bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining Capecitabine and Gemcitabine in Patients With Advanced Pancreatic Carcinoma: A Phase I/II Trial
Authors: Hess Viviane , Salzberg Marc , Borner Markus , Morant Rudolf , Roth Arnaud D. , Ludwig Christian , Herrmann Richard 
Published: December 2002

Purpose: Preclinical studies indicate positive interactions between capecitabine, an oral fluorouracil precursor, and gemcitabine, the current standard treatment for advanced pancreatic carcinoma (APC). In this study, we investigated the addition of capecitabine to gemcitabine treatment for patients with APC. Patients and Methods: This multicenter study included patients naïve to chemotherapy who had histologically or cytologically confirmed, nonresectable or metastatic pancreatic carcinoma. Gemcitabine was given at a fixed dose of 1,000 mg/m2 on days 1 and 8 of a 21-day cycle. Capecitabine was given in increasing doses orally bid for 14 days followed by a 1-week rest. The maximum-tolerated dose (MTD) was defined as one dose level below the dose causing dose-limiting toxicity (DLT) in ≥ one third of a cohort of six patients. We included an additional 15 patients at the MTD. Results: Thirty-six patients were included. DLT occurred at a dose of 800 mg/m2 bid of capecitabine and consisted of myelotoxicity and mucositis. Hand-foot syndrome was not observed, and other toxic effects were mild. Thus, in this regimen, the recommended dose of capecitabine is 650 mg/m2 bid. In 27 patients with measurable disease, we observed one complete and four partial remissions. In addition, significant drops (> 50% from baseline value) of the tumor marker CA 19–9 occurred in 14 of 24 assessable patients. Conclusion: The combination of capecitabine and gemcitabine is well tolerated, with apparent efficacy in patients with APC. Therefore, it is currently being compared with gemcitabine monotherapy in a phase III study.
Phase I Clinical Trial of Intrathecal Topotecan in Patients With Neoplastic Meningitis
Authors: Blaney Susan M. , Heideman Richard , Berg Stacey , Adamson Peter , Gillespie Andy , Geyer J. Russell , Packer Roger , Matthay Kate , Jaeckle Kurt , Cole Diane , Kuttesch Nancy , Poplack David G. , Balis Frank M. 
Published: December 2002

Purpose: A phase I trial of intrathecal (IT) topotecan was performed to determine the optimal dose, the dose-limiting toxic effects, and the incidence and severity of other toxic effects in patients 3 years and older with neoplastic meningitis. Patients and Methods: Twenty-three assessable patients received IT topotecan administered by means of either lumbar puncture or an indwelling ventricular access device (Ommaya reservoir). Intrapatient dose escalation from 0.025 mg to 0.2 mg was performed in the first cohort of patients. Subsequent cohorts of patients were treated at fixed dose levels of 0.2 mg, 0.4 mg, or 0.7 mg. Serial samples of CSF for pharmacokinetic studies were obtained in a subset of patients with Ommaya reservoirs. Results: Arachnoiditis, characterized by fever, nausea, vomiting, headache, and back pain, was the dose-limiting toxic effect in two of four patients enrolled at the 0.7 mg dose level. The maximum-tolerated dose (MTD) was 0.4 mg. Six of the 23 assessable patients had evidence of benefit manifested as prolonged disease stabilization or response. Conclusion: The MTD and recommended phase II dose of IT topotecan in patients who are 3 years or older is 0.4 mg. A phase II trial of IT topotecan in children with neoplastic meningitis is in progress.
Prostate-Specific Antigen Kinetics as a Measure of the Biologic Effect of Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Serologic Progression of Prostate Cancer
Authors: Rini Brian I. , Weinberg Vivian , Bok Robert , Small Eric J. 
Published: December 2002

Purpose: To determine the biologic effect of granulocyte-macrophage colony-stimulating factor (sangramostim, GM-CSF; Immunex Corporation, Seattle, WA) as measured by prostate-specific antigen (PSA) kinetics in patients with serologic progression of prostate cancer after definitive local therapy. Patients and Methods: Patients with prostate cancer who had undergone previous definitive surgical or radiation therapy with nonmetastatic, recurrent disease as manifested by a rising PSA between 0.4 ng/mL and 6.0 ng/mL were enrolled on this phase II trial. Patients received 250 μg/m2/day of subcutaneous GM-CSF on days 1 through 14 of a 28-day cycle. PSA was measured at day 1 of each cycle. Results: Thirty patients with serologic progression of prostate cancer were treated. The median pretreatment PSA was 2.9 ng/mL. Of the 29 evaluable patients, three patients (10%; 95% confidence interval, 2% to 27%) achieved a 50% reduction in PSA. For the patients (n = 26) in whom the on-treatment PSA doubling time could be calculated, the median PSA doubling time increased from 8.4 months to 15 months (P = .001), and the median slope of the PSA versus time curve decreased with treatment (P = .004). Therapy was well tolerated by all patients, with an average treatment duration of 16.5 cycles (range, 5 to 33). Conclusion: GM-CSF has a biologic effect in patients with serologic progression of prostate cancer after definitive local therapy, as measured by PSA declines and modulation of PSA kinetics.
Limb anomalies: Developmental and evolutionary aspects
Authors: Gurrieri Fiorella , Kjaer Klaus W. , Sangiorgi Eugenio , Neri Giovanni 
Published: December 2002

AbstractIn this review we describe the developmental mechanisms involved in the making of a limb, by focusing on the nature and types of interactions of the molecules that play a part in the regulation of limb patterning and characterizing clinical conditions that are known to result from the abnormal function of these molecules. The latter subject is divided into sections dealing with syndromal and nonsyndromal deficiencies, polydactylies, and brachydactylies. Conditions caused by mutations in homeobox genes and fibroblast growth factors and their receptor genes are listed separately. Since the process of limb development has been conserved for more than 300 millions years, with all the necessary adaptive modifications occurring throughout evolution, we also take into consideration the evolutionary aspects of limb development in terms of genetic repertoire, molecular pathways, and morphogenetic events. © 2002 Wiley‐Liss, Inc.
Two new cases of analphoid marker chromosomes
Authors: Spiegel Miriam , Hickmann Gabriele , Senger Gabriele , Kozlowski Peter , Bartsch Oliver 
Published: December 2002

AbstractSupernumerary marker chromosomes (SMCs) without detectable alphoid DNA represent a rare and interesting class of rearranged marker chromosomes. These SMCs are predicted to have a neocentromere and have been referred to as neocentric marker chromosomes (NMCs). We report the molecular cytogenetic characterization of two new cases of neocentromere‐containing chromosomes, one on 1q43∼44 and one on 15q26. Both cases were examined using fluorescence in situ hybridization (FISH) with various alpha‐satellite DNA probes, and no alphoid DNA was detected. In case 1, the NMC originated from the distal long arm of chromosome 1 by chromosomal microdissection and reverse painting. This marker lacked detectable chromosome 1q subtelomeric sequences, and therefore appeared to be a small ring chromosome. After genetic counseling with a high risk for a MCA/MR syndrome (trisomy 1q43 → q44), the family continued the pregnancy. At age 6 months, the infant demonstrated no congenital or developmental anomalies. This is the first published example of a NMC derived from chromosome 1q. The marker may be one of the smallest, if not the smallest, human NMC reported to date. In case 2, fetal ultrasonography indicated a complex heart defect (abnormal return of lower vena cava, atrial septum malformation) and bilateral hydronephrosis. Molecular cytogenetic analysis showed an inverted duplication of the distal long arm of chromosome 15 (tetrasomy 15q24 → qter). The pregnancy was terminated. Autopsy demonstrated polycystic left kidney and dysplastic right kidney. Case 2 represents the ninth report of a neocentromere on distal chromosome 15q, suggesting that this region may possibly especially support the formation of neocentromeres. © 2002 Wiley‐Liss, Inc.
Overexpression of nPKC θ is inhibitory for agrin‐induced nicotinic acetylcholine receptor clustering in C2C12 myotubes
Authors: Miles Kathryn , Wagner Michael 
Published: December 2002

AbstractProtein kinase C (PKC) activity has been implicated in nicotinic acetylcholine receptor (nAChR) cluster disruption but the specific PKC isoforms involved have not been identified. We first tested whether phorbol esters, which activate PKCs, regulate agrin‐induced nAChR clustering in C2C12 cells. We found that extended phorbol ester treatment (6 hr) increased nAChR clustering by two‐fold. This increase correlated in time with downregulation of PKCs, as indicated by the disappearance of cPKC α, suggesting that the presence of PKCs is inhibitory for maximal nAChR clustering. To address the question whether nPKC θ, a specific PKC isoform restricted in expression to skeletal muscle and localized to neuromuscular junctions, regulates agrin‐induced nAChR cluster formation we overexpressed an nPKC θ ‐green fluorescent protein (GFP) fusion protein in C2C12 myotubes. The number of nAChR clusters was significantly reduced in nPKC θ‐GFP compared to GFP overexpressing myotubes at less‐than‐maximal clustering concentrations of agrin. These data indicate that nPKC θ activity inhibits nAChR cluster formation. To examine whether nPKC θ activation by phorbol esters regulates agrin‐induced nAChR clustering, we treated overexpressing myotubes overnight with maximal agrin concentrations followed by phorbol esters for 1 hr. Phorbol ester treatment reduced preexisting nAChR cluster numbers in nPKC θ‐GFP compared to GFP‐overexpressing myotubes, suggesting that stimulating nPKC θ activity disrupts nAChR clusters in the presence of maximal clustering concentrations of agrin. Together these findings, that nPKC θ activity inhibits agrin‐induced nAChR cluster formation and disrupts preexisting agrin‐induced nAChR clusters, suggest that nPKC θ activity is inhibitory for agrin function. © 2002 Wiley‐Liss, Inc.
Impairment of protein homeostasis and decline of proteasome activity in microglial cells from adult Wistar rats
Authors: Stolzing Alexandra , Grune Tilman 
Published: December 2002

AbstractCommon symptoms of different neurodegenerative diseases start to develop in the second half of the human life. Several of these diseases, including Alzheimer's and Parkinson's disease, are accompanied by severe disturbances of protein metabolism and homeostasis in the brain. Because microglial cells are, to some extent, responsible for the maintenance of this homeostasis, age‐related functional changes of the microglia are important. We established, therefore, the preparation of cultures of primary microglial cells isolated from adult animals in comparison to the widely used standard model, primary microglial cells isolated from newborn animals. In addition, we investigated changes in the activation and in the protein homeostasis within these cells. The protein turnover seems to be significantly impaired in microglial cells isolated from adult animals and this seems to be accompanied by a decline in proteasomal function, but not in the protease content. We were also able to demonstrate higher cell surface molecule expression and a higher basal NO release of microglia isolated from adult animals in comparison to the microglia isolated from newborn rats; however, the PMA stimulated oxidative burst was abolished completely in cells from adult animals. Microglia from adult animals were also not able to upregulate their protein metabolism after activation. From these investigations it was concluded that microglial cells from adult animals have significantly different metabolic properties in comparison to the widely used microglial cells from newborn animals. © 2002 Wiley‐Liss, Inc.
Unstable Climate Oscillations during the Late Holocene in the Eastern Bransfield Basin, Antarctic Peninsula
Authors: Khim Boo-Keun , Yoon Ho Il , Kang Cheon Yun , Bahk Jang Jun 
Published: December 2002

AbstractCore A9-EB2 from the eastern Bransfield Basin, Antarctic Peninsula, consists of pelagic (diatom ooze-clay couplets and bioturbated diatom ooze) and hemipelagic (bioturbated mud) sediments interbedded with turbidites (homogeneous mud and silt–clay couplets). The cyclic and laminated nature of these pelagic sediments represents alternation between the deposition of diatom-rich biogenic sediments and of terrigenous sediments. Sediment properties and geochemical data explain the contrasting lamination, with light layers being finer-grained and relatively rich in total organic carbon and biogenic silica content. Also, the high-resolution magnetic susceptibility (MS) variations highlight distinct features: high MS values coincide with clastic-rich sections and low MS values correspond to biogenic sections. The chronology developed for core A9-EB2 accounts for anomalous ages associated with turbidites and shows a linear sedimentation rate of approximately 87 cm/103 yr, which is supported by an accumulation rate of 80 cm/103 yr calculated from 210Pb activity. The late Holocene records clearly identify Neoglacial events of the Little Ice Age (LIA) and Medieval Warm Period (MWP). Other unexplained climatic events comparable in duration and amplitude to the LIA and MWP events also appear in the MS record, suggesting intrinsically unstable climatic conditions during the late Holocene in the Bransfield Basin of Antarctic Peninsula.
Late Quaternary Spring-Fed Deposits of the Grand Canyon and Their Implication for Deep Lava-Dammed Lakes
Authors: Kaufman Darrell S. , O'Brien Gary , Mead Jim I. , Bright Jordon , Umhoefer Paul 
Published: December 2002

AbstractOne of the most intriguing episodes in the Quaternary evolution of the Grand Canyon of the Colorado River, Arizona, was the development of vast lakes that are thought to have backed up behind lava erupted into the gorge. Stratigraphic evidence for these deep lava-dammed lakes is expectedly sparse. Possible lacustrine deposits at six areas in the eastern canyon yielded no compelling evidence for sediment deposited in a deep lake. At two of the sites the sediment was associated with late Quaternary spring-fed pools and marshes. Water-lain silt and sand at lower Havasu Creek was deposited ∼3000 cal yr ago. The deposit contains an ostracode assemblage similar to that living in the modern travertine-dammed pools adjacent to the outcrop. The second deposit, at Lees Ferry, formed in a spring-fed marsh ∼43,000 cal yr ago, as determined by 14C and amino acid geochronology. It contains abundant ostracode and mollusk fossils, the richest assemblages reported from the Grand Canyon to date. Our interpretation of these sediments as spring-fed deposits, and their relative youth, provides an alternative to the conventional view that deposits like these were formed in deep lava-dammed lakes that filled the Grand Canyon.
Probability Density Functions as Botanical-Climatological Transfer Functions for Climate Reconstruction
Authors: Kühl Norbert , Gebhardt Christoph , Litt Thomas , Hense Andreas 
Published: December 2002

AbstractWe present a new procedure, the pdf method (pdf=probability density function), for reconstructing Quaternary climate utilizing botanical data. The procedure includes the advantages of the indicator species method by considering the fossil and modern presence and absence of taxa rather than their frequencies, thus avoiding the need for modern analog plant communities. Overcoming the problematic use of absolute limits to describe climate response ranges is the main progress of the pdf method in comparison to the indicator species method. This advantage results from estimating probability density functions (pdfs) for monthly mean January and July temperature conditional on the present day occurrence of single taxa. Gaussian distributions sufficiently approximate pdfs of many, although not all, studied taxa. On the assumption of statistical independence, the procedure calculates a joint pdf as the product of the pdfs of the individual taxa. This algorithm weights each taxon according to the extent of its climate response range expressed by its covariance structure. We interpret the maximum of the resulting pdf as the most likely climate and its confidence interval as the uncertainty range. To avoid an artificial reduction of uncertainty arising from the use of numerous similar pdfs, a preselection method is proposed based on the Mahalanobis distance between pdfs. The pdf method was applied to the Carpinus phase of a profile from Gröbern, Germany, that spans the last interglaciation (Eemian). The reconstructed most probable January and July temperatures of about 0.0°C and 18.4°C barely differ from the modern values of −0.5°C and 18.3°C.
Drought-Related Changes in Two Hunter–Gatherer California Populations
Authors: Weiss Elizabeth 
Published: December 2002

AbstractSkeletal remains from two California cemeteries bracketing a severe drought that began around 1200 yr B.P. are analyzed to determine drought-related quality of life changes in Native Americans. Cemetery 1 predates the drought at 2895±160 yr B.P. to 1845±90 yr B.P. and Cemetery 2 dates it at 1100±90 yr B.P. to 1220±200 yr B.P. Quality of life was assessed through femoral computerized tomography scan measures of cortical thickness, age at adult death, and pathology/trauma frequency. After controlling for age and sex differences, changes from Cemetery 1 to Cemetery 2 showed decreases in cortical thickness and age at death and increases in pathology and trauma frequency.
Treatment and outcome of Taiwanese patients with 6‐pyruvoyltetrahydropterin synthase gene mutations
Authors: Chien Y.‐H. , Chiang S.‐C. , Huang A. , Lin J.‐M. , Chiu Y.‐N. , Chou S.‐P. , Chu S.‐Y. , Wang T.‐R. , Hwu W.‐L. 
Published: December 2002

AbstractTen cases of tetrahydrobiopterin (BH4) deficiency were identified in 1,337,490 newborns screened in a Chinese population in Taiwan. The high incidence of BH4 deficiency in the Taiwanese population may be explained by a founder effect, since all of the patients revealed 6‐pyruvoyltetrahydropterin synthase gene mutations, and grouping N52S and P87S mutations together constituted 88.9% of the disease alleles. BH4 supplementation with restriction of high‐protein foods gave control of plasma phenylalanine within normal range, and levadopa itself prevented seizure. However, the average intelligence quotient (IQ) score of these patients was only 76 ± 14 (56–98). Statistically, the age of starting medication, including 5‐hydroxytrytophan (5‐HTP), was inversely correlated to IQ scores of these patients. We suggest the combination of BH4, levodopa and 5‐HTP as the standard protocol to commence the treatment of BH4 deficiency as early as possible, although prenatal brain damage could have existed.
Decreasing serum VLCFA levels in ageing X‐ALD female carriers
Authors: Stradomska T. J. , Tylki‐Szymańska A. 
Published: December 2002

AbstractAdrenoleukodystrophy is an X‐linked severe demyelinating disease with pathognomonic accumulation of saturated very long‐chain fatty acids (VLCFA) in tissues and body fluids in affected males. The identification of women heterozygotes is also based on increased serum VLCFA concentrations. We describe the results of measuring serum VLCFA concentrations in 59 females of various ages with heightened risk of carrier status. In female carriers aged 22–50 years we found serum VLCFA concentrations in a range characteristic of heterozygotes; VLCFA levels were normal in female carriers aged 55–64 years. In women aged 37–50 years in whom repeat studies of VLCFA concentration were performed after 5 years, a reduction in VLCFA was observed. The results we obtained point to a reduction of serum VLCFA concentrations as X‐ALD heterozygotes age.
Traumatic life events and suicide risk among jail inmates: The influence of types of events, time period and significant others
Authors: Blaauw E. , Arensman E. , Kraaij V. , Winkel F. W. , Bout R. 
Published: December 2002

AbstractRelationships between traumatic life events and suicide risk were studied in two samples of jail inmates with a low (N = 216) and a high (N = 51) suicide risk. Although nonsuicidal inmates reported a high prevalence of traumatic life events, suicidal inmates reported even higher prevalence rates. Suicidal inmates reported more episodes of sexual abuse, physical maltreatment, emotional maltreatment, abandonment, and suicide attempts by significant others. They also had experienced more traumatic life events during childhood, later life, and detention. It is concluded that traumatic life events are associated with suicide risk and that such an association remains in a population with a high prevalence of traumatic life events. It is also concluded that suicide risk is dependent of the type of life event, the timing of the event, and the type of persons involved in the event.
Evaluating Attributions for an Illness Based Upon the Name: Chronic Fatigue Syndrome, Myalgic Encephalopathy and Florence Nightingale Disease
Authors: Jason Leonard A. , Taylor Renee R. , Plioplys Sigita , Stepanek Zuzanna , Shlaes Jennifer 
Published: December 2002

AbstractIn recent years, considerable discussion has occurred about stigma surrounding the name given to an illness currently known as chronic fatigue syndrome (CFS). Although patients and medical personnel have expressed varying opinions on this issue, no studies have evaluated how beliefs about the illness change based upon the type of name used for diagnostic purposes. Proposals have been put forth to rename the illness with an eponym (a famous patient's or researcher's name) or with a less trivial sounding, more medically based type of name. In this study, attributions about CFS were measured in three groups of medical trainees. All groups read the same case study of a person with classic symptoms of chronic fatigue syndrome, with the only difference being in the type of name given. Trainees then were asked to provide attributions about certain aspects of the illness, including its cause, severity, and prognosis. Results suggested that, across name conditions, most trainees appeared to consider the symptom complex of CFS a serious illness resulting in poor quality of life. In addition, findings indicated that the name, chronic fatigue syndrome, may be regarded less seriously than the Myalgic Encephalopathy name with respect to some important aspects of the illness. In this study, specialty of medical trainee also played a role in how the illness was perceived.
Children exposed to warfare: A longitudinal study
Authors: Dyregrov Atle , Gjestad Rolf , Raundalen Magne 
Published: December 2002

AbstractFollowing the 1991 Gulf War a group of 94 children in Iraq were interviewed at 6 months, 1 year, and 2 years after the war. The group was exposed to the bombing of a shelter where more than 750 were killed. Selected items from different inventories, including the Impact of Event Scale (IES) assessed children's reactions. Results reveal that children continue to experience sadness and remain afraid of losing their family. Although there was no significant decline in intrusive and avoidance reactions as measured by the IES from 6 months to 1 year following the war, reactions were reduced 2 years after the war. However, the scores were still high, indicating that symptoms persist, with somewhat diminished intensity over time.