Gene/Protein Disease Symptom Drug Enzyme Compound
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Intraclass correlation coefficients are useful statistics for estimating interrater reliability. The ICC provides a means for quantifying the level of rater agreement as well as rater consistency. The ICC is easier to use than the Pearson r when more than two raters are involved and can be computed when data are missing on some subjects (Haggard, 1958). Use of this statistic allows the researcher to decide whether or not to include rater effects in estimating IRR and to determine the precision of the reliability estimate. Information about the various types of intraclass correlations and their use is frequently absent from psychometric references commonly used by nurse researchers, resulting in confusion about correct usage and interpretation. Because different values are obtained depending on which ICC formula is selected, ICC formulae reported in the literature can have varying interpretations. For this reason, it is important for researchers to become familiar with the various forms of intraclass correlations and to report the version used in their calculations and the rationale for their choice.
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PMID:Intraclass correlations as estimates of interrater reliability in nursing research. 156 90

There have been many reports of late regarding the safety and effectiveness of injectable contraceptives, yet there is still considerable confusion and uncertainty. The attempt is made in this discussion to clarify the issues by outlining the results of recent research in animal and human subjects. The current state of knowledge on injectable hormonal contraceptives is summarized. Attention is directed to the following: injectable preparations available for contraception; animal studies; human studies (pharmacology, effectiveness, bleeding problems, metabolic effects, neoplasia, return of fertility, and effects on progeny). Some data from animal studies have raised concern about the possible carcinogenicity of depot-medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN), but certain animal models used appear to be inappropriate for studying the effects of these steroids in human subjects. A large number of clinical trials, including multicenter studies organized by the World Health Organization (WHO) have been carried out in many countries with both DMPA and NET-EN. The 2 steroid preparations have a similar mechanism of action in inhibiting gonadotropin production by the pituitary gland, which thus prevents ovulation. They do, however, show certain pharmacological differences. The differences in formulation are reflected in the levels of steroid found in the blood. From both DMPA and NET-EN the continuation rates have been found to vary markedly among different populations, ranging from 15% to nearly 90% at 1 year. Pregnancy rates (method failures) have been consistently low with DMPA, less than 1 pregnancy/100 woman years of use. The pregnancy rate reported with NET-EN has varied according to the interval between injections. A dose of 200 mg every 12 weeks resulted in a pregnancy rate considered to be unacceptably high (3.6/100 woman years) in 1 clinical trial undertaken by WHO. A more frequent administration of NET-EN in the same trial resulted in a pregnancy rate of less than 1/100 woman years at 18 months. The majority of women who receive DMPA or NET-EN experience some disruption of their normal menstrual cycle, defined as a cycle of 26-35 days' duration in which bleeding/spotting lasts for 2-8 weeks. Women frequently report irregular bleeding, spotting, and amenorrhea, but heavy or prolonged bleeding is uncommon. DMPA and NET-EN appear to be acceptable methods of fertility regulation.
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PMID:Facts about injectable contraceptives: memorandum from a WHO meeting. 621 18

v-ryk is the oncogene in the avian acute oncogenic retrovirus RPL30, its cellular counterpart, c-ryk, is described in this report. To avoid the confusion caused by another gene with the same name, we renamed v-ryk to be v-eyk, thereby changing the proto-oncogene's name to c-eyk. c-eyk is expressed highly in chicken spleen and moderately in many other tissues including embryonic tissues. Its cDNA is 3061 base pairs encoding a receptor-type protein tyrosine kinase (PTK) of 974 amino acids. Compared to c-Eyk, v-Eyk is a truncated PTK lacking the extracellular and transmembrane regions of c-Eyk in addition to two amino acid changes. c-Eyk has two C2-type Ig domains and two FN-III domains in its extracellular region, forming a new subfamily of receptor-type PTK together with UFO/Axl/Ark. As suggested by Ig/Fn-III domains in many cell adhesion molecules, this subfamily of PTK may mediate cell-cell interaction.
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PMID:The proto-oncogene of v-eyk (v-ryk) is a novel receptor-type protein tyrosine kinase with extracellular Ig/GN-III domains. 750 87

Anaplastic large-cell lymphoma (ALCL) comprises a group of non-Hodgkin's lymphomas (NHLs) that were first described in 1985 by Stein and co-workers and are characterized by the expression of the CD30/Ki-1 antigen (Stein et al., 1985). Approximately half of these lymphomas are associated with a typical chromosomal translocation, t(2;5)(p23;q35). Much confusion about the exact classification and clinicopathological features of this subgroup of NHL was clarified with the identification of NPM-ALK (nucleophosmin-anaplastic lymphoma kinase) as the oncogene created by the t(2;5) (Morris et al., 1994). With the discovery of NPM-ALK as the specific lymphoma gene mutation, this NHL subtype could be redefined on the molecular level. This achievement was enhanced by the availability of specific antibodies that recognize ALK fusion proteins in paraffin-embedded lymphoma tissues. Several excellent recent reviews have summarized the histopathological and molecular findings of ALCL and their use in the classification of this lymphoma entity (Anagnostopoulos and Stein, 2000; Benharroch et al., 1998; Drexler et al., 2000; Foss et al., 2000; Gogusev and Nezelof, 1998; Kadin and Morris, 1998; Ladanyi, 1997; Morris et al., 2001; Shiota and Mori, 1996; Skinnider et al., 1999; Stein et al., 2000). This review will focus on the molecular function and signal transduction pathways activated by ALK fusion oncogenes, with recent advances and possible clinical implications to be discussed.
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PMID:Translocations involving anaplastic lymphoma kinase (ALK). 1160 14

Histopathology has a vital role in determining breast cancer management and pathologists must be part of the clinical team. Carcinoma size, grade, and especially lymph node status remain the best available prognostic factors. Metastatic carcinoma in axillary nodes is more important than any other prognostic factor presently available. ER status is an important predictor of response to endocrine manipulation, but its independent prognostic significance, and that of micrometastatic disease, circulating carcinoma cells and other molecular factors, even well-studied ones such as HER2 status, are less clear. Pathology is the first clinical speciality to subject its practice to rigorous scientific analysis, and it has stood up well. However, workers without appropriate experience in Pathology or scientific design have created difficulties by undertaking poorly planned studies with ill-defined end-points, lacking appropriate quality control. New analytical techniques and therapeutic targets make it essential that we learn from past mistakes and integrate pathologists into the research teams pursing clinical trials and the assessment of new bio-markers. Without this, input resource will be wasted on false leads that could have been curtailed. Morphology alone will not be enough to select patients likely to benefit in trials of new therapies, but selection 'tests' must be appropriate. The confusion of tests for selection of patients to receive Herceptin shows what happens when this process fails. Much of the microarray data being put into data-bases has no quality control, and meta-analysis of this data will produce even more conflict than the clinical trials. This can be avoided, as the ability to standardise is available.
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PMID:What the clinician needs from the pathologist: evidence-based reporting in breast cancer. 1188 5

As a result of major recent advances in understanding the biology of gastrointestinal stromal tumors (GIST), specifically recognition of the central role of activating KIT mutations and associated KIT protein expression in these lesions, and the development of novel and effective therapy for GISTs using the receptor tyrosine kinase inhibitor STI-571, these tumors have become the focus of considerable attention among pathologists, clinicians, and patients. Stromal/mesenchymal tumors of the gastrointestinal tract have long been a source of confusion and controversy with regard to classification, line(s) of differentiation, and prognostication. Characterization of the KIT pathway and its phenotypic implications has helped to resolve some but not all of these issues. Given the now critical role of accurate and reproducible pathologic diagnosis in ensuring appropriate treatment for patients with GIST, the National Institutes of Health (NIH) convened a GIST workshop in April 2001 with the goal of developing a consensus approach to diagnosis and morphologic prognostication. Key elements of the consensus, as described herein, are the defining role of KIT immunopositivity in diagnosis and a proposed scheme for estimating metastatic risk in these lesions, based on tumor size and mitotic count, recognizing that it is probably unwise to use the definitive term benign for any GIST, at least at the present time.
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PMID:Diagnosis of gastrointestinal stromal tumors: a consensus approach. 1207 1

As a result of major recent advances in understanding the biology of gastrointestinal stromal tumors (GISTs), specifically recognition of the central role of activating KIT mutations and associated KIT protein expression in these lesions, and the development of novel and effective therapy for GISTs using the receptor tyrosine kinase inhibitor STI-571, these tumors have become the focus of considerable attention by pathologists, clinicians, and patients. Stromal/mesenchymal tumors of the gastrointestinal tract have long been a source of confusion and controversy with regard to classification, line(s) of differentiation, and prognostication. Characterization of the KIT pathway and its phenotypic implications has helped to resolve some but not all of these issues. Given the now critical role of accurate and reproducible pathologic diagnosis in ensuring appropriate treatment for patients with GIST, the National Institutes of Health convened a GIST workshop in April 2001 with the goal of developing a consensus approach to diagnosis and morphologic prognostication. Key elements of the consensus, as described herein, are the defining role of KIT immunopositivity in diagnosis and a proposed scheme for estimating metastatic risk in these lesions, based on tumor size and mitotic count, recognizing that it is probably unwise to use the definitive term "benign" for any GIST, at least at the present time.
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PMID:Diagnosis of gastrointestinal stromal tumors: A consensus approach. 1450 50

At a meeting in November 1991, the International Medical Advisory Panel (IMAP) of the International Planned Parenthood Federation (IPPF) was asked by the South Asia Region of IPPF to consider a report by the Bangladesh Family Planning Program concerning the operational implications of using more than one formulation of injectable contraceptive in a geographic area. The report states that depot medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN) are very similar in terms of continuation rates, use-effectiveness levels, and reported side effects. However, they differ in administration schedule (DMPA is given at three month intervals; the other is given at two) and viscosity (NET-EN is more viscous and requires a larger bore needle than the other), which can lead to delivery problems for outreach programs. 50% of the contraceptive methods offered and used in these programs are injectables. Maintaining both types of injectables can lead to fieldworker confusion and error, disruption of fieldworker work routines, managerial burden, and supply shortages. IMAP recommends that family planning program managers select one progestogen-only injectable formulation and keep to it, to ensure that only one formulation is used in a particular geographic area. DMPA and NET-EN should not be considered medically interchangeable. They have different formulations and different periods of effectiveness. There is no data on the medical consequences of women receiving the two interchangeably because of program problems or errors.
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PMID:Choice of injectables in family planning programmes. 1232 72

Clinically, it is difficult to differentiate between nipple duct adenomas (NDAs) and Paget's disease of the nipple. These lesions share similar morphological and histological characteristics. Clear cell types present in NDA, epidermal clear cells (ECC) and Toker cells (TC), share immunoreactive similarities to Paget cells which can lead to confusion in classification. The aim of this study was to obtain information on the characteristics and histogenesis of ECC and TC, to distinguish these cells from Paget cells. Ten nipple epidermal with NDA were compared to 25 histologically normal nipples. Samples were analyzed for cytokeratins (CKs) 7, 8 and 18, carcinoembryonic antigen (CEA), c-erbB-2/HER2 expression and human papillomavirus (HPV-) DNA. In 13 out of 25 normal nipples the staining sequence demonstrated that ECC and TC cell types are immunoreactive with CKs 7, 8 and 18 in the basal region of the epidermis. In contrast, aggregated CKs 7, 8 and 18-immunoreactive ECC and TC were identified in the epidermal of 8 of the 10 NDA cases. In 2 cases, TC were continuous with the underlying NDA, suggesting that TC might be of ductal origin and migrate through the galactophorous ostia. In NDAs and 25 histologically normal nipples, ECC and TC were negative for CEA, c-erbB-2/HER2 and HPV-DNA. ECC and TC, normally present in the nipple epidermis, may proliferate and form aggregates in the presence of an underlying NDA. These cells show immunoreactivity for CKs 7, 8 and 18 but are negative for c-erbB-2/HER2, CEA and HPV-DNA and should not lead to the mistaken diagnosis of Paget's disease.
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PMID:Characteristics of clear cells and Toker cells in the epidermis of underlying nipple duct adenoma. 1255 78

Although the majority of mesenchymal lesions of the gastrointestinal tract are neoplastic in nature, nonneoplastic reactive processes may involve the gastrointestinal tract and mesentery, causing diagnostic confusion with more aggressive neoplasms, such as fibromatosis or gastrointestinal stromal tumors. In this study, we report a series of fibroinflammatory lesions of the gastrointestinal tract that we think represent a relatively cohesive group of tumors and describe the clinical and pathologic features of this entity, which we have termed "reactive nodular fibrous pseudotumor." The tumors affected five patients (four male and one female patient) who ranged in age from 48 to 71 years (mean 56 years). Two patients presented with acute abdominal pain without a significant past medical history, two had incidental lesions discovered during evaluation for other medical conditions, and one was found to have an abdominal mass. Three patients had a history of abdominal surgery. The tumors were multiple in three patients and solitary in two patients. In four cases, at least one of the tumors involved the small intestine or colon, and the lesion was confined to the peripancreatic soft tissue in one case. The tumors were firm, tan-white, ranged in size from 4.3 to 6.5 cm in greatest dimension, and were grossly well circumscribed. All of the lesions were of low to moderate cellularity and composed of stellate or spindled fibroblasts arranged haphazardly or in intersecting fascicles. Three cases had microscopically infiltrative borders. The stroma was rich in collagen, which was wire-like, keloidal, or hyalinized. Intralesional mononuclear cells were sparse but were more numerous peripherally and frequently arranged in lymphoid aggregates. Immunohistochemical stains demonstrated that all of the tumors stained for vimentin, 80% stained for CD117 or muscle specific actin, 60% stained for smooth muscle actin or desmin, and none of the tumors stained for CD34, S-100 protein, or anaplastic lymphoma kinase-1. Follow-up information was available in all cases: four patients had no residual disease following surgical resection (mean follow-up 16.3 months) and one patient who had an incomplete surgical resection had stable disease at 26 months. In summary, we report a series of distinct intraabdominal fibroinflammatory pseudotumors that we have collectively termed "reactive nodular fibrous pseudotumors." These lesions are uncommon and may infiltrate the bowel wall, thereby mimicking primary bowel neoplasms or intraabdominal fibromatosis. Recognition of these nonneoplastic lesions is important, as they pursue a benign clinical course, but may be confused with other mesenchymal neoplasms that require more aggressive treatment.
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PMID:Reactive nodular fibrous pseudotumor of the gastrointestinal tract and mesentery: a clinicopathologic study of five cases. 1510 9


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