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Background: Approximately 6 million U.S. patients present to emergency departments annually with symptoms suggesting acute cardiac ischemia. Triage decisions for these patients are important but remain difficult.Objective: To test whether computerized prediction of the probability of acute ischemia, used with electrocardiography, improves the accuracy of triage decisions.Design: Controlled clinical trial.Setting: 10 hospital emergency departments in the midwestern, southeastern, and northeastern United States.Patients: 10689 patients with chest pain or other symptoms suggestive of acute cardiac ischemia.Intervention: The probability of acute ischemia predicted by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), either automatically printed or not printed on patients' electrocardiograms.Measurements: Emergency department triage to a coronary care unit (CCU), telemetry unit, ward, or home. Other measurements were the bed capacity of the CCU relative to that of the telemetry unit; training or supervision status of the triaging physician; and patient diagnoses and outcomes based on clinical, electrocardiographic, and creatine kinase data.Results: For patients without cardiac ischemia, in hospitals with high-capacity CCUs and relatively low-capacity cardiac telemetry units, use of ACI-TIPI was associated with a reduction in CCU admissions from 15% to 12%, a change of -16% (95% CI, -30% to 0%), and an increase in emergency department discharges to home from 49% to 52%, a change of 6% (CI, 0% to 14%; overall P=0.09). Across all hospitals, for patients evaluated by unsupervised residents, use of ACI-TIPI was associated with a reduction in CCU admissions from 14% to 10%, a change of -32% (CI, -55% to 3%); a reduction in telemetry unit admissions from 39% to 31%, a change of -20% (CI, -34% to -2%); and an increase in discharges to home from 45% to 56%, a change of 25% (CI, 8% to 45%; overall P=0.008). Among patients with stable angina, in hospitals with high-capacity CCUs, use of ACI-TIPI was associated with a reduction in CCU admissions from 26% to 13%, a change of -50% (CI, -70% to -17%), and an increase in discharges to home from 20% to 22%, a change of 10% (CI, -29% to 71%; overall P=0.02). At hospitals with high-capacity telemetry units, use of ACI-TIPI was associated with a reduction in telemetry unit admissions from 68% to 59%, a change of -14% (CI, -27% to 1%), and an increase in emergency department discharges to home from 10% to 21%, a change of 100% (CI, 22% to 230%; overall P=0.02). Among patients with acute myocardial infarction or unstable angina, use of ACI-TIPI did not change appropriate admission (96%) to the CCU or telemetry unit at hospitals with high-capacity CCUs or telemetry units.Conclusions: Use of ACI-TIPI was associated with reduced hospitalization among emergency department patients without acute cardiac ischemia. This result varied as expected according to the CCU and cardiac telemetry unit capacities and physician supervision at individual hospitals. Appropriate admission for unstable angina or acute infarction was not affected. If ACI-TIPI is used widely in the United States, its potential incremental impact may be more than 200000 fewer unnecessary hospitalizations and more than 100000 fewer unnecessary CCU admissions. [ABSTRACT FROM AUTHOR]

Objectives: This study compared diagnostic accuracy of conventional troponin/traditional coronary artery disease (CAD) assessment and highly sensitive troponin (hsTn) I/advanced CAD assessment for acute coronary syndrome (ACS) during the index hospitalization., Background: hsTnI and advanced assessment of CAD using coronary computed tomography angiography (CTA) are promising candidates to improve the accuracy of emergency department evaluation of patients with suspected ACS., Methods: We performed an observational cohort study in patients with suspected ACS enrolled in the ROMICAT II (Rule Out Myocardial Infarction/Ischemia using Computer Assisted Tomography) trial and randomized to coronary CTA who also had hsTnI measurement at the time of the emergency department presentation. We assessed coronary CTA for traditional (no CAD, nonobstructive CAD, ≥50% stenosis) and advanced features of CAD (≥50% stenosis, high-risk plaque features: positive remodeling, low <30-Hounsfield units plaque, napkin-ring sign, spotty calcium)., Results: Of 160 patients (mean age: 53 ± 8 years, 40% women) 10.6% were diagnosed with ACS. The ACS rate in patients with hsTnI below the limit of detection (n = 9, 5.6%), intermediate (n = 139, 86.9%), and above the 99th percentile (n = 12, 7.5%) was 0%, 8.6%, and 58.3%, respectively. Absence of ≥50% stenosis and high-risk plaque ruled out ACS in patients with intermediate hsTnI (n = 87, 54.4%; ACS rate 0%), whereas patients with both ≥50% stenosis and high-risk plaque were at high risk (n = 13, 8.1%; ACS rate 69.2%) and patients with either ≥50% stenosis or high-risk plaque were at intermediate risk for ACS (n = 39, 24.4%; ACS rate 7.7%). hsTnI/advanced coronary CTA assessment significantly improved the diagnostic accuracy for ACS as compared to conventional troponin/traditional coronary CTA (area under the curve 0.84, 95% confidence interval [CI]: 0.80 to .88 vs. 0.74, 95% CI: 0.70 to 0.78; p < 0.001)., Conclusions: hsTnI at the time of presentation followed by early advanced coronary CTA assessment improves the risk stratification and diagnostic accuracy for ACS as compared to conventional troponin and traditional coronary CTA assessment. (Multicenter Study to Rule Out Myocardial Infarction/Ischemia by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Sensitive troponin (Tn) assays have been developed for the evaluation of patients with suspected acute coronary syndrome (ACS). We sought to compare the performance of a commercially available sensitive Tn I (sTnI) and precommercial highly sTnI (hsTnI) method to conventional Tn (cTn) assays., Methods: Among patients with acute chest pain but normal cTn in the emergency department of 6 centers, sTnI and hsTnI were measured at baseline, 2 and 4 hours after presentation. Diagnostic accuracy of sTnI and hsTnI relative to cTn for diagnosis during index hospitalization as well as their associations with coronary artery disease in patients randomized to coronary computed tomographic angiography (CTA) was assessed., Results: Overall, 322 patients were enrolled, of whom 161 had a CTA; 28 had ACS (8.7%), including 21 with unstable angina pectoris (UAP). Both sTnI and hsTnI values at baseline and second draw had significantly higher sensitivity for ACS and UAP than cTn and had significantly greater area under the receiver operator characteristic curve than cTn at first and second draws. Compared with cTn, 29% of ACS cases previously categorized as UAP were reclassified to acute myocardial infarction with sTnI or hsTnI. An hsTnI below limit of detection had 100% negative predictive value for ACS or significant coronary artery stenosis in those randomized to CTA., Conclusions: In patients with acute chest discomfort, use of sTnI and hsTnI methods led to significant improvement in the early diagnostic accuracy for ACS, reclassifying one-third of UAP to myocardial infarction. Very low values for hsTnI excluded underlying coronary artery disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Successful shock management requires prompt identification, classification, and treatment; however, the triage of patients with non-hemorrhagic shock to the trauma room can lead to delayed diagnosis with increased morbidity and mortality., Objective: Our goal is to emphasize the importance of shock identification and classification to facilitate the delivery of the appropriate and timely therapy, no matter how the patient is triaged., Case Report: We describe a patient triaged as a trauma patient with suspected hemorrhagic shock yet who was found to have anaphylaxis as the etiology of his condition. Abdominal anaphylaxis, a less recognized presentation of anaphylaxis, is reviewed and discussed., Conclusions: We hope to increase awareness of a less common presentation of anaphylaxis and discuss its management., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: It is unclear whether an evaluation incorporating coronary computed tomographic angiography (CCTA) is more effective than standard evaluation in the emergency department in patients with symptoms suggestive of acute coronary syndromes., Methods: In this multicenter trial, we randomly assigned patients 40 to 74 years of age with symptoms suggestive of acute coronary syndromes but without ischemic electrocardiographic changes or an initial positive troponin test to early CCTA or to standard evaluation in the emergency department on weekdays during daylight hours between April 2010 and January 2012. The primary end point was length of stay in the hospital. Secondary end points included rates of discharge from the emergency department, major adverse cardiovascular events at 28 days, and cumulative costs. Safety end points were undetected acute coronary syndromes., Results: The rate of acute coronary syndromes among 1000 patients with a mean (±SD) age of 54±8 years (47% women) was 8%. After early CCTA, as compared with standard evaluation, the mean length of stay in the hospital was reduced by 7.6 hours (P<0.001) and more patients were discharged directly from the emergency department (47% vs. 12%, P<0.001). There were no undetected acute coronary syndromes and no significant differences in major adverse cardiovascular events at 28 days. After CCTA, there was more downstream testing and higher radiation exposure. The cumulative mean cost of care was similar in the CCTA group and the standard-evaluation group ($4,289 and $4,060, respectively; P=0.65)., Conclusions: In patients in the emergency department with symptoms suggestive of acute coronary syndromes, incorporating CCTA into a triage strategy improved the efficiency of clinical decision making, as compared with a standard evaluation in the emergency department, but it resulted in an increase in downstream testing and radiation exposure with no decrease in the overall costs of care. (Funded by the National Heart, Lung, and Blood Institute; ROMICAT-II ClinicalTrials.gov number, NCT01084239.).

Study Objective: Health care reform in Massachusetts improved access to health insurance, but the extent to which reform affected utilization of the emergency department (ED) for conditions potentially amenable to primary care is unclear. Our objective is to determine the relationship between health reform and ED use for low-severity conditions., Methods: We studied ED visits, using a convenience sample of 11 Massachusetts hospitals for identical 9-month periods before and after health care reform legislation was implemented in 2006. Individuals most affected by the health reform law (the uninsured and low-income populations covered by the publicly subsidized insurance products) were compared with individuals unlikely to be affected by the legislation (those with Medicare or private insurance). Our main outcome measure was the rate of overall and low-severity ED visits for the study population and the comparison population during the period before and after health reform implementation., Results: Total visits increased from 424,878 in 2006 to 442,102 in 2008. Low-severity visits among publicly subsidized or uninsured patients decreased from 43.8% to 41.2% of total visits for that group (difference=2.6%; 95% confidence interval [CI] 2.25% to 2.85%), whereas low-severity visits for privately insured and Medicare patients decreased from 35.7% to 34.9% of total visits for that group (difference=0.8%; 95% CI 0.62% to 0.98%), for a difference in differences of 1.8% (95% CI 1.7% to 1.9%)., Conclusion: Although overall ED volume continues to increase, Massachusetts health reform was associated with a small but statistically significant decrease in the rate of low-severity visits for those populations most affected by health reform compared with a comparison population of individuals less likely to be affected by the reform. Our findings suggest that access to health insurance is only one of a multitude of factors affecting utilization of the ED., (Copyright © 2010 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Background: Many studies have shown differences in cardiac care by racial/ethnic groups without accounting for institutional factors at the location of care., Objective: Exploratory analysis of the effect of hospital funding status (public vs private) on emergency department (ED) triage decision making for patients with symptoms suggestive of acute coronary syndromes (ACSs) and on the likelihood of ED discharge for patients with confirmed ACS., Study Design and Setting: Secondary analysis of data from a randomized controlled trial of 10,659 ED patients with possible ACS in five urban academic public and five private hospitals. The main outcome measures were the sensitivity and specificity of hospital admission for the presence of ACS at public and private hospitals and the adjusted odds of a patient with ACS not being hospitalized at public versus private hospitals., Results: Of 10,659 ED patients, 1,856 had confirmed ACS. For patients with suspected ACS, triage decisions at private hospitals were considerably more sensitive (99 vs 96%; p<.001) but less specific (30 vs 48%; p<.001) than at public hospitals. The difference between hospital types persisted after adjustment for multiple patient-level and hospital-level characteristics., Conclusion: Significant differences in triage for patients with suspected ACS exist between public and private hospital EDs, even after adjustment for multiple patient demographic, clinical, and institutional factors. Further studies are needed to clarify the causes of the differences.

Failure to diagnose patients who have acute coronary syndromes (ACSs)-either acute myocardial infarction (AMI) or unstable angina pectoris (UAP)-who present to the emergency department (ED) remains a serious public health issue. Better understanding of the pathophysiology of coronary artery disease has allowed the adoption of a unifying hypothesis for the cause of ACSs: the conversion of a stable atherosclerotic lesion to a plaque rupture with thrombosis. Thus, physicians have come to appreciate UAP and AMI as parts of a continuum of ACSs. This article reviews the state of the art regarding the diagnosis of ACSs in the emergency setting and suggests reasons why missed diagnosis continues to occur, albeit infrequently.

We studied the impact on triage and outcome of patients presenting to the emergency department (ED) with symptoms suggestive of an acute coronary syndromes (ACS) but without a complaint of pain. Data from a prospective clinical trial of patients with symptoms suggesting an ACS in the EDs of 10 US hospitals comparing patient demographics, clinical variables, and outcomes was used to perform a secondary analysis. Of 10,783 subjects, a final diagnosis of an ACS was confirmed in 24% of which 35% had acute myocardial infarction (AMI) and 65% unstable angina pectoris (UAP). Pain was absent in 6.2% of patients with acute ischemia and in 9.8% of those with AMI. Compared to similar patients who presented with pain, patients with painless ischemia were older, were more commonly women, had more cardiac and related diseases. Among patients with AMI, fewer patients without pain were admitted to critical care units compared to similar patients with pain. Among patients with AMI, logistic regression predicting lack of pain identified age, heart failure and diabetes, with only age and heart failure among all with ACS. After controlling for clinical features, lack of pain during acute ischemia predicted increased hospital mortality. We concluded that age and heart failure are independently associated with painless ACS, in addition to diabetes among those with AMI. Lack of pain predicts increased hospital mortality in patients with ACI through mechanisms that remain to be elucidated. There is a need for greater awareness in the general public of the different manifestations of ACS to enhance the recognition of and prompt response to their symptoms.

Background: Resting myocardial perfusion imaging (MPI) improves the triage of patients presenting to the emergency department (ED) with symptoms suggestive of acute cardiac ischemia (ACI). In the ED setting the presence of diabetes mellitus (DM) is a predictor of ACI and hospitalization, but the role of resting MPI in patients with DM is unknown., Methods and Results: A secondary data analysis of a prospective, multicenter, randomized, controlled trial of ED evaluation strategies in patients with symptoms suggestive of ACI and normal or nondiagnostic electrocardiograms was performed. In the main trial 2475 patients were randomized to receive either the usual ED evaluation strategy (n = 1260) or the usual strategy supplemented by results from resting MPI by use of single photon emission computed tomography (SPECT) technetium 99m sestamibi (n = 1215). Patients with diabetes (n = 341) were evaluated separately. Imaging results, final diagnoses, effect on triage, and prognostic value of the SPECT imaging were compared between diabetic and nondiabetic patients. Of the 341 patients with diabetes, 153 (45%) were randomized to the imaging strategy. Patients with DM had higher rates of hospitalization (66% vs 49.6%, P = .0001) and ACI (21.1% vs 12.0%, P < .001) than patients without DM. Among diabetic patients without ACI, the admission rate was 63% in the usual strategy group versus 54% in the imaging strategy group (relative risk [RR] = 0.91 [95% CI, 0.76-1.06]; P = .24). There was no difference in the magnitude of this reduced risk of admission compared with patients without DM (RR = 0.84 [95% CI, 0.77-0.92]; P = .0002 for patients without DM and P = .35 for interaction of diabetes and RR reduction)., Conclusions: Acute resting MPI with Tc-99m sestamibi is associated with improved triage decision making in symptomatic ED patients with diabetes.

We studied the impact on triage and outcome of the presence of left ventricular hypertrophy (LVH) and left/right bundle branch block (LBBB/RBBB) on the initial ED electrocardiogram (ECG) for patients with symptoms suggestive of an acute coronary syndrome (ACS). Secondary analysis of data from a prospective clinical trial of patients with chest pain or other symptoms suggesting ACS in six U.S. hospitals comparing patient demographics, clinical variables, and outcomes was used. Of 5,324 study patients, 3% had ECG-LVH, 3% had LBBB, 3% had RBBB, and 43% had ischemic ST segment or T wave abnormalities. Compared with patients without ST segment or T wave abnormalities, patients with ECG-LVH or BBB were older and were more likely to have a chief complaint of shortness of breath or a history of cardiac or related diseases. Patients with ECG-LVH or BBB had more diagnoses of congestive heart failure (CHF) and ACS compared with patients without these ECG abnormalities and were just as likely to have ACS as their diagnosis compared with patients with ischemic ST segment or T wave abnormalities. Having ECG-LVH or BBB did not alter the true-positive rate for ACS but increased the false-positive rate by almost 50%. Patients with ECG-LVH had approximately 3.5 times the 30-day mortality rate as those without these ECG abnormalities. It appears that for patients with symptoms suggestive of ACS, the presence of ECG-LVH or BBB did not alter the ability of ED clinicians to identify patients with ACS but was associated with a 50% higher false-positive admission rate compared with similar patients without these ECG abnormalities. With a short-term mortality rate 3.5 times that for patients without ECG-LVH, selected patients with ECG-LVH and symptoms suggesting ACS might benefit from hospitalization for further evaluation.

A better understanding of coronary syndromes allow physicians to appreciate UAP and AMI as part of a continuum of ACI. ACI is a life-threatening condition whose identification can have major economic and therapeutic importance as far as threatening dysrhythmias and preventing or limiting myocardial infarction size. The identification of ACI continues to challenge the skill of even experienced clinicians, yet physicians continue (appropriately) to admit the overwhelming majority of patients with ACI; in the process, they admit many patients without acute ischemia [2], overestimating the likelihood of ischemia in low-risk patients because of magnified concern for this diagnosis for prognostic and therapeutic reasons. Studies of admitting practices from a decade ago have yielded useful clinical information but have shown that neither clinical symptoms nor the ECG could reliably distinguish most patients with ACI from those with other conditions. Most studies have evaluated the accuracy of various technologies for diagnosing ACI, yet only a few have evaluated the clinical impact of routine use. The prehospital 12-lead ECG has moderate sensitivity and specificity for the diagnosis of ACI. It has demonstrated a reduction of the mean time to thrombolysis by 33 minutes and short-term overall mortality in randomized trials. In the general ED setting, only the ACI-TIPI has demonstrated, in a large-scale multicenter clinical trial, a reduction in unnecessary hospitalizations without decreasing the rate of appropriate admission for patients with ACI. The Goldman chest pain protocol has good sensitivity for AMI but was not shown to result in any differences in hospitalization rate, length of stay, or estimated costs in the single clinical impact study performed. The protocol's applicability to patients with UAP has not been evaluated. Single measurement of biomarkers at presentation to the ED has poor sensitivity for AMI, although most biomarkers have high specificity. Serial measurements can greatly increase the sensitivity for AMI while maintaining their excellent specificity. Biomarkers cannot identify most patients with UAP. Finally, diagnostic technologies to evaluate ACI in selected populations, such as echocardiography, sestamibi perfusion imaging, and stress ECG, may have very good to excellent sensitivity; however, they have not been sufficiently studied.

Context: Observational studies of acute myocardial perfusion imaging in emergency department (ED) patients with chest pain have suggested high sensitivity and negative predictive value for acute cardiac ischemia, but use of this method has not been prospectively tested., Objective: To assess whether incorporating acute resting perfusion imaging into an ED evaluation strategy for patients with suspected acute ischemia but no initial electrocardiogram (ECG) changes diagnostic of acute ischemia improves clinical decision making for initial ED triage., Design, Setting, and Patients: Prospective, randomized controlled trial conducted at 7 academic medical centers and community hospitals between July 1997 and May 1999 among 2475 adult ED patients with chest pain or other symptoms suggestive of acute cardiac ischemia and with normal or nondiagnostic initial ECG results., Intervention: Patients were randomly assigned to receive either the usual ED evaluation strategy (n = 1260) or the usual strategy supplemented with results from acute resting myocardial perfusion imaging using single-photon emission computed tomography with injection of 20 to 30 mCi of Tc-99m sestamibi (n = 1215), interpreted in real time by local staff physicians and with results provided to the ED physician for incorporation into clinical decision making., Main Outcome Measure: Appropriateness of triage decision either to admit to hospital/observation or to discharge directly home from the ED., Results: Among patients with acute cardiac ischemia (ie, acute myocardial infarction [MI] or unstable angina; n = 329), there were no differences in ED triage decisions between those receiving standard evaluation and those whose evaluation was supplemented by a sestamibi scan. Among patients with acute MI (n = 56), 97% vs 96% were hospitalized (relative risk [RR], 1.00; 95% confidence interval [CI], 0.89-1.12), and among those with unstable angina (n = 273), 83% vs 81% were hospitalized (RR, 0.98; 95% CI, 0.87-1.10). However, among patients without acute cardiac ischemia (n = 2146), hospitalization was 52% with usual care vs 42% with sestamibi imaging (RR, 0.84; 95% CI, 0.77-0.92)., Conclusions: Sestamibi perfusion imaging improves ED triage decision making for patients with symptoms suggestive of acute cardiac ischemia without obvious abnormalities on initial ECG. In this study, unnecessary hospitalizations were reduced among patients without acute ischemia, without reducing appropriate admission for patients with acute ischemia.

Identification of patients with acute cardiac ischemia (ACI) remains challenging. The object of this study was to examine the role of clinical findings in the diagnosis/triage of emergency department (ED) patients with symptoms suggestive of ACI. The study was designed as a secondary data analysis of a multicenter prospective controlled clinical trial. It was set in 10 midwest, southeast, and northeast U.S. hospitals, and 10,689 patients with chest pain or other symptoms suggesting ACI presenting from May 1993 to December 1993, participated. The results indicated that ACI patients were more likely to have chest pain as a chief complaint or presenting symptom (P = 0.001). The presenting symptom of nausea was more commonly associated with a final diagnosis of ACI (P = 0.003). Shortness of breath as the chief complaint and presenting symptoms of abdominal pain, nausea, dizziness, and fainting were less frequent among patients with a final diagnosis of ACI (P = 0.001). A past history of diabetes mellitus, myocardial infarction, or angina pectoris was more frequently associated with a final diagnosis of ACI (P = 0.001). A lower pulse rate in patients with a final diagnosis of ACI (P = 0.001) was not considered clinically significant. Median first and highest systolic blood pressures (SBPs) were higher, median lowest SBPs were lower, median diastolic blood pressure of the lowest SBPs were lower, and initial and highest pulse pressures were wider in patients with a final diagnosis of ACl (P = 0.001). On arrival, these blood pressure variables in AMI patients, subsequently classified as Killip class 4, were above the threshold for this classification. Rales were more commonly present in patients with a final diagnosis of ACI (P = 0.001). All primary ST-segment abnormalities, Q waves, and T-wave abnormalities, except T-wave flattening, were seen more frequently in patients with a final diagnosis ACI (P = 0.001). Normal ECGs were more frequently associated with a non-ACI final diagnosis, yet 20% of AMI patients and 37% of Unstable Angina Pectoris (UAP) patients had normal ECGs. It can be concluded that certain clinical features can help to identify ED patients with ACI. Initially normal ECGs can be seen in 20% of patients with AMI and 37% of patients with UAP. Patients with ACI can present with "normal" blood pressures and develop cardiogenic shock. Clinical outcome data for ACI patients are presented.

Vertically transmitted HIV disease constitutes a significant problem in pediatrics. In order to characterize some of the possible host factors involved in HIV replication in fetuses and newborns, we surveyed the HIV-1 LTR binding factors present in nuclear extracts from cord blood mononuclear cells. A series of electrophoretic mobility shift assays (EMSAs) showed that protein extracts from cord blood interacted with several regions of the HIV LTR. The most prominent binding activities involved the NF-kB sites, but other regions of the LTR also showed factor binding with the cord blood extracts. Some of these cord blood extract binding activities displayed qualitative differences when compared to adult peripheral blood mononuclear cell extracts in EMSA and UV cross-linking studies. Transient transfection experiments indicated that the NF-kB and Sp1 sequences were important for wild type levels of expression in cord blood cells, but that additional sequences 5' to the NF-kB sites also contributed activity. Thus, factors that interact with many of the well-known HIV LTR regulatory sites are present in cord blood cells. However, certain qualitative differences distinguished cord blood and adult peripheral blood binding activities and these may contribute to pathogenesis of HIV infection in neonates.

Human immunodeficiency virus type 1 (HIV-1) isolates classified as syncytium-inducing (SI) or non-SI (NSI) in the MT-2 T-cell line exhibit characteristic sequence differences in the V1-V2 and V3 regions of the env gene. Seven HIV-1 isolates were phenotyped as NSI or SI in the MT-2 cell line. Unexpectedly, all four NSI viruses induced large syncytia 4 to 8 days postinoculation in a panel of five primary CD4+ T-cell lines (including two clones) generated from the peripheral blood of normal donors by exposure to infectious HIV-1, inactivated HIV-1, or Epstein-Barr virus. The primary T-cell lines yielded neither HIV-1 provirus nor infectious HIV by PCR analysis or exhaustive coculture with phytohemagglutinin-treated blast cells. Three isolates (TC354, PK1, and PK2) were biologically cloned and retained their SI or NSI phenotypes in MT-2 and primary T-cell lines. The biologically cloned provirus DNA was also used to clone and sequence the relevant V2 and V3 regions of the env genes. The amino acid sequences of the V2 and V3 regions were characteristic of patterns already reported for the NSI, switch NSI, and SI phenotypes, respectively. This evidence precludes the possibility that these results were due to contamination of the NSI isolates with SI virus. The results unequivocally indicate that HIV-1 isolates with the NSI genotype and phenotype in MT-2 cells may actively induce syncytia in cloned CD4+ T cells in vitro and support the view that direct cytopathic effects may contribute to the steady decline in CD4+ T cells in asymptomatic HIV-1-seropositive patients without detectable SI virus.

Respiratory syncytial virus (RSV) can inhibit the proliferative response of human peripheral blood mononuclear cells (PBMC) in vitro. This inhibition is mediated by an extracellular RSV-induced factor. In the present study, the factor was clearly identified as interferon (IFN)-alpha. The RSV-induced IFN-alpha bound strongly to PBMC and inhibited the anti-RSV proliferative response only when added within the first few days of stimulation. There was, however, no concomitant decrease in the production of interleukin (IL)-2 nor in the cell surface expression of CD25, CD71, and HLA-DR. Inhibition by RSV-induced IFN-alpha was unrelated to the levels of IL-1, -2, and -6 or of IFN-gamma induced by RSV in vitro or to the presence of IL-1 inhibitor, tumor necrosis factor-alpha, prostaglandin, or IL-10. Immunosuppression by IFN-alpha may significantly affect the outcome of infection and reinfection with RSV.

Background: Although exanthem subitum (ES) is generally a mild, self-limiting disease of early childhood, some cases of ES are complicated by seizures and encephalopathy. The presence of human herpesvirus-6 (HHV-6) DNA in cerebrospinal fluid (CSF) of these patients suggests that HHV-6 can infect the central nervous system (CNS) causing encephalitis., Objectives: To demonstrate HHV-6 infection in two patients with serious CNS complications. The patients, a child and an adult, failed to develop the characteristic rash normally associated with ES., Study Design: Peripheral blood mononuclear cells (PBMCs) and CSF were examined for the presence of HHV-6 or viral DNA, using virus isolation techniques and the polymerase chain reaction (PCR). Serum samples were tested by immunofluorescence (IF) and enzyme linked immuno-sorbent assay (ELISA) for the presence of anti-HHV-6 IgM and anti-HHV-6 IgG respectively., Results: HHV-6 was isolated from the PBMCs of the adult patient and the presence of virus in these cells was confirmed using electron microscopy. HHV-6 DNA was detected in CSF taken early during the infection in both patients, together with anti-HHV-6 IgM antibodies and increasing levels of anti-HHV-6 IgG., Conclusions: The diagnosis of HHV-6 infection in these patients was confirmed either by virus isolation or by the detection of HHV-6 DNA in the CSF, and the results of serology. These cases show that HHV-6 infection may result in serious CNS complications, in children and adults.

The 104 skin biopsies from 34 patients who attended a Renal Transplant Unit in Brisbane over 12 months included 40 squamous cell carcinoma (SCC), 22 solar keratoses, 4 hyperkeratoses, 18 warts and 11 basal cell carcinoma (BCC). Human papillomavirus (HPV) DNA was identified by Southern blot hybridisation using, as individual probes, purified insert DNA from recombinant HPV 1, 2, 3 or 3/10, 4, 5 or 5/8, 7, 11, 16, 18 and 41 under relaxed conditions and characterised by restriction enzyme analysis and Southern blot hybridisation under more stringent conditions. Genomic HPV DNA was characterised in 7 skin biopsies from 4 renal allograft recipients (RARs): HPV 1A in a SCC (20 copies/cell) and a BCC (10 copies/cell) from the one patient, HPV 36 (20 copies/cell) in a SCC, HPV 1A [symbol: see text] 1000 copies/cell) in a wart and HPV 2B (200-800 copies/cell) in 3 warts from the one patient. Only HPV 1A in the SCC exhibited a significant degree of subtype variation. HPV DNA was identified in another 5 skin biopsies from another 4 RARs: HPV 3A in a wart and a hyperkeratosis, HPV 3/10-related DNA in 2 solar keratoses and HPV 5/8-related DNA in another (20-50 copies/cell). The incidence of HPV 5 (or 5-related HPVs) in RAR SCC was very low and that of HPV DNA in RAR warts was lower than that recorded elsewhere but this was not due to insensitivity of the assays. There was no evidence for a role for HPV in the aetiology of skin cancer in RARs in south-eastern Queensland but the possibility remains that as yet unidentified HPV types are involved.

The effect of respiratory syncytial virus (RSV) on the cellular immune response of human mononuclear cells in vitro was examined. Inhibition by RSV of the lymphocyte response to phytohemagglutinin in vitro was confirmed using cells from human umbilical cord blood. In addition, RSV significantly inhibited both the proliferative and T cell colony responses of human mononuclear cells to Epstein-Barr virus. An RSV-specific cellular immune response was induced in vitro by stimulation of mononuclear cells from RSV-seropositive donors with beta-propiolactone-inactivated RSV. This RSV-specific response was significantly inhibited by infectious RSV itself, and the inhibition was mediated by an extracellular factor produced by RSV-infected mononuclear cells. A similar inhibition in vivo of the RSV-induced cellular immune response may contribute significantly to delayed recovery from primary infection and to reduced resistance to subsequent infections.