Interaction of PLD1b with actin in antigen-stimulated mast cells.

Phosphatidic acid, the product of phospholipase D catalysed phosphatidylcholine hydrolysis is an important signalling molecule that has been implicated in regulation of actin cytoskeleton remodelling and secretion from mast cells. We show that human PLD1b (hPLD1b) is an actin-binding protein and the N-terminus is predominantly involved in this interaction. Protein kinase C (PKC) is a major upstream regulator of PLD activity and PKC phosphorylation sites have been identified within the N-terminus of PLD1b at serine 2 and threonine 147. Over-expression of wild type hPLD1b in mast cells showed that antigen stimulation significantly enhanced co-localisation of PLD1b with actin structures. Mutation of serine 2 to alanine abolished antigen-induced co-localisation whereas mutation of threonine 147 had less dramatic effects on co-localisation. The absence of co-localisation of PLD1b (S2A) with actin coincides with a significant decrease in PLD activity in cells expressing the PLD1b (S2A) mutant. In resting RBL-2H3 cells, mutation of serine 2 to aspartate resulted in constitutive co-localisation of PLD with the actin cytoskeleton, coincident with restored PLD activity. These results reveal that serine 2 is an important regulatory site involved in controlling PLD enzyme activity and the interaction between PLD and actin.

Declining critical care research publications by authors from U.S. Institutions, 1990-1999.

PURPOSE: To determine whether the proportion of authors from U.S. institutions to those from non-U.S. institutions has changed for published critical care research in three critical care journals over the past ten years. METHOD: The authors of designated critical care clinical or laboratory investigations published from 1990 to 1999 in the three leading U.S. critical care journals, American Journal of Respiratory and Critical Medicine, Chest, and Critical Care Medicine, were evaluated according to the locations of their institutions (U.S. versus non-U.S.) through a review of these publications. RESULTS: The proportion of authorship by investigators from U.S. institutions has declined for critical care research publications from 61% of all authors in 1990 to 41% in 1999 (p < .00001). Statistically significant declines in the proportions of authors from U.S. institutions to those from non-U.S. institutions occurred in the American Journal of Respiratory and Critical Care Medicine (p < .05) and Critical Care Medicine (p < .00001), but not in Chest (p = .69). CONCLUSIONS: The reasons for the decline in authorship by investigators from U.S. institutions are speculative and likely multifactorial. They are, however, consistent with other published data showing limited non-clinical time allocated for education activities for critical care faculty. Anecdotal concerns expressed by many faculty that rising clinical commitments necessitated by current health care and reimbursement pressures preclude research and educational academic activities are supported by these data.

Credentialing for critical care in small hospitals.

OBJECTIVE: To assess credentialing practices for critical care admissions and procedures in smaller hospitals within the United States. METHODS: A questionnaire was sent to credentialing coordinators of 500 randomly selected American Hospital Association hospitals with fewer than 300 beds. MEASUREMENTS AND MAIN RESULTS: Most hospitals validate qualifications for intensive care unit (ICU) admitting and procedural privileges through recommendations only. Fewer (16%) require a specified prior number of procedures to have been performed, and 9% require prospective supervision before privileges are granted. Critical care subspecialists are present in 57% of these hospitals and tend to be in the larger facilities with more critical care beds. Criteria for ICU admission and procedure privileges appear to be inclusive, because family medicine, obstetrics-gynecology, orthopedic surgery, and neurology specialists are often credentialed. The presence of a critical care subspecialist is associated with fewer hospitals credentialing family medicine specialists for ICU admission and procedures but not obstetrician-gynecologists, orthopedic surgeons, or neurologists. CONCLUSIONS: This is a brief descriptive report of hospital policies that define which physicians are permitted to care for critically ill/injured patients in small U.S. hospitals. The presence of a critical care specialist appears to influence only slightly the ICU credentialing processes for other selected specialists.

Challenges in donor care.

This article is provided as a self-study feature on care of organ donors. Questions and possible responses are provided. Review all the responses for each question.

Using pressure-limited mechanical ventilation in caring for organ donors.

Pressure-limited (controlled) ventilation is commonly employed to provide mechanical ventilation in the intensive care unit when lung compliance is poor or when airway resistance is irreversibly high. Modification of the inspiratory-expiratory ratio to include inspiratory-expiratory ratio reversal and permissive hypercapnia can also be used when lung disease or injury is severe. Because other donor organs often can be saved for transplantation even when the lungs have been badly damaged, the organ procurement coordinator should adopt pressure-limited ventilation as well as inspiratory-expiratory ratio reversal and permissive hypercapnia as potentially helpful methods while providing mechanical ventilation to selected donors.

Teaching critical appraisal during critical care fellowship training: a foundation for evidence-based critical care medicine.

OBJECTIVE: To determine whether fellowship training in critical care medicine with critical appraisal exercises improves the ability and confidence of fellows to evaluate the medical literature. DESIGN: Prospective, interventional pilot study. SETTING: Multidisciplinary critical care medicine training program at a large university hospital. INTERVENTION: Fellows were given three didactic sessions covering study design, analysis, and critical appraisal techniques. During the course of the year, each fellow was required to review one article from the literature and present a critique of this article to the group and faculty (Journal Club). Fellows were guided in the preparation of this presentation by one of the critical care medicine faculty. Finally, a written analysis and critique of the article was performed by each fellow. MEASUREMENTS AND MAIN RESULTS: A test was given to each fellow at the beginning and end of the academic year. This test consisted of two pairs of articles on therapy for acute lung injury. For the pretest, each fellow was assigned, at random, one pair of articles. Fellows were given 1 hr to review both articles and to fill out a six-point test to assess their ability and confidence to appraise each article. At the end of the year, each fellow was tested on the opposite pair, the tests were graded in a blinded fashion and the results of each test were compared. Six fellows completed both pre- and posttests. These paired results were analyzed separately, whereas results for another six fellows were conducted as an unpaired analysis. Mean scores increased both for the paired analysis (4.1+/-0.7 vs. 5.1+/-0.5; p = .015) and for the unpaired analysis (4.3+/-0.6 vs. 5.0+/-0.5; p = .012). Self-reported confidence in critical appraisal also increased (2.5+/-0.5 vs. 3.9+/-0.7; p = .004 and 2.6+/-0.5 vs. 3.9+/-0.6; p < .001, respectively). CONCLUSION: Critical appraisal exercises used in the training of critical care medicine fellows appear to improve both ability and confidence to appraise relevant medical literature.

Abnormalities in fluids, electrolytes, and metabolism of organ donors.

Abnormal serum concentrations of electrolytes, hormones, and glucose are common throughout donor care. The organ procurement coordinator must properly interpret and plan treatment for these changes to prevent intracellular dysfunction in donor organs. This article describes abnormalities in magnesium, phosphorous, calcium, sodium, potassium, and glucose levels; polyuria; and thyroid and pituitary changes. Their potential consequences are discussed, and recommendations for treatment options are presented.

Maintaining acid-base balance in organ donors.

An abnormal blood pH may cause the loss of donor organs through harmful physiological consequences. The organ procurement coordinator must correctly analyze the acid-base abnormality and treat its cause while normalizing the blood pH. We recommend that treatment of acidemia or alkalemia be first directed toward changing parameters on the mechanical ventilator, using the Paco2 to modify blood pH. Thereafter, hydrochloric acid or sodium bicarbonate may be administered to correct the calculated metabolic acid-base deficit. The types of acidosis or alkalosis, dead space effect during mechanical ventilation, base excess, base deficit, and the appropriate evaluation of blood lactate are also discussed as related to the correction of the acid-base status throughout donor care.

Management of variations in blood pressure during care of organ donors.

The organ procurement coordinator commonly must correct and maintain the arterial blood pressure during donor care. This article reviews considerations in the accurate measurement of the blood pressure, causes of hypertension and hypotension, and desirable standards to use in order to provide adequate organ perfusion. Recommendations are presented for treatment of hypotension in a titrated response of intravenous fluids, inotropic support, and vasopressor infusion to maintain the mean arterial pressure above 65 mm Hg. Collaborative interaction between the coordinator and physician consultant remains important throughout management of blood pressure changes during donor care.

Recommendations for mechanical ventilation during donor care.

The organ procurement coordinator usually directs adjustments to the mechanical ventilator during donor care. It is often difficult to achieve optimal oxygen uptake and carbon dioxide removal while avoiding barotrauma or undesirable effects on the cardiac output. Interrelationships among a variety of ventilator parameters must be understood in order to achieve the desired goal of providing the best organs possible. These recommendations review the key ventilator parameters of tidal volume; positive end-expiratory pressure; auto-positive end-expiratory pressure; fraction of inspired oxygen; and flowrate and frequency and their interactions in controlling peak, plateau, and mean and end-expiratory airway pressures.

Compensation for teaching in critical care.

OBJECTIVES: To determine the financial or nonclinical time critical care program directors or teaching faculty members receive as compensation for their educational activities. To compare compensation types and amounts among critical care specialties and between university vs. nonuniversity sponsoring institutions. DATA SOURCES AND EXTRACTION: Survey returns (46%) from critical care fellowship directors listed in the American Medical Association Graduate Medical Education Directory. Information was stratified according to fellowship specialty and type of sponsoring hospital and compared by chi-square analysis and the Kruskal-Wallis test. CONCLUSIONS: Most program directors (77%) and faculty (82%) receive no specified compensation for education-related activities. Multidisciplinary programs are more likely to compensate faculty members than other specialty-specific programs (p = .006). Most programs sponsored by university or military/federal hospitals do not provide specified compensation (79% and 100%, respectively). Overall, community hospital-based programs provide a greater percentage of compensation to directors and faculty than university programs (for directors, p = .02; odds ratio, 3.85; for faculty, p = .001; odds ratio, 8.4). When compensation is specified, it is most often financial and it averages 18% of the salary (range, 5% to 100%) for directors and 19% of the salary for faculty (range, 5% to 50%). When reduced clinical time is provided (5% of program directors, 2% of faculty), it averages 13% (range, 8% to 18%) for directors and 18% (range, 10% to 25%) for faculty. Alternative methods for assigning educational compensation are discussed.

Regulation of coagulation abnormalities and temperature in organ donors.

The 3 most common reasons for abnormal coagulation of blood in organ donors result from prior medications, consumption or dilution of coagulation factors and platelets during massive transfusion, and disseminated intravascular coagulation. Evaluation and treatment of these conditions are reviewed, and recommendations are provided for ordering appropriate laboratory tests and blood bank products.

Current considerations in the issue of brain death.

Brain death is an anatomically and physiologically complex process. The societal and psychological implications of brain death and organ donation are equally complex, and they have profound ramifications. Because the vast majority of organ donors die as a consequence of catastrophic intracranial processes, neurosurgeons are in a unique position to positively influence the supply of transplantable organs. Enhanced knowledge of the physiology of evolving brain death will improve the care of potential organ donors and increase the probability of successful transplantation. Likewise, better information about patient and family directives, beliefs, grieving, concurrent exposure to other health care workers, and experiences in the hospital environment will assist the neurosurgeon in providing the family with the opportunity for donation. Neurosurgeons can also play a leading role in the multidisciplinary approach required to support the families of potential organ donors during the transition from neurointerventional therapy to somatic support. New federal regulations on organ donation and a review of the literature about the "art of asking" are presented.

Research curricula in critical care fellowships--a survey.

OBJECTIVES: To determine curriculum requirements and educational methods used by Critical Care fellowship training programs in fulfilling Residency Review Committee requirements for a research experience during Critical Care subspecialty training. DATA SOURCE: Responses from 163 (67%) of the 245 directors of accredited Anesthesiology, Medicine, Pediatric, and Surgical Critical Care fellowship training programs listed in the American Medical Association Graduate Medical Education Directory. DATA EXTRACTION: Survey information accepted as valid for each program was tabulated to answer study questions. DATA SYNTHESIS: Most (89%) Critical Care programs with 2- or 3-yr curricula meet Residency Review Committee requirements and provide nonclinical time for research. Only 63% of 1-yr curricula from Anesthesiology and Medicine provide a required research experience. Formal instruction in research topics is provided by lecture, journal club, or research conference in approximately 90% of fellowships. Academic productivity from fellowship programs is high, but not correlated with a program's requirement for research. CONCLUSION: Compliance with current Residency Review Committee requirements for active participation in research is poor for 1-yr fellowship curricula. Reasons for this failure are discussed and a modified requirement is proposed.

Changes in serum catecholamine levels in patients who are brain dead.

Prospective blood samplings from 15 patients admitted with a Glasgow Coma Score of less than 7 were obtained to observe and compare epinephrine, norepinephrine, and dopamine serum levels in patients with brain injury before, after, and in the absence of brain death. Nine of the patients developed or were admitted after brain death. Wide variations in catecholamine blood levels over time were documented, and subgroup analysis precluded useful statistical comparison or inference of the data. The data are presented therefore as descriptive observations only. No apparent differences were noted between similarly injured patients in whom brain death did not develop and patients before brain death or between patients with penetrating versus nonpenetrating brain injury. Brain death was preceded by hypertension and corresponding elevations in serum catecholamine levels in one patient with complete data. Catecholamine levels appeared to fall after brain death in most patients. Only minimal changes in myocardial histology were present in three donor hearts, and the two transplanted hearts functioned satisfactorily. Serum catecholamine measurement or monitoring does not provide a precise method of determining potential injury to the donor heart before or after brain death. Other experimental data and clinical observation indicate that some hearts may be injured in the donor during the evolution of brain death. Pharmacologic intervention may prevent such injury in experimental animals but must be used before brain death is induced. Such interventions should be studied in selected human donors before brain death to determine whether cardiac function is improved in the donor or recipient.

Hormonal changes in brain dead patients.

Thirty neurologically impaired (Glasgow Coma Score less than 7) patients were evaluated to determine if changes in serum levels of thyroid hormone, cortisol, insulin, or lactate suggest that replacement therapy is needed before removal of organs for donation. Serum levels of free thyroxine (fT4), thyroid-stimulating hormone (TSH), reverse T3 (rT3), cortisol, insulin, and lactate were monitored in 16 patients before and after brain death and in 14 additional patients who were similarly compromised but did not become brain dead. Low fT3, normal fT4, and normal or high rT3 as found in most patients were consistent with a variant of the euthyroid sick syndrome although TSH was elevated in some patients. Cortisol, insulin, and lactate levels were also normal or high. No correlation was found between low thyroid hormones and elevated lactate or the amount of vasopressor needed to sustain BP. No significant changes occurred in hormone or lactate levels after brain death. The explanation for an elevated lactate remains unclear but we do not believe this single finding justifies the diagnosis of a hypothyroid state in these patients or the administration of thyroid hormone to brain dead organ donors.