Selected complementary methods and nursing care of the hypertensive client.

The National Institutes of Health and the World Health Organization have targeted the treatment of mild or borderline hypertension as a critical health care issue. Conventional practitioners' focus on more intensive treatment for blood pressure elevations in the lower ranges is accompanying the consumer-driven movement toward the use of complementary methods. Over 60 million Americans used herbal therapies in the past year, and visits to complementary care practitioners are expected to increase beyond the 425 million now made annually. The purpose of this article is to identify four herbs that consumers commonly select for the treatment of hypertension and identify nursing care considerations for their use. Additionally, the article reviews research on the effectiveness of acupuncture for hypertension, along with nursing care implications for patients.

Meridian therapy: current research and implications for critical care.

The National Institutes of Health recently recommended further research on the efficacy of acupuncture and allocated Federal funds to stimulate clinical studies. Their decision was based on a growing body of successful research outcomes in which acupuncture was used in the treatment of acute and chronic pain, nausea, circulatory functions, and mood-related behavioral disorders. Despite a burgeoning body of clinical research, the ability to generalize findings has been affected by design flaws, sample type and size, and multiple methods of acupuncture site stimulation. Complicating the communication of findings is use of the term acupuncture when other strategies are used to stimulate the point, such as electrical probes and low-intensity laser. A more appropriate term for acupuncture is meridian therapy, because it encompasses all methods used to treat an acupoint. The purpose of this article is to define meridian therapy with a focus on current clinical perspectives, to review research outcomes in areas important to the care of critically ill patients, to identify issues related to the application of meridian therapy in the clinical arena, and to elaborate practitioner preparation and licensure requirements.

Cognitive pathways and historical research.

The nursing literature is replete with articles detailing the logical reasoning processes required by the individual scientist to implement the rigors of research and theory development. Much less attention has been focused on creative and critical thinking as modes for deriving explanations, inferences, and conclusions essential to science as a product. Historical research, as a particular kind of qualitative research, is dependent on and compatible with such mental strategies as logical, creative, and critical thinking. These strategies depict an intellectual framework for the scientist examining archival data and offer a structure for such inquiry. A model for analyzing historical data delineating the cognitive pathways of logical reasoning, creative processing, and critical thinking is proposed.

Inhibition of protein synthesis in small cell lung cancer cells induced by the diphtheria toxin-related fusion protein DAB389 GRP.

DAB389 GRP is composed of the catalytic and transmembrane domains of diphtheria toxin fused to gastrin-releasing peptide (GRP). DAB389 GRP is selectively targeted to, and inhibits protein synthesis in, cell lines expressing GRP receptors. Protein synthesis in 5'ET4 cells (BALB/3T3 fibroblasts transfected with the gene encoding the GRP receptor) was inhibited by 50% in the presence of 20 pM DAB389 GRP (IC50, 20 pM). DAB389 GRP did not inhibit protein synthesis in untransfected BALB/3T3 cells. A second neuropeptide-conjugated toxin, DAB389 SP, directed to cells expressing substance P receptors, was not cytotoxic to 5'ET4 cells, nor was DAB389 GRP cytotoxic to substance P receptor-bearing cells. DAB389 GRP cytotoxic effects were receptor specific and were inhibited either by excess GRP or anti-GRP antibody. Cytotoxicity was mediated by passage through an acidic vesicle, because addition of 10 microM chloroquine to the reaction inhibited cytotoxicity. DAB389 GRP and DAB389 SP were tested on a number of tumor cell lines. DAB389 GRP inhibited protein synthesis in AR42J rat pancreatic acinar cells and HuTu 80 human duodenal adenocarcinoma cells with IC50s of 65 and 200 pM, respectively. DAB389 SP had an IC50 of 9.5 pM for the AR42J cells and 12 nM for the HuTu 80 cell line. A number of small cell lung cancer cell (SCLC) lines were tested, and the IC50 for DAB389 GRP ranged from 1.1 to 85 nM. Sensitivity to DAB389 GRP appeared to be based on receptor number and receptor type (i.e., GRP or neuromedin B preferring). SCLC cells were also sensitive to DAB389 SP, with IC50s ranging from 2.4 to 11.5 nM. These results suggest that a potential use exists for diphtheria-based fusion toxins as therapeutic agents for treatment of SCLC and other neuropeptide receptor-bearing cancers.

Single-agent high-dose melphalan salvage therapy for Hodgkin's disease: cost, safety, and long-term efficacy.

BACKGROUND: Few data are available on the cost, safety, and long-term efficacy of single-agent high-dose melphalan (HDM) followed by autologous bone marrow (ABMT) or blood stem cell (ABSCT) transplantation in the salvage therapy of Hodgkin's disease (HD). PATIENTS AND METHODS: From February 1981 to September 1996, 23 patients with relapsed (n = 15) or refractory (n = 8) HD received salvage therapy with HDM 140-200 mg/m2 followed by non-cryopreserved ABMT (n = 18) or cryopreserved ABSCT (n = 5). The cost of HDM/ABSCT in 1996, from initial consultation until transfer back to referring physician, was determined and compared to the estimate costs of two multi-agent regimens commonly used for HD. RESULTS: HDM was well tolerated with no early transplant-related mortality. The five-year overall and progression-free survival rates were 52% and 50%, respectively. The average total cost in Canadian funds of HDM/ABSCT in 1996 was $34,400/patient. This cost was estimated to be $4,700-6,800 cheaper per patient than the multi-agent high-dose regimens. CONCLUSION: These data suggest that HDM is safe, feasible, active, and reasonably inexpensive salvage therapy for patients with relapsed/refractory HD.

Genetic construction and properties of a diphtheria toxin-related substance P fusion protein: in vitro destruction of cells bearing substance P receptors.

We have genetically replaced the native receptor binding domain of diphtheria toxin with an extended form of substance P (SP): SP-glycine (SP-Gly). The resulting fusion protein, DAB389SP-Gly, is composed of the catalytic and transmembrane domains of diphtheria toxin genetically coupled to SP-Gly. Because native SP requires a C-terminal amide moiety to bind with high affinity to the SP receptor, the precursor form of the fusion toxin, DAB389SP-Gly, was converted to DAB389SP by treatment with peptidylglycine-alpha-amidating monooxygenase. We demonstrate that following conversion, DAB389SP is selectively cytotoxic for cell lines that express either the rat or the human SP receptor. We also demonstrate that the cytotoxic action of DAB389SP is mediated via the SP receptor and dependent upon passage through an acidic compartment. To our knowledge, this is the first reported use of a neuropeptide as the targeting ligand for a fusion toxin; and the first instance in which an inactive precursor form of a fusion toxin is converted to the active form by a posttranslational modification.

DAB389 interleukin-2 receptor binding domain mutations. Cytotoxic probes for studies of ligand-receptor interactions.

Site-directed mutagenesis was used to generate point mutations in the diphtheria toxin-related fusion protein, DAB389 interleukin-2 (IL-2). Thr-439, in the IL-2 receptor binding domain of the fusion toxin, was changed to a Pro residue. The resultant fusion toxin, DAB389 IL-2(T439P), was 300-fold less cytotoxic than wild type DAB389 IL-2, partially as the result of a 100-fold decrease in binding affinity for the high affinity form of the IL-2 receptor. However, DAB389 IL-2(T439P) stimulated DNA synthesis to a greater extent than expected. Studies of intoxication kinetics indicated that the increased stimulation might result from an increased contact time between the mutated IL-2 receptor binding domain and the receptor, perhaps due to a decreased internalization rate. Another mutant, DAB389 IL-2(Q514D), in which a Gln residue at position 514 was changed to an Asp, was 2000-fold less cytotoxic than wild type DAB389 IL-2. This mutant had a 50-fold decrease in binding affinity, did not stimulate DNA synthesis and also had a reduced rate of intoxication. Gln-514 appears to play a role in receptor binding and activation, whereas Thr-439 appears to be involved with receptor binding and signaling internalization of the fusion toxin-receptor complex.

Therapy of untreated acute myeloid leukemia in the elderly: remission-induction using a non-cytarabine-containing regimen of mitoxantrone plus etoposide.

PURPOSE: The University of Manitoba Adult Acute Leukemia Study Group sought to examine the safety, efficacy, and impact on quality of life of a non-cytarabine-containing remission-induction regimen followed by intermediate-dose cytarabine (IDARA-C) postremission therapy for the management of untreated acute myeloid leukemia (AML) in patients age 60 to 80 years. PATIENTS AND METHODS: Eligible patients received mitoxantrone 10 mg/m2 and etoposide 100 mg/m2 on days 1 to 5. Complete remitters received a single course of cytarabine 0.5 mg/m2 every 12 hours on days 1 to 6. Cytogenetic and immunophenotyping studies were performed at diagnosis and were examined for prognostic importance. The Functional Living Index-Cancer (FLI-C) was used in the longitudinal assessment of quality of life. RESULTS: A total of 37 (55%) of 67 eligible patients achieved remission, 34 (92%) of whom did so with a single course. The induction mortality rate was 12%. The median disease-free and overall survival times were 8.4 and 9.2 months, respectively. CD34 stem-cell phenotype, poor performance status, and high cytogenetic complexity score were independent covariates of failure to achieve remission. Very complex karotype combined with CD34 stem-cell phenotype to predict induction death in 67% of cases (P = .0003). Cytotoxic therapy-related gut epithelial damage was maximal during weeks 2 and 3 of therapy. Complete remitters and partial responders exhibited significantly improved global FLI-C scores following completion of therapy. CONCLUSION: Mitoxantrone plus etoposide was an effective and well-tolerated first-line induction regimen for AML in the elderly that should be studied further in comparison to the standard cytarabine/anthracycline-based therapy.

Historical concept analysis of empathy.

An analysis of the concept empathy was performed on archival, narrative accounts of Civil War nursing care using concept analysis strategies. Archival model cases are presented with elucidation of critical attributes, antecedents and consequences, and empirical referents of the concept. The antecedent phenomena of patient cues and consequent phenomena of patient responses serve to clarify instances of nurse empathy and establish preliminary and terminal boundaries of the concept. Empirical referents of the critical attributes identification, introjection, and intervention further explicate this abstract construct. Analysis of contrary, related, and borderline cases extracted from the historical accounts serve to clarify empathy. Most notable to the analysis is the existence of nursing interventions as a critical attribute and the nature of patient responses. Preliminary examination of the model cases indicates patient outcomes improve when empathy is extant in the interaction.

The Johari Window: a strategy for teaching therapeutic confrontation.

Planned and purposeful confrontation can increase patient self-awareness of deleterious attitudes and behaviors affecting physical, mental, emotional, and social functioning. Teaching the application of therapeutic confrontation from the perspective of the conceptual model, The Johari Window, broadens the student's understanding of its appropriate use in a wide variety of patient care situations.

An inhibitor domain in c-Fos regulates activation domains containing the HOB1 motif.

The c-Fos protein has three activation modules at its C-terminus, two of which contain motifs (HOB1 and HOB2) which are also present in the activation domains of c-Jun. Here we show the existence of two additional activation modules at the N-terminus of c-Fos, one of which contains a second HOB1 motif (HOB1-N). The N-terminus also contains an inhibitor domain (ID1) which silences HOB1 activity. GAL4 fusion experiments showed that ID1 can specifically silence HOB1-containing activation domains from c-Fos or c-Jun when linked in cis, but will not affect other distinct activation domains. The c-Fos related protein, FosB, also contains an inhibitor domain. Mutagenic and deletion analyses identify an inhibitor motif (IM1) conserved between c-Fos and FosB, which is required for inhibitor function. Mutagenesis of IM1 enhances the ability of c-Fos to activate an AP1 bearing promoter. Finally, squelching experiments suggest that c-Fos ID1 binds a limiting protein involved in inhibition. These results demonstrate the existence of a new class of inhibitor domain within transcriptional activators, which acts in a sequence specific manner to inhibit a subset of activation domains.

Phosphorylation of the c-Fos and c-Jun HOB1 motif stimulates its activation capacity.

The c-Fos and c-Jun proteins bind an AP1 site and activate transcription synergistically. These two proteins have a common activation domain which has two co-operating motifs, HOB1 and HOB2. The HOB1 motif of c-Jun includes S73 which is required for Ha-Ras-induced super-activation and phosphorylation by MAP kinase-like enzymes. Since c-Fos HOB1 has a conserved Thr residue (T232) analogous to c-Jun S73 we have proposed that c-Fos HOB1 will be regulated in the same way as c-Jun HOB1. Here we show that the HOB1-containing activation domain of c-Fos is stimulated by Ha-Ras in vivo and phosphorylated by a MAP kinase family member in vitro and that mutating T232 to Ala abolishes both functions. Collectively these results suggest that phosphorylation of the HOB1 motif increases its activation capacity. To provide direct evidence for this we change the context of c-Fos T232 to a PKA recognition site, and show that HOB1 activity is now stimulated by the catalytic subunit of PKA. This 'PKA specificity' experiment represents a novel and powerful way to analyse phosphorylation events involved in a variety of biological functions.

c-Fos-induced activation of a TATA-box-containing promoter involves direct contact with TATA-box-binding protein.

Transcriptional activation in eukaryotes involves protein-protein interactions between regulatory transcription factors and components of the basal transcription machinery. Here we show that c-Fos, but not a related protein, Fra-1, can bind the TATA-box-binding protein (TBP) both in vitro and in vivo and that c-Fos can also interact with the transcription factor IID complex. High-affinity binding to TBP requires c-Fos activation modules which cooperate to activate transcription. One of these activation modules contains a TBP-binding motif (TBM) which was identified through its homology to TBP-binding viral activators. This motif is required for transcriptional activation, as well as TBP binding. Domain swap experiments indicate that a domain containing the TBM can confer TBP binding on Fra-1 both in vitro and in vivo. In vivo activation experiments indicate that a GAL4-Fos fusion can activate a promoter bearing a GAL4 site linked to a TATA box but that this activity does not occur at high concentrations of GAL4-Fos. This inhibition (squelching) of c-Fos activity is relieved by the presence of excess TBP, indicating that TBP is a direct functional target of c-Fos. Removing the TBM from c-Fos severely abrogates activation of a promoter containing a TATA box but does not affect activation of a promoter driven only by an initiator element. Collectively, these results suggest that c-Fos is able to activate via two distinct mechanisms, only one of which requires contact with TBP. Since TBP binding is not exhibited by Fra-1, TBP-mediated activation may be one characteristic that discriminates the function of Fos-related proteins.

The nature and evolution of phenomenological empathy in nursing: an historical treatment.

This study is an historical analysis of the nature and evolution of phenomenological empathy in nursing covering the period from 1861 through 1981. Nursing archival data were analyzed beginning with the inception of modern American nursing during the Civil War. The categories patient cues, empathy, nursing interventions, and patient responses were applied to the qualitative data. Analysis generated 119 instances of phenomenological empathy. The findings showed that patient cues were not a factor in precipitating nurse empathy, whereas patient responses to nursing interventions showed positive outcomes. A conceptual model of phenomenological empathy comprised of four major constructs and 18 concepts was derived from the archival data.

Conserved motifs in Fos and Jun define a new class of activation domain.

Fos and Jun form a tight heterodimeric complex that activates transcription by AP1 sites. We have recognized that two adjacent regions of the Jun A1 activation domain are conserved in the Fos protein, and we refer to these two homologous regions as homology box 1 (HOB1) and homology box 2 (HOB2). Using GAL4 chimeras, we show that the HOB1/HOB2 region of Fos and Jun is an independent activation domain in which HOB1 and HOB2 act cooperatively to activate transcription. This cooperativity is retained after the replacement of Fos HOB1 or HOB2 with the equivalent domain of Jun or when duplicated HOB1/HOB1 and HOB2/HOB2 combinations are generated. In the Fos protein, HOB1 or HOB2 can also cooperate with a distinct domain at the carboxyl terminus of the protein. Using the HOB2 consensus sequence as a guide, we identified a HOB2-containing activation domain in the CCAAT/enhancer binding protein (C/EBP) protein. This HOB2 motif can cooperate with as yet undefined sequences in C/EBP and will function even when linked to Jun HOB1. Thus, HOB1 and HOB2 represent inert "cooperating modules" that are combined to generate a functional activation domain. Each of these modules has the potential to cooperate with both distinct and identical domains. The presence of HOB-like modules in three different transcription factors indicates that the HOB motifs characterize a new class of activation domain. These motifs can be used now to identify other transcription factors with such modular characteristics.

Differentiation of K562 leukemia cells along erythroid, macrophage, and megakaryocyte lineages.

K562 is a human leukemic cell line used as model of hematopoietic differentiation. A variety of differentiation-inducing agents was used in this study, and the expression of surface membrane antigens associated with specific lineages of differentiation and changes in the cytochemistry of the induced cells were monitored. Sodium butyrate, hemin, retinoic acid, dimethyl sulfoxide (DMSO), phorbol myristate acetate (PMA), and interferon induced unique alterations in the binding of monoclonal antibodies specific for erythroid, granulocytic, monocytic, and megakaryocytic lineages. Hemoglobinization, Sudan Black B, glycogen content, nonspecific esterase, alkaline phosphatase, and 5'-nucleotidase staining were also altered. K562 cells were terminally differentiated with PMA to nitroblue tetrazolium-(NBT) positive macrophages. Expression of 3-fucosyl-N-acetyl lactosamine, previously thought to be myeloid specific but found on all early hematopoietic progenitors, was modulated during differentiation to nonmyeloid lineages. Lineage infidelity was noted during functional differentiation along all hematopoietic lineages. The presence of multiple lineage surface markers and cytoplasmic characteristics in leukemic cells is not indicative of lack of potential to differentiate. K562 cells cannot be compared to any normal stage of hematopoietic differentiation, but they do have the capacity to differentiate along erythroid, macrophage, and megakaryocytic lineages.

Ultrastructure and steroid-binding studies in leiomyomatosis peritonealis disseminata.

Leiomyomatosis peritonealis disseminata (LPD) is characterized by the development of numerous leiomyomata throughout the peritoneal cavity which appear grossly malignant but histologically benign. The etiology of this disorder has been controversial. The tenth reported case of LPD is presented with ultrastructural evidence that these tumors arise from smooth muscle cells. The cytoplasmic estrogen and progesterone bindings by these tumors were ninefold and twofold greater than receptor concentrations in normal myometrium from the same patient. In addition to the steroid binding data, the strong association of this disorder with pregnancy or, as in this case, oral contraceptives suggests that the stimulus for neoplastic initiation and growth is hormonally related.