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2.
Pflege ; 10(5): 262-72, 1997 Oct.
Article in German | MEDLINE | ID: mdl-9400263

ABSTRACT

This paper takes a close look at nursing publications that are concerned with the theoretical knowledge of "standards". The central question is: "What are the intentions and characteristics to which standards are linked in nursing literature?" Diverse definitions and synonyms of standards are discussed as well. There is a considerable irregularity in the terminology of standards and similar terms in the investigated literature. Therefore, the term "standard" is treated by the author as a general one that embraces many definitions and has to be differentiated for a closer approach. Thus, four different kinds of features have been developed in the course of the analytic work: "intentions", "range of validity", "contents" and "structure". These four areas form a basis for a more definite description of the various kinds of standards. Based on her findings, the author give recommendations on how the actual linguistic confusion can be effectively dealt with.


Subject(s)
Nursing Care/standards , Practice Guidelines as Topic/standards , Semantics , Terminology as Topic , Communication Barriers , Diffusion of Innovation , Humans , Reproducibility of Results
3.
Leukemia ; 7(2): 268-73, 1993 Feb.
Article in English | MEDLINE | ID: mdl-8426481

ABSTRACT

The principal objective of this study was to investigate whether follicular center cell lymphomas occur among B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). We used a molecular genetic/immunohistochemical approach and analysed 21 cases with the primary site in the gastrointestinal tract. Only two bcl-2 gene rearrangements were detected in our series and were found in two out of seven lymphomas with a nodular growth pattern. A chromosomal translocation t(14;18) was demonstrated by comigration of rearranged bcl-2 and JH sequences in one of these two cases. Additionally, both lymphomas showed bcl-2 protein positive neoplastic follicles, CD10 expression, and lack of vimentin. Therefore, these two cases were defined as follicular lymphomas. In contrast to the two follicular lymphomas of MALT, three other, nodular growing, bcl-2 protein positive lymphomas were found to have no bcl-2 gene rearrangements, to be CD10 negative and to express vimentin. These three lymphomas might be composed of neoplastic extrafollicular cells which secondarily invaded reactive follicles. We conclude that the presence of bcl-2 protein positive follicles is consistent with both a follicular and extrafollicular origin of a B lymphoma of MALT. However, the detection of a bcl-2 gene rearrangement is the most valuable criterion in such a situation, and additional immunophenotypic criteria, such as CD10 expression and lack of vimentin within the neoplastic population, further substantiate the diagnosis of a follicular lymphoma in MALT.


Subject(s)
Gene Rearrangement , Lymphoma, B-Cell/genetics , Lymphoma, Follicular/genetics , Stomach Neoplasms/genetics , Translocation, Genetic , Adult , Aged , Aged, 80 and over , Female , Humans , Lymphoma, B-Cell/metabolism , Lymphoma, B-Cell/pathology , Lymphoma, Follicular/metabolism , Lymphoma, Follicular/pathology , Male , Middle Aged , Proto-Oncogene Proteins/analysis , Proto-Oncogene Proteins c-bcl-2 , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology
4.
Leukemia ; 4(8): 584-9, 1990 Aug.
Article in English | MEDLINE | ID: mdl-1697012

ABSTRACT

Deoxycoformycin (DCF) has been reported to cause immediate reduction and dysfunction of T lymphocytes, but the long-term effects on immune functions are still not known. As cytokine production is regulated by T helper-inducer lymphocytes and might represent a parameter for functional integrity of immunocompetent cells, we have measured the production of interleukin-2 (IL-2), tumor necrosis factor (TNF), and interferons (IFN) by peripheral mononuclear cells (PMNC) from 10 patients with hairy cell leukemia 11-24 months after end of therapy with DCF. The patients were in continuous remission at the time of study. Despite an absolute reduction in CD3+ and CD4+ lymphocytes. there were no significant differences in IL-2 or TNF release between patients and controls. Except for a significant reduction in IFN-alpha release stimulated by Newcastle disease virus (NDV), IFN productions induced by other mitogens (phytohemagglutinin, PHA; Concanavalin A, ConA; pokeweed mitogen, PWM) and viral antigens were within normal range. There was also a decrease in proliferative responsiveness to PHA, but responses to ConA, PWM, and other viral antigens were normal. In five of the patients, we have monitored closely the changes in IL-2, TNF, and IFN before, during, and after treatment and could demonstrate a rapid normalization of initially decreased IL-2 release in all cases and also of TNF if the initial production was reduced. This study shows that, even though the absolute number of T lymphocytes and helper cells are reduced in the long-term observation after DCF treatment, the capacity to produce IL-2, TNF, and IFN-gamma was within normal range. Parallel to this observation, no opportunistic infections or frequency of infectious complications occurred in these patients.


Subject(s)
Interferons/biosynthesis , Interleukin-2/biosynthesis , Leukemia, Hairy Cell/drug therapy , Pentostatin/therapeutic use , Tumor Necrosis Factor-alpha/biosynthesis , Adult , Aged , Female , Humans , Leukemia, Hairy Cell/immunology , Leukemia, Hairy Cell/metabolism , Leukocyte Count/drug effects , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Remission Induction , T-Lymphocytes/drug effects , Time Factors
5.
Leuk Res ; 13(4): 269-78, 1989.
Article in English | MEDLINE | ID: mdl-2785618

ABSTRACT

Deoxycoformycin (DCF) is a specific inhibitor of adenosine deaminase (ADA) and has been shown to be active in lymphoid neoplasms. Cytotoxicity is thought to be mediated by the accumulation of deoxyadenosine (AdR) and deoxyadenosine triphosphate (dATP) which inhibits ribonucleotide reductase and DNA synthesis in rapidly proliferating cells. Others suggested mechanisms leading to cell death particularly in non-dividing cells include depletion of ATP and NAD pools, inhibition of S-adenosylhomocysteine (SAH) hydrolase and induction of DNA strand breaks. In patients with high leukemic counts who were subsequently treated with DCF, we have studied (a) the levels of ADA, ecto-5'-nucleotidase (5NT), deoxyadenosine kinase (AdR-kinase) and SAH-hydrolase in the leukemic cells; [b) the in-vitro effects of DCF on dATP, ATP, NAD, SAH-hydrolase levels and on DNA strand breaks; and (c) the correlation between these parameters with clinical response to DCF. No significant difference in ADA, 5NT, AdR-kinase and SAH-hydrolase activities could be found between responders and non-responders. Incubation of the leukemic cells in vitro with DCF caused an inhibition of ADA, an accumulation of dATP, a moderate reduction in ATP and NAD levels, a suppression of SAH-hydrolase activity and an increase in DNA strand breaks in practically all the leukemic samples, irrespective of clinical response. Our results show that neither measurement of these enzymes nor studies of these biochemical sequelae of ADA inhibition in vitro predicts clinical responsiveness to DCF therapy.


Subject(s)
Adenosine Deaminase Inhibitors , Antineoplastic Agents/pharmacology , Coformycin/pharmacology , Leukemia/enzymology , Nucleoside Deaminases/antagonists & inhibitors , Ribonucleosides/pharmacology , Adenosine Triphosphate/blood , Adenosylhomocysteinase , Coformycin/analogs & derivatives , DNA Damage , Deoxyadenine Nucleotides/blood , Humans , Hydrolases/blood , Leukemia/blood , Leukemia/drug therapy , Leukemia, Hairy Cell/blood , Leukemia, Hairy Cell/drug therapy , Leukemia, Hairy Cell/enzymology , Leukemia, Lymphocytic, Chronic, B-Cell/blood , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/enzymology , Leukemia, Prolymphocytic/blood , Leukemia, Prolymphocytic/drug therapy , Leukemia, Prolymphocytic/enzymology , Leukemia, Prolymphocytic, T-Cell/blood , Leukemia, Prolymphocytic, T-Cell/drug therapy , Leukemia, Prolymphocytic, T-Cell/enzymology , NAD/blood , Pentostatin
6.
Blood ; 72(6): 1884-90, 1988 Dec.
Article in English | MEDLINE | ID: mdl-3264192

ABSTRACT

Deoxycoformycin (DCF), an adenosine deaminase (ADA) inhibitor, has been shown to be active in lymphoid neoplasms. The mechanism of cytotoxicity might involve accumulation of deoxyadenosine triphosphate (dATP), depletion of the nicotinamide adenine dinucleotide (NAD) and ATP pool, induction of double-stranded DNA strand breaks, or inhibition of S-adenosyl homocysteine hydrolase (SAH-hydrolase). We have investigated the biochemical changes in the circulating malignant cells of patients with chronic leukemia/lymphoma who were treated with DCF (4 mg/m2 weekly). Blood samples were taken from 17 patients with 60% or more circulating leukemic cells before, 4, 24, and 48 hours and five days after the first administration of DCF. Leukemic cells were separated and studied for changes in ADA, dATP, ATP, NAD, and SAH-hydrolase levels and DNA strand breaks and the data analyzed according to clinical response. Inhibition of ADA activity was found in all except one patient at 4 to 24 hours after the first administration of DCF. dATP started to accumulate at four hours, reached a maximum level between 24 and 48 hours, and returned to base values on the fifth day. Intracellular ATP and NAD levels were transiently reduced in some of the patients. However, no correlation between these changes and a clinical response could be found. DNA strand breaks could be studied in 13 patients. A significant increase in DNA breaks at 24 to 48 hours was found in six of the seven responders but only in one of the six nonresponders. At 24 hours, SAH-hydrolase levels were reduced in all seven responders studied, but only in two of the seven nonresponders. The difference in inhibition of SAH-hydrolase was statistically significant (P = .0023). These results suggest that DNA strand breaks and inhibition of SAH-hydrolase correlate with clinical response.


Subject(s)
Coformycin/therapeutic use , Leukemia, Hairy Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Neoplastic Cells, Circulating , Ribonucleosides/therapeutic use , Sezary Syndrome/drug therapy , Adenosine Deaminase Inhibitors , Adenosylhomocysteinase , Coformycin/analogs & derivatives , DNA, Neoplasm/analysis , Drug Evaluation , Humans , Hydrolases/blood , Leukocyte Count , Neoplasm Proteins/blood , Nucleotides/blood , Pentostatin
7.
Cancer ; 58(1): 96-9, 1986 Jul 01.
Article in English | MEDLINE | ID: mdl-3011239

ABSTRACT

Differences in activities of the purine degradative enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'-nucleotidase (5'NT), have been observed among different classes of lymphoid malignancies. Recent studies have shown that hairy cell leukemia (HCL) may respond to treatment with the ADA inhibitor, 2-deoxycoformycin. This study demonstrates that the cells of HCL have significantly lower levels of ADA and 5'NT (P always less than 0.01) when compared to levels in normal B- or T-lymphocytes, but have higher levels of PNP (P less than 0.001 for both comparisons). Recent studies have shown that when treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), cells of B-cell chronic lymphatic leukemia (B-CLL) acquire phenotypic characters of HCL. The authors have therefore also investigated the changes in enzyme pattern of B-CLL after incubation with TPA B-CLL cells are characterized by low levels of ADA, PNP, and 5'-NT, but TPA caused a marked increase in PNP activity (P less than 0.001, t test for paired samples), a pattern similar to HCL. The results from biochemical studies are thus in accordance with the hypothesis that HCL cells are more mature than B-CLL cells. The special enzyme profile of HCL suggests that a PNP inhibitor might also be effective in the treatment of this disease.


Subject(s)
Leukemia, Hairy Cell/enzymology , Leukemia, Lymphoid/enzymology , Lymphocytes/enzymology , Purines/metabolism , 5'-Nucleotidase , Aminohydrolases/analysis , Cells, Cultured , Fluorescent Antibody Technique , Humans , Lymphocyte Activation , Lymphocytes/drug effects , Nucleotidases/analysis , Phenotype , Purine-Nucleoside Phosphorylase/analysis , Tetradecanoylphorbol Acetate/pharmacology
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