Platelet factor 4 upregulates matrix metalloproteinase-1 production in gingival fibroblasts.

BACKGROUND AND OBJECTIVE: Periodontitis is a highly prevalent chronic inflammatory disease that causes tooth loss, morbidity and confers an increased risk for systemic disease. Tissue destruction during periodontitis is due in large part to collagen-degrading matrix metalloproteinases (MMPs) released by resident cells of the periodontium in response to proinflammatory cytokines. Platelets are immune-competent blood cells with a newly recognized role in chronic inflammation; however, their role in the pathogenesis of periodontitis is undefined. Consequently, the objective of this study was to assess the effect of platelet factor 4 (PF4), a major platelet-derived cytokine, on MMP-1 (collagenase) expression in human gingival fibroblasts (HGFs). MATERIAL AND METHODS: HGFs were cultured in the presence or absence of recombinant PF4. Pro-MMP-1 secretion was quantified by enzyme-linked immunosorbent assay analysis of the cell culture supernatants. MMP-1 transcription was quantified by real-time polymerase chain reaction. Regulation of MMP-1 production by the p44/42 MAP kinase (MAPK) signaling pathway was examined in the presence or absence of PF4. RESULTS: Exposure to PF4 caused a ~ 2-3-fold increase in MMP-1 transcription and secretion from cultured HGFs. PF4 treatment also enhanced phosphorylation of p44/42 MAPK, which has been previously shown to induce MMP-1 expression in fibroblasts. Blockade of p44/42 MAPK signaling with the cell-permeant inhibitors PD98059 and PD184352 abrogated PF4-induced pro-MMP-1 transcription upregulation and release from cultured HGFs. CONCLUSION: We conclude that PF4 upregulates MMP-1 expression in HGFs in a p44/42 MAPK-dependent manner. These findings point to a previously unidentified role for platelets in the pathogenesis of periodontal diseases.

Cerebral tissue O2 saturation during prolonged robotic surgery in the steep Trendelenburg position: an observational case series in a diverse surgical population.

Demands associated with the Trendelenburg position (TP) are well known yet there is little attention given to regional cerebral tissue O2 saturation (SctO2) in those undergoing robotic surgery in the TP with CO2 insufflation (C-INSF). This is the first study to report on SctO2 in a wide range of patients undergoing lengthy TP and robotic surgery. We measured SctO2 during robotic surgery in patients in the TP with C-INSF, as well as a control robotic thyroid surgery group who were supine with no C-INSF. We recorded relevant variables and periods of cerebral desaturation (CD). We studied 42 patients in 25°-45° of TP for ≥125 min. Management was at the providers' discretion. The INVOS(®) 5100C Cerebral Oximeter (Covidien, Boulder, CO) recorded SctO2. CD was defined as a >20 % decrease from baseline SctO2 or a value ≤55 % for ≥10 min. Patients were assessed for adverse outcome. The sample consisted of 13 males and 29 females aged 22-73, BMI 22-36 had general (N = 3), urological (N = 14) and gynecological (N = 25) surgery; two patients had CD lasting 150 and 190 min and two had episodic CD lasting 10-35 min. The four were female aged 22-60 in 38°-45° of TP. Eleven cases had multiple episodic CD for ≤15 min, 27 TP cases had no CD. Other observations included a consistent fall in SctO2 with phenylephrine; an increased SctO2 with ephedrine; and FiO2 and EtCO2 being generally strong, direct modifiers of SctO2. High MAP was inconsistently associated with high SctO2. BMI had no observed effect on SctO2. Pulse oximetry was ≥97 % in all cases. We observed no adverse cerebral events on follow-up. Additional clinical studies are warranted.

An algorithm for evaluating the ethics of a placebo-controlled trial.

The purpose of this article is to clarify the decision points that are important to consider when evaluating the ethics of a placebo-controlled trial. The ethical requirements for research involving human subjects are reviewed, and the rationale for and potential problems with concomitant placebo control are explained. A series of case discussions are used to illustrate each decision point. The critical decision points in the evaluation of the ethics of a placebo-controlled trial are as follows: (i) Is placebo being used in place of standard therapy? (ii) Is standard therapy likely to be effective? (iii) Is the toxicity of standard therapy such that patients routinely refuse this treatment? (iv) Could the use of placebo result in severe suffering or irreversible harm? (v) Is the variability in the placebo response such that it is reasonable to consider other options for the control group? (vi) Would a reasonable person with an average degree of altruism and risk aversiveness agree to participate in this study? The algorithm presented in this article gives researchers and research monitors (such as Institutional Review Board members) the tools they need to evaluate the ethics of a study that uses concomitant placebo control.

Analysis of noteworthy indicators on the anesthesia record: a prospective, multiregional study.

A national sample of anesthesia records were studied prospectively for the presence or absence of predetermined, noteworthy record indicators judged important in documenting a basic core of information describing the monitoring and care provided in a generic clinical setting. Only records involving the administration of a volatile anesthetic for the purpose of achieving general anesthesia, prepared by providers with at least 6 months of experience in anesthesia care were examined. No identifying patient, provider, or institutional data were recorded. Indicators were scored in a "present/absent" format. All data were pooled; the goal was to describe the overall phenomena in terms of frequency of compliance. A total of 4,989 anesthesia records were evaluated in terms of 13 record indicators. Those missed ranged from 0.0% (patient identification) to 28.6% (notation regarding emergence). Ten were omitted on less than 6% of the records: 3 (surgery and/or anesthesia start time, notation regarding emergence, surgical positioning noted) were omitted on more han 13.0% of the records. Given he observed inconsistencies, perhaps the anesthesia record needs redesign or the rationale behind documentation requires increased emphasis in educational and equally assurance programs.

Preanesthesia detection of equipment faults by anesthesia providers at an academic hospital: comparison of standard practice and a new electronic checklist.

We hypothesized that our institutional standard practice for preanesthesia equipment checkout, based in part on US Food and Drug Administration recommendations, failed to detect a significant number of faults (absent or nonfunctional equipment). We designed a new, computer-based, highly interactive electronic checklist that emulated the checklist methods used in aviation and military settings and compared it to our standard practice in the detection of faulty equipment. Using a randomized, cross-over design, anesthesia providers searched for prearranged faults over a 2-day period using both the electronic and standard approaches. Faults (easy and difficult) found, faults missed, and time to complete the checkout were recorded. The electronic checklist was superior to standard practice in the detection of "easy" and "difficult" equipment faults. However, even when the electronic checklist was used, a high proportion of difficult faults were missed. Whether the failure represents a need for improved checkout procedures and provider training or better equipment design will require further study.

AANA journal course: update for nurse anesthetists--the ruddy globule: the erythrocyte--its biology, chemistry, and functional variations.

Red blood cells were first observed in the mid-1600s and termed ruddy globules for their conspicuous shape and color. Since that time, the functional significance of this extraordinary membranous pouch of proteins and electrolytes has been carefully detailed. The architecture of the red blood cell, the biochemistry of hemoglobin, the mechanics of the oxygen-hemoglobin affinity-altering diphosphoglycerate compounds, and the variants of hemoglobin are reviewed. Far from being a simple transport vehicle of oxygen to and from tissues, the red blood cell is a multifunctional entity whose absence would make life as we know it impossible.

AANA Journal course: update for nurse anesthetists-accelerated detoxification from opioid addiction under anesthesia: the Midas touch or the emperor's new clothes?

Opioids are highly addictive substances that include natural and synthetic chemicals that mimic the effects of morphine or bind to morphine receptor sites. Traditional assisted withdrawal is a process that takes several days to weeks and is associated with a host of painful and difficult symptoms. Recently, accelerated detoxification using opioid antagonists administered while the patient is anesthetized has been promoted, with centers proliferating nationwide. Published studies of rapid detoxification under anesthesia are highly variable in quality and control, and long-term outcome data are incomplete. Well-controlled, carefully designed studies are needed to appropriately assess the efficacy, safety, and cost-effectiveness of the approach.

Liquid ventilation innovations in ventilatory management.

The goal of mechanical ventilation is to maintain adequate gas exchange by opening and stabilizing alveolar units with minimal detriment to the pulmonary and circulatory systems. The optimal ventilatory strategy may be difficult to achieve, especially in patients with respiratory failure. Total liquid ventilation is a process whereby a liquid perfluorocarbon (PFC) replaces both the functional residual capacity and the tidal volume within the lung. Gas exchange is accomplished by mechanically assisted inspiration and expiration of tidal volumes of the liquid using a liquid ventilator. The PFC liquid is then oxygenated and purged of carbon dioxide by a membrane lung. Perfluorocarbons are excellent media for gas exchange due to their extraordinary gas solubility and diffusibility of oxygen and carbon dioxide. Partial liquid ventilation (PLV) is a modified method of the total liquid ventilation technique. In PLV, a functional residual capacity of PFC liquid is maintained in the lung, and the patient is ventilated with a conventional gas mechanical ventilator. Studies of the acute respiratory distress syndrome in animal models and in human series have demonstrated encouraging results using PLV and PFC. The high density, low surface tension, and other qualities of PFC in the setting of PLV may offer a highly innovative approach that can be directed toward the management of patients in respiratory failure.

Review of chemical, medication, and anesthesia toxicity in the OR.

A host of toxic substances exist in the OR. The toxicity of prep solutions, cleaning chemicals, common medications, and trace anesthetic gases varies greatly. Nurses use, direct others in the use of, or administer potential toxins while breathing air that may be contaminated to some degree with anesthetic vapors. Often, the OR nurse is the neighborhood resource when questions about the toxicity of common chemicals and drugs arise. A general knowledge of the toxicity of these substances improves the nurse's ability to assess the risk from trace anesthetic gases, prevent injury to patients, provide first aid when potentially dangerous exposure occurs, and direct others in the safe use of OR chemicals.

Institutional review board approval and publication of human research results.

OBJECTIVE: To determine if journals' instructions for authors require that manuscripts being considered for publication indicate that studies involving human subjects had appropriate institutional review board (IRB) approval. DESIGN: A descriptive study of the ethical guidelines published in the Instructions for Authors sections of the 102 English-language biomedical research journals listed in the 1995 Abridged Index Medicus. INTERVENTION: Literature review. MAIN OUTCOME MEASURE: Policy regarding IRB approval of studies that involve human subjects. RESULTS: Of the 102 journals surveyed, 48 (47%) require IRB approval of studies involving human subjects as a prerequisite for publication, and 25 (24%) do not present or refer the author to any information related to human research ethics. Of the remaining journals, 15 (15%) referred authors to the Uniform Requirements for Manuscripts Submitted to Biomedical Journals, 3 (3%) to the Declaration of Helsinki, and 10 (10%) simply indicated that informed consent should be obtained. There was only 1 medical specialty (anesthesiology) in which all the representative journals presented the same ethical requirement. In the 48 journals that clearly required IRB approval of studies, 37 (77%) documented IRB approval with a statement in the manuscript, 7 (15%) required a separate signed statement from the author, and 4 (8%) did not mention a method of documentation. CONCLUSIONS: The results of this study suggest that about half of the 102 English-language biomedical research journals listed in the 1995 Abridged Index Medicus do not publish guidelines indicating that IRB approval of studies involving human research subjects is a requirement for publication. The manner in which publication requirements related to ethical standards are presented in biomedical research journals is extremely variable.

AANA journal course: update for nurse anesthetists--the control of ventilation and its modification by anesthetic-related drugs.

Ventilation is normally precisely linked to body metabolic needs. A variety of drugs, commonly utilized in anesthesia, can profoundly alter the body's response to ventilatory challenges. This installment of the AANA Journal course describes the control of the respiratory drive and the effects that anesthetic drugs have on ventilation in humans. Knowledge of such effects will go a long way in preventing what might otherwise be catastrophic complications.

How does the peer review process influence AANA journal article readability?

This study examined the readability of the AANA Journal, quantifying the effect of peer review on case and research reports published from 1992 to 1994. Gunning and Flesch index-based computer analysis, as well as human comparative analysis, was undertaken. Computer and human assessment of readability revealed improvement as papers evolved from submitted to published versions; however, at publication the manuscripts remained in the "difficult" readability range. Although this study provides evidence that peer review improves readability, it may be that, due to a professed need for scientific purity and an imposed sense of scholarship, nursing and other biomedical journals may overemphasize a style and approach that paradoxically make transfer of information unreasonably difficult.

Comparative aspects of the airway during general anesthesia in obese sufferers of sleep apnea and matched normals.

This study involved subjective evaluation of airway patency, linear measurement of orocraniofacial architecture, and blood pressure measurement in 38 obese sufferers of sleep apnea and 38 matched controls. The study demonstrated that airway management in the sleep apnea group was difficult on both induction and emergence from general anesthesia. Moreover, a smaller, compressed oropharynx was observed in the sleep apnea group. In addition, patients with sleep apnea were characteristically hypertensive. More nursing research is needed to enhance understanding of patients afflicted with sleep apnea and to improve their life quality.

A review of the transmission of viral hepatitis for gastroenterology nurses.

This article focuses on viral hepatitis because of the potentially devastating consequences of this disease group to gastroenterology nurses. Recent landmark work has reaffirmed the high risk of occupational exposure to viral hepatitis and the need for inoculation of all healthcare workers. Gastroenterology nurses, by virtue of their professional activities, are at particular risk. The various forms of viral hepatitis are reviewed and appropriate nursing interventions are discussed in this article.

AANA journal course: update for nurse anesthetists--"is it okay to breast feed my baby after anesthesia?" A scientific basis for an informed response.

Many breast-feeding women are exposed to anesthetic drugs. The question of breast feeding following an anesthetic is a highly relevant issue in part because it is desirable to allow breast feeding to resume quickly while minimizing the potential for drug-related infant morbidity. The physiology of breast milk production and the factors influencing the transfer of drugs into breast milk is reviewed. Generally there is incomplete or sparse information on the potential effects upon the suckling infant. Despite this, certain reasonable conclusions and recommendations can be developed. Among these include a substantive risk with high-dose and long-standing therapies, particular vulnerability in the premature neonate or when a mother is receiving multidose therapy, and consideration of temporarily interrupting the feeding schedule where sufficient doubt exists. Overall, the importance of breast feeding must be carefully considered in light of the potential for side effects in each maternal/child scenario.

Orocephalometry and airway control in obese sleep-disordered breathers, obese normals, and matched controls undergoing general anesthesia.

Airway patency in conscious, normal humans is maintained by a complex orchestration of airway dilator muscles and reflex pathways yet is easily perturbed. Using patients at high risk for airway obstruction during anesthesia, as well as matched controls, this study sought (1) to determine if selected observations would contribute to our understanding of upper airway obstruction, and (2) to scientifically ground our clinical airway management interventions. The "at risk" patients tended to differ significantly from the controls with respect to a number of anthropometric and subjective measures which sought to describe the obstructive phenomena. At risk subjects were characterized as having a much greater incidence of induction and emergence obstruction, an abbreviated mental-hyoid distance, a flattened, compressed anterior-posterior craniofacial architecture, retrognanthism, relative macroglossia, and a narrower, bulky oropharynx. A theoretical model of airway obstruction was proposed characterizing the pharynx as a "collapsible tube" especially vulnerable in conditions such as sleep disordered breathing.