Imaging Giardia intestinalis cellular organisation using expansion microscopy reveals atypical centrin localisation.

Advanced imaging of microorganisms, including protists, is challenging due to their small size. Specimen expansion prior to imaging is thus beneficial to increase resolution and cellular details. Here, we present a sample preparation workflow for improved observations of the single-celled eukaryotic pathogen Giardia intestinalis (Excavata, Metamonada). The binucleated trophozoites colonize the small intestine of humans and animals and cause a diarrhoeal disease. Their remarkable morphology includes two nuclei and a pronounced microtubular cytoskeleton enabling cell motility, attachment and proliferation. By use of expansion and confocal microscopy, we resolved in a great detail subcellular structures and organelles of the parasite cell. The acquired spatial resolution enabled novel observations of centrin localization at Giardia basal bodies. Interestingly, non-luminal centrin localization between the Giardia basal bodies was observed, which is an atypical eukaryotic arrangement. Our protocol includes antibody staining and can be used for the localization of epitope-tagged proteins, as well as for differential organelle labelling by amino reactive esters. This fast and simple technique is suitable for routine use without a superresolution microscopy equipment.

[Acute Traumatic Intervertebral Disc Herniation]. / Akutní traumatická hernie intervertebrálního disku.

Acute traumatic intervertebral disc herniation of the thoracic spine is a rather rare injury with only a few reported cases to date. In this manuscript, we present a case of a 58-year-old male patient who sustained a car accident-related high-energy trauma, resulting in a disc herniation of the thoracic spine. Furthermore, we also discuss the possible implications of late diagnosis of such condition. The patient was initially referred from the Emergency Department as a case of head contusion with a left upper limb paresis. Due to only minimal bony trauma visible on the initial spine CT scan, the neurological deficit was attributed to the cranial trauma. The diagnosis of a traumatic disc herniation was therefore established only after the rapid onset of paraparesis, which gradually progressed into paraplegia, and a following spine MRI scan. Despite the subsequent urgent spinal decompression, the neurological functions of the lower limbs were not restored. This manuscript addresses the indications for performing MRI scans in polytrauma patients with a CT-verified spine trauma. Although it may be complicated to perform routine MRI scans in all such patients in daily practice, it can certainly help diagnose such injuries earlier and thus prevent potential permanent neurological damage to the patients. Key word: spine injury, traumatic disc herniation, thoracic spine, spine surgery.

A patient with severe metformin-associated lactic acidosis complicated by acute coronary syndrome: a case report.

INTRODUCTION: Metformin-associated lactic acidosis (MALA) is a rare but life-threatening condition. Here, we report the outcome of a patient with MALA complicated by acute coronary syndrome. CASE PRESENTATION: A 47-year-old obese woman of Caucasian ethnicity was admitted for syncope and tachypnea with Kussmaul breathing. She had a type-2 diabetes and was on oral antidiabetic therapy. Hemoglobin A1c was 6.6%. On admission, a severe acute kidney injury (serum creatinine: 1251 µmol/L) with hyperkalemia (7.5 mmol/L) and severe lactic acidosis (ph:7.042, bicarbonate: 9.9 mmol/L, partial pressure of carbon dioxide: 21.8 mmHg, lactate: 20.0 mmol/L) was found. Despite bicarbonate therapy, ph further decreased. Within 2.5 h of admission, a temporary hemodialysis catheter was placed, and one session of a high-efficiency hemodialysis was performed. 8 h after admission, a continuous venovenous hemodiafiltration was initiated and maintained for 2 days. The metformin therapy was stopped. Supplemental oxygen, intravenous catecholamines (4 days) and antibiotic therapy (7 days) were applied. During this therapy of lactic acidosis, an acute coronary syndrome evolved by day 2 after admission and resolved by day 5 in hospital. After recovery, the patient was transferred to a general ward on day 7 and left the hospital on day 11. By discharge, both the acute kidney injury and the acute coronary syndrome were reversible. CONCLUSION: In the patient with MALA complicated by acute coronary syndrome, the combination of a high-efficiency hemodialysis and, consecutively, continuous venovenous hemodiafiltration led to a favorable outcome.

[Non-Hodgkin´s B-lymphoma of the ovaries with an unfavourable prognosis - incidental finding during caesarean section]. / Non-Hodgkinuv B-lymfom ovarií s nepríznivou prognózou - náhodný nález pri císarském rezu.

OBJECTIVE: Presentation of a rare finding non-Hodgkin´s B-lymphoma of the ovary in a patient during caesarean section. DESIGN: Case report. SETTINGS: Department of Obstetrics and Gynaecology, Regional Hospital Liberec, a.s.; First Internal Clinic - Clinic of Hematology, First Faculty of Medicine and General University Hospital, Charles University in Prague; Department of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University in Praque and Motol University Hospital. RESULTS: Pregnant woman, 31-years old, primiparous, with a history of caesarean section was examinated in our department due to nonspecific abdominal pain during her pregnancy. During the caesarean section of fetal indication we found bilateral ovarian tumours. We performed unilateral adnexectomy. Preliminary diagnosis from frozen section was thecoma, but final diagnosis (after definitive histology, imunohistochemistry and molecular investigation) was high-grade B-cell non-Hodgkin´s lymphoma with c-myc and bcl-6 gene rearrangement (double-hit lymphoma) resulting in an unfavourable prognosis. The patient consequently completed 6 cycles of chemotherapy with a biological treatment, and achieved a complete remission. However, after 6 months, an early generalisation to the CNS appeared, leading to intracranial hypertension refractory to anithypertensive and anti-oedematous therapy, consequently leading to death. CONCLUSION: Non-Hodgkin´s lymphoma of the ovary in pregnancy is a rare adnexal tumour whose treatment requires interdisciplinary cooperation.

Histologic, Clinical, and Radiologic Findings of Alveolar Bone Expansion and Osteomyelitis of the Jaws in Cats.

The objective of this study was to characterize clinical, radiologic, and histologic patterns of alveolar bone expansion and osteomyelitis in cats. Based on case materials submitted as surgical biopsy specimens, alveolar bone pathology was diagnosed in 28 cats. These cats had a total of 37 oral lesions with clinical and radiologic changes that involved bone and/or teeth, including periodontitis, bone expansion, tooth resorption, and/or chronic osteomyelitis; 32 lesions were evaluated by histopathology. Canine teeth were affected in 19 cats (27 affected teeth), with bilateral lesions in 5 (26.3%) cats. The caudal premolar and/or molar regions were affected in 10 cats (10 affected sites). All biopsy sites evaluated by a review of clinical images and/or radiographs had evidence of periodontitis. Clinical photographs showed expansion of alveolar bone in 13 of 16 (81%) biopsy sites evaluated. Radiologically, rarifying osseous proliferation of alveolar bone was seen at 26 of 27 (96%) biopsy sites, and tooth resorption occurred at 15 of 18 (83%) sites. Histologically, the tissue samples from canine sites had compressed trabeculae of mature remodeled bone, loose fibrous stroma with paucicellular inflammation, and mild proliferation of woven bone. Tissue samples from the premolar/molar biopsy sites were often highly cellular with mixed lymphoplasmacytic and chronic suppurative inflammation, ulceration with granulation tissue, and robust proliferation of woven bone. Alveolar bone expansion and osteomyelitis in cats occurs in conjunction with periodontal inflammation and frequently with tooth resorption.

[Aneurysmal subarachnoid hemorrhage]. / Aneurysmatisch bedingte Subarachnoidalblutung.

Acute subarachnoid hemorrhage (SAH) is a severe and acute life-threatening cerebrovascular disease. Approximately 80% of all acute non-traumatic SAHs are the result of a ruptured cerebrovascular aneurysm. Despite advances in diagnosis and treatment a high morbidity and mortality still exists. Apart from the primary cerebral damage there are also secondary complications, such as vasospasm, rebleeding, hydrocephalus, cerebral edema or hydrocephalus. For an appropriate therapy an understanding of the extensive pathophysiology, the options in diagnostics and therapy and the complications of the disease are essential. Anesthesiologists are decisively involved in the therapy of the primary and secondary damages and subsequently in the outcome as well. This article provides an overview of the perioperative and intensive care management of patients with SAH.

[Histiocytic necrotizing lymphadenitis / Kikuchi-Fujimoto disease (HNL/K-F) and its differential diagnosis: analysis of 19 patients]. / Histiocytární nekrotizující lymfadenitida /Kikuchiho-Fujimotova choroba (HNL/K-F) a její diferenciální diagnostika: analýza 19 prípadu

Histiocytic necrotizing lymphadenitis / Kikuchi-Fujimoto disease (HNL/K-F) is being recognized with an increasing frequency not only in the East Asia but also on the American continents and in the Europe. Still the diagnostics of HNL/K-F is not easy and difficulties with its proper classification persist. In a group of 19 patients diagnosed primarily or as consults at our department there were 12 woman and 7 men. An average age at diagnosis was 28 years, median 25 years. Cervical lymph nodes were involved in 18 patients. Bilateral lymphadenopathy was present in one patient, the remaining 17 were unilateral. Inguinal lymph node was affected in one patient. In one other patient there were enlarged retroperitoneal lymph nodes simultaneously with a cervical lymphadenopathy. The size of the lymph nodes varied between 5 mm to 32 mm. The subclassification showed the necrotizing type in 14 patients, in one there was a predominant xanthomatous tissue reaction around the necrotic areas (xanthomatous type), and in 4 patients the disease was recognized as the proliferative type without necrosis (in two with a variously intense apoptosis of the proliferating lymphocytes). Of 10 consult cases the tumor was primarily evaluated as B cell lymphoma not otherwise specified (1x), peripheral T cell lymphoma (1x), classical Hodgkin lymphoma of mixed cellularity (1x); two patients were submitted with a differential diagnosis between peripheral T cell lymphoma and HNL/K-F; in one diagnosis of probable EBV lymphadenitis and in one diagnosis HNL/K-F was made. There were no data submitted in the remaining three cases. The authors stress diagnostic features which should lead to the diagnosis of the disease and should prevent unnecessary oncological staging investigations and potential chemotherapy for a lymphoma. Among diagnostic features of HNL/K-F identification of the proliferating cells - CD8 activated lymphocytes with apoptotic decay prevail, there are frequent plasmacytoid monocytes and a striking reaction of macrophages which are CD68/myeloperoxidase positive. There are virtually no neutrophil granulocytes and there is a miminal participation of plasma cells. In case of necrotizing and xanthomatous type infectious causes are to be ruled out as well. In case we still need to distinguish HNL/K-F from a lymphoma PCR analysis of a rearrangement of the immunoreceptor gene in T cell population should be investigated.

Maxillary ameloblastic fibroma in a dog.

A 4-year-old spayed female Golden Retriever was presented for evaluation of a rostral maxillary gingival mass. An en bloc resection was performed after histologic diagnosis of ameloblastic fibroma from an incisional biopsy specimen. Histologically, the tumor was composed of (1) poorly differentiated vimentin-positive mesenchymal cells that surrounded islands and (2) thin anastomosing trabeculae of odontogenic epithelium that variably coexpressed pancytokeratin and vimentin. To the authors' knowledge, this is the first report of ameloblastic fibroma in a dog. The clinical, radiographic, and histologic findings in this case are compared to those in other domestic animals and humans.

A standardised diagnostic approach to pituitary neuroendocrine tumours (PitNETs): a European Pituitary Pathology Group (EPPG) proposal.

The 2017 World Health Organization (WHO) classification proposes to type and subtype primary adenohypophyseal tumours according to their cell lineages with the aim to establish more uniform tumour groups. The definition of atypical adenoma was removed in favour of high-risk adenoma, and the assessment of proliferative activity and invasion was recommended to diagnose aggressive tumours. Recently, the International Pituitary Pathology Club proposed to replace adenoma with the term of pituitary neuroendocrine tumour (PitNET) to better reflect the similarities between adenohypophyseal and neuroendocrine tumours of other organs. The European Pituitary Pathology Group (EPPG) endorses this terminology and develops practical recommendations for standardised reports of PitNETs that are addressed to histo- and neuropathologists. This brief report presents the results of EPPG's consensus for the reporting of PitNETs and proposes a diagnostic algorithm.

[Sedation concepts with volatile anaesthetics in intensive care: practical use and current experiences with the AnaConDa system]. / Sedierung mit volatilen Anästhetika auf der Intensivstation : Praktische Anwendung und derzeitige Erfahrungen mit dem AnaConDa-System.

The use of volatile anaesthetics in intensive care medicine has so far been limited by the lack of equipment suitable for daily routine use and the need for an anaesthetic machine. The new Anaesthetic Conserving Device (AnaConDa) enables the routine use of volatile anaesthetics for long-term sedation via intensive care ventilators. The Anaesthetic Conserving Device replaces the common heat and moisture exchanger in the ventilation circuit. The volatile anaesthetic is continuously applied in liquid status via a syringe pump to a form of mini-vaporiser where the anaesthetic agent is vaporised. The expired anaesthetic gas is stored in the carbon filter and approximately 90% of the gas is resupplied into the breathing cycle. The current experiences suggest that volatile anaesthetics present an alternative for long-term sedation in intensive care units, providing optimised pathways, from a medical as well as from an economical point of view. It must, however, be emphasized that the use of volatile anaesthetics for longer periods of time is an off-label use and should only undertaken by medical professionals at their own risk.

Etiology and clinical relevance of elevated platelet count in ICU patients : A retrospective analysis.

BACKGROUND: Thrombocytosis is a common phenomenon in critically ill patients. Although thrombocytosis is an independent risk factor for complications, it does not seem to influence mortality in intensive care (ICU) patients. OBJECTIVES: Our investigation aimed to evaluate the etiological and clinical relevance of a platelet count greater than 450 × 109/l in ICU patients. MATERIALS AND METHODS: Patients admitted for a minimum of 4 days to an interdisciplinary ICU during a 45-month period were enrolled in this retrospective observational study. Thrombocytopenic patients (platelet count <150 × 109/l in at least one measurement) were excluded. The study patients were divided into two groups: thrombocytosis group (thrombocytes >450 × 109/l in at least one measurement) and control group (thrombocytes = 150 - 450 × 109/l during ICU stay). Univariate and multiple regression analysis were used to determine the influence of severe co-morbidities on the development of thrombocytosis and the association of elevated platelet count with thrombotic embolism, length of stay (LOS) in ICU, and mortality. RESULTS: A total of 307 patients were analyzed, of whom thrombocytosis was observed in 119 cases. Independent risk factors for the development of thrombocytosis included SIRS, mechanical ventilation, and acute bleeding. Increasing age reduced the risk of thrombocytosis. Thromboembolism occurred in 16 patients (13.4%) with an elevated platelet count and only in nine patients (4.7%) with physiological platelet values (OR: 3.1; 95% CI: 1.3-7.2; p = 0.009). Mean duration of LOS was significantly longer in patients with thrombocytosis (25.2 vs.11.7 days, p < 0.0001). Elevated platelet count showed a negative correlation with ICU mortality (OR: 0.32; 95%-CI: 0.12-0.83; p = 0.019). CONCLUSION: In our retrospective analysis the occurrence of thrombocytosis in a cohort of interdisciplinary ICU patients was associated with a higher rate of complications and longer LOS in the ICU. Despite these findings, thrombocytosis seems to reduce mortality in critical ill patients.

Use of catheters with the AgION antimicrobial system in kidney transplant recipients to reduce infection risk.

Microbial blood infection represents a high risk for immuno-suppressed patients. Of all catheter-related infections in the bloodstream, 90% result from the use of central venous catheters, the main cause being microbial colonization at the catheter's insertion point or the catheter hub. Between January 2003 and December 2004, 102 patients received a renal transplant including 57 who received a triple-lumen central venous catheter (CVC) during the procedure. Two catheters were used: a standard polyurethane catheter placed in the jugular veina or the subclavian veina for group I, and polyurethane catheters with the AgION antimicrobial system always placed in the subclavian veina for group II. Care and maintenance of the CVCs was standardized in both groups. After catheter removal, the tips were analyzed microbiologically. Of 57 (43.9%) CVCs, 25 were found to be contaminated. In the first group 24 out of 41 CVCs (58.5%) showed bacterial growth, whereas in group II only one catheter (6.6%) had a biofilm. The most common contaminant (18 out of 25, 72%) was Staphylococcus epidermidis. In group II, two patients had positive blood cultures yet a microbiologically sterile CVC. None of the catheters with the AgION antimicrobial system had to be removed owing to local infection or intolerance. The continuous release of silver ions increases the protection against bacteria and fungi during the entire time of catheterization. Use of catheters with the AgION antimicrobial system lead to a marked reduction in catheter-associated infections of the bloodstream.

Local and systemic hemorheological effects of cerebral hyper- and hypoperfusion in a porcine model.

Using a well defined pig model, we investigated whether cerebral hypertension and hypotension influence hemorheological factors. After surgical preparation and stabilization, periods of hyperventilation, controlled periods of cerebral perfusion pressure increases and decreases were utilized. After each period, blood samples were collected from the cannulated femoral artery and vein, and from the superior sagittal sinus. Erythrocyte deformability, whole blood and plasma viscosity and hematological parameters were determined. Erythrocyte deformability significantly worsened in arterial samples after hypertension and hypotension, and in sinus samples it was impaired after hypotension period. Hematocrit significantly increased in arterial and sinus samples during hypertensive period, accompanied by similar alterations in whole blood viscosity. We conclude that hemodynamic changes caused by hyperventilation, hyper- or hypotension can influence hemorheological factors, and suggest that the rheological alterations can affect local hemodynamic and metabolic conditions.

Cost-effectiveness of captopril therapy after myocardial infarction.

OBJECTIVES: This study sought to assess the cost-effectiveness of captopril therapy for survivors of myocardial infarction. BACKGROUND: The recent randomized, controlled Survival and Ventricular Enlargement (SAVE) trial showed that captopril therapy improves survival in survivors of myocardial infarction with an ejection fraction < or = 40%. The present ancillary study was designed to determine how the costs required to achieve this increase in survival compared with those of other medical interventions. METHODS: We developed a decision-analytic model to assess the cost-effectiveness of captopril therapy in 50- to 80-year old survivors of myocardial infarction with an ejection fraction < or = 40%. Data on costs, utilities (health-related quality of life weights) and 4-year survival were obtained directly from the SAVE trial, and long-term survival was estimated using a Markov model. In one set of analyses, we assumed that the survival benefit associated with captopril therapy would persist beyond 4 years (persistent-benefit analyses), whereas in another set we assumed that captopril therapy incurred costs but no survival benefit beyond 4 years (limited-benefit analyses). RESULTS: In the limited-benefit analyses, the incremental cost-effectiveness of captopril therapy ranged from $3,600/quality-adjusted life-year for 80-year old patients to $60,800/quality-adjusted life-year for 50-year old patients. In the persistent-benefit analyses, incremental cost-effectiveness ratios ranged from $3,700 to $10,400/quality-adjusted life-year, depending on age. The outcome was generally not sensitive to changes in estimates of variables when they were varied individually over wide ranges. In a "worst-case" analysis, incremental cost-effectiveness ratios for captopril therapy remained favorable ($8,700 to $29,200/quality-adjusted life-year) for 60- to 80-year old patients but were higher ($217,600/quality-adjusted life-year) for 50-year old patients. CONCLUSIONS: We conclude that the cost-effectiveness of captopril therapy for 50- to 80-year old survivors of myocardial infarction with a low ejection fraction compares favorably with other interventions for survivors of myocardial infarction.

A chemical phylogeny of group I introns based upon interference mapping of a bacterial ribozyme.

Despite its small size, the 205 nt group I intron from Azoarcus tRNA(Ile) is an exceptionally stable self-splicing RNA. This IC3 class intron retains the conserved secondary structural elements common to group I ribozymes, but lacks several peripheral helices. These features make it an ideal system to establish the conserved chemical basis of group I intron activity. We collected nucleotide analog interference mapping (NAIM) data of the Azoarcus intron using 14 analogs that modified the phosphate backbone, the ribose sugar, or the purine base functional groups. In conjunction with a complete interference set collected on the Tetrahymena group I intron (IC1 class), these data define a "chemical phylogeny" of functional groups that are important for the activity of both introns and that may be common chemical features of group I intron catalysts. The data identify the functional moieties most likely to play a conserved role as ligands for catalytic metal ions, the substrate helix, and the guanosine cofactor. These include backbone functional groups whose nucleotide identity is not conserved, and hence are difficult to identify by standard phylogenetic sequence comparisons. The data suggest that both introns utilize an equivalent set of long range tertiary interactions for 5'-splice site selection between the P1 substrate helix and its receptor in the J4/5 asymmetric bulge, as well as an equivalent set of 2'-OH groups for P1 helix docking into most of the single stranded segment J8/7. However, the Azoarcus intron appears to make an alternative set of interactions at the base of the P1 helix and at the 5'-end of the J8/7. Extensive differences were observed within the intron peripheral domains, particularly in P2 and P8 where the Azoarcus data strongly support the proposed formation of a tetraloop-tetraloop receptor interaction. This chemical phylogeny for group I intron catalysis helps to refine structural models of the RNA active site and identifies functional groups that should be carefully investigated for their role in transition state stabilization.

The use of complementary and alternative therapies to treat anxiety and depression in the United States.

OBJECTIVE: This study presents data on the use of complementary and alternative therapies to treat anxiety and depression in the United States. METHOD: The data came from a nationally representative survey of 2,055 respondents (1997-1998) that obtained information on the use of 24 complementary and alternative therapies for the treatment of specific chronic conditions. RESULTS: A total of 9.4% of the respondents reported suffering from "anxiety attacks" in the past 12 months; 7.2% reported "severe depression." A total of 56.7% of those with anxiety attacks and 53.6% of those with severe depression reported using complementary and alternative therapies to treat these conditions during the past 12 months. Only 20.0% of those with anxiety attacks and 19.3% of those with severe depression visited a complementary or alternative therapist. A total of 65.9% of the respondents seen by a conventional provider for anxiety attacks and 66.7% of those seen by a conventional provider for severe depression also used complementary and alternative therapies to treat these conditions. The perceived helpfulness of these therapies in treating anxiety and depression was similar to that of conventional therapies. CONCLUSIONS: Complementary and alternative therapies are used more than conventional therapies by people with self-defined anxiety attacks and severe depression. Most patients visiting conventional mental health providers for these problems also use complementary and alternative therapies. Use of these therapies will likely increase as insurance coverage expands. Asking patients about their use could prevent adverse effects and maximize the usefulness of therapies subsequently proven to be effective.

Impact of physician experience on triage of emergency room patients with acute chest pain at three teaching hospitals.

PURPOSE: To determine whether the experience of the physician (as measured by postgraduate training level or time during the academic year) who performs the initial evaluation affects the triage of patients with acute chest pain. PATIENTS AND METHODS: Prospective data on the presenting clinical features, initial triage, final diagnosis, and complications were collected for 7,857 patients who presented to the emergency rooms of three teaching hospitals, including 1,118 (14%) with acute myocardial infarction (AMI), 2,477 (32%) with acute ischemic heart disease (AIHD) (i.e., AMI or unstable angina), and 335 (4%) with major complications. The experience of the evaluating physicians, who were in their first three postgraduate years in 93% of cases, was measured in three ways: (1) postgraduate training level, (2) month during the academic year, and (3) number of patients with acute chest pain previously evaluated. Multivariate logistic regression analyses that adjusted for hospital site and 20 clinical variables estimated the odds ratios for admission to the coronary care unit (CCU) and hospital associated with each incremental increase in physician experience. RESULTS: With more experience (as measured by postgraduate training level or time during the academic year), the sensitivity of physicians for admitting patients with AMI, AIHD, or major complications to the hospital increased. For example, each incremental increase in postgraduate training level carried a 1.4 increase in the adjusted odds ratio for admission of a patient with AIHD to the hospital (p less than 0.05), corresponding to an increase in the probability of admission from 93% to 97%. However, increasing physician experience was also associated with an elevated false-positive rate in admitting patients without these diagnoses to the CCU and hospital. Thus, each incremental increase in postgraduate training level carried a 1.2 increase in the adjusted odds ratio for admission of a patient without AIHD to the CCU and hospital (p less than 0.005), corresponding to an increase in the probability of admission from 34% to 47%. By receiver operating characteristic curve (ROC) regression analyses, these changes in triage patterns were consistent with movement along a single ROC curve, rather than a shift to a new or better ROC curve. CONCLUSIONS: As the experience of the physician who performed the initial evaluation increased, there was a lower threshold for admitting all patients with and without AMI, AIHD, or major complications to the CCU and hospital without a detectable improvement in diagnostic accuracy.

Patient race and decisions to withhold or withdraw life-sustaining treatments for seriously ill hospitalized adults. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

PURPOSE: Patient race is associated with decreased resource use for seriously ill hospitalized adults. We studied whether this difference in resource use can be attributed to more frequent or earlier decisions to withhold or withdraw life-sustaining therapies. SUBJECTS AND METHODS: We studied adults with one of nine illnesses that are associated with an average 6-month mortality of 50% who were hospitalized at five geographically diverse teaching hospitals participating in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). We examined the presence and timing of decisions to withhold or withdraw ventilator support and dialysis, and decisions to withhold surgery. Analyses were adjusted for demographic characteristics, prognosis, severity of illness, function, and patients' preferences for life-extending care. RESULTS: The mean (+/- SD) age of the patients was 63 +/- 16 years; 16% were African-American, 44% were women, and 53% survived for 6 months or longer. Of the 9,076 patients, 5,349 (59%) had chart documentation that ventilator support had been considered in the event the patient's condition required such a treatment to sustain life, 2,975 charts (33%) had documentation regarding major surgery, and 1,293 (14%) had documentation of discussions about dialysis. There were no significant differences in the unadjusted rates of decisions to withhold or withdraw treatment among African-Americans compared with non-African-Americans: among African-Americans, 33% had a decision made to withhold or withdraw ventilator support compared with 35% among other patients, 14% had a decision made to withhold major surgery compared with 12% among other patients, and 25% had a decision made to withhold or withdraw dialysis compared with 30% among other patients (P >0.05 for all comparisons). After adjustment for demographic characteristics, prognosis, illness severity, function, and preferences for care, there were no differences in the timing or rate of decisions to withhold or withdraw treatments among African-Americans compared with non-African-American patients. CONCLUSION: Patient race does not appear to be associated with decisions to withhold or withdraw ventilator support or dialysis, or to withhold major surgery, in seriously ill hospitalized adults.

Long-term survival of emergency department patients with acute chest pain.

To evaluate the long-term prognosis of patients with acute chest pain, prospective clinical data and long-term follow-up data (mean 30.1 +/- 9.4 months) were collected for 1,956 patients who presented to the emergency department of an urban teaching hospital with this chief complaint. During follow-up of the 1,915 patients who were discharged alive from the emergency department or hospital, there were 113 (6%) cardiovascular deaths. No differences were detected in the post-discharge cardiovascular survival rates after 3 years of experience with patients who were discharged from the emergency department with a known prior diagnosis of angina or myocardial infarction (89%) and patients who had been admitted and found to have acute myocardial infarction (85%), angina (87%), or other cardiovascular diagnoses (87%). Patients who were discharged from either the hospital or the emergency department without cardiovascular diagnoses had an excellent prognosis. Multivariate Cox regression analysis identified 5 independent correlates of cardiovascular mortality after discharge: age, prior history of coronary disease, ischemic changes on the emergency department electrocardiogram, congestive heart failure and cardiogenic shock. These findings indicate that the postdischarge cardiovascular mortality of patients with chest pain who are discharged from the emergency department with a known history of coronary disease is similar to that of admitted patients with angina or myocardial infarction. These data suggest that the same types of prognostic evaluation strategies that have been developed for admitted patients with ischemic heart disease should also be considered when such patients present to the emergency department but are not admitted.

Inhalation of PM2.5 does not modulate host defense or immune parameters in blood or lung of normal human subjects.

We tested the hypothesis that exposure of healthy volunteers to concentrated ambient air particles (CAPS) between 0.1 and 2.5 microm in diameter is associated with modulation of human alveolar macrophage (AM) function, cytokine production, and immune phenotype in both blood and lung. Thirty-eight volunteers were exposed to either filtered air or CAPS from the immediate environment of the U.S. Environmental Protection Agency human studies facility in Chapel Hill, North Carolina, USA. Particle concentrations in the chamber during the exposures ranged from 23.1 to 311.1 microg/m3. No symptoms were noted by volunteers after the exposure. Eighteen hours after exposure, analysis of cells obtained by bronchoalveolar lavage (BAL) showed a mild increase in neutrophils in both the bronchial (8.4 +/- 2%) and alveolar fractions (4.2 +/- 1.7%) in subjects exposed to the highest concentration of CAPS compared to neutrophils in the fluids of those exposed to filtered air (bronchial fraction 2.7 +/- 0.6%; alveolar fraction 0.8 +/- 0.3%). There was no change in the percentage of lymphocytes or AMs recovered in the lavage after inhalation of the highest particle levels (mean 207 microg/m3). There was also no change in the proportion of lymphocytes in the BAL expressing CD3, CD4, CD8, CD19, nor activation markers CD25 or CD69. Particle inhalation did not affect the expression of CD11b, CD64, CD16, CD14, CD71 on AM, nor was there an effect on phagocytosis or oxidant generation following stimulation with zymosan A. IL-6 and IL-8 levels detected by enzyme-linked immunoabsorbent assay in the BAL were unrelated to inhaled particle levels. The distribution of lymphocyte subsets in blood obtained 18 hr after exposure to CAPS did not differ from that found before exposure. We conclude that ambient air particles are capable of inducing a mild inflammation in the lower respiratory tract but have no effect on immune phenotype or macrophage function under the conditions tested.