Aliskiren is a non-peptide, orally active renin inhibitor with poor absorption and low bioavailability (~2.6%). In order to improve the current drug delivery system, a commercially available, biodegradable copolymer, poly(lactide-co-glycolide) (PLGA), was employed for a nanoparticle (NP) reformulation of aliskiren. An emulsion-diffusion-evaporation technique was implemented where aliskiren and PLGA were dissolved in dichloromethane, ethyl acetate, or ethyl acetate/acetone. To an aqueous phase containing 0.25% w/v didodecyldimethylammonium bromide (DMAB) as stabilizer, the previously prepared organic phase was added drop-wise. Following sonication, NP diffusion was expedited with the addition of water, and the organic phase was evaporated to form a suspension. Centrifugation was performed at 10,000 rpm, and the supernatant was analyzed for drug entrapment efficiency via ultraviolet-visible spectroscopy as well as particle morphology with the use of a transmission electron microscope (TEM). Having the highest entrapment efficiency (82.68 ± 1.18 %), ethyl acetate was used as the organic solvent in further testing, such as examining the effects of variation in DMAB stabilizer concentration (0.10, 0.25, 0.50, or 1.00% w/v) and centrifugation speed (10,000 or 12,000 rpm). The optimum formulation was ascertained through observing certain NP characteristics, such as entrapment efficiency particle size, zeta potential, and polydispersity index (PDI). A NICOMP Particle Sizer was used to measure particle size, zeta potential, and PDI. The smallest NP size (67.27 ± 0.87 nm) was accomplished with 0.50% w/v DMAB concentration using a centrifugation speed of 12,000 rpm, while the highest zeta potential (18.73 ± 0.03 mV) was detected with the 1.00% w/v DMAB concentration and a 10,000 rpm centrifugation speed. Further, the best entrapment efficiency and PDI (82.68 ± 1.18 % and 0.15 ± 0.03, respectively) were accomplished with 0.25% w/v DMAB and centrifugation at 10,000 rpm. The most favorable formulation yielding the highest zeta potential (18.73 ± 0.03 mV) was observed when DMAB stabilizer was 1.00% w/v and centrifuged at 10,000 rpm. Particle size and entrapment efficiency for this formulation were 75.67 ± 0.89 nm and 71.62 ± 0.11 %, respectively.

Nurses' ability to recognize and respond to postoperative patients who require emergent medical care and need immediate assistance during a code blue in the first 10 minutes is essential to improve patient outcomes. This is particularly important for the project site, a 44-bed inpatient surgical specialty hospital located in the Northeast, providing care for patients with head and neck cancer, as the hospital does not have an internal code blue response team. An adjacent facility responds to all code blue emergencies and takes approximately 10 minutes for the team to respond. The purpose of this DNP project was to develop an evidence based, theory supported educational effort using a rapid response in-situ simulation program with 2 simulation scenarios specific to the patient population. As a first step in the DNP project, 2 simulation scenarios were developed and then evaluated by a panel of 4 expert nurse educators using a modified National League of Nursing/Jeffries Simulation Design Scale. The qualitative evaluation the expert nurse educators provided strengthened the simulation design for each simulation scenario. The revised simulation scenarios, respiratory distress/pulseless electrical activity, and the postoperative patient with unstable hemodynamics, as part of the education rapid response in-situ simulation program, have the potential to improve the nurse's ability to recognize early warning signs of respiratory distress and hemodynamic instability from postoperative complications. The simulation program has the potential for positive social change by empowering the nurses to provide quality patient care and improve patient outcomes during a code blue event.

Q fever, as a recognized clinical entity, is often referred to as a new disease of man. Pneumonic in character but lacking clean-cut pathognomic characteristics, in all probability Q fever has been confused in the past with influenza, primary atypical pneumonia (1), or included as an undifferentiated disease under "virus pneumonia." Geddis Smith (2), writing in 1941, stated: ••• influenza, pneumonia, "pleurisy", or bronchitis • • • form a nosological jungle in which bacteria and viruses roam at will, despoiling the human race and defying both classification and control. Symptoms overlap and no one knows how many different diseases lurk behind them..

Secondary polycythemia is defined as an absolute erythrocytosis caused by an enhanced stimulation of red blood cell production. One of the most common methods of monitoring the degree of polycythemia is the measurement of the hematocrit. The hematocrit is the measurement of the volume of red blood cells.expressed as a percentage of the volume of whole blood in a sample. This measurement is usually done using one of two methods: (1) the Coulter Model S® or (2) the centrifuged micro-hematocrit method. However, we have noted a significant difference in the hematocrit values determined by these two methods when the hematocrits exceed 54 percent. As many as 10 hematocrit units of difference have been reported (1 hematocrit unit = ml of packed erythrocytes/100 ml of whole blood). Several questions arise: (1) does this variation in hematocrit (hct) values increase in proportion to the increase in hematocrit; (2) is there a relationship between the fibrinogen level and the amount of trapped plasma in the centrifuged micro-hct; (3) is there a relationship between the red blood cell count (RBC), mean corpuscular volume (MCV), and whole blood viscosity; (4) which measurement is a better indicator of the degree of polycythemia and the increase in viscosity. To answer these questions data from the Coulter Model S®: centrifuged micro-hct, whole blood viscosity and fibrinogen determination were evaluated. With these data it was planned to determine if it would be possible (1) to construct a nomogram establishing the relationship between the micro-hat and Coulter S® hct greater than 50 percent for the conversion of one value to the other, and (2) to assess the degree of polycythemia and the need for phlebotomy by the use of each measurement.

This was a study of detection systems for DQ alpha HLA polymorphism that could be exploited for the demonstration of simulated chimerism. Polymorphic segments of DO alpha DNA were amplified by the polymerase chain reaction (PCR). Simulated chimerism was represented by a mixture of minor and major component DNA. The goal was to detect minor component DNA in the presence of major component DNA utilizing various laboratory techniques. Techniques studied included probe strip typing with the AmpliType HLA-DO Alpha test kit, allele-specific amplification, polyacrylamide gel electrophoresis, restriction enzymes, and Southern transfer combined with a peroxidase detection system. The AmpliType HLA-DO Alpha test kit had a detection sensitivity of at least 0.2%. This is much better than the 10% detection sensitivity in non-PCR techniques. When the 3.0 DC alpha type was mixed as the minor component with undiluted 1.1 DQ alpha type, the detection sensitivity for the 3.0 DC alpha type increased to a detection level of 0.1%. The allele-specific primers were able to specifically amplify the minor component DNA in the presence of major component DNA. Major component DNA did not amplify and thus did not compete with the minor component DNA for Taq polymerase. The allele-specific primers provided an overall detection sensitivity of 0.2%. Background interference prevented detection of minor component bands on both polyacrylamide gels stained with ethidium bromide and on Southern blots reacted with the peroxidase detection system.

The immune system is critical for the maintenance of homeostasis. Due to the fact that a coordinated effort between organ systems is required for internal stability, it has been postulated that the immune system interacts with the neuroendocrine system. Clinical, anatomical, and receptor studies have provided evidence for a bi-directional communication between the nervous and immune systems. The goal of the present studies was to determine the potential influence of the sympathetic nervous system (SNS) on the primary antibody forming cell (AFC) response. The adrenergic neurotoxin, 6-hydroxydopamine (6-OHDA), has been utilized extensively by researchers to explore the possible relationship between SNS and the antibody response. However, the literature describing the humoral effects observed following 6-OHDA treatment is irresolute. In an attempt to provide insight into these apparent discrepancies, studies were conducted comparing the effects of 6-OHDA and its non-neurotoxic congener, 5-hydroxydopamine (5-OHDA). Both chemicals, when added directly into cultures containing naive splenocytes, suppressed the in vitro AFC response. Analysis following in vivo treatment with 6-OHDA or 5-OHDA revealed that while both chemical treatments resulted in suppression of the AFC response following in viva sensitization, only the splenocytes from 6-OHDA treated mice were suppressed when subsequently sensitized in vitro. Pretreatment with desmethylimipramine (DMI) blocked the observed 6-OHDA- and 5-OHDA-induced immunosuppression displayed in vivo, indicating that the uptake of the chemicals into adrenergic neurons was required. As an alternative method for removing the sympathetic influence in the spleen, studies were conducted with chlorisondamine, a non-competitive ganglionic blocker. While direct addition of chlorisondamine was without effect in the in vitro-in vitro AFC response, the in viva AFC response following chlorisondamine treatment was significantly suppressed. In addition to the suppression of the primary AFC response, 6-OHDA and chlorisondamine treatment resulted in a time dependent increase in the level of DNA fragmentation in the thymus. Analysis of serum corticosterone levels in 6-OHDA- and chlorisondamine-treated mice revealed that both treatments elevated levels of serum corticosterone. Given the potential role of corticosterone in the 6-OHDA- and chlorisondamine-induced immunosuppression, studies were conducted to determine if the glucocorticoid receptor antagonist, RU-486, was able to block the DNA fragmentation in the thymus and the suppression of the AFC response demonstrated after 6-OHDA or chlorisondamine treatment. While RU-486 was effective at blocking the 6-OHDA- and chlorisondamine-induced thymic effects, it was unable to block the suppression of the primary AFC response. Collectively, these studies reveal that removal of the peripheral SNS by either sympathectomy with 6-OHDA or ganglionic blockade with chlorisondamine can result in 1) thymic alterations which are mediated by increased levels of corticosterone and 2) suppression of the primary AFC response which is independent of the elevated corticosterone levels. Importantly, these results provide evidence for positive modulation of the humoral immune response by the sympathetic nervous system.

Two enzymes, a 7α-hydroxysteroid dehydrogenase (7α-HSDH) and an NADH-dependent flavin oxidoreductase (NADH:FOR), have been purified to apparent electrophoretic homogeneity from the intestinal anaerobe Eubacterium sp. VPI 12708. Using a protocol consisting of four chromatographic separations, the 7α-HSDH was purified by a factor of over 1200-fold with more than a 30% final recovery. Subunit molecular mass was estimated to be 32 Kdal by SDS-PAGE, while native molecular mass estimates from gel filtration were 124 Kdal. The purified 7α-HSDH was able to utilize a variety of bile acids containing an unhindered 7α-hydroxy moiety as substrates, existing either as free acids or glycine or taurine conjugates. The presence of an oxo moiety at position 3 or 12 profoundly altered the kinetic values for this enzyme. The structural gene for the 7α-HSDH was cloned on a 3.8 Kb Kpnl-Pstl fragment and was sequenced using the dideoxy chain termination method. An open reading frame of 798 bp encoding a 266 amino acid protein was detected. The N terminal amino acid sequence of the purified protein was identical to the first 22 amino acids predicted from the open reading frame. Putative transcriptional promotor and terminator regions along with a tentative ribosome binding site were also located. Northern blot analysis indicated that this protein was expressed constitutively on an approximately 1 Kb monocistronic message. During sequence analysis, the 7α-HSDH was found to be highly homologous to several members of the short-chain, non-zinc alcohol/polyol dehydrogenase superfamily. Using a five step protocol, the NADH:FOR was also purified to homogeneity. A final purification of greater than 5OO-fold with an 11 % recovery was obtained. The purified protein had a subunit molecular mass of 72 Kdal and a native mass of 210 Kdal, suggesting that it exists either as a dimer or a trimer. Northern blot, Western blot, and activity stains of native gels all indicated that the NADH:FOR is a cholate-inducible protein. N-terminal amino acid sequence determination revealed a significant homology to enoate reductase from Clostridium kluyveri. Since the enoate reductase is involved in the reduction of a variety of α/β unsaturated carboxylates, this homology may be indicative of the physiological function of the NADH:FOR in Eu. sp VPI 12708.

The problem to be investigated is: What are the emotional needs of patients, who are approaching death, as revealed by the patients themselves? The review of literature pointed out that almost all the data published about the dying patient were the thoughts of those around him rather than his own thoughts. Since the patient is our concern, it would seem logical to ask him what his needs are. Nurses recognize as one of their responsibilities of assisting a patient toward a peaceful death when curative goals are beyond grasp. If the patient dies and his needs are not met, or his distress unrelieved, how could his death be peaceful? The investigator feels that one way by which death could be made more peaceful is by ascertaining the patient's emotional needs and trying to meet them.

Understanding volition and preferences for occupation is a critical underpinning of effective occupational therapy services that promote and preserve identity for persons with moderate dementia. Although it has been posited that this population has significant difficulty expressing volition for daily occupations, little research has examined the role of volition in guiding engagement in occupations. This phenomenological study provides an in-depth description and analysis of volition in eight persons with moderate dementia. Guiding questions related to understanding patterns of past life interests, outward demonstration of volition, volitional continuity. and the relationship of the social environment to volition and engagement in daily occupations, were used. Maximum variation sampling was used to recruit from one memory-support assisted living in a Midwestern continuing care retirement community. Participants were enrolled sequentially over an 11-month period. Participant observation and interviews of family and staff were the main data collection methods. The Volitional Questionnaire (VQ) was used to gain additional data about participants’ volition, and the Mini-Mental Status Exam (MMSE) provided a general indicator of cognitive impairment. Data analysis used van Manen’s phenomenological approach to uncover the phenomenon of volition. Three major themes emerged, and had a dynamic interaction: a) variation in volitional expression in the areas of interests, values, and personal causation, b) redefining meaningful occupation, reflected in four categories, and c) potency of the social environment, highlighting the pervasive influence of other people on participants’ volition. Participants’ lived experience of volition reflected the importance of the dynamic between the social environment and the person.The findings of this study support the importance of assessing volition for individuals in the context of their social world in order to maximize function and minimize excess disability. Further research is needed to address caregivers’ perceptions about volition, as well as examining the use of the VQ and specific intervention strategies that target volition.

This research investigated market and organizational factors that influence the strategic decisions of teaching hospitals to participate in strategic hospital alliances (SHAs). It described the characteristics of both teaching hospitals and the health care environment in which they operate. This research also examines the association of these factors with the strategic position of teaching hospitals in terms of their dominance in the market or within their organizations. The theoretical model used two concepts from institutional theory--coercive and normative pressures. It was argued that coercive pressures in the market facilitated the decision to participate in SHAs and gain market and Organizational dominant positions. Alternatively, normative organizational pressures were argued to hinder the process of participating in SRAs and gaining market and organizational dominance. An important finding of this research was that high levels of SRA penetration had a negative influence on all three dependent variables , SRA participation, market dominance, and organizational dominance. This finding suggests that as market consolidation advances, teaching hospitals may find it difficult to participate in SRAs or gain positions of dominance. In addition to the SRA penetration measure there were a number of other relationships of interest. SRA participation was related to the percent of large employers in the market and the teaching hospital's net revenue . Market dominance was related to the percent of large group practices and the percent of primary care physicians in the market as well as the profit status of the teaching hospital. Organizational dominance was related to the profit status and the administrative structure of the teaching hospital.