bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical significance of alterations of chromosome 8 detected by fluorescence in situ hybridization analysis in pathologic organ‐confined prostate cancer
Authors: Tsuchiya Norihiko , Slezak Jeffrey M. , Lieber Michael M. , Bergstralh Erik J. , Jenkins Robert B. 
Published: October 2002

AbstractLoss of 8p22 and gain of 8q24 are known to be common chromosomal alterations in prostate cancer. We have previously demonstrated that concurrent 8q24 overrepresentation and 8p22 loss were associated with a poor prognosis in patients with high‐grade, locally advanced prostate cancer. We evaluated the alteration of 8p22 and 8q24 in a large cohort of pathologic organ‐confined prostate cancer using fluorescence in situ hybridization (FISH) analysis. All 195 patients with Gleason scores > 5, pathologic stage T2N0M0 (pT2N0M0) prostate cancer, who underwent a radical prostatectomy at the Mayo Clinic between 1987 and 1991, and for whom blocks were available, were selected for this study. The median follow‐up period was 9.5 years, and endpoints of this study were biochemical and clinical disease progression. The latter includes local as well as systemic disease progression. FISH analysis using paraffin‐embedded tissues was performed for 8p22 (LPL), centromere 8 (8cen), and 8q24 (MYC) and was successful for 156 tumors (80.0%). Of these tumors, 104 (66.6%) had one or more numeric alterations of the 3 loci evaluated. An increased copy number of 8q24 was observed in 66 (42.3%) tumors, of which 20 (12.8%) had an additional increase (AI) of 8q24, and 46 (29.5%) had a gain of 8q24 with an equivalent gain of 8cen. Losses and gains of 8p22 were detected in 81 (51.9%) and 20 (12.8%) tumors, respectively. An AI of 8q24 was significantly associated with the tumor Gleason score (P = 0.042). Univariate analysis indicated that loss of 8p22 was a significant predictor of biochemical and clinical disease progression (P = 0.025 and P = 0.011, respectively). Furthermore, the group with loss of 8p22 concurrent with an AI of 8q24 (Loss 8p22‐any 8cen‐AI 8q24) had an increased rate of biochemical disease progression (P = 0.052). Multivariate analysis demonstrated that neither individual nor the Loss‐any‐AI combination of alterations was a significant independent predictor of disease progression when adjusting for Gleason score, preoperative PSA levels, and DNA ploidy. These data suggest that loss of 8p22 is associated with a poor prognosis, specifically when it is accompanied by AI of 8q24 in pT2N0M0 prostate cancer. © 2002 Wiley‐Liss, Inc.
Genomewide DNA hypomethylation is associated with alterations on chromosome 8 in prostate carcinoma
Authors: Schulz Wolfgang A. , Elo Jussi P. , Florl Andrea R. , Pennanen Sari , Santourlidis Simon , Engers Rainer , Buchardt Martin , Seifert Hans‐Helge , Visakorpi Tapio 
Published: October 2002

AbstractTo elucidate the relationship between genomewide DNA hypomethylation and chromosome instability, 55 prostate carcinoma specimens were analyzed for extent of hypomethylation by Southern blot analysis of LINE‐1 sequence methylation and for loss or gain of chromosomal material by comparative genomic hybridization. Seventeen (31%) tumors showed strong hypomethylation of DNA, whereas four (7%) displayed slight hypomethylation and the rest of the tumors normal‐level methylation. Chromosomal aberrations were observed in 34 carcinomas. The most frequent chromosomal alterations were loss of 13q in 18 cases and aberrations in 8p (loss) or 8q (gain) in 16 cases. The presence of chromosomal loss or gain was significantly associated with the presence of strong hypomethylation. A striking correlation (P = 0.00001) was observed between aberrations on chromosome 8 and hypomethylation, whereas no association was seen between DNA hypomethylation and loss of 13q. The association between DNA hypomethylation and the presence of metastases was statistically significant (P = 0.044), and both chromosomal alterations and DNA hypomethylation tended to be more frequent in higher‐stage tumors. In conclusion, the data indicate that hypomethylation is associated with chromosomal instability in prostate cancer. Specifically, a surprisingly strong association between alterations on chromosome 8 and genomewide hypomethylation was found. This association suggests that DNA hypomethylation and alterations in chromosome 8 may be mechanistically linked to each other in prostate carcinoma. © 2002 Wiley‐Liss, Inc.
High sensitivity of detection of TP53 somatic mutations by fluorescence‐assisted mismatch analysis
Authors: Tessitore Alessandra , Christiana Di Rocco Zorika , Cannita Katia , Ricevuto Enrico , Toniato Elena , Tosi Mario , Ficorella Corrado , Frati Luigi , Gulino Alberto , Marchetti Paolo , Martinotti Stefano 
Published: October 2002

AbstractWe analyzed exons 5–9 of the TP53 gene in 41 breast cancers using direct sequencing, PCR‐SSCP (single‐strand conformation polymorphism), and fluorescence‐assisted mismatch analysis (FAMA), to test the level of specificity and sensitivity of each method. A major issue for the correct detection of TP53 somatic mutations in primary tumors is often represented by the large amount of normal DNA, which can cause excessive dilution of the mutant allele, with consequent possible false‐negative results. High sensitivity upon dilution of the mutant allele has been demonstrated for FAMA, a method based on the chemical cleavage of a mismatch within heteroduplex DNA molecules. Exons 5–9 of the TP53 gene were analyzed by FAMA using only two long bifluorescent fragments. Differences in sensitivity, accuracy, and specificity were observed among the above‐mentioned procedures. Thirteen of the 41 samples (31.7%) revealed TP53 genetic alterations by automated sequencing, 19 samples (46.3%) were positive for SSCP, whereas 14 samples (34%) showed variants detectable by FAMA. Seven samples were positive in SSCP, but negative in both FAMA and sequencing assays; however, 2 SSCP‐negative samples revealed evident signals by FAMA, indicating the presence of TP53 mutations. One of the latter samples showed the alteration by sequence analysis, whereas the other failed to reveal the mutation signal even by sequencing, as a consequence of the very small amount of the mutant allele resulting from the excess of contaminating normal DNA. Our results show that FAMA may represent a suitable and accurate assay for the routine diagnosis of TP53 somatic mutations in DNAs from solid tumor biopsies.
Design of studies using DNA microarrays
Authors: Simon Richard , Radmacher Michael D. , Dobbin Kevin 
Published: October 2002

AbstractDNA microarrays are assays that simultaneously provide information about expression levels of thousands of genes and are consequently finding wide use in biomedical research. In order to control the many sources of variation and the many opportunities for misanalysis, DNA microarray studies require careful planning. Different studies have different objectives, and important aspects of design and analysis strategy differ for different types of studies. We review several types of objectives of studies using DNA microarrays and address issues such as selection of samples, levels of replication needed, allocation of samples to dyes and arrays, sample size considerations, and analysis strategies. Genet. Epidemiol. 23:21–36, 2002. © 2002 Wiley‐Liss, Inc.
Ceramide levels are inversely associated with malignant progression of human glial tumors
Authors: Riboni Laura , Campanella Rolando , Bassi Rosaria , Villani Roberto , Gaini Sergio M. , Martinelli‐Boneschi Filippo , Viani Paola , Tettamanti Guido 
Published: October 2002

AbstractCeramide represents an important sphingoid mediator involved in the signaling pathways that control cell proliferation, differentiation, and death. To determine whether ceramide levels correlate with the malignant progression of human astrocytomas, we investigated these levels in surgical specimens of glial tumors of low‐grade and high‐grade malignancy. Tumor samples obtained from 52 patients who underwent therapeutic removal of primary brain tumors were used. The tumors were classified according to standard morphologic criteria and were grouped into tumors of low‐grade and high‐grade malignancy. Sections of normal brain tissue adjacent to the tumor were also analyzed in 11 of the 52 patients. After extraction and partial purification, ceramide was measured by quantitative derivatization to ceramide‐1‐phosphate using diacylglycerol kinase and [γ‐32P]ATP. Ceramide levels were significantly lower in the combined high‐grade tumors compared with low‐grade tumors and in both tumor groups compared with peritumoral tissue. The results indicate an inverse correlation between the amount of ceramide and tumor malignancy as assessed by both the histological grading and ganglioside pattern. Moreover, overall survival analysis of 38 patients indicates that ceramide levels are significantly associated with patient survival. The present findings indicate that ceramide is inversely associated with malignant progression of human astrocytomas and poor prognosis. The downregulation of ceramide levels in human astrocytomas emerges as a novel alteration that may contribute to glial neoplastic transformation. The low ceramide levels in high‐grade tumors may provide an advantage for their rapid growth and apoptotic resistant features. This study appears to support the rationale for the potential benefits of a ceramide‐based chemotherapy. GLIA 39:105–113, 2002. © 2002 Wiley‐Liss, Inc.
Carers, ethics and dementia: a survey and review of the literature
Authors: Hughes Julian C. , Hope Tony , Savulescu Julian , Ziebland Sue 
Published: October 2002

AbstractBackgroundMuch has been written on ethical issues in dementia, but usually from the point of view of the various professionals involved. Whilst there has been an increasing amount of interest in the psychosocial problems that face the carers of people with dementia, the ethical nature of some of these problems has largely been ignored.ObjectiveTo review the literature on ethical issues in dementia from the perspective of the main, non‐professional carers of people with dementia.MethodA systematic literature search using Medline, Clinpsych and CINAHL databases between 1982 and 2000. A pilot study of carers.ResultsThe lay perspective provides both a wide variety of issues and unique approaches. Although in the literature quantitative research answers some questions, it is qualitative research that deepens our understanding of the issues from the perspective of carers.ConclusionIt is particularly qualitative research that brings out the ethical issues for carers, which tend to be more varied than the ethical issues raised in the professional literature. Awareness of such issues could inform and shape the support given to carers. Copyright © 2002 John Wiley & Sons, Ltd.
Views of elderly patients on cardiopulmonary resuscitation before and after treatment for depression
Authors: Eggar Richard , Spencer Amanda , Anderson David , Hiller Louise 
Published: October 2002

AbstractObjectiveTo investigate elderly patients decision to accept cardiopulmonary resuscitation (CPR) before and after treatment for depression.MethodsA Prospective cohort study set within a specialist psychiatrist hospital for the elderly. The subjects were 50 consecutively admitted day and in‐patients with depression. Changes in the acceptability of CPR between baseline and end of treatment for depression together with patient characteristics were measured and compared.Results49 patients completed the study; all but one of the 17 patients who initially declined CPR accepted once recovered and none who initially accepted later changed their minds (p = 0.0001).ConclusionsThe study demonstrates that depressed elderly people frequently decline CPR but accept after recovery from depression. The presence of depression should be specifically considered if an elderly person unexpectedly declines CPR. Copyright © 2002 John Wiley & Sons, Ltd.
Factor structure of the hospital anxiety and depression scale in older patients with major depression
Authors: Flint Alastair J. , Rifat Sandra L. 
Published: October 2002

AbstractObjectiveSymptomatic anxiety has prognostic significance in major depression. In theory, the Hospital Anxiety and Depression Scale (HADS) should be a useful instrument for measuring the severity of symptomatic anxiety in late‐life depression. However, the dimensional structure of the HADS has not been evaluated in elderly depressed patients; it is not known whether the scale actually functions as a bidimensional measure of anxiety and depression in this population. The purpose of this exploratory study, therefore, was to examine the factor structure of the HADS in older patients with major depression.MethodThe HADS was completed by 213 patients, aged 60 years or older, with DSM‐III‐R unipolar major depression. Principal components analysis was performed on the full 14‐item HADS and on each of its subscales.ResultsTwo distinct factors, which corresponded to the instrument's depression and anxiety subscales, emerged. The two‐factor structure proved reasonably stable when the study group was randomly divided into two halves. Analysis of the subscales resulted in a single factor for each. The subscales had high internal reliability.ConclusionsThese findings confirm that the HADS functions as a bidimensional measure of depression and anxiety in older patients with major depression. The results suggest that the HADS is a valid instrument for measuring severity of anxiety, independent of other depressive symptoms, in this population. Copyright © 2002 John Wiley & Sons, Ltd.
Negative symptoms, depression and Alzheimer's disease
Authors: Vercelletto Martine , Martinez Florence , Lanier Sophie , Magne Christine , Jaulin Philippe , Bourin Michel 
Published: October 2002

AbstractObjectivesTo apply the negative symptoms (NS) concept used in schizophrenia to patients with AD, to compare the results with the frontal lobe perfusion in ethyl cysteinate dimmer (ECD) single‐photon emission computed tomography (SPECT) and with the apolipoprotein E genotype.Method32 patients with a diagnosis of probable AD were assessed by the Positive and Negative Symptoms Scale (PANSS‐N), the Montgomery and Asberg Depression Scale (MADRS), the NeuroPsychiatric Inventory (NPI), and the Mini‐Mental Status Examination (MMSE). Each patient underwent ECD SPECT and APO E genotyping. PANSS‐N, MADRS, NPI, and MMSE were administered to 19 normal elderly control subjects.ResultsThe mean PANSS‐N score for AD patients (20.56, SD: 8, range: 7–40) was significantly higher (p < 0.001) than that of controls (7, SD: 0). MADRS scores were not significantly different (p = 0.75) between AD patients (9.03, SD: 6.14, range: 0–25) and controls (6.2, SD: 3.61, range: 1–15). The NPI apathy score (0–12) was correlated with PANSS‐N (p < 0.001). Correlation between prominent frontal hypoperfusion (six cases) and NS was at the limit of significance. No relation was found between epsilon E4 and NS.ConclusionThis consideration is important in distinguishing between depression and AD. Copyright © 2002 John Wiley & Sons, Ltd.
Gender related differences in clinical characteristics and hospital based resource utilization among older adults with schizophrenia
Authors: Sajatovic Martha , Sultana Dilara , Bingham C. Raymond , Buckley Peter , Donenwirth Karl 
Published: October 2002

AbstractObjectiveThis report is an analysis of gender related differences in clinical characteristics and hospital based health resource utilization among older adults with schizophrenia and schizoaffective disorder in an acute care, state hospital over a one‐year period.MethodsThis retrospective record review is an analysis of age of illness onset, psychiatric and medical comorbidity, hospital utilization, and psychotropic medication use.ResultsThere were a total of 66 individuals with either schizophrenia or schizoaffective disorder. Mean age of this group was 55.2 ± 4.62 years. Women were significantly over‐represented among individuals with late onset schizophrenia and schizoaffective disorder. Men with schizophrenia had more comorbid substance abuse compared to women with schizophrenia (p < 0.05). Women and men did not differ significantly in hospital length of stay, amount or type of antipsychotic medication prescribed, or in utilization of seclusion/restraint in hospital. Both genders had substantial utilization of antipsychotic medication. Use of conventional antipsychotic medication monotherapy was always associated with use of anti‐extrapyramidal symptom (anti‐EPS) medication, while use of atypical antipsychotic medication monotherapy was more rarely associated with use of anti‐EPS medication.ConclusionsIn later life, women and men may have some areas of differing health care needs. Women in particular may benefit from psychoeducational approaches that address the experience of psychiatric illness of relatively recent onset (for example, symptom identification and acceptance of illness). Men may benefit from particular emphasis on treatment of comorbid substance abuse disorders. Copyright © 2002 John Wiley & Sons, Ltd.
The prevalence of major depression or dysthymia among aged Medicare Fee‐for‐Service beneficiaries
Authors: McCall Nancy T. , Parks Peggy , Smith Kevin , Pope Greg , Griggs Michelle 
Published: October 2002

AbstractResearch ObjectiveEstimates of the prevalence of major depression vary widely. Current estimates range from 2 to 14 % depending upon the definition and procedure for diagnosis. Further, most estimates are for special populations, either living in selected geographic areas or receiving specific types of medical care. A national survey of Medicare Fee‐for‐Service (FFS) beneficiaries provides an opportunity to assess the current level of major depression or dysthymia among a diverse population of older Americans.Study DesignThe Health Outcomes Survey (HOS) was administered to a national random sample of 1,000 Medicare FFS beneficiaries. We used the Mental Component Summary (MCS) measure of the SF‐36 to estimate the prevalence of major depression or dysthymia. Logistic regression was used to examine associated factors.ResultsThe response rate was 61.7%. Using an MCS score of 42 or lower, prevalence of major depression or dysthymia was estimated to be 25% for respondents age 65 years and older. Logistic regression analysis revealed that the likelihood of major depression or dysthymia was associated with years of education (Odds Ratio (OR) = 0.87), difficulties performing activities of daily living (OR = 1.72), and Medicaid enrollment (OR = 2.67).ConclusionsThe results revealed that one‐quarter of the respondents reported mental health problems consistent with major depression or dysthymia. This is higher than previously reported. Like previous studies, years of education, physical impairment, and poverty are strong predictors of major depression or dysthymia. The high rate of major depression or dysthymia implies there may be considerable unmet need among elderly Medicare FFS beneficiaries for diagnosing and treating mental illness. Copyright © 2002 John Wiley & Sons, Ltd.
The clinical profile of older patients' response to antidepressants—an open trial of sertraline
Authors: Mottram P. G. , Wilson K. C. M. , Ashworth L. , Abou‐Saleh M. 
Published: October 2002

AbstractBackgroundA number of studies have examined the predictive utility and time to response of rating scales and demographic variables. Very few community samples have been examined in this way, and no studies examining the prognostic validity of early symptomatic response have been found in the literature.ObjectivesThis study aims to describe how treatment response is reflected in rating scales in older community residents treated with sertraline and to explore the utility of these instruments in predicting response.MethodsThe study examines the open label therapeutic and continuation phases of a maintenance trial.Results225 older depressed community residents were treated (openly) with sertraline. Fifty‐three percent had a good outcome, 13% did not respond to sertraline and had a poor long‐term prognosis. Increased age was associated with poor outcome and increased anxiety symptoms with a good outcome. In the compliant sub‐sample, GMS/AGECAT schizophrenia symptoms were associated with poor response to treatment. Baseline HDRS items and related symptom clusters were not of predictive utility, however early changes in HDRS score (improvement from baseline of four or more by four weeks) was associated with good outcome. All symptom clusters improved within two weeks of treatment with sleep symptoms improving by six weeks. Optimum symptomatic improvement was achieved by eight weeks.ConclusionsClinicians in primary care can expect 53% response to treatment. In the absence of symptomatic improvement by one month (HDRS score of four or more) treatment should be reviewed. Optimum treatment response is usually achieved within eight weeks. Copyright © 2002 John Wiley & Sons, Ltd.
Search for ideal sulfinyl dienophile and dipolarophile
Authors: García Ruano José L. , Martín Castro Ana M. , Rodríguez Ramos Jesús H. 
Published: October 2002

AbstractBy analysis, the advantages and drawbacks of the differently substituted vinyl sulfoxides so far reported, (Z)‐3‐p‐tolylsulfinyl acrylonitriles are proposed as the best sulfinyl dienophiles. The stereoselective synthesis of these compounds was optimized by hydrocyanation of sulfinyl alkynes with Et2AlCN. Their behavior as chiral dienophiles and dipolarophiles is responsible for the high stereocontrol of Diels–Alder and 1,3‐dipolar reactions, respectively. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:453–462, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10066
Practical synthesis of thiirene 1‐oxides that possess two bulky alkyl substituents
Authors: Nakayama Juzo , Takahashi Kenta , Ono Yutaka , Morita Michiyo , Sugihara Yoshiaki , Ishii Akihiko 
Published: October 2002

AbstractAcetylenes that possess two bulky alkyl substituents reacted with sulfur dichloride to furnish the corresponding 2,3‐dialkyl‐2,3‐dichlorothiiranes (5) nearly quantitatively. The alkaline hydrolysis of 5 afforded 2,3‐dialkylthiirene 1‐oxides (10) in high yields. These two reactions could be successively carried out in one flask, and 2,3‐di‐tert‐butyl‐, 2,3‐di‐(1‐adamantyl)‐, and 2‐(1‐adamantyl)‐3‐tert‐butylthiirene 1‐oxides (10a–c) were obtained in 70, 80, and 90% yields, respectively, based on the starting acetylenes, thus providing the most convenient synthesis of thiirene 1‐oxides. Disulfur dichloride also reacted with acetylenes to give 5 in good yields with the elimination of one sulfur atom. Although the alkaline hydrolysis of 5 provided 10 exclusively, acid hydrolysis gave a mixture of α‐oxothioketone 9 and thiirene 1‐oxide 10 in modest yields. All thiirene 1‐oxides 10a–c isomerized to produce α‐oxothioketones 9 in high yields when heated in boiling toluene. Reactions of a bis‐acetylene (18) with disulfur dichloride and with sulfur dichloride gave a dihydropentathiepin (19) in high yields. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:424–430, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10070