Labor epidural placement in a woman with a cervical spinal cord stimulator.

A 37-year-old female, gravida 1 para 0, in active labor at term, with a cervical spinal cord stimulator in situ, presented for epidural analgesia for labor. She had received the cervical spinal cord stimulator some 30 months before, to treat chronic regional pain syndrome I. She was taking no medication, and was thin but otherwise healthy. The cervical spinal cord stimulator electrodes entered the C7-T1 interspace, and their end was in the epidural space at the C3 level. The electrodes were fixed to a cervical spinous process, crossed the midline high in the back and then went down the left side of her back parallel to her spine to the generator, which was in her buttock. The electrode cable could be felt high on the left side of her back, but not in her lumbar region. After consultation, it was felt safe and reasonable to proceed with labor epidural anesthesia. The procedure took place with the patient sitting, using a standard reusable 17-gauge Tuohy needle. Subsequent analgesia was acceptable. The patient also observed about 20 min after receiving the epidural medication that suddenly she could move her right hand more easily and that it felt warm. Her labor and delivery proceeded uneventfully. The spinal cord stimulator continued to function well throughout the entire process. She noticed that the feeling in her right hand returned to baseline after the delivery.

The putative oncoprotein Bcl-3 induces cyclin D1 to stimulate G(1) transition.

Bcl-3 is a distinctive member of the IkappaB family of NF-kappaB inhibitors because it can function to coactivate transcription. A potential involvement of Bcl-3 in oncogenesis is highlighted by the fact that it was cloned due to its location at a breakpoint junction in some cases of human B-cell chronic lymphocytic leukemia and that it is highly expressed in human breast tumor tissue. To analyze the effects of Bcl-3 dysregulation in breast epithelial cells, we created stable immortalized human breast epithelial cell lines either expressing Bcl-3 or carrying the corresponding vector control plasmid. Analysis of the Bcl-3-expressing cells suggests that these cells have a shortened G(1) phase of the cell cycle as well as a significant increase in hyperphosphorylation of the retinoblastoma protein. Additionally, the cyclin D1 gene was found to be highly expressed in these cells. Upon further analysis, Bcl-3, acting as a coactivator with NF-kappaB p52 homodimers, was demonstrated to directly activate the cyclin D1 promoter through an NF-kappaB binding site. Therefore, our results demonstrate that dysregulated expression of Bcl-3 potentiates the G(1) transition of the cell cycle by stimulating the transcription of the cyclin D1 gene in human breast epithelial cells.

Tumor necrosis factor alpha-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II.

Nuclear factor kappaB (NF-kappaB)/Rel transcription factors are key regulators of a variety of genes involved in immune and inflammatory responses, growth, differentiation, apoptosis, and development. In unstimulated cells, NF-kappaB/Rel proteins are sequestered in the cytoplasm by IkappaB inhibitor proteins. Many extracellular stimuli, such as tumor necrosis factor alpha (TNFalpha), cause rapid phosphorylation of IkappaB at N-terminal serine residues leading to ubiquitination and degradation of the inhibitor. Subsequently, NF-kappaB proteins translocate to the nucleus and activate gene expression through kappaB response elements. TNFalpha, as well as certain other stimuli, also induces the phosphorylation of the NF-kappaB proteins. Previously, we have shown that TNFalpha induces RelA/p65 phosphorylation at serine 529 and that this inducible phosphorylation increases NF-kappaB transcriptional activity on an exogenously supplied reporter (). In this report, we demonstrate that casein kinase II (CKII) interacts with p65 in vivo and can phosphorylate p65 at serine 529 in vitro. A CKII inhibitor (PD144795) inhibited TNFalpha-induced p65 phosphorylation in vivo. Furthermore, our results indicate that the association between IkappaBalpha and p65 inhibits p65 phosphorylation by CKII and that degradation of IkappaBalpha allows CKII to phosphorylate p65 to increase NF-kappaB transactivation potential. These data may explain the ability of CKII to modulate cell growth and demonstrate a mechanism whereby CKII can function in an inducible manner.

Evaluating and improving the practice of family-centered care.

Evaluating and improving the practice of family-centered care involves planning the evaluation effort collaboratively with families, gathering information from a variety of audiences, investigating the different arenas of family-centered care, following growth in family-centered practice over time, using a variety of evaluation approaches, and integrating evaluation with efforts to change toward family-centered approaches to care. Resources available to guide the evaluation effort include guidelines for reviewing written materials in a unit, program, clinic, or practice; written surveys and checklists; guidelines for focus groups or interviews; suggestions for using health care scenarios to gather information about family-centered approaches to care; and questions for nurses to use to reflect on their own practice.

Identification of nucleotide binding sites in the poliovirus RNA polymerase.

Poliovirus RNA polymerase (3Dpol) was cross-linked to [32P]ribonucleoside triphosphates (NTPs) by reduction of oxidized NTP-protein complexes. Cross-linked complexes were digested with cyanogen bromide, and resulting peptides were fractionated by reverse-phase HPLC. 32P-Labeled peptides were purified by secondary HPLC fractionation and/or additional digestion with endoproteinases Glu-C, TPCK-trypsin, or Asp-N followed by another HPLC fractionation. N-Terminal sequences of the major [32P]-peptides were determined, and approximate sizes of these peptides were obtained by SDS-polyacrylamide gel electrophoresis. Two major NTP binding sites in 3Dpol were found. One site was between Asp-266 and Met-286; possible binding residues in this fragment were Lys-276, Lys-278, or Lys-283. A second binding site was between Ala-57 and Met-74 with Lys-61 or Lys-66 as possible binding residues. Alignment of these regions on the known structure of HIV-1 reverse transcriptase allowed us to predict the position of the downstream nucleotide binding site in the conserved "fingers" subdomain present near the active site cleft of both RNA and DNA polymerases. The N-terminal nucleotide binding site is not contained within a region that is conserved among other polymerases.

Association of BK virus with failure of prophylaxis against hemorrhagic cystitis following bone marrow transplantation.

PURPOSE: Hemorrhagic cystitis (HC) after bone marrow transplantation (BMT) has been ascribed to cyclophosphamide metabolites. HC has also been associated with excretion of the BK type of polyomavirus. The relative contributions of cyclophosphamide metabolites and BK virus in the development of HC following BMT are unknown. PATIENTS AND METHODS: We conducted a randomized trial to compare mesna with forced diuresis for prophylaxis against HC in 147 BMT recipients. We studied the association of BK virus with HC in 95 consecutive BMT recipients by prospectively monitoring urinary excretion of BK virus using polymerase chain reaction amplification of viral gene sequences. RESULTS: HC occurred in 37 of 147 (25.2%) transplant recipients. The incidence of HC was similar in patients given mesna (26.8%, 19 of 71) or forced diuresis (23.7%, 18 of 76), and in recipients of allogeneic (27.2%, 18 of 64) or autologous marrow (22.9%, 19 of 83). The incidence of HC was unrelated to primary disease, preparative regimen, or occurrence of graft-versus-host disease (GVHD). Excretion of BK virus was demonstrated in 50 of 95 patients (52.6%); 38 patients (40%) had persistent BK viruria (> or = two consecutive positive samples). HC occurred in 19 of 38 patients (50%) with persistent BK viruria, in one of 12 (8.3%) with only a single urine sample positive for BK virus, and in none of 45 who did not excrete BK virus (P < .0001). Shedding of BK virus also had a strong temporal correlation with onset of HC (r = .95). CONCLUSION: Mesna and forced diuresis are equally effective in abrogating the urothelial toxicity of preparative regimens for BMT. Since HC after BMT is virtually always associated with persistent BK viruria, strategies aimed at the prevention or elimination of viruria in BK seropositive recipients are warranted.

The clinical application of research utilization: amphotericin B.

PURPOSE/OBJECTIVES: To describe the first application of the research utilization process by clinical nurses using the Stetler-Marram Model of Research Utilization to the practice of amphotericin B administration; to share the findings; and to discuss issues encountered in the process and their solutions. DATA SOURCES: Published articles identified through computerized literature searches, published abstracts and books, personal communication with one author, and an informal survey of other cancer centers' amphotericin B infusion practices; research articles were selected for review if studies included settings and patient populations similar to those of the authors and if they used experimental designs. DATA SYNTHESIS: Studies were reviewed for scientific merit and clinical applicability according to the Stetler-Marram model; findings were used to develop a specific nursing protocol for infusion times of amphotericin B based on clinical criteria. CONCLUSIONS: The Stetler-Marram model helped staff nurses decide how to apply research findings to practice, although using it was difficult and required mentorship. A research base exists for amphotericin B administration time but not for test doses or premedications to prevent or minimize side effects. IMPLICATIONS FOR NURSING PRACTICE: Staff nurses can use the Stetler-Marram model but need resources and support from individuals, committees, and administration. A specific protocol representing a practice change was implemented and may be applicable to other settings.

Advanced practice nurses' application of the Stetler model for research utilization: improving bereavement care.

PURPOSE: To describe the role of the advanced practice nurse in applying the Stetler Model for Research Utilization, to demonstrate advanced practice nurse use of the model as applied to improving bereavement care, and to discuss problems and opportunities that advanced practice nurses encountered when applying a research utilization model to a clinical problem. DATA SOURCES: Published articles identified through computerized literature searches; both assessment- and intervention-focused research articles were selected for review if the study populations and settings were comparable to those of the authors and the research design used was experimental or quasi-experimental. DATA SYNTHESIS: The Stetler model guided formal review of selected research reports for applicability and feasibility of translation into clinical practice. Final recommendations were made for departmental implementation to improve bereavement care. CONCLUSIONS: The Stetler model facilitates implementation of research findings into clinical nursing practice, practice change recommendations based on research utilization can be both clinical and organizational in nature, and advanced practice nurses have an important departmental role to play in a formal research utilization process. IMPLICATIONS FOR NURSING PRACTICE: Advanced practice nurses are ideally suited for leadership roles in the research utilization process; however, research utilization task forces require that individuals who already face multiple demands on their clinical time invest a significant amount of time. Despite this, it is advantageous for advanced practice nurses to adopt and apply a formal research utilization model in their practice.