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PubMedDate not supplied

Group risk classification of non-Hodgkin's lymphoma.

Between 1980 and 1982, 162 patients with non-Hodgkin's lymphoma were treated with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP) or CHOP plus bleomycin. At the moment when the patient were diagnosed all clinical characteristics were evaluated according to a multiple regression analysis model, which has the following three factors associated to bad prognosis: a quick clinical evolution (less than three months) bone marrow infiltration and high levels of lactate dehydrogenase (LDH). The Cox model of analysis also agreed that a quick clinical evolution and the high levels of LDH were bad prognosis factors. These two factors were associated with poor complete remission and short survival rates. A mathematical model was built based on the last two factors. Five groups of patients were observed with increasing risk of a poor response and a short survival rates, which allowed us to identified three prognostic groups with clear differences in both the duration of remission and survival. These groups were low, moderate and high-risk. Results analysis in this paper have important clinical implications for the design of the prospective clinical trials in patients with malignant lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

[Prognostic factors of multiple myeloma].

Multiple myeloma is a heterogeneous disease with survival ranging from a few months to many years. Several clinical parameters (S beta 2-M) are a direct expression of the tumor burden and have been shown by univariate analysis to be related to patient survival. Durie and Salmon developed a myeloma staging system that analyzed the presenting clinical features, response to treatment and survival duration. But this classification is not related to the intrinsic malignancy (labeling index). Many new parameters (genetic alterations, plasma cell evaluation; serum marqueurs, immune dysregulation) related to patient response to chemotherapy and survival duration have been identified. However, they have not yet been included in standard staging and compared with the recognized prognostic parameters in multivariate analysis. There is a need to create a new international myeloma staging system based on biological features of the disease.

Humans↗

PubMed2002

Extranodal marginal zone B cell lymphomas of the uvea: an analysis of 13 cases.

The majority of primary lymphoproliferative lesions of the uvea represent low-grade B cell lymphomas and often display a prominent plasmacellular differentiation. The purpose of the current study was to classify the uveal lymphoproliferations according to the REAL classification; examine the immune profile of the plasmacellular differentiated tumour cells using the plasma cell-related antigens multiple myeloma oncogene-1-protein (MUM1), Vs38c, CD38 and CD138; and to compare this profile with that of mature reactive plasma cells. Following fixation, 13 lymphoproliferative lesions of the uvea were categorized on the basis of their morphology and immunophenotype according to the REAL classification. Included in the immunohistochemistry were B cell-specific activator protein (BSAP), MUM1, Vs38c, CD38 and CD138. Nested polymerase chain reaction (PCR) was also performed on DNA extracted from paraffin sections for the detection of gene rearrangements of the heavy immunoglobulin chain (IgH). All of the 13 uveal tract lymphoproliferative lesions represented malignant lymphoma of B cell non-Hodgkin type and could be diagnosed as 'extranodal marginal zone B cell lymphomas' (EMZL). The degree of plasmacellular differentiation varied between the tumours. In contrast to their non-plasmacytoid counterparts, the 'plasmacytoid' EMZL tumour cells were negative for the B cell markers CD20 and BSAP, and demonstrated heterogeneous positivity for the markers MUM1, Vs38c, CD38 and CD138. The most consistent marker was MUM1, being observed in all tumours. Co-expression of all plasma cell markers was observed in four (31%) uveal EMZL. Loss of CD138 expression was observed in six (46%) tumours, of Vs38c expression in five (38%) and of CD38 in one (7%) tumour. Although the diagnosis of malignant lymphoma was unequivocally based on morphological and immunophenotypical features, the molecular analysis was able to demonstrate clonal B cell populations in only one uveal EMZL. All uveal lymphoid proliferations investigated represented EMZL, with the corresponding morphology and immunophenotype as seen in EMZL in other extranodal locations. MUM1, followed by CD38 expression, were the most constant plasma cell antigens in the plasmacytoid EMZL tumour cells, with both Vs38c and CD138 positivity being lost in many tumours. Aberrant immune profiles of plasma cell-related antigens may be of help in the establishment of malignancy in uveal lymphoproliferative lesions, particularly where interpretation of light chain expression and/or PCR results is difficult.

ADP-ribosyl Cyclase↗

PubMed2002

Systemic lupus erythematosus: diagnostic application of magnetization transfer ratio histograms in patients with neuropsychiatric symptoms--initial results.

PURPOSE: To explore the diagnostic potential of magnetization transfer ratio (MTR) histogram analysis in patients with neuropsychiatric systemic lupus erythematosus (SLE) by using multivariate discriminant analysis (MDA). MATERIALS AND METHODS: Volumetric magnetization transfer imaging was performed in nine patients with active non-thromboembolic, neuropsychiatric SLE, 10 patients with SLE who had had neuropsychiatric SLE previously, 10 patients with SLE but no history of neuropsychiatric SLE, 10 patients with inactive multiple sclerosis, and 10 healthy control subjects. For each subject, an MTR histogram of the whole brain was generated, and an MDA score was produced for each histogram. Each patient was assigned to a clinical subgroup on the basis of these MDA scores. For assignment, binary comparisons between subgroups were made. The accuracy of this classification method was assessed and compared with that of conventional MTR histogram analysis. RESULTS: With MDA, the success rate of binary classification was 60%-100%, depending on which two groups were compared. When the different clinical subgroups were separated, MDA parameters were always better than conventional MTR histogram parameters, with P values ranging from.05 to less than 1 x 10(-6) of those attained with the best conventional parameter. CONCLUSION: With MDA, MTR histograms of brain tissue may provide diagnostic information for individual patients in the clinical context of SLE.

Adult↗

PubMed1999

Genetic analysis of the Drosophila ellipsoid body neuropil: organization and development of the central complex.

The central complex is an important center for higher-order brain function in insects. It is an intricate neuropil composed of four substructures. Each substructure contains repeated neuronal elements which are connected by processes such that topography is maintained. Although the neuronal architecture has been described in several insects and the behavioral role investigated in various experiments, the exact function of this neuropil has proven elusive. To describe the architecture of the central complex, we study 15 enhancer-trap lines that label various ellipsoid body neuron types. We find evidence for restriction of gene expression that is correlated with specific neuronal types: such correlations suggest functional classifications as well. We show that some enhancer-trap patterns reveal a single ellipsoid body neuron type, while others label multiple types. We describe the development of the ellipsoid body neuropil in wild-type animals and propose developmental mechanisms based on animals displaying structural mutations of this neuropil. The experiments performed here demonstrate the degree of resolution possible from the analysis of enhancer-trap lines and form a useful library of tools for future structure/function studies of the ellipsoid body.

Animal Structures↗

PubMed1994

Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection.

BACKGROUND/AIMS: Prognostic analysis on hepatocellular carcinoma (HCC) in patients undergoing hepatectomy is necessary to determine the clinical value of hepatectomy on prognosis. METHODS: Survival and disease-free survival were analyzed in 104 HCC patients undergoing hepatectomy using clinicopathologic factors by univariate and multivariate analyses. The value of the International Union Against Cancer (UICC) TNM classification on prognosis was assessed in the patients. RESULTS: In multivariate analysis, portal vein invasion was the most influential factor. The difference between stage 1 and 2 or stage 3 and 4A using UICC's TNM classification was not significant with respect to survival or disease-free survival. The UICC's classification was modified as follows; stage 1, solitary tumor without vascular invasion; stage 2, solitary or multiple tumor(s) involving adjacent to vessel branch; stage 3, tumor(s) involving major vessel branch or with regional lymph nodal metastasis; and stage 4, tumor(s) with distant metastasis. The differences between each stage in the modified classification were significant with respect to disease-free survival. CONCLUSIONS: The UICC's TNM classification was not of prognostic significance. Further studies on survival in patients with HCC are necessary to evaluate the value of the UICC's TNM classification; some modification may be necessary.

Adolescent↗

PubMed1990

Flow cytometric DNA analysis of parathyroid tumors. Implication of aneuploidy for pathologic and biologic classification.

The previous cytometric studies on parathyroid tumors have provided conflicting data regarding the relationship between DNA content and histopathology, resulting from differences in technical methods and data analysis. This study measured nuclear DNA of parathyroid tumors by flow cytometry in fresh material and determined whether DNA aneuploidy really assists in making a pathologic diagnosis of carcinoma or not. From May 1987 through April 1989, 65 consecutive patients operated on for primary hyperparathyroidism had DNA analysis of the freshly excised parathyroid tumors. Three of the patients had metastatic lesions of parathyroid carcinoma in the lung, cervical lymph nodes, and lung and mediastinal lymph nodes, respectively. Pathologic classifications of the lesions from the other 62 patients were 54 adenomas, four carcinomas, and four hyperplasias. In all the latter patients, hyperplasia was associated with a multiple endocrine neoplasia syndrome. Unequivocal evidence of aneuploidy was found in all of the metastatic lesions and 60% of the primary lesions of the carcinomas, in 9% of the adenomas and in 50% of the hyperplasias. Therefore, parathyroid carcinomas were more apt to be aneuploid than were adenomas (P = 0.0015, both-sided testing). In each of the cases of aneuploid hyperplasia, a small aneuploid peak was found. The high incidence of aneuploidy in patients with multiple endocrine neoplasia type 1 may indicate the presence of clonal heterogeneity of hyperplastic glands and the presence of an abnormal subset of cells that have malignant potential. Cell distribution analysis did not provide any significant information beyond ploidy level. In conclusion, DNA flow cytometric analysis of DNA ploidy patterns is a valuable adjunct to the histopathologic diagnosis of parathyroid neoplasms.

Adenoma↗

PubMed2000

[Multiple endocrine neoplasia type 2; MEN 2].

Multiple endocrine neoplasia type 2 (MEN 2) is an inherited disorder as an autosomal dominant trait, characterized by medullary thyroid carcinoma (MTC). MEN 2 is classified with associated diseases into three subtypes: MEN 2A, MEN 2B and familial MTC. It has recently been shown to be associated with germline mutation in the RET proto-oncogene. Genetic testing allows easily for accurate diagnosis of presymptomatic gene carriers and surgical treatment at an early stage of the disease. In this review we delivered the classification, clinical feature, mutation in RET, mutation analysis, and management of MEN 2, and we discuss recent progress of research on the molecular basis and how genetic testing could be used for clinical management of affected patients or individuals in at-risk families.

Carcinoma, Medullary↗

PubMed2026

Longitudinal whole-genome analysis of bluetongue virus identifies conserved serotype-specific genomes and distinct genomic constellations within a Colorado sheep flock (2021-2023).

Bluetongue virus (BTV) is a segmented double-stranded RNA virus of ruminants transmitted by Culicoides spp. biting midges. Although the genome consists of ten segments, classification into serotypes is primarily based on genome segment 2. However, reassortment among genomic segments is a major driver of BTV evolution and diversity. This study used longitudinal whole-genome sequencing to characterize BTV genomes collected from 2021 to 2023 within a single sheep flock in Colorado, where multiple serotypes co-circulate. Whole-genome sequences were generated from fourteen blood samples representing four serotypes: BTV-6, -11, -13, and -17. Longitudinal sampling identified multiple BTV serotypes within individual sheep across consecutive years. Tanglegram analysis comparing segment phylogenies to the segment 2 tree demonstrated incongruent topologies across all genomic segments, suggestive of reassortment or the circulation of distinct genomic constellations. Nucleotide-level comparisons revealed high sequence homology among same-serotype samples from the same year, while the greatest genetic divergence was observed among BTV-17 genomes collected in different years. Additionally, all BTV-13 genomes contained a previously undescribed nonsynonymous substitution in segment 10 predicted to extend the encoded protein by three amino acids. Together, these findings demonstrate that highly conserved BTV genomes and distinct genomic constellations can be detected at the flock level across multiple years. This longitudinal whole-genome approach reveals the genetic complexity of endemic BTV populations, including novel variants and genomic patterns consistent with reassortment that are lost with conventional serotyped-based approaches, highlighting the need to integrate whole-genome characterization into endemic BTV monitoring programs.

Animals↗

PubMed1996

A hospital-based twin register of the heritability of DSM-IV unipolar depression.

OBJECTIVES: To estimate the contribution of genes and shared family environment to the liability to DSM-IV major depression and to examine the influence of certain proband characteristics on twin concordance. METHODS: We studied 177 probands with major depressive disorder ascertained via the Maudsley Hospital Twin Register (London, England) and their same-sex co-twins. Diagnostic assessments were carried out blind to zygosity and information on the other member of the twin pair. Probandwise concordances were used to compute correlations in liability, and model fitting was performed using maximum likelihood procedures. RESULTS: The probandwise concordance was 46% in monozygotic (n = 68) and 20% in dizygotic (n = 109) twins, a statistically highly significant difference. There was no evidence of a sex difference in heritability or of shared environmental effects. Depending on the assumed population risks for DSM-IV, major depression estimates of heritability were between 48% and 75%. A duration of longest episode of less than 13 months, multiple episodes, and an endogenous rather than neurotic pattern of symptoms as established by the International Classification of Diseases, Ninth Revision, in the proband were associated with a trend toward a higher monozygotic-dizygotic concordance ratio. Using log-linear analysis, only the association between duration of episodes and monozygotic-dizygotic concordance ratio was significant. CONCLUSIONS: Liability to DSM-IV major depression has a substantial heritable component, and there is no evidence of an effect of shared family environment. Some proband characteristics, especially shorter duration of episodes, may be associated with a larger degree of genetic determination.

Adult↗

PubMed2026

Immune subtyping of colorectal adenoma identifies a subtype with activated adaptive immunity ahead of progressing to cancer.

BACKGROUND: Colorectal adenomas (CRA) represent precursor lesions with varying risks of malignant transformation. However, molecular subtyping, particularly immune-related classification, remains underexplored in adenomas. This study aims to characterize the immune landscape of CRA through immune subtyping and evaluate its association with cancer progression, gene expression signatures, and functional pathways. METHODS: We conducted a retrospective analysis of transcriptomic data from multiple cohorts of CRA samples. Immune subtypes were identified using non-negative matrix factorization (NMF) based on immune-related genes. Diverse deconvolution algorithms were used to estimate immune cell infiltration. The immune status alteration in premalignant lesion was further consolidated by single-cell transcriptome data. Differential gene expression analysis was performed between subtypes, followed by functional enrichment analyses (Gene Ontology [GO] and Kyoto Encyclopedia of Genes and Genomes [KEGG]). RESULTS: Two distinct immune subtypes were identified: an immune-enriched subtype characterized by high lymphocyte infiltration and elevated expression of immune-related genes, and an immune-deficient subtype with suppressed immune activity. Differential expression analysis revealed significant upregulation of immune response genes (e.g., CD4, CD86, HLA-DRA) in the immune-enriched subtype. GO and KEGG analyses highlighted enrichments in leukocyte transendothelial migration, chemokine signaling, and antigen processing and presentation pathways. Single-cell result revealed an early occurrence of TIGIT activation and exhausted CD8 T cell features in adenoma when compared to normal tissue. CONCLUSION: This study delineates distinct immune subtypes within CRAs. The immune-enriched subtype demonstrates activated adaptive immunity and may reflect a higher potential for immune surveillance, while the immune-deficient subtype exhibits stromal features suggestive of progressive transformation. These findings provide insights into early immune microenvironment alterations and may inform strategies for risk stratification and immunoprevention in colorectal carcinogenesis.

Colorectal adenoma↗

PubMed2003

Risk factors for conversion to laparotomy during gynecologic laparoscopy.

STUDY OBJECTIVE: To identify risk factors and short-term outcomes associated with conversion from laparoscopic surgery to laparotomy. DESIGN: Case control study (Canadian Task Force classification II-2). SETTING: Large urban, academic medical center. SUBJECTS: All 2530 gynecologic laparoscopies, including those converted to laparotomy. INTERVENTION: Laparoscopic surgery. MEASUREMENTS AND MAIN RESULTS: Statistical analysis was performed to compare risk factors in converted versus non-converted cases. Multiple logistic regression analysis was performed using variables found to be significant on univariate analysis. Of 2530 laparoscopies identified, 159 (6.3%) were converted to laparotomy; 323 were selected by random number assignment from the remaining cases for the control group. The following factors were significantly associated with unintended laparotomy (OR; 95% CI): surgeon inexperience (2.43; 1.38, 4.17), level of laparoscopic complexity (3.19; 1.20, 5.10), body mass index greater than 30 kg/m(2) (2.45; 1.40, 4.41), suspicion of malignancy (17.45; 7.32, 43.57), history of laparotomy (1.34; 1.02, 1.78), presence of adhesions (2.30; 1.37, 3.76), and intraoperative technical difficulty (17.86; 7.32, 43.57). When stratified by level of complexity, experience in laparoscopy does not appear to confer protection during level 1 laparoscopic procedures (0.42; 0.12, 1.37) but does significantly reduce the frequency of conversion during level 2 procedures (0.39; 0.72, 0.93). Age, parity, bowel injury, vascular injury, and history of pelvic inflammatory disease and endometriosis did not increase the risk of conversion. Compared with controls, patients who were converted experienced significantly greater blood loss (p < 0.001), longer operating room time (p < 0.001), and longer hospital stay (p < 0.001). CONCLUSION: All women undergoing laparoscopy should be counseled that unintended laparotomy is a known risk and has additional morbidity over laparoscopy alone. Less-experienced surgeons attempting complicated procedures significantly increase the risk of conversion.

Academic Medical Centers↗

PubMed1993

Concurrent validity of the Minnesota Child Development Inventory with high-risk infants.

Investigated the validity and clinical utility of the Minnesota Child Development Inventory (MCDI) as a developmental screening instrument with a sample of 280 premature infants identified as medically and socioeconomically high risk for developmental delays. Correlational analyses demonstrated significant correlations between the MCDI scales and the criterion Bayley Mental Age Equivalent score. Results of a moderator multiple regression analysis indicated that parent and child characteristics have a statistically significant "moderating" influence on the validity of the MCDI although the clinical significance of this finding may be minimal. A prediction-performance matrix analysis revealed a high degree of classification specificity (92%) but a relatively low sensitivity rating (56%). Findings suggest that the MCDI is a valid and useful screening instrument for high-risk infants but should be used diagnostically only in conjunction with other measures.

Adolescent↗

PubMed2002

The Celera Discovery System.

The Celera Discovery System (CDS) is a web-accessible research workbench for mining genomic and related biological information. Users have access to the human and mouse genome sequences with annotation presented in summary form in BioMolecule Reports for genes, transcripts and proteins. Over 40 additional databases are available, including sequence, mapping, mutation, genetic variation, mRNA expression, protein structure, motif and classification data. Data are accessible by browsing reports, through a variety of interactive graphical viewers, and by advanced query capability provided by the LION SRS search engine. A growing number of sequence analysis tools are available, including sequence similarity, pattern searching, multiple sequence alignment and Hidden Markov Model search. A user workspace keeps track of queries and analyses. CDS is widely used by the academic research community and requires a subscription for access. The system and academic pricing information are available at http://cds.celera.com.

Animals↗

PubMed2005

Metabolomics: opening another window into aging.

Metabolomics is based on the simultaneous analysis of multiple low-molecular-weight metabolites from a given sample. As such, metabolomics seeks the most up-to-date information about the state of interaction between an organism and its environment. The ability to use metabolomics approaches for classification and mechanistic studies may influence and augment our ability to study and address the aging process scientifically and clinically.

Aging↗

PubMed2006

Prognostic significance of expression patterns of c-erbB-2, p53, p16INK4A, p27KIP1, cyclin D1 and epidermal growth factor receptor in oesophageal adenocarcinoma: a tissue microarray study.

AIMS: To correlate immunohistochemical expression patterns and prognosis in oesophageal adenocarcinoma. METHODS: The expression of c-erbB-2, p53, p16INK4A, p27KIP1, cyclin D1 and epidermal growth factor receptor (EGFR) was studied in a series of 137 primarily resected oesophageal adenocarcinoma samples. The expression analysis on protein level was performed on routine paraffin wax-embedded material, with immunohistochemical staining of the samples, assembled on a tissue microarray. The results were correlated with clinicopathological features (pT, pN and G) and survival. RESULTS: 22 (16%) tumours showed an overexpression of the c-erbB-2 oncoprotein. Expression of EGFR was observed in 72 (55%) cases, accumulation of p53 in 68 (52%) cases and of cyclin D1 in 102 (77%) cases. Loss of p16INK4A expression was observed in 101 (76%) cases and low expression of p27KIP1 in 91 (71%) cases. Expression of these proteins did not correlate with tumour stage, grade, Lauren's or World Health Organization classification or lymph node status. On univariate survival analysis, more advanced tumour stage (p = 0.002), lymph node involvement (p = 0.003), high tumour grade (p = 0.017) and lack of EGFR expression (p = 0.034) were found to be associated with poorer survival. On multiple regression analysis, only tumour stage (p = 0.03) and lymph node involvement (p = 0.004) were shown to have an association with the survival of the patient. CONCLUSION: The immunohistochemical expression of c-erbB-2 oncoprotein, cylin D1, p16INK4A, p27KIP1, p53 and EGFR in most oesophageal adenocarcinomas suggests their implication in the pathogenesis of this entity. None of the molecular markers assessed, however, was of prognostic value. Identification of any marker superior to or even approaching the prognostic value of conventional histopathological markers (pT and pN) was therefore not possible.

Adenocarcinoma↗

PubMed2005

The development of more than one histologic type of lymphoma in the same patient is frequent and confers a worse prognosis.

BACKGROUND AND OBJECTIVES: Distinct types of lymphoma may develop in the same patient either simultaneously or sequentially. The frequency and clinical significance of this phenomenon are still only partially known. DESIGN AND METHODS: We conducted a retrospective analysis of all cases of lymphomas of different histology occurring in the same patient, denoting these cases as multiple histology lymphoma (MHL). The clinicopathologic characteristics of these cases were compared with those of cases with a single histology (SHL). The histologic classifications were made according to the REAL classification by the same pathologists throughout the study period. RESULTS: MHL were identified in 46 of 347 (13%) consecutive cases of lymphoma diagnosed at a single institution. They presented more frequently in stage III-IV (p=0.008), but the age, sex, and IPI score of patients with MHL did not differ from those of patients with SHL. Small lymphocytic/lymphoplasmacytic subtype was more frequent (16.1% vs 3%, p<0.0001) and Hodgkin's lymphoma (4% vs 16%; p=0.004) less frequent in MHL. Response rates to treatment were similar (85% vs 77.5%), whereas 5-year overall survival was significantly lower for MHL than for SHL (31% vs 67%; p=0.015). Among MHL, 14 cases were diagnosed simultaneously and 32 sequentially, after a median of 18 months. The two subgroups with simultaneous and sequential presentation did not differ in their demographic, clinicopathologic or prognostic characteristics. INTERPRETATION AND CONCLUSIONS: Lymphomas of different histology develop frequently in the same patient, either simultaneously or sequentially. Patients with MHL form a subgroup with few peculiar presenting clinicopathologic features but a markedly worse prognosis, thus warranting prospective biological and clinical studies.

Humans↗

PubMed1987

Multiple shift patient classification: is it necessary?

Efficient, cost-effective patient classification systems are an essential component of information needed for staffing projections, budgeting, productivity monitoring, and determining the cost of nursing services. Data collection on every shift is typical of GRASP-based patient classification systems. In this study, comparisons among multiple shift measurements showed that no relevant information was being gained by multiple daily assessments of patient care requirements.

Cost-Benefit Analysis↗