Activated macrophages utilize glycolytic ATP to maintain mitochondrial membrane potential and prevent apoptotic cell death.

This corrects the article DOI: 10.1038/cdd.2010.27.

Activated macrophages utilize glycolytic ATP to maintain mitochondrial membrane potential and prevent apoptotic cell death.

We have previously analysed the bioenergetic consequences of activating J774.A1 macrophages (MΦ) with interferon-γ (IFN-γ) and lipopolysaccharide (LPS) and found that there is a nitric oxide (NO)-dependent mitochondrial impairment and stabilization of hypoxia-inducible factor (HIF)-1α, which synergize to activate glycolysis and generate large quantities of ATP. We now show, using tetramethylrhodamine methyl ester (TMRM) fluorescence and time-lapse confocal microscopy, that these cells maintain a high mitochondrial membrane potential (ΔΨ(m)) despite the complete inhibition of respiration. The maintenance of high ΔΨ(m) is due to the use of a significant proportion of glycolytically generated ATP as a defence mechanism against cell death. This is achieved by the reverse functioning of F(o)F(1)-ATP synthase and adenine nucleotide translocase (ANT). Treatment of activated MΦ with inhibitors of either of these enzymes, but not with inhibitors of the respiratory chain complexes I to IV, led to a collapse in ΔΨ(m) and to an immediate increase in intracellular [ATP], due to the prevention of ATP hydrolysis by the F(o)F(1)-ATP synthase. This collapse in ΔΨ(m) was followed by translocation of Bax from cytosol to the mitochondria, release of cytochrome c into the cytosol, activation of caspases 3 and 9 and subsequent apoptotic cell death. Our results indicate that during inflammatory activation 'glycolytically competent cells' such as MΦ use significant amounts of the glycolytically generated ATP to maintain ΔΨ(m) and thereby prevent apoptosis.

Risk factors for cardiovascular and cerebrovascular death among African Americans and Hispanics in Los Angeles, California.

OBJECTIVE: To describe the risk factors associated with cardiovascular mortality in the African American (AA) and Hispanic populations in Los Angeles County in an effort to define causes for the excess mortality seen in AAs. METHODS: This was a longitudinal analysis of all-cause, cardiovascular, and cerebrovascular mortality in a large, prospective multiethnic cohort of individuals aged 45-74 years. Death rates between AA and Hispanic men and women during the six-year period from 1993 to 1998 due to hypertension, cardiomyopathy, acute myocardial infarction (AMI), ischemic heart disease, and stroke were compared. RESULTS: There were 1,157 deaths due to cardiovascular disease (CVD) or cerebrovascular disease among the 71,798 eligible members of the cohort included in these analyses. Age-adjusted mortality rates were two to five times higher in AAs as compared with Hispanics (e.g., 373.15 in AAs for hypertensive disease vs 50.37 in Hispanics). A history of hypertension was the most common significant risk factor for CVD; other risk factors significantly associated with CVD mortality included cigarette smoking and a past history of diabetes and stroke. Adjusting for these factors did not remove the significance of AA ethnicity as a risk factor for CVD mortality in either subjects reporting or subjects not reporting hypertension at baseline. CONCLUSIONS: The evidence for both higher relative severity and higher incidence of hypertensive disease among AAs, and the consistency of the effect across gender, suggests that a major determinant of risk may be a gene environment interaction.

Bedside echocardiography by emergency physicians.

STUDY OBJECTIVE: Timely diagnosis of a pericardial effusion is often critical in the emergency medicine setting, and echocardiography provides the only reliable method of diagnosis at the bedside. We attempt to determine the accuracy of bedside echocardiography as performed by emergency physicians to detect pericardial effusions in a variety of high-risk populations. METHODS: Emergency patients presenting with high-risk criteria for the diagnosis of pericardial effusion underwent emergency bedside 2-dimensional echocardiography by emergency physicians who were trained in ultrasonography. The presence or absence of a pericardial effusion was determined, and all images were captured on video or as thermal images. All emergency echocardiograms were subsequently reviewed by the Department of Cardiology for the presence of a pericardial effusion. RESULTS: During the study period, a total of 515 patients at high risk were enrolled. Of these, 103 patients were ultimately deemed to have a pericardial effusion according to the comparative standard. Emergency physicians detected pericardial effusion with a sensitivity of 96% (95% confidence interval [CI] 90.4% to 98.9%), specificity of 98% (95% CI 95.8% to 99.1%), and overall accuracy of 97.5% (95% CI 95.7% to 98.7%). CONCLUSION: Echocardiography performed by emergency physicians is reliable in evaluating for pericardial effusions; this bedside diagnostic tool may be used to examine specific patients at high risk. Emergency departments incorporating bedside ultrasonography should teach focused echocardiography to evaluate the pericardium.

Evaluation of a hospital-wide resuscitation team: does it increase survival for in-hospital cardiopulmonary arrest?

OBJECTIVE: To assess the impact (defined not only with regard to patient outcome but also to record keeping for evaluation of care) of a formal, structured resuscitation team for in-hospital cardiopulmonary resuscitation over the year following its creation. METHODS: This is a "before and after" study in which charts of all patients needing resuscitation during the two-year period were reviewed and data arranged in the Utstein Style of in-hospital reporting of cardiac arrests. The review was limited to adults (> or = 18 years of age) in nonICU settings. RESULTS: A total of 220 events were identified. Demographics and presenting rhythms for the two periods under review were similar. For the period of August 1996-August 1997 (group 1), there were 70 resuscitation events recorded with a return of spontaneous circulation (ROSC) rate of 21/70 (30%). For the period of August 1997-August 1998 (group 2), 150 events were recorded and the ROSC rate was significantly higher 87/150 (58%)) (P=0.0002). ROSC after ventricular fibrillation and ventricular tachycardia was similar in both groups (50 vs 57%) (P = 1.00) but an improvement in survival was seen in group 2 from events of bradycardia perfusing rhythm (25% vs 84%) (P = 0.0003). Survival from PEA/Asystole was also improved during period 2 (18 vs 48%) (P = 0.013). Survival to discharge was seen in 3/50 (6%) of patients in period 1 and 18/102 (18%) of patients in period 2 (P = 0.09). CONCLUSIONS: The formation of a structured, formalized hospital resuscitation team was associated with an increase in the number of recorded events, in the number of patients experiencing ROSC and in the percentage of patients who were discharged from the hospital. Facilities with no formal resuscitation team or with no skilled, practiced resuscitator on their current team should consider implementation of a similar strategy.

Type and crossmatch of the trauma patient.

OBJECTIVE: To identify a population of trauma patients in the emergency department (ED) that do not require emergent blood transfusion via a combination of clinical risk factors that are readily accessible and easily obtained. METHOD: A review of trauma patients was conducted for a 6-month period. Crossmatched patients were identified and examined for clinical characteristics and whether transfusion was performed. Risk factors for transfusion were identified and a model was developed for predicting likelihood of transfusion. RESULTS: Six hundred fifty-four patients were crossmatched, with emergent transfusion occurring in 81 (12.4%). Four risk factors were identified: systolic blood pressure < 90 mm Hg, Glasgow Coma Scale score < 9, pulse > 120 beats/min, and high-risk injury (trauma to the chest between the midclavicular lines, abdominal injury with diffuse tenderness, survival of a fatal vehicular crash, ejection from a vehicle, or stab or gunshot wound to the trunk). Patients with no risk factors were shown to have a 2.2% incidence of transfusion with no emergent transfusions occurring in the ED. CONCLUSION: Trauma patients with no risk factors at presentation were less likely to require emergent blood transfusion, especially in the setting of the ED.

Three common presentations of ascariasis infection in an urban Emergency Department.

In the United States, approximately 4 million people per year are infected with Ascaris lumbricoides. We reviewed the common presentations of complications of Ascariasis infection in the Emergency Department (ED) and the diagnostic tools and treatment available. This was a retrospective case review conducted on all patients diagnosed with Ascariasis (using ICD-9 codes) over a 6-year period at Los Angeles County and University of Southern California Medical Center. Three patients with distinct complications secondary to Ascariasis were chosen, and all ED and inpatient records were reviewed. The patient's age, sex, race, presenting symptoms, data, outcome, and ED course and diagnosis were recorded. The three cases included a periappendiceal abscess, Loeffler's syndrome, and biliary colic/choledocholithiasis. The first patient underwent a computed tomography-guided drainage of the abscess. The second patient received supportive care and antibiotic therapy secondary to a superimposed bacterial pneumonia. The third patient underwent endoscopic retrograde cholangiopancreatography with sphincterotomy. All three patients had a stool ova and parasites positive for A. lumbricoides, and all received a 3-day course of mebendazole. Symptomatic cases of Ascariasis may present to EDs in the United States. Important diagnostic tools for the ED include chest X-ray, X-ray of the kidney-ureter-bladder and ultrasonography. Single-dose medications given in the ED are very effective in eradicating A. lumbricoides infection, thus avoiding hospitalization.

Emergency department presentations of typhoid fever.

Typhoid fever, a systemic infectious disease caused by Salmonella typhi, is classically characterized by fever, paradoxical bradycardia, abdominal pain, and a rose colored rash. This was a retrospective review of 21 confirmed cases over a 5-year period. Mean age was 32.6 years (range 2-60 years), and Mexico (7/21) and El Salvador (3/21) represented the most common countries of origin. Recent travel to an endemic area was noted in 14 patients. The most common complaints were fever (15/21), headache (10/21), abdominal pain (9/21), and diarrhea (6/21). Average duration of symptoms before presentation to the Emergency Department (ED) was 7.9 days. High fever associated with bradycardia was noted in 12 patients. Leukopenia was present in 7 patients. Blood culture was the most sensitive confirmatory test while the Widal test was positive in 7 out of 11 cases. Fever of unknown origin (12/21), followed by presumed typhoid fever (3/21) were the most common ED diagnoses. It is important to recognize that patients with typhoid fever may present to EDs in the US and this disease should be included in the differential diagnosis of febrile patients from Latin America or those with a history of recent travel to endemic countries.

Ultrasound training for emergency physicians--a prospective study.

OBJECTIVES: Bedside ultrasound examination by emergency physicians (EPs) is being integrated into clinical emergency practice, yet minimum training requirements have not been well defined or evaluated. This study evaluated the accuracy of EP ultrasonography following a 16-hour introductory ultrasound course. METHODS: In phase I of the study, a condensed 16-hour emergency ultrasound curriculum based on Society for Academic Emergency Medicine guidelines was administered to emergency medicine houseofficers, attending staff, medical students, and physician assistants over two days. Lectures with syllabus material were used to cover the following ultrasound topics in eight hours: basic physics, pelvis, right upper quadrant, renal, aorta, trauma, and echo-cardiography. In addition, each student received eight hours of hands-on ultrasound instruction over the two-day period. All participants in this curriculum received a standardized pretest and posttest that included 24 emergency ultrasound images for interpretation. These images included positive, negative, and nondiagnostic scans in each of the above clinical categories. In phase II of the study, ultrasound examinations performed by postgraduate-year-2 (PGY2) houseofficers over a ten-month period were examined and the standardized test was readministered. RESULTS: In phase I, a total of 80 health professionals underwent standardized training and testing. The mean +/- SD pretest score was 15.6 +/- 4.2, 95% CI = 14. 7 to 16.5 (65% of a maximum score of 24), and the mean +/- SD posttest score was 20.2 +/- 1.6, 95% CI = 19.8 to 20.6 (84%) (p < 0. 05). In phase II, a total of 1,138 examinations were performed by 18 PGY2 houseofficers. Sensitivity was 92.4% (95% CI = 89% to 95%), specificity was 96.1% (95% CI = 94% to 98%), and overall accuracy was 94.6% (95% CI = 93% to 96%). The follow-up ultrasound written test showed continued good performance (20.7 +/- 1.2, 95% CI = 20.0 to 21.4). CONCLUSIONS: Emergency physicians can be taught focused ultrasonography with a high degree of accuracy, and a 16-hour course serves as a good introductory foundation.

Elevated mortality rates from circulatory disease in African American men and women of Los Angeles County, California--a possible genetic susceptibility?

OBJECTIVE: Reports of higher mortality in African Americans have often focused on socioeconomic differences. Such differences do not explain the excess mortality in African Americans compared with Hispanics in Los Angeles County. We suggest the existence of genetic factors to explain at least some of the differences in mortality risk. METHODS: We compared the mortality rates from circulatory diseases in African American and Hispanic adults of Los Angeles County for 1988 to 1992 with the frequency of the angiotensin-converting enzyme (ACE) genotype. RESULTS: African American adults 45 to 74 years old had a 2-fold higher overall mortality rate than Hispanics. The largest differences were seen for hypertensive disease and cardiomyopathy in men; the most striking differences were seen in the youngest age group. Rates were lower in women than in men, but African American women also showed substantial excess compared with Hispanics. ACE genotype also showed a significant difference between the Hispanic and African American population; the latter had a significantly higher prevalence of the DD genotype, which is associated with a higher level of circulating enzyme, and lower prevalence of the II genotype, which is associated with a lower enzyme level. CONCLUSION: African American adults aged 45 to 74 years in Los Angeles County have a substantial excess mortality from hypertensive diseases compared with a similar Hispanic population. The frequency of the ACE DD genotype was higher in African Americans than in Hispanics. These studies may indirectly support the possibility of a genetic contribution to the excess hypertensive disease mortality in African Americans.

Priapism after androstenedione intake for athletic performance enhancement.

Priapism is a relatively rare condition characterized by persistent painful erection of the corpora cavernosum that occurs unrelated to sexual stimulation or desire. It has been associated with cocaine exposure, sickle cell anemia, anticoagulant therapy, neoplastic syndromes, diabetes, and the use of psychotropic medications. Androstenedione is a testosterone precursor used by athletes to enhance performance; the lay press has recently touted this substance as an over-the-counter sexual stimulant. We describe an otherwise healthy man with 2 episodes of priapism after the use of androstenedione. The patient did not have any factors known to precipitate priapism.

"Medical clearance" of psychiatric patients without medical complaints in the Emergency Department.

This study was conducted to evaluate the benefit of comprehensive "medical clearance" (history, physical examination, vital signs, laboratory, radiography) in patients presenting to the Emergency Department (ED) with isolated psychiatric complaints. All patients 16 years and older who presented with a psychiatric complaint and required a psychiatric evaluation before discharge from the ED were included in the study. Data, obtained in a 5-month consecutive, retrospective chart review, included patient age, sex, initial complaint, past medical and psychiatric history, initial vital sign measurement, physical examination findings, laboratory analysis (electrolytes, complete blood count, toxicology screen), chest X-ray study results, and final disposition. The number of patients who could have been referred to a psychiatric unit after a history, physical examination, and stable vital signs, without additional laboratory or radiographic studies, was determined. There were 212 patients who met the inclusion criteria, and all their charts were available for review. Eighty patients (38%) presented with isolated psychiatric complaints coupled with a documented past psychiatric history. All received a comprehensive "medical clearance" in the ED followed by a psychiatric consultation. None of the patients had positive screening laboratory or radiographic results. All were either dispositioned home or to the psychiatric ED. The remaining 132 patients (62%) presented to the ED with medically based chief complaints or past medical history requiring further evaluation in the ED before discharge. The initial complaints of these patients correlated directly with the need for laboratory and radiographic "medical clearance" in the ED. Patients with a primary psychiatric complaint coupled with a documented past psychiatric history, negative physical findings, and stable vital signs who deny current medical problems may be referred to psychiatric services without the use of ancillary testing in the ED.

Central retinal vein occlusion due to hyperviscosity syndrome.

A 57-year-old man with no previous medical history entered the emergency department with 2 days of painless vision loss in the left eye. The patient was diagnosed with central retinal vein occlusion (CRVO) and admitted for treatment. Further work-up revealed that the cause of his CRVO was a hyperviscosity syndrome secondary to multiple myeloma. The patient received two rounds of plasmapheresis with slight recovery of vision and was discharged 28 days later.

Serial abdominal ultrasound in the setting of trauma.

Ultrasound is gaining wide acceptance in Emergency Medicine as an inexpensive and accurate examination modality. One of the leading uses of this technology is in the initial assessment of the trauma patient, where the ultrasound examination is often used to determine the need for immediate laparotomy or further diagnostic study. We present a series of four patients, all of whom sustained blunt or penetrating abdominal trauma. In each case, the initial screening abdominal ultrasound was negative for free intraperitoneal (i.p.) fluid but, when repeated by the same practitioner, became positive. These cases demonstrate the need for serial ultrasounds in evaluating the patient with abdominal trauma. Future studies of trauma ultrasound should investigate the utility of serial sonographic examinations.

Ultrasonography of flank pain in the emergency department: renal cell carcinoma as a diagnostic concern.

Acute flank pain is a common emergency department presenting symptom, and bedside ultrasound is being used increasingly in its evaluation. Emergency renal ultrasonography concentrates on the focused presence or absence of hydronephrosis as is often seen in patients with acute flank pain secondary to renal colic. We present three cases in which other abnormal sonographic signs not commonly taught prompted further investigation, revealing renal cell carcinoma. Baseline knowledge of sonographic characteristics of tumors will benefit the occasional emergency patient who has unsuspected renal carcinoma.