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Adherence to CPR guidelines during perioperative cardiac arrest in a developing country.

UNLABELLED: BACKGROUND AND GOAL OF STUDY: Cardiopulmonary resuscitation (CPR) is an integral part of anaesthetic training. In Nigeria, these skills are taught mainly during medical school and postgraduate training. International guidelines were introduced in 2000 and new guidelines were produced in November 2005. The study sought to assess how closely anaesthetists in a Nigerian teaching hospital abide by the 2000 guidelines. MATERIALS AND METHODS: All perioperative cardiac arrests in adults that occurred in a 1-year-period were studied prospectively. All patients <15 years and cardiac arrests occurring outside the direct supervision of the anaesthetists were excluded. Time and duration of arrest, cardiac arrest rhythm and management were documented along with immediate outcome. RESULTS: Thirteen cardiac arrests occurred in 2147 perioperative cases (incidence: 6/1000). Seven patients had non ventricular fibrillation/pulseless ventricular tachycardia (VF/VT) rhythms. The mean age of patients was 30.23+/-11.06 years. Orotracheal intubation, manual ventilation with 100% O(2) and external chest compressions were instituted in all cases. The mean duration of arrest was 25.66+/-13.34 min. All patients received adrenaline (epinephrine) and atropine. The median interval between adrenaline doses was 7.5 min. Only one cycle of defibrillation was given to patients in VF/VT. Immediate survival occurred in five patients (38.46%). CONCLUSION: Anaesthetists in our hospital are not applying proper resuscitation guidelines. The lack of organised simulation practice resulted in deficient knowledge and skills. There is a need for continuing training in basic and advanced resuscitation for all anaesthetists according to the guidelines.

Adrenergic Agonists↗

Effects of cyclosporine A and methotrexate on CD18 expression in recipients of rat cardiac allografts.

Recent advances in the study of the molecular basis of inflammation suggest that cell-cell interactions mediated by specific adhesion molecules could be new targets for immunosuppression. Methotrexate (MTX)-treated cells in vitro have demonstrated decreased neutrophil-endothelial cell adhesion associated with increased release of adenosine from endothelial cells, while the direct role of cyclosporine A (CSA) in the regulation of cell adhesion molecule (CAM) expression is less well-defined. Since the adhesion of leucocytes to endothelial cells via CAMs is necessary for leucocyte extravasation and infiltration into graft tissue during allograft rejection, these studies have addressed the hypothesis that MTX treatment of cardiac transplant recipients may affect cellular adherence by downregulating cell adhesion molecule expression. Using a vascularized method of rat cardiac transplantation, our studies have previously demonstrated that low doses of the immunosuppressive agents CSA and MTX, when used in combination, significantly increase allograft survival. According to reverse transcriptase-polymerase chain reaction (RT-PCR) methodology to measure changes in steady-state CD18 mRNA levels, and immunohistochemistry to assess transplant CD18 protein levels in situ, both CD18 transcript and protein levels were significantly increased in untreated allografts when compared to isograft tissues on days 3 through to 7 post-transplant. Whereas, both low-dose CSA alone and low-dose MTX alone treatment resulted in similar levels of graft leucocyte infiltration, MTX-treated recipients demonstrated lower levels of CD18 expression when compared to low-dose CSA alone treatment. The results of immunohistochemical staining for T cells, where significantly fewer T cells were observed in rat cardiac allografts after low-dose MTX treatment alone compared to low-dose CSA treatment, were noteworthy. Results of these studies indicate that CD18 expression and infiltrating T cell numbers in Brown Norway (BN) to Lewis (Lew) rat cardiac allografts are significantly diminished with low-dose MTX treatment. The immunosuppressive effects of MTX, therefore, may be related to its ability to interfere with an early step during the cell-mediated immune response, namely the firm binding or 'adhesion' of leucocytes to the endothelium during transendothelial migration.

Animals↗

Oral appliance therapy for obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive, complete or partial closure of the upper airway during sleep, resulting in sleep fragmentation and oxygen desaturation. The disorder causes significant morbidity, particularly in terms of impairment of daytime functioning and the impact this has on quality of life. There is also evidence that links OSA to long-term cardiovascular morbidity, including hypertension, myocardial infarction, and stroke, and increased risk of motor vehicle accidents. There is clear evidence that effective treatment of OSA provides major benefit to patients. Nasal continuous positive airway pressure (CPAP) is the current treatment of choice, but its cumbersome nature makes tolerance and compliance less than optimal. This gives rise to the need for other alternatives that are equally effective, but more tolerable. There is growing interest in the use of oral appliances to treat snoring and OSA. The rationale is that advancement of the mandible and tongue impacts positively on upper airway caliber and function. There are many such types of appliances, and they have potential advantages over CPAP in that they are unobtrusive, make no noise, do not need a power source, and are potentially less costly. There is a growing evidence base to support the use of oral appliances in the management of OSA. Recent evidence from randomized controlled trials indicates that oral appliance therapy is effective in controlling OSA in up to 50% of patients, including some patients with more severe forms of OSA. This is associated with a significant improvement in symptoms, including snoring and daytime sleepiness. This evidence is strong for short term, and emerging for long-term treatment of OSA with oral appliances. Whilst direct comparisons with CPAP indicate the superiority of CPAP overall, similar outcomes between the two treatments appear to be achieved in a substantial subgroup of patients. Patient acceptance has, in general, been in favor of oral appliances. Notwithstanding the expanding role of oral appliance therapy, there are a number of limitations that are yet to be overcome. Key issues include the inability to reliably predict treatment outcome, the apparent need for an acclimatization period to attain maximal efficacy of treatment, uncertainty about selection of the appropriate 'dosage' of mandibular advancement required to control OSA in the individual patient, uncertainty about the influence of appliance design on treatment outcome and adverse effects, adherence to treatment, and potential long-term complications of therapy. These issues require resolution before oral appliance therapy can surpass CPAP as first-line treatment for OSA.

Continuous Positive Airway Pressure↗

Locomotory invasion of human cervical epithelium and avian fibroblasts by HeLa cells in vitro.

The locomotory invasive ability of HeLa cells was tested against: (a) embryonic chick heart fibroblasts (CHF); and (b) normal epithelial cells from human cervix (HCE) in explant confrontations. Data for analyses were obtained from replicate cultures fixed 24 h after junction and from 24-h time-lapse films. The mean invasion index for HeLa versus CHF did not indicate significant obstruction but analyses of hourly radial advance and orientation frequencies showed that obstruction eventually developed as postjunctional incubation time increased. Early contacts between HeLa and CHF demonstrated non-reciprocity of type I contact inhibition of locomotion by the tumour cells, which continued moving in their original direction to underlap contact-inhibited fibroblasts and eventually to occupy spaces vacated by them. When CHF population density increased and free space diminished, HeLa cells displayed directional and probably substrate-dependent contact inhibition. The high invasion index of HeLa versus HCE was largely due to occupation of previous HCE territory by tumour cells and only occasionally to actual infiltration of the epithelial sheet. After contact with HeLa, ruffling substrate-adherent marginal epithelial cells displayed contractile, type I contact inhibition of locomotion. After orientation changes, they gradually retreated. Against HCE, HeLa cells exhibited non-reciprocity of type I contact inhibition and continued radially forward, following the retreating epithelial margin. They did not move onto exposed upper surfaces of epithelial cells and did not underlap marginal cells firmly adherent to the substratum. Invasion of the epithelial sheet was seen only when initial access beneath a cell with a non-adherent margin was available. The contact relationships of isolated invading HeLa cells with their epithelial neighbours suggested successive non-reciprocal contact inhibition reactions.

Animals↗

Viral safety of clotting factor concentrates.

The efforts to reduce the risk of viral disease due to clotting factor concentrates have been quite successful. However, additional steps need to be taken to protect the users of these products. First, all patients should be vaccinated against hepatitis B. Second, vaccines against other viruses need to be developed. There is a great deal of interest in an HIV vaccine, and a vaccine against hepatitis C would also be a great boon to the "at risk" population. Third, more effective inactivation procedures need to be implemented in the manufacturing of concentrates other than Factor VIII, including Factor IX Complex, Coagulation Factor IX (Human), and Anti-Inhibitor Coagulant Complex. Despite the advances that have been made, it should be remembered that none of these procedures is perfect and the risk will never be reduced to zero. This is because the plasma pools will always contain infectious virus and the manufacturing process, regardless of how carefully controlled, cannot be made fail-safe. Errors will be made that result in contamination or inadequate treatment of products. For this reason, strict adherence to standard operating procedures and good manufacturing practices is essential. The investments of time, money, and hard work that have been made toward improving the safety of clotting factor concentrates have yielded a handsome return thus far. It is hoped that continued efforts in this direction will result in even greater benefits.

Blood Coagulation Factors↗

Prevention interventions with persons living with HIV/AIDS: state of the science and future directions.

The National Institutes of Health (NIH/NIMH), the Centers for Disease Control and Prevention (CDC), and the HIV/AIDS Bureau of the Health Resources and Services Administration (HRSA) support the CDC's Serostatus Approach to Fighting the HIV Epidemic (SAFE; Janssen et al., 2001). One aim of the strategy is to help individuals living with HIV (and their partners) adopt and sustain HIV and STD risk reduction, treatment adherence, and effective strategies for coping with HIV/AIDS. Efficacious interventions are needed by community organizations and clinics that provide evidence-based services. To expedite translation from research to practice, we convened scientist-practitioners, HIV treatment and prevention providers, and community/consumer members. In this article, we include an overview of prevention trials with HIV-positive persons presented at the meeting, discuss strengths and limitations, recommendations for future research, and discuss sponsoring agencies' plans for advancing prevention tailored for persons living with HIV.

Centers for Disease Control and Prevention, U.S.↗

Abnormal neutrophil chemotaxis in Gaucher disease.

The tendency towards infection described in Gaucher disease patients has been attributed to their post-splenectomy state. We noticed that certain patients with intact spleen have also suffered from recurrent pyogenic infections, thus an attempt to study their neutrophil function has been made. Nine of 29 patients studied expressed significant decrease in neutrophil chemotaxis directed towards zymosan activated serum or N-formyl-methionyl-leucyl-phenylalanine. Random migration was significantly impaired in five of those nine patients. Adherence of neutrophils to nylon fibres and O2- production were intact. The patients with impaired chemotaxis were significantly afflicted by their disease (early onset of symptoms and severity score index > 10) and most of them had genotypes associated with severe disease (1448/1448 and 1226/84GG). No correlation was found with the spleen status. Three of the patients with impaired chemotaxis, and none of the patients with normal neutrophil function, suffered from recurrent pyogenic infections. It is suggested that the described neutrophil migration impairment may contribute to the tendency towards infection in certain patients with advanced Gaucher disease.

Adolescent↗

Tuberculosis in patients with human immunodeficiency virus infection.

Tuberculosis (TB) is the major opportunistic infection of human immunodeficiency virus (HIV)-infected persons worldwide. Human immunodeficiency virus infection is the most potent known risk factor for reactivation of latent Mycobacterium tuberculosis infection, and TB disease appears to increase the rate of HIV progression. Pulmonary disease is seen in most patients, including a large proportion of those with extrapulmonary disease. Failure to suspect TB and to order the appropriate diagnostic tests is the most common reason for diagnostic delays. With advancing HIV infection, tuberculin skin test reactivity decreases along with reactivity to nonspecific antigens such as mumps, tetanus toxoid, and Candida; anergy testing need not be a routine component of tuberculosis screening of HIV-infected persons. The diagnosis depends on identifying the organism on smears or cultures; direct amplification tests may facilitate rapid identification of M. tuberculosis, but the relatively low sensitivity in smear-negative specimens limits their use. Also, these tests must be used in conjunction with the clinical assessment, and they must always be performed in conjunction with microscopy and standard culture. Shorter courses of combination preventive therapy of patients with latent tuberculous infection are effective, but the potential advantages of improved adherence and reduced costs of shorter courses should be balanced with an increased risk secondary to ongoing TB exposure in areas with a high TB prevalence. Six months of treatment for active tuberculosis is recommended, unless the response of a particular patient is slow or otherwise suboptimal. The use of highly active antiretroviral therapy (HAART) made a remarkable impact on the course or HIV disease, but raises several issues with respect to HIV-related TB. Drug interactions necessitate either a non-rifamycin-based regimen or a rifabutin-based regimen in patients on HAART treated for TB.

AIDS-Related Opportunistic Infections↗

An ethical analysis of exception from informed consent regulations.

Federal regulations enacted in 1996 allow clinical research with an exception from informed consent in select emergency circumstances. Such research is only permitted when the therapy may directly benefit the research participant and it is not possible to conduct the research with informed consent. Among others, protective mechanisms include a process of community consultation and public disclosure and the establishment of a mandatory data safety monitoring board. Although the regulations do not preserve the right of self-determination of the research participant, the author argues that they do provide an ethical means to advance the science of resuscitation.

Beneficence↗

The role of oral direct thrombin inhibitors in the treatment of venous thromboembolism.

Unfractionated heparin and warfarin have been the mainstay of treatment of venous thromboembolism (VTE) for approximately half a century. However, both agents are difficult to dose accurately, require frequent blood testing and dosage adjustment, and can cause serious adverse effects. Oral direct thrombin inhibitors may provide more predictable anticoagulation with oral dosing, without the need for frequent blood test monitoring and without the adverse effects seen with conventional agents. The oral direct thrombin inhibitor closest to being marketed is ximelagatran, which has been through phase III trials. Available data thus far suggest that the efficacy and safety of this agent may allow it to replace both heparin (and low-molecular-weight heparin) and warfarin for VTE treatment and long-term prophylaxis. Concerns about ximelagatran that require further study are a 5-9% rate of transient elevation in liver enzyme levels, drug interactions, how patient adherence can be ensured in the absence of blood tests, and whether alterations in renal or hepatic function will require dosage adjustments. Although there is more to learn about ximelagatran, available data suggest that it is likely to be the most significant therapeutic advance in this area in over 50 years.

Administration, Oral↗

Evaluations of blood compatibility via protein adsorption treatment of the vascular scaffold surfaces fabricated with polylactide and surface-modified expanded polytetrafluoroethylene for tissue engineering applications.

Blood compatibility was evaluated by short-term in vitro blood perfusion on candidate vascular scaffold surfaces of a biodegradable, porous polylactide scaffold and a chemically surface-modified expanded polytetrafluoroethylene (ePTFE) over a clinical ePTFE, by measuring blood cell adhesion either directly or after adsorption treatment with albumin and fibrinogen. The results indicated that the extent of blood cell adhesion was affected by scaffold surface properties and pre-adsorption of proteins such as fibrinogen and albumin. Surface morphologies and porosity of the scaffolds were characterized by scanning electron microscopy and porosimetry, and the amount of fibrinogen and albumin adsorbed on the scaffolds was measured and verified by employing radiolabeled C(14) albumin and I(125) fibrinogen by a scintillation counter and a gamma counter, respectively. Even though treatment of fibrinogen adsorption on the samples in advance led to higher induction of blood cell adhesion than those with no fibrinogen adsorption, the polylactide scaffold surface itself induced highest amount of the adhered blood cells in this study judged by analyses of their surface area. These results would be employed as guidance in determining a choice of the implant methods, in vitro versus in vivo tissue engineering, of the novel chemically modified ePTFE and the biodegradable polylactide scaffolds.

Adsorption↗

Monoclonal antibody production by receptor-mediated electrically induced cell fusion.

Fusion of myeloma cells and B lymphocytes to form hybridomas which produce monoclonal antibodies has been a major advance, but the poor efficiency and randomness of viral or polyethylene glycol fusion techniques generally gives poor yields of specific, high affinity antibodies. High voltage electrical fields with dielectrophoresis to ensure cell alignment can fuse a limited number of cells under direct microscopic examination, but it is not possible to identify B-cells destined to secrete relevant antibodies. However, B-cells express, on their surface, antigen receptor immunoglobulins of the same antigenic specificity as the secreted antibodies. Binding of antigen to surface immunoglobulins stimulates proliferation and differentiation of B-cells into plasma cells. Here we report the use of the selective, high affinity interaction of antigen with surface immunoglobulins on B-cells to facilitate a close adherence to myeloma cells. The antigen, covalently conjugated to avidin, binds to the surface immunoglobulins on B-cells. This B-cell-antigen-avidin complex binds to biotin covalently attached to the surface of myeloma cells. An intense electric field across a bulk cell suspension then produces selective fusion of cells in contact, that is, of myeloma cells with B-cells which make the appropriate antibody. We have used this technique with several antigens, and all resultant hybridomas secrete appropriate antibodies with very high affinity.

Animals↗

Psychopharmacologic treatment strategies for depression, bipolar disorder, and schizophrenia.

Patients with serious psychiatric disorders are frequently treated by primary care physicians, who may have difficulty keeping up with recent advances in psychiatry. This paper presents an updated synopsis for three major psychiatric illnesses: major depression, bipolar disorder, and schizophrenia. Current definitions, updated diagnostic criteria, short- and long-term treatment strategies with algorithms, and special challenges for the clinician are discussed for each of these illnesses. On the basis of each illness's distinct characteristics, five treatment principles are emphasized: 1) Treatment strategies should be long-term and should emphasize adherence, 2) treatment choice should be empirical, 3) combinations of medications may be helpful, 4) a combination of psychosocial and pharmacologic treatments may be more useful than either alone, and 5) the family or "significant others" as well as a consumer organization need to be involved. Some of the new directions in dinical research to refine these strategies and meet these challenges are also described.

Algorithms↗

Expression of MCAM/MUC18 by human melanoma cells leads to increased tumor growth and metastasis.

The cell surface adhesion molecule MCAM (MUC18) is strongly expressed by advanced primary and metastatic melanomas but is weaker and less frequent in nevus cells. Previous studies have shown that MCAM expression correlates with tumor thickness and metastatic potential of human melanoma cells in nude mice. To provide direct evidence that MCAM plays a role in tumor growth and metastasis of human melanoma, the nonmetastatic MCAM-negative primary cutaneous melanoma SB-2 cells were transfected with MCAM cDNA and analyzed subsequently for changes in their tumorigenic and metastatic potential. Enforced expression of MCAM in SB-2 cells rendered them highly tumorigenic and increased their metastatic potential in nude mice as compared with parental and control transfected cells. The transfected cells displayed increased homotypic adhesion, increased attachment to human endothelial cells, decreased ability to adhere to laminin, and increased invasiveness through Matrigel-coated filters. Anti-MCAM monoclonal antibody reversed these functions in the transfected cells but not in control cells. The above changes in function attributed to the expression of MCAM may underlie the contribution of MCAM/MUC18 to the malignant phenotype.

Animals↗

Overview of clinical trials in medical rehabilitation: impetuses, challenges, and needed future directions.

The goal of clinical trials is to provide the strongest possible basis for inferring that the observed results of a health-oriented intervention are attributable to that intervention and not to other factors. Particularly strong causal inferences can be drawn from the randomized clinical trial in which participants are assigned on a random basis to either the intervention of interest or to a comparison condition. This article explains the reasons for that contention and explores its implications for medical rehabilitation research. Among the topics discussed are: the role of evidence-based practice in fostering interest in randomized clinical trials; a contextual view of randomized clinical trials that emphasizes strategies of investigation and the goals of particular studies; two key distinctions, efficacy-oriented vs. effectiveness-oriented clinical trials and pragmatic vs. explanatory clinical trials; the sequencing of different study designs, including randomized clinical trials; and needed advances in treatment theory, treatment fidelity, and adherence.

Evidence-Based Medicine↗

The vagina as an ecologic system. Current understanding and clinical applications.

Recent advances in understanding the mechanisms of dominance of the healthful microecology by Lactobacillus acidophilus through microbicidal enzyme systems has led to renewed interest in ecologic approaches to vaginal health maintenance and treatment of vaginosis and vaginitis. Review of pertinent research suggests that due to inadequate adherence of lactobacilli from dairy sources, contaminants in commercial sources, and lack of evidence of effectiveness in sparse clinical trials, intravaginal applications of L. acidophilus cannot be recommended. Bacterial vaginosis is described in this article as a microecologic shift in the dominant organism of the microecology from L. acidophilus to Gardnerella vaginalis. This results in conditions favorable to vaginal establishment of many anaerobic organisms. The ability to identify and nurture healthful lactobacilli in the vaginal microflora is suggested as a future direction for health-enhancement-oriented research, practice, and screening.

Female↗

The measurement conundrum in exercise adherence research.

This paper has two purposes. It first prefaces a symposium titled "Exercise adherence and behavior change: prospects, problems, and future directions." The symposium describes the progress made during the past 5 years toward understanding the adoption and maintenance of physical activity and exercise. Specifically, research is discussed that has tested the applicability to physical activity of four psychological models of behavior: Reasoned Action, Planned Behavior, Social-Cognitive Theory, and the Transtheoretical Model of stages of change. Recent exercise interventions in clinical/community settings also are discussed to illustrate how theoretical models can be implemented to increase and maintain exercise. The second purpose of this paper is to provide a brief summary of the contemporary literatures on the determinants of physical activity and interventions designed to increase and maintain physical activity. The summary focuses on the measurement problems that have limited the advances made in theory and application in these areas of research. Progress toward resolving the measurement problems during the past 5 years is contrasted with earlier scientific consensus.

Data Collection↗

Immunotherapy of solid cancer using dendritic cells pulsed with the HLA-A24-restricted peptide of carcinoembryonic antigen.

Carcinoembryonic antigen (CEA), an oncofetal glycoprotein overexpressed in most gastrointestinal and lung cancers, is a candidate molecule for cancer immunotherapy. Recently, a CEA-derived 9-mer peptide, CEA652 (TYACFVSNL), has been identified as the epitope of cytotoxic T lymphocytes restricted with human leukocyte antigen (HLA)-A24, which is present in 60% of the Japanese population and in some Caucasians. The authors performed a clinical study of a vaccine using autologous dendritic cells (DCs) pulsed with CEA652 and adjuvant cytokines, natural human interferon alpha (nhuIFN-alpha), and natural human tumor necrosis factor alpha (nhuTNF-alpha), for the treatment of patients with CEA-expressing advanced metastatic malignancies. Ten HLA-A24 patients with advanced digestive tract or lung cancer were enrolled in the study to assess toxicity, tolerability and immune responses to the vaccine. DCs were generated from plastic adherent monocytes of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (PBMCs) in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4). Generated DCs showing an immature phenotype were loaded with CEA652 and injected into patients intradermally and subcutaneously with 50% of the dose administered by each route every 2 weeks for a total of ten vaccinations. The total dose of administered DCs ranged from 2.7x10(7)cells to 1.6x10(8)cells. Adjuvant cytokines, i.e., 1x10(6) U/body of nhuIFN-alpha and nhuTNF-alpha, were administered to patients twice a week during the vaccination period. No severe toxicity directly attributable to the treatment was observed, and the vaccine was well tolerated. In the delayed-type hypersensitivity (DTH) skin test, two patients showed a positive skin response to peptide-pulsed DCs after vaccination, although none of the patients tested positive prior to vaccination. In the two patients who showed a positive skin response disease remained stable for 6 and 9 months respectively. These results suggest that active immunization using DCs pulsed with CEA652 peptide in combination with the administration of adjuvant cytokines is a safe and feasible treatment procedure.

Adult↗