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PubMed2005

Temporal relationship between elevation of epstein-barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis.

CONTEXT: Infection with Epstein-Barr virus (EBV) has been associated with an increased risk of multiple sclerosis (MS), but the temporal relationship remains unclear. OBJECTIVE: To determine whether antibodies to EBV are elevated before the onset of MS. DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study conducted among more than 3 million US military personnel with blood samples collected between 1988 and 2000 and stored in the Department of Defense Serum Repository. Cases were identified as individuals granted temporary or permanent disability because of MS. For each case (n = 83), 2 controls matched by age, sex, race/ethnicity, and dates of blood sample collection were selected. Serial samples collected before the onset of symptoms were available for 69 matched case-control sets. MAIN OUTCOME MEASURES: Antibodies including IgA against EBV viral capsid antigen (VCA), and IgG against VCA, nuclear antigens (EBNA complex, EBNA-1, and EBNA-2), diffuse and restricted early antigens, and cytomegalovirus. RESULTS: The average time between blood collection and MS onset was 4 years (range, <1-11 years). The strongest predictors of MS were serum levels of IgG antibodies to EBNA complex or EBNA-1. Among individuals who developed MS, serum antibody titers to EBNA complex were similar to those of controls before the age of 20 years (geometric mean titers: cases = 245, controls = 265), but 2- to 3-fold higher at age 25 years and older (cases = 684, controls = 282; P<.001). The risk of MS increased with these antibody titers; the relative risk (RR) in persons with EBNA complex titers of at least 1280 compared with those with titers less than 80 was 9.4 (95% confidence interval [CI], 2.5-35.4; P for trend <.001). In longitudinal analyses, a 4-fold increase in anti-EBNA complex or anti-EBNA-1 titers during the follow-up was associated with a 3-fold increase in MS risk (EBNA complex: RR , 3.0; 95% CI, 1.3-6.5; EBNA-1: RR, 3.0; 95% CI, 1.2-7.3). No association was found between cytomegalovirus antibodies and MS. CONCLUSION: These results suggest an age-dependent relationship between EBV infection and development of MS.

Adult↗
PubMed2006

Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis.

CONTEXT: Epidemiological and experimental evidence suggests that high levels of vitamin D, a potent immunomodulator, may decrease the risk of multiple sclerosis. There are no prospective studies addressing this hypothesis. OBJECTIVE: To examine whether levels of 25-hydroxyvitamin D are associated with risk of multiple sclerosis. DESIGN, SETTING, AND PARTICIPANTS: Prospective, nested case-control study among more than 7 million US military personnel who have serum samples stored in the Department of Defense Serum Repository. Multiple sclerosis cases were identified through Army and Navy physical disability databases for 1992 through 2004, and diagnoses were confirmed by medical record review. Each case (n = 257) was matched to 2 controls by age, sex, race/ethnicity, and dates of blood collection. Vitamin D status was estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum samples collected before the date of initial multiple sclerosis symptoms. MAIN OUTCOME MEASURES: Odds ratios of multiple sclerosis associated with continuous or categorical levels (quantiles or a priori-defined categories) of serum 25-hydroxyvitamin D within each racial/ethnic group. RESULTS: Among whites (148 cases, 296 controls), the risk of multiple sclerosis significantly decreased with increasing levels of 25-hydroxyvitamin D (odds ratio [OR] for a 50-nmol/L increase in 25-hydroxyvitamin D, 0.59; 95% confidence interval, 0.36-0.97). In categorical analyses using the lowest quintile (<63.3 nmol/L) as the reference, the ORs for each subsequent quintile were 0.57, 0.57, 0.74, and 0.38 (P = .02 for trend across quintiles). Only the OR for the highest quintile, corresponding to 25-hydroxyvitamin D levels higher than 99.1 nmol/L, was significantly different from 1.00 (OR, 0.38; 95% confidence interval, 0.19-0.75; P = .006). The inverse relation with multiple sclerosis risk was particularly strong for 25-hydroxyvitamin D levels measured before age 20 years. Among blacks and Hispanics (109 cases, 218 controls), who had lower 25-hydroxyvitamin D levels than whites, no significant associations between vitamin D and multiple sclerosis risk were found. CONCLUSION: The results of our study suggest that high circulating levels of vitamin D are associated with a lower risk of multiple sclerosis.

Adolescent↗
PubMed1996

Analysis of the recurrence patterns for nonsyndromic cleft lip with or without cleft palate in the families of 3,073 Danish probands.

The identification of several putative susceptibility loci for nonsyndromic cleft lip with or without cleft palate (CL +/- P) has sparked a renewed interest in the genetics of this condition. However, prior to undertaking linkage studies for complex traits such as CL +/- P it is desirable to have some understanding of the number and nature of the loci involved in disease susceptibility. The ability to obtain valid estimates of these parameters is contingent on the availability of family data which are unbiased by factors that distort the true familial recurrence pattern. In an effort to obtain such data, 2 centralized data repositories (the Danish Central Person Registry and the Danish Facial Cleft Database), were linked and used to estimate the risks to first, second, and third-degree relatives of 3,073 CL +/- P probands born in Denmark from 1952 to 1987. Analyses of these data excluded single locus and additive multilocus inheritance of CL +/- P, and provided evidence that CL +/- P is most likely determined by the effects of multiple interacting loci. Under a multiplicative model, no single locus can account for more than a threefold increase in the risk to first-degree relatives of CL +/- P probands. These data provide further evidence that nonparametric linkage methods (ex. affected relative pair studies) are likely to represent a more realistic approach for identifying CL +/- P susceptibility loci, than are traditional pedigree-based methods. However, at least 100 and more realistically several hundred (300-500) affected sib pairs are likely to be required to detect linkage to CL +/- P susceptibility loci.

Cleft Lip↗
PubMed1996

Loss of the position-dependent reinnervation of regenerated toad (Bufo marinus) glutaeus muscle.

The terminations of motor axons in the toad glutaeus muscle show a course dependency on the segmental origins of the axons on the spinal cord. Rostral axons in spinal nerve 8 innervate muscle fibres near the ventral surface of the muscle, while caudal axons in spinal nerve 9 innervate fibres mostly towards the opposing dorsal surface. Axons originating between these extremes tend to innervate the central regions of the muscle. A similar topographic projection is reestablished after denervation and when regenerating axons reinnervate the muscle via entirely novel pathways (Brown and Everett [1991] J. Comp. Neurol. 309:495-506). The findings are compatible with the graded expression of a determinant within the glutaeus muscle that biases the formation of synapses between positionally matched muscle fibres and motor axons. In the present work, we provide strong support for this view by showing that when the muscle is reinnervated by axons arising from only one spinal nerve, they expand their projection and form synapses in the muscle in a topographically appropriate manner. In a second experiment, we tested whether a muscle that had regenerated from its resident myogenic (satellite) cell population would be similarly reinnervated. This experiment was prompted by the work of others (Donoghue et al. [1992] Cell 69:67-77) showing that the myogenic precursor cells in adult muscle are a repository of "positional memory." In our experiments, a glutaeus muscle was removed from adult toads and soaked in bupivacaine for a brief period to destroy the muscle fibres before being sutured back into its normal position in the limb. The distribution of motor units in the muscles was determined by glycogen depletion after allowing 3-4 months for the muscles to regenerate from their satellite cell population and to become reinnervated. We found that muscle fibres belonging to single motor units were dispersed widely in the regenerated muscles and showed no topographic organisation. We conclude that the positional cues that direct topographic map formation are available to motor axons when they reinnervate a denervated mature muscle, but play no role in the reinnervation of a regenerated muscle.

Animals↗
PubMed1999

Widespread intraspecies cross-contamination of human tumor cell lines arising at source.

We present a panoptic survey of cell line cross-contamination (CLCC) among original stocks of human cell lines, investigated using molecular genetic methods. The survey comprised 252 consecutive human cell lines, almost exclusively tumor-derived, submitted by their originators to the DSMZ and 5 additional cell repositories (CRs), using a combination of DNA profiling (4-locus minisatellite and multilocus microsatellite probes) and molecular cytogenetics, exploiting an interactive database (http://www.dsmz.de/). Widespread high levels of cross-contaminants (CCs) were uncovered, affecting 45 cell lines (18%) supplied by 27 of 93 originators (29%). Unlike previous reports, most CCs (42/45) occurred intraspecies, a discrepancy attributable to improved detection of the more insidious intraspecies CCs afforded by molecular methods. The most prolific CCs were classic tumor cell lines, the numbers of CCs they caused being as follows: HeLa (n = 11), T-24 (n = 4), SK-HEP-1 (n = 4), U-937 (n = 4) and HT-29 (n = 3). All 5 supposed instances of spontaneous immortalization of normal cells were spurious, due to CLCC, including ECV304, the most cited human endothelial cell line. Although high, our figure for CCs at the source sets a lower limit only as (i) many older tumor cell lines were unavailable for comparison and (ii) circulating cell lines are often obtained indirectly, rather than via originators or CRs. The misidentified cell lines reported here have already been unwittingly used in several hundreds of potentially misleading reports, including use as inappropriate tumor models and subclones masquerading as independent replicates. We believe these findings indicate a grave and chronic problem demanding radical measures, to include extra controls over cell line authentication, provenance and availability.

Cell Culture Techniques↗
PubMed1999

Design of a state-based workers' compensation information system.

BACKGROUND: California policy makers have long been hampered by a lack of credible information for use in making legislative or administrative changes to address serious problems in the workers' compensation system. In 1993, the legislature directed the California Division of Workers' Compensation to develop a Workers' Compensation Information System (WCIS). METHODS: An advisory committee developed key questions and identified data sources regarding injury/illness incidence, costs, promptness of benefit delivery, adequacy of benefits, satisfaction with services, and other outcomes. RESULTS: Key data elements were identified, mostly from existing mandated reporting forms for employers and physicians, and from standardized medical billings. Data collection will be carried out using: 1) rapid electronic data interchange (EDI) for a minimum number of data elements; 2) electronic collection of data on medical services for a sample of claims; and 3) surveys to address adequacy of benefits, satisfaction with services, return to work, and other outcomes. A state-based repository will analyze data and provide de-identified public use data files. CONCLUSIONS: The proposed WCIS will provide information to improve the performance and to increase the accountability of all the participants in California's Workers' Compensation system. More importantly, it will provide information which will allow improved quality in the provision of mandated benefits to injured workers.

Benchmarking↗
PubMed1988

Integrated Academic Information Management Systems (IAIMS). Part III. Implementation of integrated information services. Library/computer center partnership.

Information technologies are changing the traditional role of the library from that of a repository of information to that of an aggressive provider of information services utilizing electronic methods. In many cases, the library cannot realistically achieve this transformation independently but must work with the computer center to reach its objectives. Various models of the integration of libraries and computer centers are thus emerging. At the University of Maryland at Baltimore the Health Sciences Library and the Information Resources Management Division have developed a partnership based on functional relationships without changing the organizational structure. Strategic planning for an Integrated Academic Information Management System (IAIMS) acted as a catalyst in the process. The authors present the evolution of the partnership and discuss current projects being developed jointly by the two units.

Academic Medical Centers↗
PubMed2000

Ethical guideposts for allelic variation databases.

Basically, a mutation database (MDB) is a repository where allelic variations are described and assigned within a specific gene locus. The purposes of an MDB may vary greatly and have different content and structure. The curator of an electronic and computer-based MDB will provide expert feedback (clinical and research). This requires ethical guideposts. Going to direct on-line public access for the content of an MDB or to interactive communication also raises other considerations. Currently, HUGO's MDI (Mutation Database Initiative) is the only integrated effort supporting and guiding the coordinated deployment of MDBs devoted to genetic diversity. Thus, HUGO's ethical "Statements" are applicable. Among the ethical principles, the obligation of preserving the confidentiality of information transferred by a collaborator to the curator is particularly important. Thus, anonymization of such data prior to transmission is essential. The 1997 Universal Declaration on the Human Genome and Human Rights of UNESCO addresses the participation of vulnerable persons. Researchers in charge of MDBs should ensure that information received on the testing of children or incompetent adults is subject to ethical review and approval in the country of origin. Caution should be taken against the involuntary consequences of public disclosure of results without complete explanation. Clear and enforceable regulations must be developed to protect the public against misuse of genetic databanks. Interaction with a databank could be seen as creating a "virtual" physician-patient relationship. However, interactive public MDBs should not give medical advice. We have identified new social ethical principles to govern different levels of complexity of genetic information. They are: reciprocity, mutuality, solidarity, and universality. Finally, precaution and prudence at this early stage of the MDI may not only avoid ethically inextricable conundrums but also provide for the respect for the rights and interests of all those involved.

Adult↗
PubMed2000

MuStaR and other software for locus-specific mutation databases.

As the human genome sequencing project nears completion, there has been a vast increase in the rate at which disease and nondisease associated variant sequences are being sought and detected. This has heightened the need for software with which to accumulate allelic variant (mutation) data, and with which to make the data accessible to the scientific community. Many ad hoc solutions have been developed by those interested in specific genes and diseases, and the creation of central databases which hold data for all genes has provided an alternative repository for some of the locus data. Despite this, few specialised software tools exist for researchers to create their own locus-specific allelic variant databases. This article describes methods available to potential curators, including software systems developed with the sole purpose of generating locus-specific mutation databases. In particular, the authors' own software, MuStaRtrade mark, is described. MuStaRtrade mark allows curators to maintain a database on a laptop computer if desired, while being able to export the data to an automatically generated Website which will run on any cgi compliant Web server. Searching the database and the submission of new mutations are made possible through fill-in Web forms. A number of other software tools which may be of use to curators are also described.

Chromosome Mapping↗
PubMed2000

UMD (Universal mutation database): a generic software to build and analyze locus-specific databases.

The human genome is thought to contain about 80,000 genes and presently only 3,000 are known to be implicated in genetic diseases. In the near future, the entire sequence of the human genome will be available and the development of new methods for point mutation detection will lead to a huge increase in the identification of genes and their mutations associated with genetic diseases as well as cancers, which is growing in frequency in industrial states. The collection of these mutations will be critical for researchers and clinicians to establish genotype/phenotype correlations. Other fields such as molecular epidemiology will also be developed using these new data. Consequently, the future lies not in simple repositories of locus-specific mutations but in dynamic databases linked to various computerized tools for their analysis and that can be directly queried on-line. To meet this goal, we devised a generic software called UMD (Universal Mutation Database). It was developed as a generic software to create locus-specific databases (LSDBs) with the 4(th) Dimension(R) package from ACI. This software includes an optimized structure to assist and secure data entry and to allow the input of various clinical data. Thanks to the flexible structure of the UMD software, it has been successfully adapted to nine genes either involved in cancer (APC, P53, RB1, MEN1, SUR1, VHL, and WT1) or in genetic diseases (FBN1 and LDLR). Four new LSDBs are under construction (VLCAD, MCAD, KIR6, and COL4A5). Finally, the data can be transferred to core databases.

Chromosome Mapping↗
PubMed2000

PAHdb: a locus-specific knowledgebase.

PAHdb is an online relational locus-specific "mutation database" (http://www.mcgill.ca/pahdb) for the human phenylalanine hydroxylase gene (symbol PAH) and its associated phenotypes (protein, metabolic, clinical). When combined with associated information (population distribution of allele, haplotype association, etc.) PAHdb functions as a knowledgebase. From the outset, and in the absence of raw data (e.g., sequence gels), PAHdb has instead been an annotated repository of information about mutations maintained by a team of curators. It is also disease-oriented, being focused on a variant phenotype (hyperphenylalaninemia (HPA) and its most important form of disease, phenylketonuria (PKU)) resulting from primary dysfunction of the PAH enzyme (EC 1.14.16.1); it is "patient friendly" in that it contains information for those personally involved with HPA/PKU (MIM# 261600). PAHdb also serves its community through direct interaction.

Alleles↗
PubMed1998

HLA haplotype sharing in rheumatoid arthritis sibships: risk estimates subdivided by proband genotype.

There is a well-known association between rheumatoid arthritis (RA) and HLA-DR4. Recent research has indicated that both DR4 haplotypes are important in disease predisposition (favoring a recessive mode of inheritance). Others have suggested that certain combinations of genotypes, in particular Dw4/Dw14 heterozygotes, may be more important than others. We examined the mode of inheritance of RA using data from the Arthritis and Rheumatism Council's national repository of family material [Worthington et al. (1994) Br J Rheumatol 33:970-976]. There were 85 affected sibships consisting of 77 sib pairs, 6 trios, 1 quintuplet, and 1 sextuplet. The affected sibs shared two, one, and zero parental HLA haplotypes in a ratio of 0.42:0.43:0.15, which was significantly different from random expectations (P = 0.00009). Risk estimates for RA to sibs were calculated based on an overall sibling recurrence risk of 3.9%. Risks for those sharing two, one, and zero parental HLA haplotypes were 6.5% [95% confidence interval (CI) = 5.1-7.9%], 3.3% (95% CI = 2.6-4.0%), and 2.5% (95% CI = 1.5-3.5%), respectively. We also examined the risk of RA based on the DRbeta1 genotype status of sib and proband. After excluding genotypic combinations with small numbers, the highest genotype-specific risks were seen for sibs sharing two haplotypes with either a DRbeta1*0401/DRbeta1*0404 (12.5%, 95% CI = 6.9-15.2%) or a DRbeta1*0401/DRbeta1*0408 (11.1%, 95% CI = 4.5-15.1%) proband. An independent assessment based on the AGFAP methodology confirmed the increase in risk for these genotypes, in particular for DRbeta1*0401/DRbeta1*0408. The excess being due to *0401/*0408 rather than to *0401/*0404 may explain why the Dw4/Dw14 effect is not always observed.

Alleles↗
PubMedDate not supplied

Strategic constraints in health informatics: are expectations realistic?

In response to demands to enhance the efficiency and accountability of health systems, a range of different information technologies are being promoted. These technologies include integrated hospital systems, community health information networks and data repositories. However, the record of such technologies inside and outside the health industry suggest that such technologies cannot necessarily be relied on. The reason identified is that information systems are inherently logical and rational systems, and often come into conflict with the less rational social systems of organizations. Health information is identified in terms of three basic dimensions of information; that associated with managers; with professionals; and, with patients. The information of these dimensions are focused on very different objectives, have different structures and functions and are controlled by very different social processes. The information is also very complex and diverse within the dimensions. In the clinical encounter the clinician draws on specialist expertise, satisfies administrative requirements, and provides a clinical record. Thus, these dimensions converge at that point. However, collecting information is costly, and an efficient service demands economy in data collection. However, the technologies being promoted demand 'complete' data acquisition based on consistent and stable data definitions and data structures. The article argues that there is, thus, a conflict between the requirements of these technologies, and the realities of providing efficient services within a changing organizational, professional and social environment.

Clinical Medicine↗
PubMed1999

Memory phenotype CD8(+) T cells persist in livers of mice protected against malaria by immunization with attenuated Plasmodium berghei sporozoites.

Natural exposure to Plasmodium parasites induces short-lived protective immunity. In contrast, exposure to radiation-attenuated sporozoites (gamma spz) promotes long-lasting protection that is in part mediated by CD8(+) T cells that target exoerythrocytic stage antigens. The mechanisms underlying the maintenance of long-lasting protection are currently unclear. The liver is a repository of Plasmodium antigens and may support the development and / or homing of memory T cells. While activated CD8(+) T cells are presumed to die in the liver, the fate of anti-Plasmodium CD8(+) T cells remains unknown. We propose that inflammatory conditions in the liver caused by Plasmodium parasites may allow some effector CD8(+) T cells to survive and develop into memory cells. To support this hypothesis, in this initial study we demonstrate that liver mononuclear cells from P. berghei gamma spz-immune mice transferred protection to naive recipients and moreover, that CD4(+) and CD8(+) T cells responded to Plasmodium antigens by up-regulating activation / memory markers. While CD4(+) T cells under went a transient activation following immunization with gamma spz, CD8(+) T cells expanded robustly after spz challenge and exhibited stable expression of CD44(hi) and CD45RB(lo) during protracted protection. These results establish a key role for intrahepatic T cells in long-lasting protection against malaria.

Animals↗
PubMedDate not supplied

Mining protein data from two-dimensional gels: tools for systematic post-planned analyses.

There is a considerable need to develop comprehensive, systematic mechanisms to analyze the vast number of proteins that orchestrate various cellular functions and to identify proteins associated with disease or that are affected by pharmacological agents. Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) continues to be relied upon to analyze protein constituents of cells and tissues. We have developed a Laboratory Information Processing System (LIPS) as a computer-based tool for capturing quantitative and qualitative changes in thousands of proteins detected in 2-D gels of various types. Protein databases have been developed to serve as a repository for data processing of the basic and derived data and of findings derived from different studies. There have been remarkable advances both in database technology as well as in the computer hardware that have benefited our effort at mining protein data from 2-D gels. We here review our current efforts aimed at improving the performance and features of our 2-D related protein databases, with particular emphasis on the tools we utilize for database mining via a systematic analysis of information known as post-planned analysis.

Acrylic Resins↗
PubMed2002

Bioinformatics of cellular signalling.

The completion of the human genome sequencing provides a unique opportunity to understand the complex functioning of cells in terms of myriad biochemical pathways. Of special significance are pathways involved in cellular signalling. Understanding how signal transduction occurs in cells is of paramount importance to medicine and pharmacology. The major steps involved in deciphering signalling pathways are: (a) identifying the molecules involved in signalling; (b) figuring out who talks to whom, i.e. deciphering molecular interactions in a context specific manner; (c) obtaining the spatiotemporal location of the signalling events; (d) reconstructing signalling modules and networks evoked in specific response to input; (e) correlating the signalling response to different cellular inputs; and (f) deciphering cross-talk between signalling modules in response to single and multiple inputs. High-throughput experimental investigations offer the promise of providing data pertaining to the above steps. A major challenge, then, is the organization of this data into knowledge in the form of hypothesis, models and context-specific understanding. The Alliance for Cellular Signaling (AfCS) is a multi-institution, multidisciplinary project and its primary objective is to utilize a multitude of high throughput approaches to obtain context-specific knowledge of cellular response to input. It is anticipated that the AfCS experimental data in combination with curated gene and protein annotations, available from public repositories, will serve as a basis for reconstruction of signalling networks. It will then be possible to model the networks mathematically to obtain quantitative measures of cellular response. In this paper we describe some of the bioinformatics strategies employed in the AfCS.

Animals↗
PubMed2001

Agamma-haplotypes: a new group of genetic markers for thalassemic mutations inside the 5' regulatory region of the human Agamma-globin gene.

This study illustrates the relationship between a group of nucleotide variations within the 5' regulatory region of the Agamma-globin gene [Agamma-588 A-->G, Agamma-499 T-->A and the 4-bp deletion (Agamma-225 to -222 AGCA)] and the spectrum of delta- and beta-thalassemia mutations in the Hellenic population. These sequence variations, screened by means of denaturing gradient gel electrophoresis, form four separate frameworks (Agamma-haplotypes), each one of which was found to be linked in cis with certain delta- and beta-thalassemia mutations found in the Hellenic population. In addition, two novel base substitutions inside the 5' regulatory region of the Agamma-globin gene (Agamma-521 C-->A and Ay-500 C-->T) were identified during this study, which together with Agamma-haplotypes seem to be silent polymorphisms during adult life, as indicated by transient expression assays. Our data show that Agamma-haplotypes represent genetic markers for the spectrum of thalassemic mutations, found in the Hellenic population and can constitute an important genetic repository upon which mutations leading to thalassemia and hemoglobinopathies occurred.

5' Untranslated Regions↗
PubMed1977

Histopathologic review of lymphoma cases from the Southwest Oncology Group.

Lymphoma Pathology Panel and Repository (LPPR) review of pathologic material from 354 patients registered on Southwest Oncology Group clinical trials substantiated the diagnosis of Hodgkin's disease (Lukes-Butler classification) in 175 (94%) of 186 cases and the diagnosis of non-Hodgkin's lymphoma (Rappaport classification) in 162 (96%) of 168 cases. However, complete agreement (type and subtype) between institutional and LPPR review diagnoses was found in only 66% of confirmed cases of Hodgkin's disease and in only 58% of confirmed cases of non-Hodgkin's lymphomas. In 26 (16%) of 160 cases of non-Hodgkin's lymphoma, the initial interpretation of pattern (nodular vs diffuse) differed: 20 (25%) of 81 nodular lymphomas had been thought to be diffuse and 6 (8%) of 79 diffuse lymphomas had been diagnosed as nodular. The frequency with which initial diagnoses were confirmed on LPPR review was highest for three subtypes of lymphoma: nodular sclerosis Hodgkin's disease (88%), diffuse histiocytic lymphoma (86%), and nodular lymphocytic lymphoma (78%); rates of confirmation for all other subtypes ranged from 13-50%. The results of this analysis emphasize the necessity of having pathologic review of all cases entered on major lymphoma studies so that comparability of cases can be assured and the results of those studies placed in proper perspective.

Hodgkin Disease↗