Transplantation of mesenchymal stem cells genetically engineered to overexpress interleukin-10 promotes alternative inflammatory response in rat model of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause for long-term disability, yet the treatments available that improve outcomes after TBI limited. Neuroinflammatory responses are key contributors to determining patient outcomes after TBI. Transplantation of mesenchymal stem cells (MSCs), which release trophic and pro-repair cytokines, represents an effective strategy to reduce inflammation after TBI. One such pro-repair cytokine is interleukin-10 (IL-10), which reduces pro-inflammatory markers and trigger alternative inflammatory markers, such as CD163. In this study, we tested the therapeutic effects of MSCs that were engineered to overexpress IL-10 when transplanted into rats following TBI in the medial frontal cortex. METHODS: Thirty-six hours following TBI, rats were transplanted with MSCs and then assessed for 3 weeks on a battery of behavioral tests that measured motor and cognitive abilities. Histological evaluation was then done to measure the activation of the inflammatory response. Additionally, immunomodulatory effects were evaluated by immunohistochemistry and Western blot analyses. RESULTS: A significant improvement in fine motor function was observed in rats that received transplants of MSCs engineered to overexpress IL-10 (MSCs + IL-10) or MSCs alone compared to TBI + vehicle-treated rats. Although tissue spared was unchanged, anti-inflammatory effects were revealed by a reduction in the number of glial fibrillary acidic protein cells and CD86 cells in both TBI + MSCs + IL-10 and TBI + MSC groups compared to TBI + vehicle rats. Microglial activation was significantly increased in the TBI + MSC group when compared to the sham + vehicle group. Western blot data suggested a reduction in tumor necrosis factor-alpha in the TBI + MSCs + IL-10 group compared to TBI + MSC group. Immunomodulatory effects were demonstrated by a shift from classical inflammation expression (CD86) to an alternative inflammation state (CD163) in both treatments with MSCs and MSCs + IL-10. Furthermore, co-labeling of both CD86 and CD163 was detected in the same cells, suggesting a temporal change in macrophage expression. CONCLUSIONS: Overall, our findings suggest that transplantation of MSCs that were engineered to overexpress IL-10 can improve functional outcomes by providing a beneficial perilesion environment. This improvement may be explained by the shifting of macrophage expression to a more pro-repair state, thereby providing a possible new therapy for treating TBI.

Patient selection criteria and management guidelines for outpatient parenteral antibiotic therapy for native valve infective endocarditis.

Outpatient parenteral antibiotic therapy (OPAT) for infective endocarditis (IE) is being applied widely, despite the absence of controlled data that demonstrates that outcomes are equivalent to those with standard inpatient antibiotic therapy. We review existing OPAT guidelines, published data on the timing of complications from IE, and data on risk factors that can be used to predict complications. These data are used to propose more stringent criteria for patient selection and clinical management of OPAT for native valve IE. We recommend a conservative approach (inpatient or daily outpatient follow-up) during the critical phase (weeks 0-2 of treatment), when complications are most likely, and we recommend consideration of OPAT for the continuation phase (weeks 2-4 or 2-6 of treatment) when life-threatening complications are less likely.

Recurrent nonmenstrual toxic shock syndrome: clinical manifestations, diagnosis, and treatment.

We report 3 cases of recurrent nonmenstrual toxic shock syndrome (TSS) and review the clinical manifestations, diagnosis, and treatment. The primary sites of infection were the genital tract (in a patient who underwent cesarean delivery), the upper respiratory tract, and a breast abscess. In all 3 patients, the initial illness was not recognized to be TSS; only after development of recurrent illness with desquamation was this diagnosis entertained. Strains of Staphylococcus aureus that were isolated from 2 patients produced TSS toxin-1, whereas the third strain produced staphylococcal enterotoxin B. All 3 patients lacked antibody to the implicated toxins at the time of presentation with recurrent illness. Nonmenstrual TSS can occur in a variety of clinical settings and may be recurrent. The presence of desquamation during a febrile, multisystem illness could suggest this diagnosis and should prompt the clinician to obtain appropriate cultures for S. aureus.

Human immunodeficiency virus-specific and CD3-redirected cytotoxic T lymphocyte activity in the human female reproductive tract: lack of correlation between mucosa and peripheral blood.

CD8(+) T cell phenotype and function were assessed in the female reproductive tracts (FRTs) of 3 human immunodeficiency virus (HIV)-positive patients who had undergone hysterectomy. FRT cytotoxic T lymphocyte (CTL) lytic activity from 1 patient (patient 872) was detected by using CD3-dependent redirected-lysis assay and HIV-specific assay, concomitant with the presence of CD8(+) cells. In contrast, samples from the 2 other HIV-positive patients (patients 1356 and 1364), who also were asymptomatic for HIV-associated illnesses, demonstrated no CTL activity in any solid tissue tested by either assay, despite activity by autologous peripheral blood mononuclear cells (PBMC). This absence of CTL activity was correlated with a relative absence of CD8(+) cells in the FRT, whereas CD8(+) cells were present in PBMC. Thus, CTL activity in PBMC may fail to correlate with mucosal activity. The finding of CTL activity in the FRT of patient 872 represents the first description of CTL in upper and lower FRT tissues of an HIV-positive woman.

Analysis of intracytoplasmic sperm injection procedures related to delayed insemination and ejaculated, epididymal and testicular spermatozoa.

In all, 1210 treatment cycles were divided into three categories for retrospective analysis according to the period of delay between oocyte retrieval (occurring at a fixed time after human chorionic gonadotrophin) and intracytoplasmic sperm injection (ICSI) of <3 h, 3-5 h, >5 h (referred to as 'delayed ICSI'). Three stages from oocyte to the birth of a live baby were identified for statistical analysis, (i) fertilization (2PN zygotes), (ii) cleavage of 2PN zygotes, (iii) transferred embryo to live birth. Stages 1, 2 and 3 were analysed statistically for the three time periods. Chi-square analysis showed no significant effect of delayed ICSI on fertilization (chi(2) = 3.615, P = 0.65), and embryo transfer to birth (chi(2) = 1.840, P = 0.399). The effect on cleavage was significant (chi(2) = 9.625, P = 0.008). However, shorter incubation times produced results which were better than the traditional longer ones. The success rate at the cleavage stage was so high that the marginal advantage had very little effect on the overall process. This study of a substantial patient sample establishes that ICSI on a peri-ovulatory oocyte (<3 h after oocyte retrieval) does not compromise outcome parameters, and that longer periods of incubation (>5 h) do not offer a statistically significant advantage.

How to search for information on transcultural nursing and health subjects: Internet and CD-ROM resources.

With the proliferation of electronic resources available to search for subjects related to transcultural nursing and health, nurses must keep abreast of computer-based tools that enable them to quickly and efficiently obtain information on a variety of topics. This article provides suggestions for narrowing and focusing a search on transcultural nursing and related subjects using key terms indexed in the Cumulative Index to Nursing and Allied Health Literature, International Nursing Index, Medline, Index Medicus, and Psychological Abstracts/PsychLit. Information about accessing the Native American Resource Information Service, Education Resources Information Center, Infotrac/Expanded Academic Index, and Sociological Abstracts also is provided. In the article, selected examples of Internet sites of interest in transcultural nursing and health are identified with their universal resource locator, and they are annotated. Web sites for U.S. government agencies, organizations, and commercial groups that concern transcultural nursing and health are cited. Global transcultural health and nursing Internet resources also are included.

Transcultural perspectives in nursing administration.

Population demographics are reshaping the healthcare work force with respect to race, ethnicity, gender, national origin, sexual orientation, age, handicap, disability, and related factors as national sensitivity to various forms of diversity grows. Given the demographic trends, it is inevitable that nurse administrators will need skill in transcultural administration as they manage diversity and identify the cultural origins of conflict in the multicultural workplace. Culture influences the manner in which administrators, staff and patients perceive, identify, define and solve problems. In this article, the complex and interrelated factors that influence workplace diversity are examined.

A model for cultural change.

Using transcultural nursing administration concepts is essential for survival, growth, satisfaction, and achieving goals in the multicultural workplace. Here, a model for cultural change in diverse health care settings assesses strengths, community resources, and readiness for change.

Baclofen suppression of cocaine self-administration: demonstration using a discrete trials procedure.

We have previously reported that rats display a circadian pattern of cocaine self-administration if access to drug is limited to 10-min discrete trials that are separated by at least 20 min. In the present study, the pattern of cocaine intake (1.5 mg/kg per injection) was studied in two large groups of animals that were maintained on different 12-h light/dark cycles (3 a.m. to 3 p.m. versus 10 a.m. to 10 p.m.). Regardless of the time of light onset, a circadian pattern of cocaine self-administration was observed. Maximum cocaine intake occurred during the final 6 h of the dark period and was followed by a relative abstinence period during the light phase. This highly predictable pattern of drug taking behavior provided an opportunity to explore the effect of baclofen, a GABAB agonist, on the initiation of self-administration behavior. In two separate studies, acute treatment with baclofen (1.25-5.0 mg/kg) was shown to suppress cocaine intake for at least 4 h. Baclofen had no significant effect on responding for food reinforcement. Previous results have indicated that baclofen appears to reduce specifically the motivation to respond for cocaine. Together, these data suggest that baclofen should be considered as a possible pharmacotherapeutic agent in cocaine addiction.

Baclofen attenuates the reinforcing effects of cocaine in rats.

The effect of the GABAB agonist baclofen on cocaine self-administration in the rat was investigated. In the first experiment, rats trained to self-administer i.v. cocaine (1.5 mg/kg/inj) on a progressive ratio (PR) schedule were pretreated with various doses of baclofen (1.25, 2.5, or 5.0 mg/kg). Baclofen produced a dose-dependent decrease in the break points. In the second experiment, baclofen (2.5 mg/kg) was found to decrease significantly break points across a series of unit injection doses of cocaine (0.18, 0.37, 0.75, 1.5 mg/kg/inj). Baclofen produced only modest effects on food-reinforced responding even at the largest dose tested (5.0 mg/kg). These data suggest that baclofen may produce a specific attenuation of cocaine reinforcement. Baclofen produced no significant change in the rate of i.v. cocaine intake on a fixed ratio (FR 1) schedule. These data support a number of recent observations that rate of drug intake may be an insensitive measure of changes in the motivation to self-administer cocaine.

Research on excess deaths among American Indians and Alaska Natives: a critical review.

American Indians and Alaska Natives die younger and at higher rates proportionately than members of the general United States population. Causes of death among Native peoples in the U.S. have been the subject of numerous studies by health care professionals and social scientists. Many of these deaths are considered excess deaths, that is, deaths that occur statistically beyond the rate of incidence of the larger population. This paper examines 46 studies of excess deaths published within five years (1987 to 1993) and based on data gathered within ten years (1982 to 1992) and critiques the studies for methodology and context. Existing studies of excess death among Native peoples are limited by a lack of definitional clarity, ethnic misclassifications, lack of multidisciplinary and Native representation on research terms, superficial analysis of statistical findings, overrepresentation of data for some tribes and underrepresentation for others, bias for quantitative research methods and unbalanced prioritization.

Cultural perspectives on nursing in the 21st century.

By the year 2000, more than one fourth of the US population will consist of individuals from culturally diverse groups. Increasing numbers of international visitors and exchange students will use the US health care delivery system, and US nurses will engage in international interchanges with increasing frequency. To keep pace with these population and health care trends, US nurses will need to base their nursing care on a theoretically sound foundation that draws on knowledge from the physical, natural, and behavioral sciences, as well as on research-based theories from transcultural, cross-cultural, and international nursing. The purposes of this article are to (1) trace past, present, and future population trends among minority groups in the United States; (2) examine the ways in which transcultural nursing has provided a framework for meeting the health care needs of culturally diverse people; (3) identify current issues and trends in transcultural nursing; and (4) suggest ways in which nurses can prepare for the increasing numbers of culturally diverse individuals who are projected to need nursing care in the future.

Strategic planning: preparing for the twenty-first century.

If educational institutions for nursing are to survive these uncertain times and to experience new life in the advent of the 21st century, careful planning for the future must be undertaken. Strategic planning, a relatively new term in nursing education, is a concept designed to achieve goals in dynamic, competitive environments through the judicious allocation of resources. The primary purpose of strategic planning is to achieve success with mission while linking the institution's future to anticipated changes in the environment. Strategic planning enables an institution to function in such a manner that the acquisition of resources exceeds their depletion. The purposes of this article are to (1) provide an overview of the strategic planning process and (2) describe the strategic planning experience of one private, liberal arts college in a midwestern state. Although the case example focuses on a liberal arts college, the strategic planning process is applicable to other types of educational settings.

The effects of fructose 1,6-diphosphate, caffeine and dantrolene sodium on suxamethonium-induced contractures in denervated rat skeletal muscle.

Previously unidentified forms of suxamethonium-induced contractures have been investigated in chronically denervated rat extensor digitorum longus (EDL) muscle at 20 degrees C. Contractures were assigned to groups 1-6 on the basis of the peak tension (Tp1) during 0-10 min exposure to the drug (3.0 x 10(-5) M), (7.0 x 10(-6) M), and (3.5 x 10(-6) M) and the subsequent retention, increase, or decrease in tension (Tp2), during the further 10 min. It is proposed that four stages exist in the development of contractile changes at 1-7, 8-35, 36-70 and 70-130 days after denervation (DPD) and that contractility is lost at 147 days after denervation. Initial changes, although present in EDL muscles in group 1 at 2.0 DPD s.d. +/- 1 (n = 7) in response to the drug (3.0 x 10(-5) M), were more apparent in EDL muscles in group 2 which were identified at 5.5 DPD s.d. +/- 1.6 (n = 7) by an excessive contracture response (Tp2) to the drug (3.0 x 10(-5) M), 18.3 mN s.d. +/- 10.6. At 5.0 DPD s.d. +/- 2.7 (n = 5) contracture tension (Tp2) was commensurate with membrane depolarization, 13.1 mN/33.1 mV, but residual tension increased to 23.3 mN during the Krebs wash (80 min) whilst membrane depolarization decreased to 9.2 mV. Also, at 4.3 DPD s.d. +/- 2.3 (n = 5) tension (Tp2) increased significantly (P less than or equal to 0.05) in the presence of caffeine (4.1 x 10(-3) M).(ABSTRACT TRUNCATED AT 250 WORDS)