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Osmolytes increase the thermodynamic conformational stability of proteins, shifting the equilibrium between native and denatured states to favor the native state. However, their effects on conformational equilibria within native-state ensembles of proteins remain controversial. We investigated the effects of sucrose, a model osmolyte, on conformational equilibria and fluctuations within the native-state ensembles of bovine pancreatic ribonuclease A and S and horse heart cytochrome c. In the presence of sucrose, the far- and near-UV circular dichroism spectra of all three native proteins were slightly altered and indicated that the sugar shifted the native-state ensemble toward species with more ordered, compact conformations, without detectable changes in secondary structural contents. Thermodynamic stability of the proteins, as measured by guanidine HCl-induced unfolding, increased in proportion to sucrose concentration. Native-state hydrogen exchange (HX) studies monitored by infrared spectroscopy showed that addition of 1 M sucrose reduced average HX rate constants at all degrees of exchange of the proteins, for which comparison could be made in the presence and absence of sucrose. Sucrose also increased the exchange-resistant core regions of the proteins. A coupling factor analysis relating the free energy of HX to the free energy of unfolding showed that sucrose had greater effects on large-scale than on small-scale fluctuations. These results indicate that the presence of sucrose shifts the conformational equilibria toward the most compact protein species within native-state ensembles, which can be explained by preferential exclusion of sucrose from the protein surface.

Worldwide vaccination programs against infectious diseases and toxins are estimated to save approximately 3 million lives yearly. Tragically, however, another 3 million individuals (primarily children) die of vaccine-preventable diseases. A significant portion of this problem results from the thermal instability of many of the currently used vaccines. This review argues that modern methods of physical and chemical analysis permit for the first time characterization of the degradative pathways of thermally labile vaccines. A rigorous description of these pathways permit a more rational and systematic approach to the stabilization of vaccines. A direct result of the replacement of currently employed, primarily empirical, approaches to vaccine stabilization with a more molecular-based methodology should be the development of more universally available vaccinations against life-threatening diseases. This has the potential to have a dramatic impact on world health., (Copyright 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:218-231, 2003)

In vivo fluctuations in gonadal hormones alter hippocampal excitability and modulate both physiological and pathological hippocampal processes. To assess hormonal effects on excitability within a functional hippocampal circuit, extracellular CA1 field responses were compared in slices from intact male, intact female, orchidectomized male, and ovariectomized female rats. Secondly, the effects of in vitro applications of 17-beta estradiol, progesterone, or testosterone on baseline excitability of slices from gonadectomized rats were assessed versus pre-hormone baseline measures. Finally, using the in vitro kindling model of slice epileptogenesis, steroid hormone effects on interictal-like activity were also examined. Significant sex differences in excitatory postsynaptic potential amplitude were observed, with slices from males having larger excitatory postsynaptic potential amplitudes than those from females. Gonadectomy significantly decreased excitatory postsynaptic potential amplitude in slices from male rats. Slices from gonadectomized male and female rats also showed a decreased dendritic excitatory postsynaptic potential slope relative to slices from intact male and females rats. In vitro application of testosterone significantly increased excitatory postsynaptic potential amplitudes in slices from both orchidectomized males and ovariectomized females and the population spike amplitude of slices from ovariectomized females. Following in vitro kindling, slices from intact males showed greater spontaneous burst rates than slices from intact females, further suggesting an excitatory effect of testosterone. These results suggest: (1) a sex difference in the level of baseline excitability between slices from intact males and females as measured by excitatory postsynaptic potential amplitudes, (2) testosterone has excitatory effects on baseline physiology and kindled hippocampal responses, and (3) slices from males show a greater level of excitability than those from females in the in vitro kindling model.

We have chosen an anti-L-selectin antibody as a model protein to investigate the effects of sucrose and/or Tween 20 on protein stability during lyophilization and reconstitution. Native anti-L-selectin secondary structure is substantially retained during lyophilization in the presence of sucrose (1 or 0.125%). However, aggregation of the protein during reconstitution of lyophilized protein powders prepared without sucrose is not reduced by the presence of sucrose in the reconstitution medium. Aggregate formation upon reconstitution is completely inhibited by freeze drying the protein with sucrose and reconstituting with a 0.1% Tween 20 solution. Tween 20 (0.1%) also partially inhibits loss of native anti-L-selectin secondary structure during lyophilization. However, upon reconstitution the formulations lyophilized with Tween 20 contain the highest levels of aggregates. The presence of Tween in only the reconstitution solution appears to inhibit the transition from dimers to higher order oligomers. Potential mechanism(s) for the Tween 20 effects were investigated. However, no evidence of thermodynamic stabilization of anti-L-selectin conformation (e.g., by Tween 20 binding) could be detected., (Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1466-1477, 2001)

We report the successful use of single-shot spinal anaesthesia for elective caesarean section in a multigravid woman with Ehlers-Danlos syndrome, complicated by mitral valve prolapse. This is a rare inherited collagen disorder that has been reported to have a high pregnancy-related morbidity and mortality, particularly from uterine rupture and uncontrolled bleeding from friable vessels, coagulopathy and major vessel rupture. The literature concerning obstetric anaesthetic management for different types of Ehlers-Danlos syndrome and the management of mitral valve prolapse in pregnancy are reviewed.

Background and Objective: Colorectal services have traditionally been arranged for the convenience of hospitals rather than patients. This model is not ideal, particularly for minor interventions and diagnostic procedures. In order to address this a one-stop colorectal clinic was set up., Patients and Methods: Weekly clinics ran from 6.00 to 9.30 p.m. on Wednesdays for a period of 6 months. Patients with rectal bleeding, altered bowel habit, anorectal symptoms and those requesting screening advice were seen by a consultant or specialist registrar. Patients were asked to fill in a questionnaire at the end of their clinic attendance., Results: 197 patients were seen in 17 clinics; 134 underwent proctoscopy, 72 had a rigid sigmoidoscopy and 85 had a flexible sigmoidoscopy carried out. Twenty-four patients subsequently had a barium enema and 3 were listed for colonoscopy. The main diagnosis was haemorrhoids (n = 104); 14 colorectal neoplasms were discovered (5 cancers and 9 polyps). During the study period the number of patients waiting for lower gastrointestinal endoscopy fell from 119 to 63; 2 months after ending the pilot scheme, the number had risen to 108., Conclusion: The clinic was found to have significantly improved patient care. The majority of patients were satisfied with an evening clinic. Flexible sigmoidoscopy without sedation was well tolerated and the ability to perform this at initial assessment had a marked effect on the number of patients awaiting lower gastrointestinal endoscopy.

The effect of priming for audiogenic seizures (AGS) on the development of epileptiform activity in the hippocampus was studied using in vitro kindling (IVK) in Long-Evans rats. AGS priming consists of intense auditory stimulation during a critical period of auditory development, resulting in sound-induced clonic convulsions upon subsequent testing. Between postnatal day (PND) 28 and 50, slices from subjects primed and sham-primed for AGS on PND 18 were used for recording responses in area CA1 of hippocampus following Schaffer collateral stimulation from stratum radiatum of area CA2/CA3. The developmental priming procedure, which enhances auditory brainstem excitability, resulted in fewer afterdischarges in slices from primed subjects across initial IVK stimulation sequences. These results suggest that changes in excitability that occur with acoustic priming can initially diminish selective epileptiform response characteristics in forebrain areas such as the hippocampus.

Death resulting from plastic bag asphyxia has been recognized for >40 years, but relatively little is known about either its epidemiology or its pathophysiology. Over 15 years (1984-1998), 30 deaths were attributed to plastic bag asphyxia among the 14,560 autopsies performed in the Forensic Medicine Unit in Edinburgh. These 30 deaths involved 20 male and 10 female subjects, with an age range of 13 to 81 years. Eleven had some alcohol measurable in the blood, with four having levels >80 mg/dl. Only one individual appeared to have ingested a drug overdose, but inhaled substances within the plastic bag may have contributed to death in five cases. The absence of childhood accidental deaths may reflect successful preventive measures. The 3 accidental deaths involved adults (including 2 who died of autoerotic asphyxia), and the remaining deaths were 27 suicides. Of those who committed suicide, most (59%) had chronic psychiatric illness rather than chronic debilitating or terminal physical illness. In contrast with reports from the United States, publicity associated with "self-deliverance" did not result in an increased number of deaths from plastic bag asphyxia (4 deaths in this series). Analysis of the circumstances of all the deaths revealed them to be difficult to predict and hence prevent.

Metal-induced precipitation of protein therapeutics is being used and further developed as a processing step in protein formulation and may have utility in protein purification and bulk storage. In such processes, it is imperative that native protein structure is maintained and the metal complexation is reversible. In the current study, we investigated the effects of zinc-induced precipitation on recombinant human growth hormone (rhGH) and recombinant human nerve growth factor (rhNGF). On the addition of ethylenediaminetetraacetic acid (EDTA), the precipitates were dissolved, yielding complete recovery of native protein in both cases. Both proteins have specific metal binding sites and require specific molar ratios of zinc to protein to initiate precipitation (zinc:rhGH > 2:1; zinc:rhNGF > 18:1). Furthermore, the secondary structures of both proteins were unperturbed in soluble zinc complexes and zinc-induced precipitates, as measured by infrared and circular dichroism spectroscopies. The soluble zinc complex of rhGH had minor tertiary structural alterations, whereas zinc binding did not alter the tertiary structure of rhNGF. These studies indicated that metal-induced precipitation provides a method to maintain proteins in their native state in precipitates, which may be useful for purification, storage, and formulation., (Copyright 2000 Wiley-Liss, Inc.)

Homophobic reactions of Australian psychologists (n = 43), postgraduate psychology students (n = 17) and undergraduate psychology students (n = 44) were compared using Van de Ven's (1994) measures of cognitive, affective and behavioral dimensions of homophobia. Results suggested that undergraduates were significantly more homophobic than psychologists in their thinking, intentional behavior and feelings of fear or discomfort in relation to lesbians and gay men. No other significant group differences were found. Gender differences were found only in relation to one affective dimension of homophobia. Low levels of positive affective response to homosexuals were observed across groups and gender. The study underscores the importance of assessing homophobic response multidimensionally. Implications for the training of Australian psychologists are discussed.

The purpose of this study was to describe the patterns of cancer-related fatigue (CRF) and vigor in patients receiving chemotherapy or radiation therapy. Five studies that measured fatigue and vigor with the Profile of Mood States were used to describe the pattern of CRF and vigor during and after both types of treatment. Repeated-measures ANOVA was used to determine differences over time in each study. Results demonstrate different patterns of CRF for patients receiving chemotherapy and radiation therapy. Chemotherapy-related CRF peaks in the days after chemotherapy, whereas radiation therapy-related CRF gradually accumulates over the course of treatment. The CRF associated with both forms of treatment gradually declines over time. The prevalence, intensity, and persistence of CRF during treatment and for months after treatment is complete make this symptom one that cannot be ignored.

An Escherichia coli causing negligible mortality in embryonated chicken eggs was adapted to grow in media containing nalidixic acid. This isolate (EcNAL) was inoculated into 12-day-old embryonated eggs. Additional embryos inoculated with tryptose phosphate broth (TPB) served as controls. Six days later, all surviving eggs were moved to hatching units. One hatcher contained half of the TPB-inoculated eggs; the chicks hatching from these eggs served as negative controls. The EcNAL-inoculated eggs and the remaining TPB-inoculated eggs were moved to a second hatcher and allowed to hatch together; chicks hatching from these TPB-inoculated eggs served as contact controls. On day of hatch and at intervals thereafter, chicks from each of the treatment groups were sampled. Their body and yolk weights were recorded, and various tissues were cultured for the presence of the EcNAL bacterium. Hatchability of the EcNAL-inoculated embryos was markedly lower than that of either control group. Chicks from EcNAL-inoculated embryos also had low but detectable levels of mortality, lowered body weights, and increased yolk-to-body weight ratios. These same chicks had persistently high levels of EcNAL in the yolk and lower but detectable levels of the organism in the lungs and tracheas, which lasted a few days. The contact controls, on the other hand, were similar to the negative controls as far as having negligible mortality, steadily increasing body weights, and declining yolk-to-body weight ratios. However, in contrast to the negative controls, EcNAL was recovered primarily from the respiratory tract of the contact controls for a brief period of 3-4 days after hatch.

Purpose: The purpose of this work is to utilize electron paramagnetic resonance (EPR) spectroscopy in conjunction with analytical ultracentrifugation (AUC) to investigate the binding of surfactants to proteins with a transmembrance domain. As an example these methods have been used to study the interaction of a nonionic surfactant, C12E8, to recombinant human tissue factor (rhTF) in liquid formulations. The complementary nature of the two techniques aids in data interpretation when there is ambiguity using a single technique. In addition to binding stoichiometries, the possibility of identifying the interacting domains by using two forms of rhTF is explored., Methods: Two recombinant, truncated forms of human tissue factor were formulated in the absence of phospholipids. Neither of the recombinant proteins, produced in E. coli, contains the cytoplasmic domain. Recombinant human tissue factor 243 (rhTF 243) consists of 243 amino acids and includes the transmembrane sequences. Recombinant human tissue factor 220 (rhTF 220), however, contains only the first 221 amino acids of the human tissue factor, lacking those of the transmembrane region. EPR and AUC were used to investigate the interactions between these two forms of rhTF and polyoxyethylene 8 lauryl ether, C12E8., Results: Binding of C12E8 to rhTF 243 is detected by both EPR spectroscopy and AUC. Although a unique binding stoichiometry was not determined, EPR spectroscopy greatly narrowed the range of possible solutions suggested by the AUC data. Neither technique revealed an interaction between rhTF 220 and C12E8., Conclusions: The complementary nature of EPR spectroscopy and AUC make the combination of the two techniques useful in data interpretation when studying the interactions between rhTF and C12E8. By utilizing these techniques in this study, the binding stoichiometry of rhTF 243 to C12E8 ranges from 1.2:1 to 1.3:0.6 based on an aggregation number of 120. This binding is consistent with previously reported activity data that showed an increase in clotting rate when rhTF 243 is in the presence of C12E8 micelles. From the rhTF 220 data, it can further be concluded that the transmembrane domain of rhTF is necessary for interactions with C12E8.

Agitation- and freeze-thawing-induced aggregation of recombinant human factor XIII (rFXIII) is due to interfacial adsorption and denaturation at the air-liquid and ice-liquid interfaces. The aggregation pathway proceeds through soluble aggregates to formation of insoluble aggregates regardless of the denaturing stimuli. A nonionic surfactant, polyoxyethylene sorbitan monolaurate (Tween 20), greatly reduces the rate of formation of insoluble aggregates as a function of surfactant concentration, thereby stabilizing native rFXIII. Maximum protection occurs at concentrations close to the critical micelle concentration (cmc), independent of initial protein concentration. To study the mechanistic aspects of the surfactant-induced stabilization, a series of spectroscopic studies were conducted. Electron paramagnetic resonance spectroscopy indicates that binding is not occurring between Tween 20 and either the native state or a folding intermediate state of rFXIII. Further, circular dichroism spectroscopy suggests that Tween 20 does not prevent the secondary structural changes induced upon guanidinium hydrochloride-induced unfolding. Taken together, these results imply that Tween 20 protects rFXIII against freeze-thawing- and agitation-induced aggregation primarily by competing with stress-induced soluble aggregates for interfaces, inhibiting subsequent transition to insoluble aggregates.

Purpose/objectives: To describe the process used in proposal development and study implementation for a complex multisite project on cancer treatment-related fatigue (CRF), identify strategies used to manage the project, and provide recommendations for teams planning multisite research., Data Sources: Information derived from project team meeting records, correspondence, proposals, and personal recollection., Data Synthesis: The project was built on preexisting relationships among the three site investigators who then built a team including faculty, research coordinators, staff nurses, and students. Study sites had a range of organizational models, and the proposal was designed to capitalize on the organizational and resource strengths of each setting. Three team members drawn from outside oncology nursing provided expertise in measurement and experience with fatigue in other populations. Planning meetings were critical to the success of the project. Conference calls, fax technology, and electronic mail were used for communication. Flexibility was important in managing crises and shifting responsibility for specific components of the work. The team documented and evaluated the process used for multisite research, completed a major instrumentation study, and developed a cognitive-behavioral intervention for CRF., Conclusions: Accomplishments during the one-year planning grant exceeded initial expectations. The process of conducting multisite research is complex, especially when the starting point is a planning grant with specific research protocols to be developed and implemented over one year. Explicit planning for decision-making processes to be used throughout the project, acknowledging the differences among the study settings and planning the protocols to capitalize upon those differences, and recruiting a strong research team that included a member with planning grant and team-building expertise were essential elements for success., Implications for Nursing Practice: Specific recommendations for others planning multisite research are related to team-building, team membership, communication, behavioral norms, role flexibility, resources, feedback, problem management, and shared recognition.

Major histocompatibility complex (MHC) class II molecules are expressed in the bovine corpus luteum (CL) in a manner correlating with luteolysis. Whether bovine luteal cells can stimulate T-cell proliferation in a class II-restricted manner was investigated. Staphylococcal enterotoxin B (SEB) enhances T-cell proliferation by a mechanism requiring MHC class II molecules and was used to examine stimulation of T-cell proliferation by luteal cells. Luteal cells from midcycle or regressing CL (induced by prostaglandin F2 alpha) were cocultured with autologous T cells in the presence of no treatment, SEB (1 microgram/ml), or SEB + anti-MHC class II antibody (3 micrograms/ml); and proliferation was assessed by incorporation of tritiated thymidine. T cells proliferated in the presence of cells from regressing CL more than when in the presence of midcycle cells (118,309 +/- 20,567 vs. 75,261 +/- 12,494 cpm; p < 0.05). Anti-MHC attenuated this response of cells from regressing CL (81,108 cpm +/- 13,249; p < 0.05). Without SEB, T cells proliferated when cultured with cells from regressing, but not midcycle, CL (4637 +/- 816 vs. 2117 +/- 589 cpm; p < 0.03). These results suggest that luteal cells can function as antigen-presenting cells in vitro and that prostaglandin F2 alpha may enhance their ability to present antigen.

Integrins are heterodimeric proteins mediating cell-cell and cell-extracellular matrix adhesive connections (Springer T.A., 1990, Nature 346, 425-434) and signal transduction across the plasma membrane. The important roles of integrins in neural development and cancer, where they subserve process outgrowth and cell migration, are well documented, but information on integrins in the adult central nervous system has been slower to arrive. Now that strong evidence, both molecular biological and immunocytochemical, has been collected, it is useful to speculate on what these interesting proteins may be doing in the adult central nervous system. Suggestive data now points to roles in functions characterized in part by morphological rearrangements, such as learning and memory, and injury responses.

We have examined a potential role for integrins in an animal model of epileptogenesis termed in vitro kindling. Integrins mediate cell-cell and cell-matrix interactions, and also participate in the transduction of information from the extracellular environment to the intracellular milieu. As many extracellular matrix (ECM) molecules contain the conserved amino acid sequence arg-gly-asp-ser (RGDS) at the integrin recognition site, integrin-ECM binding can be disrupted using RGDS peptides. Hippocampal slices were washed in either RGDS, gly-gly-gly-gly (GGGG), vehicle or artificial cerebral spinal fluid (ACSF) for 1 h prior to in vitro kindling. Baseline electrophysiological responses were unaltered by RGDS peptide. The RGDS-treated slices displayed a significant decrease in the rate of spontaneous bursts, whereas the period of spontaneous bursting increased dramatically. Our results indicate that the competitive peptide, RGDS, changed hippocampal slice excitability over time, indicating that interference with ECM-integrin binding may alter neuronal signaling through an RGDS binding site.

Purpose/objectives: To test the hypotheses that preparatory informational interventions based on self-regulation theory delivered to radiation therapy (RT) recipients by staff nurses would reduce disruption in patients' usual life activities and have a positive effect on the moods of patients who tended to have pessimistic expectations about outcomes., Design: A quasi-experimental design with repeated measures., Setting: University-affiliated RT department., Sample: 226 patients receiving RT for breast or prostate cancer., Methods: The control-group patients received the nursing care that was the standard of practice before the experimental interventions were introduced. The experimental-group patients received theory-based interventions four different times from staff nurses. Patient data were collected by interview four different times., Main Research Variables: Type of nursing interventions generated, optimistic or pessimistic expectations about outcomes (Life Orientation Test), amount of disruption in usual life activities (Sickness Impact Profile), and moods (Bi-Polar Profile of Mood States)., Findings: The patients who received the self-regulation theory-based nursing interventions experienced less disruption in their usual life activities during and following RT. Among the patients who tended to be pessimistic, those who received the theory-based interventions had a more positive mood than those who did not receive the interventions., Implications for Nursing Practice: Staff nurses should use self-regulation theory-based interventions to help patients cope with RT.

Experimental autoimmune uveitis (EAU) is a T cell-mediated disease that targets the neural retina and serves as a model of human uveitis. Uveitogenic effector T cells have a Th1-like phenotype (high IFN-gamma, low IL-4), and genetic susceptibility to EAU is associated with an elevated Th1 response. Here we investigate whether the ability to produce IFN-gamma is necessary for the development of EAU by immunizing IFN-gamma-deficient (GKO) mice with the uveitogenic protein interphotoreceptor retinoid binding protein (IRBP) and characterize the associated immunologic responses. GKO mice developed EAU comparable in severity and incidence to that of their wild-type littermates. However, the cytokine profile in their uveitic eyes as well as the cytokines produced by primed lymph node cells in response to IRBP showed a distinct profile: undiminished TNF-alpha and elevated IL-5, IL-6, IL-10, and lymphotoxin (but not IL-4) responses. The inflammatory infiltrate in GKO eyes contained an excess of granulocytes and IL-5- and IL-6-producing cells, but uveitic GKO mice did not up-regulate inducible nitric oxide synthase. GKOs had enhanced lymphocyte proliferation and delayed-type hypersensitivity responses to IRBP. Histology of the delayed-type hypersensitivity lesion in GKO had superimposed elements of an allergic-like response. Anti-IRBP Ab isotypes of GKO mice showed a reduction of IgG2a, but no enhancement of IgG1. Comparison of responses in +/+ and +/- wild-type mice revealed some limited evidence of a gene-dose effect. We conclude that IFN-gamma is not required for priming of pathogenic T cells or for effecting the retinal damage and photoreceptor loss typical of EAU. However, what appears to be a grossly similar disease is caused in the GKO by a deviant type of effector response.

An intrapleural injection of carrageenan in rats induced LTB4 and LTC4/D4/E4 biosynthesis, exudate formation, and cellular influx in the pleural cavity. An injection of calcium ionophore (A23187, 100 nmol) 16-18 h after carrageenan injection augmented leukotriene biosynthesis and exudate formation, but not cellular influx. The carrageenan-induced pleurisy model modifid by A23187 administration was used to study the oral effect of CGS 23885 (N-hydroxy-N-[(6-phenoxy-2H-1-benzopyran-3-yl)-methyl]urea), a potent 5-lipoxygenase (5-LO) inhibitor, on inflammatory parameters. CGS 23885 dose-dependently (1 to 30 mg/kg) inhibited the enhanced LTB4 and LTC4/D4/E4 (1 to 10 mg/kg) biosynthesis, but had no effect on enhanced exudate formation. An inhibitory effect of CGS 23885 of small magnitude on cellular influx due to carrageenan stimulation was seen at 30 mg/kg. The concentrations of CGS 23885 in the pleural fluid were dose-related, and a positive correlation (r2=0.989) between pleural fluid concentration of LTB4 and CGS 23885 was observed. The results confirm that CGS 23885 is a specific, orally active 5-LO inhibitor which can achieve concentrations in the pleural cavity sufficient to inhibit production of LTB4 and LTC4/D4/E4 in an ongoing inflammatory response.

Integrins comprise a large family of heterodimeric proteins that mediate cell-cell and cell-extracellular-matrix adhesive connections. There is an extensive literature on their importance in neural development and cancer, but evidence for the existence of integrins in the adult CNS has emerged only recently. With growing immunohistochemical and molecular biological evidence for the presence of integrins in the adult CNS, a variety of functions from microglial migration to synaptic rearrangements can be considered for these adhesive proteins.

Purpose/objectives: To determine oncology nursing research priorities as well as the type of research needed to address these priorities., Design: Cross-sectional survey design., Setting: Mail-out survey with return, postage-paid envelope provided., Sample: A random sample of 10% of Oncology Nursing Society (ONS) members who identified patient care as their primary functional area, the ONS leadership group (e.g., Board of Directors, all committee chairs), all doctorally prepared ONS members, and all members of the ONS Advanced Nursing Research Special interest Group (N = 2,178)., Methods: The questionnaire was based on prior ONS Research Surveys and updated to reflect issues or topics that currently are relevant to oncology nurses., Main Research Variables: Priority ranking of 93 research topics organized into seven major categories., Findings: Seven hundred eighty-nine surveys were returned, for a 36% return rate. The top 10 priorities according to the priority index were pain; prevention; quality of life; risk reduction/screening; ethical issues; neutropenia/immunosuppression; patient education; stress, coping, and adaptation; detection; and cost containment., Conclusions: The top 10 research issues can be used to develop priorities for the direction of research in oncology nursing., Implications for Nursing Practice: The findings provide a basis for identifying trends in nursing practice. The fact that prevention, risk reduction, and detection appear in the top 10 suggests that nurses are moving toward a definition of practice that is not limited to managing symptoms of disease. These findings also provide guidance for forming health policy in cancer care.

Purpose/objectives: To describe the use of prevention and early detection behaviors related to the side effects of chemotherapy., Design: Cross-sectional, descriptive, and secondary analysis., Setting: A large university hospital and university-affiliated community hospital., Sample: 46 adult patients with cancer starting a cycle of IV chemotherapy who were predominantly white, married, and female., Methods: Self-report utilizing a 17-item, self-administered prevention and early detection questionnaire called the Prevention Behaviors Questionnaire (PBQ); questionnaires were completed two days and five days after treatment., Main Research Variable: Prevention and early detection behaviors., Findings: Patients reported using an average of 8.8 prevention behaviors two days after chemotherapy and 9.2 behaviors five days after chemotherapy. "Tried to think more positively" was the most frequently used behavior. Internal consistency and test-retest correlation coefficients on the questionnaire were calculated to be 0.81 and 0.78, respectively., Conclusions: The PBQ had adequate internal consistency and test-retest reliability. Patients reported using many prevention and detection behaviors, although very little is known about the efficacy of these behaviors in reducing or preventing the side effects of chemotherapy., Implications for Clinical Practice: This exploratory study does not have direct implications for practice but identifies an area for future research that may affect what nurses teach patients and how they assist patients to cope with treatment.

Dermorphin, a specific mu 1-opioid receptor agonist, has been studied for its effects on the physiology of the rat hippocampal slice. Population responses in CA3 to threshold levels of stimulation from both the Schaffer collaterals and mossy fibers were markedly enhanced in the presence of 50-100 nM dermorphin, while CA1 responses to threshold Schaffer collateral stimulation were less effected. Responses at higher stimulus levels than threshold were negligibly responsive to dermorphin, although at 500 nM dermorphin all responses became epileptiform and in some slices spontaneous bursting erupted. [L-Ala2]Dermorphin, a biologically inactive dermorphin analogue, did not increase response amplitudes nor evoke epilepsy in the slice. 5 microM naloxone blocked the effect of dermorphin on Schaffer collateral and mossy fiber-evoked responses, though less effectively in the latter case. These data provide in vitro evidence to support in vivo observations that excessive mu-opioid receptor activation can be proconvulsant in the hippocampus, but that normally the receptors may function as facilitatory modulators of responses in the threshold range.

Effects of nitric oxide synthase (NOS) inhibitors on the induction of an in vitro model of kindling were investigated in the rat hippocampal slice. It has been reported that NMDA receptor activation stimulates NOS and guanosine 3',5'-cyclic monophosphate (cGMP) production and that the interruption of this pathway interferes with LTP in the CA1 hippocampal field. Because the induction of LTP and kindling both involve NMDA receptor activation, we tested the effects of NOS inhibitors on the genesis and initial rate of interictal-like spontaneous bursts in CA1 and CA3 of the rat hippocampal slice. Experimental groups were exposed to 100 microM methyl-L-arginine (active NOS inhibitor), nitro-L-arginine (active NOS inhibitor), or methyl-D-arginine (inactive isomer of the NOS inhibitor) for 1 h prior to in vitro kindling. These results indicate that rather than preventing the induction of kindling in this model of epileptogenesis, NOS inhibition may facilitate the initiation of interictal-like spontaneous bursts in the rat hippocampal slice.

Patient's perceptions of side effects and the influence of treatment on daily activities are important considerations in choosing a chemotherapy regimen. However, there are no studies comparing patients' experiences with three commonly used chemotherapy regimens for breast cancer. The authors compared the patient-reported side effects and disruption in usual activities for cyclophosphamide and fluorouracil combined with methotrexate (CMF), doxorubicin (CAF), or mitoxantrone (CNF) in 86 women receiving treatment for breast cancer. The incidence and severity of side effects and disruption in usual activities were recorded by patients in a self-care diary (SCD) 2 and 5 days after the first and second drug cycles. Patients reported a mean of 3.2 to 4.9 side effects at each point in time. Fatigue, nausea, anorexia, taste changes, and headache were the most frequently reported side effects and did not differ in incidence among the three drug regimens. When repeated measures analysis of covariance was conducted using mean substitution for missing data and controlling for stage of disease, women receiving CAF reported more severe nausea than women receiving CMF or CNF (P < 0.05). Fatigue was significant for time; however, a distinct clinical pattern of fatigue was not apparent. Patients reported moderate levels of disruption in activities of daily living, with those receiving CAF having greater disruption. There was no difference among treatment groups in reports of overall disruption in activities. These data on patient reported experiences with side effects of chemotherapy can be used to prepare patients for specific side effects of treatment and facilitate symptom management.

beta 1 Integrin-like immunoreactivity was localized in rat brain using a polyclonal antibody raised in rabbit against rat liver beta 1 integrin. One-dimensional immunoblotting of whole rat brain membranes indicated that this antiserum recognized a single molecular species at 116,000 M(r), indicative of rat beta 1 integrins. Specific staining of beta 1 integrin-like immunoreactivity was found in the vascular structures of the brain, including microvessels, the ventricular ependymal cells, and pia mater. The pineal gland stained densely, and diffuse staining was present throughout the gray matter of the brain. This diffuse staining had a patterned appearance in certain structures, such as the apical dendritic field of CA1 in hippocampus, and occasional labeling of astrocytes, verified by labeling with GFAP on adjacent sections, was noted.

We have been examining the role of protein synthesis in the development and maintenance of spontaneous bursting in the rat hippocampal slice. We used stimulus train induced bursting (STIB) as an in vitro model for epileptogenesis, to study the effects of 3 different protein synthesis inhibitors (cycloheximide, anisomycin, puromycin) on the development of bursting. We report here that none of these inhibitors blocked the induction of bursting, suggesting that protein synthesis is not essential for the development of electrically induced bursting. However, when established spontaneous bursting was examined in the presence of cycloheximide, the duration of the bursting phase was markedly reduced, suggesting that the maintenance of spontaneous bursting in the early hours requires ongoing protein synthesis.

Inherent in the consultation process is the ability to communicate effectively, yet little emphasis is placed on written communication through consultation notes. The art of writing a consultation note is learned primarily through trial and error or by master/apprentice relationships with senior practitioners. This paper reviews the types of consultations in which advanced practitioners are involved and presents a format for preparing a comprehensive consultation note.

During development of the corpus luteum (CL), the numbers of luteinizing hormone (LH) receptors increase. Cultured bovine luteal cells from developing and mature CL were used to examine the influence of progesterone (P4) on this receptor. CL were obtained from dairy cows during the early or middle phase of the estrous cycle. In early CL, the number of receptors per cell was increased by exogenous progesterone treatment but there was no effect on receptor numbers in cells from midcycle CL. Binding affinities did not change with respect to age or treatment. Forskolin elevated endogenous progesterone and also enlarged the receptor population. The action did not appear to be an unmasking of cryptic receptors since the effect was not seen in luteal particulates. Elevation of LH receptor numbers by progesterone in immature CL may be a form of intraluteal regulation contributing to the functional maturation of these steroidogenic cells.

Electroconvulsive shock-induced seizures elevate seizure thresholds in humans and interfere with kindling in animals; opioids may mediate the anticonvulsant mechanism. In a potential model of acute electroconvulsive shock in hippocampal slices, a high-intensity tetanus via the mossy fibers substantially delayed subsequent in vitro kindling through the Schaffer collaterals. Naloxone blocked this effect, implicating the opioid system in the antiepileptogenic properties of this model.

Information about chemotherapy side effects and the efficacy of self-care activities used to deal with these side effects is needed to direct nursing interventions for patients receiving chemotherapy. Using the self-care diary (SCD) developed for this study, a sample of 49 adult patients with cancer recorded their side effects, rated the severity of each side effect, and reported on the use and efficacy of self-care activities two days after treatment. Data were collected again five days after treatment to examine the test-retest reliability of the side effect severity component of the SCD. The most common side effect, experienced by 81% of the subjects, was fatigue. Other side effects reported by more than one-third of the subjects were sleeping difficulty, nausea, decreased appetite, and changes in taste or smell. The most frequently reported side effects received mean severity scores indicative of moderate severity. The most commonly used self-care activities were rated as providing some relief to moderate relief of individual side effects. None of the reported self-care activities received mean efficacy ratings that indicated complete side effect relief.

Diisopropyl phosphorofluoridate (DFP), an insecticide, is a potent anticholinesterase that binds essentially irreversibly to acetylcholinesterase, resulting in severe, acute neurologic pathology, and less severe, but longer-lasting, delayed neuropathy. We report here on the short-term effects of bath-applied DFP on extracellularly recorded responses from CA3 and CA1 of rat hippocampus. Exposure to 10 microM DFP evokes low amplitude, spontaneous bursts in CA3 generally within 10 minutes, and the bursting does not reverse with washing. The CA1 neuronal population usually bursts synchronously with CA3, but the population events are of low amplitude and sometimes not detectable, implying a differential sensitivity to DFP. These effects were partially blocked by the muscarinic antagonist atropine, while the cholinergic antagonist gallamine had little effect. Also, the reversible anticholinesterase physostigmine could, within temporal limits, protect slices from DFP's effects, implicating the cholinergic system as the probable mediator in the first stages of DFP-induced epileptogenesis.

Hippocampal slices, from which the entorhinal cortex had been removed, were exposed to artificial cerebrospinal fluid containing no magnesium (0-Mg ACSF) to elicit interictal bursts (IIBs) and electrographic seizures (EGSs). In 0-Mg ACSF, IIBs and EGSs occurred in both area CA1 and area CA3. The IIBs in CA3 led the IIBs in CA1 by several milliseconds. The epileptiform bursts occurring during the EGSs seemed to have the opposite relationship, with bursts in CA1 leading those in CA3 by several milliseconds. When the connections between CA1 and CA2-3 were cut, the IIBs ceased in CA1 and continued in CA3. To further characterize the local differences in epileptiform activity, totally separate minislices of area CA1 and area CA2-3 were prepared. In the CA2-3 minislices, a few EGSs occurred and thereafter only persistent IIBs prevailed. Conversely, in the CA1 minislices, many spontaneous EGSs occurred for long periods of time and no IIBs were seen. Periodic stimulation of the CA1 minislices triggered IIBs that suppressed the recurrent EGSs. In the hippocampal slice exposed to low magnesium, IIBs originate in CA2-3 and are propagated to CA1, where they can have a suppressant effect on EGSs. Furthermore, unlike IIBs, the bursts making up the EGSs seem to start in CA1 and invade CA2-3.

In rat hippocampal slices, low concentrations of (+/-) baclofen (0.1 to 1.5 microM) elicited spontaneous, rhythmic sharp waves (SRSWs). These low amplitude (0.1 to 0.3 mV) SRSWs were visible with high amplification in the extracellular recordings from the CA1, CA2, and CA3 regions and were roughly synchronous in all areas. SRSW amplitude increased and frequency decreased as baclofen concentration increased up to 1.5 microM, but SRSWs were suppressed at concentrations of 5 microM and higher. The amplitude of the SRSWs was greater in the strata radiatum and the lacunosum moleculare than in the stratum pyramidale. (-)-Baclofen was much more potent in eliciting SRSWs than (+)-baclofen. Low concentrations of baclofen also caused the extracellular excitatory postsynaptic potential in the stratum radiatum of CA3b evoked by stimulation of the Schaffer collaterals to broaden and develop a secondary peak. Slices pretreated with pertussis toxin required much higher concentrations of baclofen to elicit the SRSWs, indicating that the baclofen may be eliciting the SRSWs through a G protein-sensitive mechanism. Baclofen has both inhibitory and disinhibitory effects on neurons. The appearance of these spontaneous population events suggests that, at low concentrations, the disinhibitory effects may be more powerful than the inhibitory effects.

Five lighthorse mares were actively immunized against gonadotropin releasing hormone (GnRH) to determine the relative importance of this hypothalamic hormone in the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Five mares immunized against the conjugation protein served as controls. Mares were initially immunized in November and received secondary immunizations 4 wk later, and then at 6-wk intervals until ovariectomy in June. All mares immunized against GnRH exhibited an increase (p less than 0.01) in the binding of tritiated GnRH by plasma, an indication that antibodies against this hormone had been elicited. Concentrations of LH, FSH and progesterone in weekly blood samples were lower (p less than 0.05) in GnRH-immunized mares than in controls after approximately 4 mo of immunization. However, the LH concentrations were affected to a greater degree than were FSH concentrations. All five control mares exhibited normal cycles of estrus and diestrus in spring, whereas no GnRH-immunized mare exhibited cyclic displays of estrus up to ovariectomy. All mares were injected intravenously with a GnRH analog (which cross-reacted less than 0.1% with the anti-GnRH antibodies) in May, after all control mares had displayed normal estrous cycles, to characterize the response of LH and FSH in these mares; two days later, the mares were injected with GnRH. The LH response to the analog, which was assessed by net area under the curve, was lower (p less than 0.01) by approximately 99% in mares immunized against GnRH than in control mares. In contrast, the FSH response to the analog was similar for both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

When medical students of three universities, house surgeons, general practitioners, psychiatrists, and surgeons were asked in what order would they rank the importance of various subjects in the medical school education of a general practitioner, there is remarkable agreement regarding the first three. In all, 1402 respondents rank medicine, then pediatrics, then psychiatry as most important. There are differences which reflect cultural and curriculum diversity among the student groups. The majority of respondents believe psychiatry should occupy 11% or more of the curriculum.

Using 125I-HEAT, a specific alpha 1-adrenergic antagonist, we have autoradiographically localized alpha 1-adrenergic receptors in the normal and weaver mutant mouse. Highest levels of binding in both the normal and weaver mouse were seen in the dorsal thalamus, external plexiform layer of the olfactory bulb and intermediate layers of the frontoparietal cortex. These results essentially parallel those found in the rat, with some differences in the cortical pattern that are attributable to differences between the cytological organization in the two species. Reduced levels of binding in the agranular weaver cerebellum as compared to normals indicated that binding in the normal cerebellum was to receptors on granule cell dendrites.

The relationship between auditory stimulus rate and level of [14C]2-deoxyglucose (2-DG) uptake was examined using the 2-DG technique developed by Sokoloff as an indication of glucose uptake and neural activity. Conscious restrained albino rabbits were given one monaural tone either once per second or once per minute for 45 min, or served as unstimulated controls. Autoradiographs of the inferior colliculi from these animals were compared densitometrically. It was found that the rabbits stimulated once per second had markedly elevated levels of 2-DG uptake compared to both other groups: the rabbits stimulated once per minute and to unstimulated control rabbits. In addition, the inferior colliculus autoradiographs of the rabbits stimulated with pure tones showed a distinctive banding pattern in central nucleus different from that seen in control rabbits.

Bathing hippocampal slices in artificial cerebrospinal fluid without magnesium elicits repetitive, long ictal-like discharges termed ictaform events. The ictaform events are separated by interictal periods that are initially silent with no interictal bursts. Interictal bursts appear in the later part of the interictal periods and intensify just before the next ictaform event. The GABAB agonist, baclofen, entirely suppressed interictal bursts during the interictal periods and produced a dose-dependent prolongation of the interictal period. Conversely, in slices pretreated with pertussis toxin to reduce the GABAB neurotransmission, interictal bursts were greatly increased, often occupying the entire interictal period, although the total duration of the interictal periods was not affected. Pertussis toxin pretreatment also lengthened the ictaform events. These opposing effects of baclofen and pertussis toxin suggest that GABAB neuro-transmission is important in regulating both the occurrence of interictal bursts in the interictal period, as well as the duration of ictaform events in the low magnesium model of epileptiform activity.

The iontophoretic injection of Ca2+ ions into voltage-clamped, silent neurons of Aplysia californica results in a prolonged, triphasic current response. This response consists of: a tetraethylammonium-sensitive outward current during the injection; followed by an inward current 10-30 s after the end of the injection; and finally a long, slowly increasing outward current that lasts for several minutes before returning to baseline.

P-Nitroanisole O-demethylation by perfused rat liver based on the spectral properties of the product, p-nitrophenolate, was determined continuously. Rates of p-nitrophenol production in this system were sensitive to inhibition by CO. p-Nitrophenolate production by livers of normal animals was linear for up to 30 minutes; however, rates were only linear for 1 to 2 minutes followed by a steady decline in induced (6-fold) livers from phenobarbital-treated rats. Only a small portion (24%) of this steady decline could be accounted for by the formation of conjugation products. Additionally, infusion of p-nitrophenol (14 micronM) was not associated with a decline in rate. The decline in rate in induced livers was reversed by glucose, suggesting that an intimate relationship may exist between drug and carbohydrate metabolism in the intact liver. Alteration in rates of p-nitroanisole metabolism with various inducing agents of the mixed-function oxidation system (phenobarbital; ethanol) produced parallel changes in rates of hepatic lactate production, most likely reflecting the aciton of p-nitrophenol to uncouple oxidative phosphorylation. The data support the hypothesis that the decline in rate in p-nitroanisole O-demethylation in livers from phenobarbital-treated rats is due to reduced availability of NADPH for mixed-function oxidation.