in global cognitive ability (P = 0.035) and memory (verbal: P = 0.036; visual: P = 0.007) occurred among patients in the treatment group after a 1‐year medication period. In addition, the executive function of the treatment group improved significantly (P = 0.04). No difference was found between the two groups with respect to attention or language.CONCLUSIONSThe current investigation was a preliminary study on the effect of alpha‐tocopherol on the cognitive function of patients with TLN after radiotherapy for NPC. In view of the absence of effective treatment for patients with cerebral radionecrosis, alpha‐tocopherol has the potential to be a complementary intervention for patients with cognitive dysfunction due to TLN. Cancer 2004;100:398–404. © 2003 American Cancer Society.
Long‐term outcomes after radical prostatectomy performed in a community‐based health maintenance organization
Authors: Zhang M.S. Ying , Glass Andrew , Bennett Nicole , Oyama Karen A. , Gehan Edmund , Gelmann Edward P. 
Published: January 2004

AbstractBACKGROUNDRadical prostatectomy is used widely for the treatment of patients with localized prostate carcinoma. No long‐term analysis has been reported on a series of radical prostatectomies performed in a community‐based health maintenance organization.METHODSCharts and histologic slides were reviewed from 750 patients who underwent radical prostatectomy between 1970 and 1996 at a community‐based health maintenance organization. The influences of a number of variables were analyzed for their impact on progression free survival (PFS) and overall survival (OS).RESULTSWith a median follow‐up of 6.2 years among survivors, 137 patients (18%) had progressive disease, and 149 patients (20%) died from all causes. The median OS from the date of diagnosis was 15.7 years (95% confidence interval, 13.6–17.2), similar to the expected median survival of 16.2 years. The median PFS from diagnosis was not reached, but 75% of patients were progression free ≥ 10.6 years after undergoing prostatectomy. The prognostic factors included Gleason score, age at diagnosis, and T stage. Outcomes were comparable with reports of surgical series from university‐based practices.CONCLUSIONSThe patient characteristics that had important, favorable correlation with survival included Gleason score ≤ 6, T1 or T2 tumor status, and younger age at diagnosis. Lower prostate‐specific antigen values at diagnosis, together with the former two parameters, also had a favorable correlation with PFS. Radical prostatectomy in a community‐based health maintenance organization was followed by long‐term PFS and OS comparable to outcomes reported from university‐based practices. The impact of radical prostatectomy on survival remains to be demonstrated. Cancer 2004;100:300–7. © 2003 American Cancer Society.
Stereotactic vacuum‐assisted breast biopsy in 2874 patients
Authors: Kettritz Ute , Rotter Kerstin , Schreer Ingrid , Murauer Margarete , Schulz‐Wendtland Rüdiger , Peter Daniela , Heywang‐Köbrunner Sylvia H. 
Published: January 2004

AbstractBACKGROUNDVacuum‐assisted breast biopsy (VAB) can replace surgical biopsy for the diagnosis of breast carcinoma. The authors evaluated the accuracy and clinical utility of VAB in a multicenter setting using a strict quality assurance protocol.METHODSIn the current study, VABs were performed successfully for 2874 patients at 5 sites. Benign lesions were verified by follow‐up. Surgery was recommended for malignant and borderline lesions. VAB was performed on patients with lesions rated as highly suspicious (6%), intermediate to suspicious (85%), or probably benign (9%). Fifty‐eight percent of the lesions were < 10 mm and 70% had microcalcifications.RESULTSThe authors identified 7% of patients with invasive carcinomas, 15% with ductal carcinomas in situ (DCIS), 5% with atypical ductal hyperplasias (ADH), and 0.6% with lobular carcinomas in situ. The results of the VAB necessitated an upgrade of 24% of patients with ADH to DCIS or DCIS and invasive carcinoma. Twelve percent of patients with DCIS proved to have invasive carcinoma. Seventy‐three percent of the patients had benign lesions. Only 1 false‐negative result was encountered (negative predictive value, 99.95%). Minor side effects were reported to occur in 1.4% of patients and 0.1% of patients required a subsequent intervention. Scarring relevant for mammography was rare among patients (i.e., 0.3% of patients had relevant scarring).CONCLUSIONSQuality‐assured VAB was found to be highly reliable. VAB effectively identified patients with benign lesions and assisted therapeutic decisions. Most important, only a single case of malignancy was missed. A close interdisciplinary approach assured optimal results. Cancer 2004;100:245–51. © 2003 American Cancer Society.
Phase II study of pentostatin in advanced T‐cell lymphoid malignancies
Authors: Tsimberidou Apostolia‐Maria , Giles Francis , Duvic Madeleine , Fayad Luis , Kurzrock M.D. Razelle 
Published: January 2004

AbstractBACKGROUNDThe goal of the current study was to assess the toxicity, safety, and efficacy of pentostatin in patients with T‐cell lymphoid malignancies.METHODSPatients were eligible if they had biopsy‐proven T‐cell lymphoma or leukemia and failure to respond to previous therapy or an expected complete response rate to conventional therapy of < 20%. Pentostatin was administered at an initial dose of 3.75 or 5.0 mg/m2 by intravenous bolus daily over a consecutive 3‐day period every 3 weeks.RESULTSForty‐two of 44 patients enrolled in the study were evaluable. The median age of the patients was 62 years (range, 38–86 years). Patients received a median of 3 previous therapies (range, 0–10 previous therapies). Of these patients, 32 (76%) had mycosis fungoides/Sézary syndrome and 10 patients (24%) had other T‐cell leukemias or lymphomas. The overall response rate was 54.8% (complete remission, 6 patients [14.3%]; partial remission, 17 patients [40.5%]). Durable responses were observed mainly in patients with Sézary syndrome or peripheral T‐cell lymphoma. The median follow‐up period for surviving patients was 20 months (range, 1–83+ months). The median duration of response was 4.3 months (range, 1–61 months). The most common toxicities were neutropenia, nausea, and CD4 suppression. A transient early ‘flare’ of disease was observed in some responders.CONCLUSIONSAt these doses, pentostatin was reasonably well tolerated and is an effective drug for the treatment of T‐cell lymphomas. Cancer 2004;100:342–9. © 2003 American Cancer Society.