SEARCH · PubMed Health

Results for “ADE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources

PubMed1992

Monoclonal antibody analysis of neutralization and antibody-dependent enhancement of feline infectious peritonitis virus.

Fifty-four monoclonal antibodies (MAbs) to feline infectious peritonitis virus (FIPV) were characterized according to protein specificity, immunoglobulin subclass, virus neutralization, reactivity with different coronaviruses, and ability to induce antibody-dependent enhancement (ADE) of FIPV infection in vitro. The MAbs were found to be specific for one of three structural proteins of FIPV. A total of 47 MAbs were specific for the 205-kDa spike protein (S), 3 MAbs were specific for the 45-kDa nucleocapsid protein (N), and 4 MAbs were specific for the 26- to 28-kDa membrane protein (M). The S-specific MAbs showed various degrees of cross-reactivity with strains of FIPV, feline enteric coronavirus, canine coronavirus, and porcine transmissible gastroenteritis virus. Nineteen S-specific MAbs neutralized FIPV. A total of 15 of the neutralizing MAbs induced ADE, and all but 1 were of the immunoglobulin G2a subclass. The remaining four neutralizing MAbs that did not induce ADE were of the immunoglobulin G1 subclass. Two S-specific MAbs induced ADE but were nonneutralizing. None of the N- or M-specific MAbs was neutralizing or induced ADE. On the basis of the reactivity patterns of the MAbs with FIPV and related coronaviruses, it was concluded that there is a minimum of five neutralizing sites on S. In most instances, neutralizing MAbs were able to induce ADE, demonstrating a direct relationship between neutralization and enhancement. The difference in immunoglobulin subclass between neutralizing MAbs that induced ADE and those that did not induce ADE suggests that there may be a restriction in the immunoglobulin subclasses capable of mediating ADE.

Animals↗

PubMed1999

Adverse drug events in elderly patients receiving home health services following hospital discharge.

OBJECTIVE: To assess incidence, healthcare consequences, and identify risk factors for adverse drug events (ADEs) in elderly patients receiving home health services during the month following hospital discharge. METHOD: This was a prospective cohort study of three home health agencies in Madison, Wisconsin, and its surrounding area. The sample consisted of 256 participants aged > or =65 years who were hospitalized for medical illness, received home nursing after discharge, and completed the one-month interview. The main outcome measure was self-reported ADEs (possible, probable, or definite) during the month following hospital discharge. RESULTS: Incidence of ADEs was 20%. Fifty-two participants (20.3%) reported 64 ADEs: 23 possible, 37 probable, and four definite. The most common ADEs involved the gastrointestinal tract (31.3%) and the central nervous system (31.3%). Of 53 ADEs reported to providers, 59% of the drugs were discontinued or altered. One ADE resulted in hospitalization. In logistic regression, female gender (OR = 2.26; 95% CI 1.06 to 4.77) and the interaction between number of new medications and cognition were significantly associated with ADEs. The risk of an event increased with the number of new medications at discharge; however, risk was elevated primarily for participants with lower cognition. CONCLUSIONS: ADEs were common during the month following hospital discharge, were more frequent in women, and often resulted in medication changes. Individuals at particular risk were those with lower cognition who were discharged with several new medications.

Aged↗

PubMed2003

Adverse drug events associated with hospital admission.

OBJECTIVE: To increase the knowledge base on the frequency, causality, and avoidability of adverse drug events (ADEs) as a cause for admission in internal medicine or when occurring during hospitalization. METHODS: A prospective study was performed for 6 periods of 8 days each. Epidemiologic data (e.g., age, gender, medical history), drug utilization, and adverse drug reactions on patients hospitalized during these periods were collected by a pharmacy student. RESULTS: A total of 156 patients (70 men and 86 women) were included in the study. The patients' mean age +/- SD was 66.5 +/- 18.1 years and mean length of stay was 13.2 +/- 9 days. Renal and hepatic insufficiency and previous history of drug intolerance were observed in 17.9%, 10.2%, and 2% of the hospitalized patients, respectively. Thirty-eight ADEs occurred in 32 patients; in 15 cases, ADEs were identified as the reason for admission, 10 cases occurred during hospitalization, and 13 cases were present at admission, but were not the cause of admission. The most frequent ADEs involved the neurologic (23.6%), renal (15.7%), and hematologic (13.1%) systems. Among these 38 ADEs, 22 were considered avoidable (57.9%); 20 of these were associated with therapeutic errors (inappropriate administration, drug-drug interactions, dosage error, drug not stopped despite the onset of ADEs). Patients with ADEs stayed longer in the hospital and took more drugs both before and during their hospital stay (p < 0.05). CONCLUSIONS: Most of the ADEs observed in this study were avoidable. The risk/benefit ratio of administered drugs could be improved with better knowledge of the patients' medical history and the risk factors of ADEs.

Adult↗

PubMed2005

Accuracy of adverse-drug-event reports collected using an automated dispensing system.

PURPOSE: The accuracy of adverse-drug-event (ADE) reports collected using an automated dispensing system was evaluated. METHODS: ADE reports were collected by requiring nurses on five units in a tertiary care facility to select a reason for removing two tracer drugs (dextrose injection 50% [D50] and naloxone) from an automated dispensing system (Medstation 2000, Pyxis, San Diego, CA). The accuracy of the ADE reports during a period of 4.5 months was evaluated through retrospective chart review. The sensitivity, specificity, positive predictive value, and negative predictive value of the reports were calculated. RESULTS: A review of 61 D50 transactions found that the appropriate reason for removal was selected by nursing staff 62% of the time. Twenty-seven transactions were recorded as occurring due to an ADE, and 70% of these were confirmed in the medical record. The sensitivity and specificity of the ADE reports for D50 were 55.9% (95% confidence interval [CI], 39.2-72.6%) and 70.4% (95% CI, 53.2-87.6%), respectively. A review of 32 naloxone transactions found that nurses correctly selected the reason for removal 88% of the time. Twenty-three transactions were recorded as occurring due to an ADE, and 87% of these were confirmed in the medical record. The sensitivity and specificity of the ADE reports for naloxone were 95.2% (95% CI, 86.1-104.4%) and 72.7% (95% CI, 46.4-99.1%), respectively. CONCLUSION: A Pyxis ADE reporting mechanism using the tracer drugs D50 and naloxone increased the overall reporting of ADEs.

Academic Medical Centers↗

PubMed2004

Quantifying adverse drug events : are systematic reviews the answer?

Quantifying adverse drug events (ADEs) is critical to clinicians, consumers and policy makers. Most ADE information comes from large clinical trials. Systematic reviews have become a popular tool in quantifying the efficacy of different therapeutic interventions and ADE data collected in randomised trials may be helpful in quantifying the risk associated with a specific pharmacological agent. However, clinicians who are interested in conducting systematic reviews of ADEs may face many challenges. These challenges are geared towards two main areas: poor quality of ADE reporting in randomised trials and poor indexing of ADEs in medical databases. In this review, we will discuss these challenges in detail using some examples from the literature. Where possible, we also discuss strategies that may overcome these problems. More rigourous standards of reporting ADEs in randomised trials, as well as better indexing of ADE terminology in medical databases, could one day make systematic reviews of ADEs a powerful tool for practising clinicians.

Adverse Drug Reaction Reporting Systems↗

PubMed2001

Drug-related visits to the medical emergency department: a prospective study from India.

OBJECTIVE: To analyze the contribution of adverse drug events (ADEs) to the overall number of visits to the medical emergency and to determine the proportion of events leading to hospital admissions. PATIENTS AND METHODS: All visits to the medical emergency were recorded in a prospective, non-interventional design study over a period of 8 months. The ADEs were divided into 5 categories: adverse drug reactions (ADRs), drug interactions, patient non-compliance, physician non-compliance, and drug overdose. The cases were then followed-up to assess the prorportion of ADEs lead to hospitaliztion. RESULTS: A total of 4764 patients were included in the study. 5.9% of all visits were considered to be drug-related. The highest percentage of ADEs was observed in the age group less than 20 and more than 80 years. ADRs accounted for 45% of all ADEs, followed by patient non-compliance (28%). Patient and physician non-compliance were the main causes of drug-related hospital admissions. 52% of all ADE-related visits and 55% of ADE-related admissions were considered to be preventable. Non-steroidal antiinflammatory agents, oral hypoglycemics and antitubercular drugs were responsible for 37% of all ADRs. Non-compliance was mainly seen in hypertensives, asthmatics and epileptics. CONCLUSION: ADEs account for a sizable proportion of all visits to a medical emergency unit and some are serious enough to require hospitaliztion. A large number of ADE-related visits and admissions are preventable which highlights the importance of public education on the proper use of drugs, and also the need for regulation of the practice of unregistered medical practitioners in developing countries.

Adult↗

PubMed1989

Comparison of arrhythmogenic doses of epinephrine in heartworm-infected and noninfected dogs.

The arrhythmogenic dose of epinephrine (ADE) was determined in heartworm-infected and noninfected (control) dogs during thiamylal-induced and halothane-maintained anesthesia to assess the myocardial sensitization. The ADE in heartworm-infected dogs (2.42 +/- 0.26 micrograms/kg of body weight) was significantly lower than that for the controls (3.36 +/- 0.29 micrograms/kg). After 2 weeks, ADE was determined again in these dogs after atropine treatment. Atropine treatment lowered the ADE to 1.76 +/- 0.33 micrograms/kg and 1.77 +/- 0.19 micrograms/kg in heartworm-positive and -negative dogs, respectively. After 2 weeks more, the ADE was determined after administration of prazosin, an alpha 1-antagonist. Only 2 of 6 controls and 3 of 6 heartworm-positive dogs had arrhythmias after a threefold increase of ADE. The mean ADE in the dogs that responded to treatment were 7.4 micrograms/kg and 7.2 micrograms/kg for heartworm-positive and -negative dogs, respectively. The finding of this study indicated that ADE in heartworm-infected dogs were lower than those in the control dogs, which makes the heartworm-infected dogs more vulnerable to arrhythmia during anesthesia. Atropine did not protect the dogs of either group. However, prazosin protected the dogs of both groups by significantly increasing the threshold of the ADE. On the basis of our findings, to reduce the risk of arrhythmia, we suggest that routine screening of dogs for heartworm infection be done before anesthetics are used.

Anesthesia, Inhalation↗

PubMed1993

Using a hospital information system to assess the effects of adverse drug events.

The most common adverse events experienced by hospitalized patients are drug related. While numerous studies have described the incidence and types of adverse drug events (ADEs), the actual effect of these events on patient outcomes have only been estimated. The studies that have described the effects of ADEs on patient outcomes have not stratified patients by severity of illness and hospital costs were estimated based on a percent of hospital charges. We designed a study to utilize the resources of our hospital information system to assess the attributable effects of ADEs on hospital length of stay and cost of hospitalization. This approach emphasized the difference between study patients and their matched control patients rather than overall differences between patients with and without ADEs. In addition, we used nursing acuity data to help adjust severity of illness within DRG groups and actual hospital costs were used instead of estimated costs. This study found that while the average length of stay for patients with ADEs was 8.19 days compared to 4.36 days for matched control patients, the attributable difference due to the ADEs was 1.94 days. Similar methods found that patients with ADEs had an average cost of hospitalization of $10,584 compared to $5,350 for those without and the attributable difference due to ADEs was $1,939. This indicates that the 569 ADEs at our hospital during 1992 resulted in an additional 1,104 extra patient days at a cost of $1,103,291.

Adverse Drug Reaction Reporting Systems↗

PubMedDate not supplied

Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality.

OBJECTIVE: To determine the excess length of stay, extra costs, and mortality attributable to adverse drug events (ADEs) in hospitalized patients. DESIGN: Matched case-control study. SETTING: The LDS Hospital, a tertiary care health care institution. PATIENTS: All patients admitted to LDS Hospital from January 1, 1990, to December 31, 1993, were eligible. Cases were defined as patients with ADEs that occurred during hospitalization; controls were selected according to matching variables in a stepwise fashion. METHODS: Controls were matched to cases on primary discharge diagnosis related group (DRG), age, sex, acuity, and year of admission; varying numbers of controls were matched to each case. Matching was successful for 71% of the cases, leading to 1580 cases and 20,197 controls. MAIN OUTCOME MEASURES: Crude and attributable mortality, crude and attributable length of stay, and cost of hospitalization. RESULTS: ADEs complicated 2.43 per 100 admissions to the LDS Hospital during the study period. The crude mortality rates for the cases and matched controls were 3.5% and 1.05%, respectively (P<.001). The mean length of hospital stay significantly differed between the cases and matched controls (7.69 vs 4.46 days; P<.001) as did the mean cost of hospitalization ($10,010 vs $5355; P<.001). The extra length of hospital stay attributable to an ADE was 1.74 days (P<.001). The excess cost of hospitalization attributable to an ADE was $2013 (P<.001). A linear regression analysis for length of stay and cost controlling for all matching variables revealed that the occurrence of an ADE was associated with increased length of stay of 1.91 days and an increased cost of $2262 (P<.001). In a similar logistic regression analysis for mortality, the increased risk of death among patients experiencing an ADE was 1.88 (95% confidence interval, 1.54-2.22; P<.001). CONCLUSION: The attributable lengths of stay and costs of hospitalization for ADEs are substantial. An ADE is associated with a significantly prolonged length of stay, increased economic burden, and an almost 2-fold increased risk of death.

Case-Control Studies↗

PubMed1997

The arrhythmogenic dose of epinephrine in halothane and isoflurane anesthetized dogs: an assessment of repeatability.

Repeat determinations of the arrhythmogenic dose of epinephrine (ADE) were made over two 6 h periods on 2 separate days during halothane and isoflurane anesthesia. Each of 6 dogs underwent 4 trials (2 halothane and 2 isoflurane). During each trial, the ADE was determined at baseline, 3 and 6 h. Epinephrine was infused for 3.0 min at increasing dose rates (2.5, 5.0, 10.0 and 20.0 mg/kg/min) until the arrhythmia criterion (4 or more intermittent or continuous premature ventricular contractions) was reached. The inter-infusion interval was 20 min. There were no significant differences in the measured cardiovascular parameters (SBP, DBP, MBP, and HR), arterial blood gases, or acid-base status prior to each determination during a single trial. The cardiovascular responses to epinephrine infusion were not significantly different between inhalants or determinations. The range of the ADE determined over both trials during isoflurane anesthesia was 30.12 +/- 12.21 micrograms/kg to 50.83 +/- 9.17 micrograms/kg. The baseline ADE during Day 1 of halothane anesthesia (6.70 +/- 1.36 micrograms/kg) was significantly greater than ADE determinations at 3 (4.65 +/- 0.88 micrograms/kg) and 6 h (4.61 +/- 0.87 micrograms/kg). The reduction in the ADE over time during day 2 of halothane anesthesia was not statistically significant (P = 0.0669). These results suggest that during halothane anesthesia, the ADE is not repeatable over time, and they may influence our interpretation of the results of investigations that measure alterations in the ADE due to pharmacological manipulations without repeated control ADE determinations.

Acid-Base Equilibrium↗

PubMed2004

Adverse events due to discontinuations in drug use and dose changes in patients transferred between acute and long-term care facilities.

BACKGROUND: Care transitions are commonplace for ill older adults, but no studies to our knowledge have examined the occurrence of iatrogenic harm from medication changes during patient transfer. OBJECTIVES: To identify medication changes during transfer between hospital and nursing home and adverse drug events (ADEs) caused by these changes. METHODS: Participants were residents of 4 nursing homes in the New York City metropolitan area admitted to 2 academic hospitals. Nursing home and hospital medical records were reviewed to identify changes in medication regimens between sites. Medications were matched and compared regarding dosage, route, and frequency of administration. Two physician investigators used structured implicit review to identify ADEs attributable to transfer-related medication changes. RESULTS: During a total of 122 admissions, the mean numbers of medications altered during transfer from nursing home to hospital and hospital to nursing home were 3.1 and 1.4, respectively (P<.001 for comparison). Most changes in drug use were discontinuations, followed by dose changes and class substitutions. Of 71 bidirectional transfers that were reviewed by 2 physician investigators, ADEs attributable to medication changes occurred during 14 (20%). The overall risk of ADE per drug alteration (n = 320) was 4.4% (95% confidence interval, 2.5%-7.4%). Although most medication changes (8/14) implicated in causing ADEs occurred in the hospital, most ADEs (12/14) occurred in the nursing home after nursing home readmission. CONCLUSIONS: Medication changes are common during transfer between hospital and nursing home and are a cause of ADEs. Research is needed on interinstitutional patient care and systems interventions designed to prevent ADEs.

Adverse Drug Reaction Reporting Systems↗

PubMed1998

A computer alert system to prevent injury from adverse drug events: development and evaluation in a community teaching hospital.

CONTEXT: Adverse drug events (ADEs) are the most common type of iatrogenic injury occurring in hospitalized patients. Errors leading to ADEs are often due to restricted availability of information at the time of physician order writing. OBJECTIVES: To develop, implement, and evaluate a computer alert system designed to correct errors that might lead to ADEs and to detect ADEs before maximum injury occurs. DESIGN: Prospective case series. SETTING: A 650-bed community teaching hospital in Phoenix, Ariz. PATIENTS: Consecutive sample of 9306 nonobstetrical adult patients admitted during the last 6 months of 1997. INTERVENTIONS: Thirty-seven drug-specific ADEs were targeted. Our hospital information system was programmed to generate alerts in clinical situations with increased risk for ADE-related injury. A clinical system was developed to ensure physician notification of alerts. MAIN OUTCOME MEASURES: A true-positive alert was defined as one in which the physician wrote orders consistent with the alert recommendation after alert notification. RESULTS: During the 6-month study period, the alert system fired 1116 times and 596 were true-positive alerts (positive predictive value of 53%). The alerts identified opportunities to prevent patient injury secondary to ADEs at a rate of 64 per 1000 admissions. A total of 265 (44%) of the 596 true-positive alerts were unrecognized by the physician prior to alert notification. CONCLUSIONS: Clinicians can use hospital information systems to detect opportunities to prevent patient injury secondary to a broad range of ADEs.

Computer Systems↗

PubMed2003

The epidemiology of preventable adverse drug events: a review of the literature.

BACKGROUND: A growing amount of data suggests that adverse drug events (ADEs) in hospital settings are frequent and result in substantial harm. Even though prevention is where efforts must be directed, only a few studies have reported on the preventability of these events. The objective of this article is to review the literature of ADEs and their preventability, and to report on their incidences, characteristics, risk factors, costs and prevention strategies. METHODS: We systematically searched Medline and Embase for literature published between 1980 and June 2002. All articles reporting primary data on the incidences of ADEs and their preventability in hospital settings were included. RESULTS: In the 8 articles retrieved the incidences of ADEs were between 0.7% and 6.5% of hospitalized patients; in up to 56.6% these events were judged to be preventable. Furthermore, ADEs accounted for 2.4% to 4.1% of admissions to inpatient facilities; preventability was stated in up to 69.0% of these events. A substantial body of preventable ADEs, the so-called medication errors, occur in the process of ordering, transcribing, dispensing and administrating the drugs. Further investigations into medication errors at the ordering stage reveal their occurrence in up to 57.0 per 1,000 orders. Between 18.7% and 57.7% of those errors have the potential for harm, but only in about 1% they result in preventable ADEs. IMPLICATIONS: The detection of errors having only the potential for harm by means of computerized surveillance has shown to be a useful technique in order to understand and prevent ADEs. Apart from the use of sophisticated computer techniques the participation of pharmacists in the drug prescribing process results in a tremendous error reduction. The greatest task in changing the health care system into a system with safety as its first priority is to create a culture of constant learning from mistakes among health care professionals. The appreciation of the health care teams' ideas and perceptions for improvement, and their implementation through small improvement cycles, may represent the leading strength in error reduction and health care improvement.

Adverse Drug Reaction Reporting Systems↗

PubMed2005

The impact of hospitalwide computerized physician order entry on medical errors in a pediatric hospital.

PURPOSE: Medication errors contribute significantly to the morbidity and costs of pediatric health care. The authors hypothesized that hospitalwide computerized physician order entry (CPOE) in a pediatric hospital would lead to a decrease in medication errors. METHODS: The authors retrospectively evaluated and prospectively analyzed inpatient discharge and usage and adverse drug event (ADE) rate data pre- and postintroduction of a hospitalwide implementation of CPOE in a tertiary care pediatric hospital. They compared pre- and postintervention ADEs (Student's t test) and computed the number needed to treat (NNT) analog. RESULTS: Over the 9-month study period, there were 45,615 in patient days and 8619 discharges. Pre-CPOE verbal order regulatory compliance was 80%, whereas post-CPOE increased to 95%. Transcription errors were eliminated. All ADEs pre-CPOE were 0.3 +/- 0.04 per 1000 doses, whereas post-CPOE ADEs were 0.37 +/- 0.05 per 1000 doses (P = .3). Harmful ADEs pre-CPOE were 0.05 +/- 0.017 per 1000 doses, while post-CPOE ADEs were 0.03 +/- 0.003 per 1000 doses (P = .05). Our NNT data demonstrate that CPOE would prevent 1 ADE every 64 (95% CI 25-100) patient days. CONCLUSIONS: CPOE decreases harmful ADEs in a pediatric hospital, thus leading to increased patient safety. In addition, CPOE provides an automated system for monitoring and improving health care quality.

Adverse Drug Reaction Reporting Systems↗

PubMed2004

Monoclonal antibody analysis of porcine reproductive and respiratory syndrome virus epitopes associated with antibody-dependent enhancement and neutralization of virus infection.

Enhanced infection and replication of porcine reproductive and respiratory syndrome (PRRS) virus in the presence of specific antibody has been demonstrated in vitro and in vivo, a phenomenon known as antibody-dependent enhancement (ADE). ADE is considered to be a significant obstacle to developing effective vaccines for many viruses for which ADE has been reported, since virus-specific antibodies of maternal origin or those conferred by vaccination can facilitate the entry of the virus into target cells, sometimes resulting in increased severity of the disease. In this study, the role of specific PRRS viral epitopes in ADE and/or virus neutralization (VN) was assessed in vitro using 14 monoclonal antibodies (mAbs) to 4 PRRS viral proteins: nucleocapsid (N), matrix (M), glycoprotein (GP) 5, and GP3. Each mAb recognized a distinct epitope on one of these proteins. One-way ADE and VN assays were performed in vitro using homologous PRRS virus isolates in the presence or absence of each mAb. ADE activity was determined by detecting a significant increase of progeny virus yield in porcine alveolar macrophage cultures in the presence of individual mAbs. Neutralizing activity was determined by detecting a significant reduction or complete blocking of virus replication in MARC-145 cells in the presence of individual mAbs. mAbs could be categorized into 3 groups: enhancing, neutralizing and neither. Viral epitopes which are capable of inducing neutralizing antibodies appeared to reside on the M, GP3 and GP5 proteins, while epitopes that may induce ADE-mediating antibody were associated with the N and GP5 proteins. Identification of the viral proteins and antigens and epitopes responsible for ADE- and VN-mediating antibodies may provide the basis for developing efficacious second-generation vaccines for the control of PRRS virus; yet, further epitope mapping remains to be done.

Animals↗

PubMed1997

Adenine adducts with diepoxybutane: isolation and analysis in exposed calf thymus DNA.

1,3-Butadiene (BD) is a high-volume industrial chemical and a common environmental pollutant. Although BD is classified as a "probable human carcinogen", only limited evidence is available for its tumorigenic effects in occupationally exposed populations. Animal studies show a surprisingly high sensitivity of mice to the carcinogenic effects of BD compared to rats (approximately 10(3)-fold), making interspecies extrapolations difficult. Identification and quantitation of specific BD-induced DNA adducts are important for improving our understanding of the mechanisms of BD biological effects and for explaining the observed species differences. Covalent binding of BD to DNA is probably due to its two epoxy metabolites: 3,4-epoxy-1-butene (EB) and 1,2:3,4-diepoxybutane (DEB). Both EB and DEB are direct mutagens producing frameshift and point mutations at both A:T and G:C base pairs. DEB is 100 times more mutagenic than EB and is found in quantity only in tissues of the most sensitive species (mouse). This has led to the suggestion that the higher sensitivity of mice to BD could be due to greater exposure to DEB. The present work was initiated in order to isolate and structurally characterize DEB-induced adenine adducts. The adducts were formed by reacting DEB with free adenine (Ade), 2'-deoxyadenosine (2'-dAdo), and calf thymus DNA followed by HPLC separation and analysis of the products by UV spectrophotometry, electrospray ionization mass spectrometry, and nuclear magnetic resonance. The adenine reaction resulted in three products which were identified as N-3-, N-7-, and N-9-(2'-hydroxy-3',4'-epoxybut-1'-yl)adenine. These adducts underwent acid-catalyzed hydrolysis to their corresponding (2',3',4'-trihydroxybut-1'-yl)adenines upon heating or storage. The 2'-dAdo reaction with DEB followed by acid hydrolysis yielded a single adduct, N6-(2',3',4'-trihydroxybut-1'-yl)adenine (N6-DEB-Ade). N-3-DEB-Ade and N6-DEB-Ade were also found in hydrolysates of calf thymus DNA exposed to DEB. The amounts of N-3-DEB-Ade (13/10(3) normal Ade) and N6-DEB-Ade (5/10(3) normal Ade) were slightly lower than those of the corresponding EB-induced adducts in similar experiments, suggesting comparable reactivity of the two epoxy metabolites of BD toward adenine in DNA. The findings of this study provide a basis for future analyses of BD-induced adenyl DNA adducts in vitro and in vivo.

Adenine↗

PubMed1995

Studies of complement-activating antibodies in the SIV/macaque model of acute primary infection and vaccine protection.

Questions regarding the potential impact of complement-activating antibodies on lentivirus pathogenesis and vaccine development were addressed in the SIV/macaque model by evaluating sera for activity related to complement-mediated, antibody-dependent enhancement (C'-ADE) of SIV infection in vitro. C'-ADE activity in sera obtained during acute primary infection in macaques inoculated with SIVmac251 appeared before neutralizing antibodies and coincided with the initial peak and decline of plasma antigenemia. The power of C'-ADE activity (i.e., virus production measured by p24 immunoassay) decreased as titers of neutralizing antibodies increased in these animals, suggesting a balance in the net effect between C'-ADE and neutralizing activities in vitro. Antibodies with C'-ADE activity were also induced in macaques immunized with live-attenuated SIVmac239/nef-deletion or primed with recombinant SIVmne gp120 vaccinia virus and boosted with SIVmne rgp160. The titer (i.e., last serum dilution to show enhancement), peak (i.e., serum dilution producing the greatest enhancement as measured by p24 production), and power (i.e., magnitude of p24 production at the peak titer) of C'-ADE activity in sera obtained from vaccinated macaques on the day of challenge were comparable to those of sera from infected macaques and showed no correlation with vaccine outcome, where some protected animals had C'-ADE profiles that resembled those of unprotected animals. The results of these studies suggest that antibodies having C'-ADE activity in vitro could contribute to virus replication or, alternatively, to virus clearance during the acute stage of SIV infection in macaques.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2002

Identifying clinically significant preventable adverse drug events through a hospital's database of adverse drug reaction reports.

The ability of a hospital's adverse drug reaction (ADR) database to identify common and repeated patterns of preventable adverse drug events (ADEs) was analyzed. ADR reports collected from 1994 through 2000 were extracted from a teaching hospital's ADR database. Reports were assessed concurrently in accordance with seven previously published explicit criteria for preventability. Only cases considered clinically significant were included in this analysis. Events that occurred in the ambulatory care setting were excluded. Preventable ADEs were categorized by drug or drug class, type of medication error, and the subsequent adverse outcome. Novel in this analysis was the linking of these three descriptors. Of the 2571 ADR reports assessed, 415 ADEs were deemed preventable. Of the preventable ADEs, 98 were not analyzed because they occurred in the ambulatory care setting, leaving 317 preventable ADEs in 275 inpatients (mean age +/- S.D., 48.5 +/- 23.9 years) for analysis. Although 93 drugs were associated with these ADEs, only 10 drugs accounted for more than 60% of the events. Analysis and categorization by type of error and outcome suggested that three high-priority preventable ADEs accounted for 50% of all reports: (1) overdoses of anticoagulants or insufficient monitoring and adjustments (according to laboratory test values) were associated with hemorrhagic events, (2) overdosing or failure to adjust for drug-drug interactions of opiate agonists was associated with somnolence and respiratory depression, and (3) inappropriate dosing or insufficient monitoring of insulins was associated with hypoglycemia. Analysis of a hospital ADR database identified prevalent and preventable clinically significant ADEs.

Adverse Drug Reaction Reporting Systems↗