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Papers by Daniel Eiras

Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection — United Kingdom and United States, March–August 2020

MMWR. Morbidity and Mortality Weekly Report

Open Forum Infectious Diseases

Background Personal protective equipment (PPE) and strict infection control techniques are the pr... more Background Personal protective equipment (PPE) and strict infection control techniques are the primary methods by which healthcare workers (HCW) can avoid exposure during the treatment of patients with highly pathogenic infections such as Ebola Virus Disease (EVD) or the Middle East Respiratory Syndrome coronavirus (MERS-CoV). There is currently no consensus for the types of PPE that are recommended to be worn by HCWs, nor is there a universal process for the donning and doffing of PPE. Methods HCWs from Bellevue Hospital participate in quarterly PPE trainings as part of the Special Pathogens Program (SPP), which consist of didactic sessions as well as an evaluation of donning and doffing techniques. A total of 50 HCWs completed the training curriculum in 2017. During the doffing process, PPE trainers applied corn start powder paint (Chameleon Colors; American Fork, UT) to the participants’ gloved hands between multiple steps of PPE removal. At the end of the process, the areas wher...

Case Report: Mucosal Leishmaniasis in New York City

The American Journal of Tropical Medicine and Hygiene

The Special Pathogens Research Network: Enabling Research Readiness

Health Security

Antimicrobial agents and chemotherapy, Jan 29, 2018

Nephrotoxicity is a known adverse effect of polymyxin B (PMB). Animal data suggests that once dai... more Nephrotoxicity is a known adverse effect of polymyxin B (PMB). Animal data suggests that once daily dosing may reduce the rate and delay the onset of acute kidney injury (AKI).In a multicenter, retrospective study, we evaluated adult patients with a creatinine clearance (CrCl) ≥30 mL/min who received ≥48h of PMB therapy. The primary endpoint was the difference in rate of AKI comparing once and twice daily PMB dosing. Secondary endpoints included time to AKI and recovery of renal function.Of 273 eligible patients, 100 from each group were matched based on propensity scores. In the matched groups, nephrotoxicity, defined according to RIFLE criteria, was more frequent with once versus twice daily dosing (47% vs. 17% =0.0005). After adjusting for residual differences by multivariate conditional logistic regression, once daily dosing was more likely to result in nephrotoxicity (adjusted odds ratio 2.5, 95% CI 1.413-4.541, =0.002). Among 64 patients who developed AKI, the median onset was...

Knowledge, Attitudes, and Practices Regarding Antimicrobial Use and Stewardship Among Prescribers at Acute-Care Hospitals

Infection control and hospital epidemiology, Mar 6, 2018

OBJECTIVE To assess antimicrobial prescriber knowledge, attitudes, and practices (KAP) regarding ... more OBJECTIVE To assess antimicrobial prescriber knowledge, attitudes, and practices (KAP) regarding antimicrobial stewardship (AS) and associated barriers to optimal prescribing. DESIGN Cross-sectional survey. SETTING Online survey. PARTICIPANTS A convenience sample of 2,900 US antimicrobial prescribers at 5 acute-care hospitals within a hospital network. INTERVENTION The following characteristics were assessed with an anonymous, online survey in February 2015: attitudes and practices related to antimicrobial resistance, AS programs, and institutional AS resources; antimicrobial prescribing and AS knowledge; and practices and confidence related to antimicrobial prescribing. RESULTS In total, 402 respondents completed the survey. Knowledge gaps were identified through case-based questions. Some respondents sometimes selected overly broad therapy for the susceptibilities given (29%) and some "usually" or "always" preferred using the most broad-spectrum empiric antimic...

Qualitative and Quantitative Assessment of Daily Cleaning of High-Touch Environmental Surfaces in Hospital Patient Rooms

Open Forum Infectious Diseases

Knowledge, Attitudes, and Practices of Environmental Service Workers Related to Environmental Cleaning and Healthcare-Associated Infections (HAI)

Open Forum Infectious Diseases

Quantitative Assessment of the Cleanliness of High-Touch Environmental Surfaces and Shared Equipment in the Hospital

Open Forum Infectious Diseases

Open Forum Infectious Diseases

Open Forum Infectious Diseases

Rate of nephrotoxicity was 43% with once daily vs. 22% with twice daily dosing Once daily dosing ... more Rate of nephrotoxicity was 43% with once daily vs. 22% with twice daily dosing Once daily dosing was not an independent predictor of nephrotoxicity Nephrotoxicity was multifactorial Risk factors included PMB longer duration, higher doses, and receiving >2 other nephrotoxic agents concomitantly Nephrotoxicity was reversible as most patients recovered their renal function to baseline Need further confirmation of our results in a prospective study with matched cohorts # 1804 Background: Nephrotoxicity is a known adverse effect of PMB. Animal data suggests that once daily dosing may be associated with decreased rate, severity and more gradual onset of nephrotoxicity compared to divided dosing. Clinical data evaluating the effect of PMB dosing frequency on nephrotoxicity is limited. Objective: Compare rate of acute kidney injury (AKI) with PMB once vs. twice daily dosing. Methods: In a single center, retrospective study we evaluated adult patients with Creatinine Clearance (CrCl) ≥30 mL/min who received ≥48h of PMB therapy. Nephrotoxicity was defined as development of AKI using RIFLE criteria. Results: A total of 173 patients were included (once daily n=141, twice daily n=32). Median age was 68 years (IQR 56-79), CrCl was 65 mL/min (IQR 44-91), mAPACHE II score was 14 (12-16), PMB duration of therapy was 6 days (IQR 4-11), 59% of patients received concomitant nephrotoxic agents, and these were comparable between once and twice daily dosing. Overall, rate of AKI was 43% with once vs. 22% with twice daily dosing, P=0.04 with most cases being Risk category by RIFLE (18 vs. 16%, P=0.9). No patients met ESRD. In-hospital mortality was 19% with once vs. 28% with twice daily dosing, P=0.4. Time to AKI onset (7 vs. 8 days) and peak serum creatinine (SCr) (8 vs. 8 days) was similar with once vs. twice daily dosing. In multivariate model, severe sepsis (OR 4.2, 95% CI 1.6-11.3, P=0.005), receipt of >2 concomitant nephrotoxic agents (OR 2.6, 95% CI 1.0-6.7, P=0.045), PMB duration of therapy >10 days (OR 2.6, 95% CI 1.0-4.5, P=0.02) and total dose >1,500,000 units/day (OR 2.1, P=0

Understanding Barriers to Optimal Cleaning and Disinfection in Hospitals: A Knowledge, Attitudes, and Practices Survey of Environmental Services Workers

Infection control and hospital epidemiology, Dec 13, 2016

In this study, we used an online survey to assess knowledge, attitudes, and practices related to ... more In this study, we used an online survey to assess knowledge, attitudes, and practices related to environmental cleaning and other infection prevention strategies among environmental services workers (ESWs) at 5 hospitals. Our findings suggest that ESWs could benefit from additional education and feedback as well as new strategies to address workflow challenges. Infect Control Hosp Epidemiol 2016;1-4.

Antimicrobial Agents and Chemotherapy, 2015

There is significant variation in the use of polymyxin B (PMB), and optimal dosing has not been d... more There is significant variation in the use of polymyxin B (PMB), and optimal dosing has not been defined. The purpose of this retrospective study was to evaluate the relationship between PMB dose and clinical outcomes. We included patients with bloodstream infections (BSIs) due to carbapenem-resistant Gram-negative rods who received ≥48 h of intravenous PMB. The objective was to evaluate the association between PMB dose and 30-day mortality, clinical cure at day 7, and development of acute kidney injury (AKI). A total of 151 BSIs were included. The overall 30-day mortality was 37.8% (54 of 151), and the median PMB dosage was 1.3 mg/kg (of total body weight)/day. Receipt of PMB dosages of <1.3 mg/kg/day was significantly associated with 30-day mortality (46.5% versus 26.3%;P= 0.02), and this association persisted in multivariable analysis (odds ratio [OR] = 1.58; 95% confidence interval [CI] = 1.05 to 1.81;P= 0.04). Eighty-two percent of patients who received PMB dosages of <1.3...

Fontana JF, Eiras D and Salvatore M. Human Influenza Virus Infections in ‘Human Respiratory Viral Infections’ Taylor & Francis Group, S K. Singh, Editor, 2014 pp 404-436

Cutaneous Leishmaniasis: Current Treatment Practices in the USA for Returning Travelers

Current Treatment Options in Infectious Diseases, 2015

Leishmaniasis, a protozoal infection transmitted by sandfly bite, produces a clinical spectrum of... more Leishmaniasis, a protozoal infection transmitted by sandfly bite, produces a clinical spectrum of disease ranging from asymptomatic infection to ulcerative skin and mucosal lesions to visceral involvement. Leishmaniasis is endemic in regions of Africa, the Middle East, south Asia, southern Europe, northern South America, and Central America. There has been an increase in imported leishmaniasis into developed, non-endemic countries due to increasing global travel. While pentavalent antimonials have been the mainstay of antileishmanial treatment for decades, newer therapeutic options have become available for all forms of infection, including liposomal amphotericin B, miltefosine, fluconazole, and ketoconazole. For the returning traveler with cutaneous leishmaniasis in the USA, treatment approaches are determined based on infecting species, initial presentation, extent and progression of disease, the advantages and drawbacks of available parenteral and oral drugs, and clinician-consultant experience.

Human Influenza Virus Infections

Human Respiratory Viral Infections, 2014

Hematological Oncology, 2010

Introduction: Classical Hodgkin's Lymphoma (cHL) has been frequently associated with Epstein-Barr... more Introduction: Classical Hodgkin's Lymphoma (cHL) has been frequently associated with Epstein-Barr virus (EBV), which can be found in a latent pattern in Reed-Sternberg (RS) cells. However, the impact of the presence of EBV in RS cells and its prognosis are still controversial. We analysed the presence of EBV in RS cells and its influence in the clinical evolution of patients with cHL treated in two public hospitals in the city of São Paulo, Brazil. Materials and Methods: We selected 97 patients with cHL from 1994 to 2004. Patients were only included in this study if they had (1) >18 years, (2) negative HIV serology, (3) undergone similar chemotherapy protocols, (4) paraffin blocks available with enough material for systematic review and histological reclassification and for detection of EBV in RS cells by in situ hybridization and immunohistochemistry and (5) clinical, epidemiological and laboratorial parameters available after a thorough chart review. Results: EBV was identified in 52.5% of the cases. Mixed cellularity (MC) subtype was more common in EBV-related tumours (25.5%) ( p ¼ 0.005). There was no difference on age, gender, stage and the presence of B symptoms between the two groups. The presence of EBV did not influence event free survival (EFS) ( p ¼ 0.38) or overall survival (OS) ( p ¼ 0.80) with a median follow-up of 80 months. Conclusion: We demonstrate that the prevalence of EBV-related cHL in this Brazilian population is 52.5% and, that, the presence of EBV does not change the clinical evolution and OS of patients treated with similar chemotherapy protocols.

Role of IL-6 in an IL-10 and IL-4 Double Knockout Mouse Model Uniquely Susceptible to Acetaminophen-Induced Liver Injury †

Chemical Research in Toxicology, 2007

Drug-induced hepatitis remains a challenging problem for drug development and safety because of t... more Drug-induced hepatitis remains a challenging problem for drug development and safety because of the lack of animal models. In the current work, we discovered a unique interaction that makes mice deficient in both IL-10 and IL-4 (IL-10/4-/-) highly sensitive to the hepatotoxic effects of acetaminophen (APAP). Male C57Bl/6 wild type (WT) and mice deficient in one or more cytokines were treated with 120 mg/kg APAP. Within 24 h after WT, IL-10-/-, IL-4-/-, or IL-10/4-/- mice were administered APAP, 75% of the IL-10/4-/- mice died of massive hepatic injury while all other genotypes were resistant to liver toxicity at this dose of APAP. The unique susceptibility of IL-10/4-/- mice was associated with reduced levels of liver glutathione and remarkably high serum levels of IL-6 and several proinflammatory factors including TNF-alpha, IFN-gamma, macrophage inflammatory protein-1alpha (MIP-1alpha), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), and osteopontin (OPN) as well as nitric oxide (NO). IL-6 appeared to have a causal role in controlling the unique susceptibility of IL-10/4-/- mice to APAP-induced liver disease (AILD) because IL-6 neutralizing antibody reversed the high sensitivity of these mice to AILD. Moreover, IL-10/4/6-/- mice were also resistant to the enhanced susceptibility to AILD and expressed relatively low levels of most proinflammatory factor genes that were elevated in the IL-10/4-/- mice. In conclusion, liver homeostasis following AILD appears to be highly dependent on the activities of both IL-10 and IL-4, which together help prevent overexpression of IL-6 and other potential hepatotoxic factors.

Healthcare Disparities in the Treatment of Acute Chest Pain

Academic Emergency Medicine, 2007

American Journal of Infection Control, 2006

Inappropriate use of antibiotics contributes to antimicrobial resistance worldwide. In Latin Amer... more Inappropriate use of antibiotics contributes to antimicrobial resistance worldwide. In Latin America, antibiotics are easily obtained over the counter. In the United States, the Latino population is the largest and fastest growing immigrant group. Hence, it is necessary to understand Latino cultural practices in regards to antibiotic use to develop effective interventions that reduce inappropriate antibiotic use among this population. We conducted a systematic review of descriptive and intervention studies measuring knowledge, attitudes, and practices of antibiotic use among Latinos in the United States. The search yielded only 11 descriptive studies and no interventions. The literature suggests that many Latinos in the United States self-prescribe antibiotics because of financial and sociocultural barriers and inaccurately believe that antibiotics help treat viral infections. Increased access to health care and appropriate culturally tailored interventions specific to Latinos are needed to promote judicious antibiotic use among Latinos. (Am J Infect Control 2006;34:495-502.)

Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection — United Kingdom and United States, March–August 2020

MMWR. Morbidity and Mortality Weekly Report

Open Forum Infectious Diseases

Background Personal protective equipment (PPE) and strict infection control techniques are the pr... more Background Personal protective equipment (PPE) and strict infection control techniques are the primary methods by which healthcare workers (HCW) can avoid exposure during the treatment of patients with highly pathogenic infections such as Ebola Virus Disease (EVD) or the Middle East Respiratory Syndrome coronavirus (MERS-CoV). There is currently no consensus for the types of PPE that are recommended to be worn by HCWs, nor is there a universal process for the donning and doffing of PPE. Methods HCWs from Bellevue Hospital participate in quarterly PPE trainings as part of the Special Pathogens Program (SPP), which consist of didactic sessions as well as an evaluation of donning and doffing techniques. A total of 50 HCWs completed the training curriculum in 2017. During the doffing process, PPE trainers applied corn start powder paint (Chameleon Colors; American Fork, UT) to the participants’ gloved hands between multiple steps of PPE removal. At the end of the process, the areas wher...

Case Report: Mucosal Leishmaniasis in New York City

The American Journal of Tropical Medicine and Hygiene

The Special Pathogens Research Network: Enabling Research Readiness

Health Security

Antimicrobial agents and chemotherapy, Jan 29, 2018

Nephrotoxicity is a known adverse effect of polymyxin B (PMB). Animal data suggests that once dai... more Nephrotoxicity is a known adverse effect of polymyxin B (PMB). Animal data suggests that once daily dosing may reduce the rate and delay the onset of acute kidney injury (AKI).In a multicenter, retrospective study, we evaluated adult patients with a creatinine clearance (CrCl) ≥30 mL/min who received ≥48h of PMB therapy. The primary endpoint was the difference in rate of AKI comparing once and twice daily PMB dosing. Secondary endpoints included time to AKI and recovery of renal function.Of 273 eligible patients, 100 from each group were matched based on propensity scores. In the matched groups, nephrotoxicity, defined according to RIFLE criteria, was more frequent with once versus twice daily dosing (47% vs. 17% =0.0005). After adjusting for residual differences by multivariate conditional logistic regression, once daily dosing was more likely to result in nephrotoxicity (adjusted odds ratio 2.5, 95% CI 1.413-4.541, =0.002). Among 64 patients who developed AKI, the median onset was...

Knowledge, Attitudes, and Practices Regarding Antimicrobial Use and Stewardship Among Prescribers at Acute-Care Hospitals

Infection control and hospital epidemiology, Mar 6, 2018

OBJECTIVE To assess antimicrobial prescriber knowledge, attitudes, and practices (KAP) regarding ... more OBJECTIVE To assess antimicrobial prescriber knowledge, attitudes, and practices (KAP) regarding antimicrobial stewardship (AS) and associated barriers to optimal prescribing. DESIGN Cross-sectional survey. SETTING Online survey. PARTICIPANTS A convenience sample of 2,900 US antimicrobial prescribers at 5 acute-care hospitals within a hospital network. INTERVENTION The following characteristics were assessed with an anonymous, online survey in February 2015: attitudes and practices related to antimicrobial resistance, AS programs, and institutional AS resources; antimicrobial prescribing and AS knowledge; and practices and confidence related to antimicrobial prescribing. RESULTS In total, 402 respondents completed the survey. Knowledge gaps were identified through case-based questions. Some respondents sometimes selected overly broad therapy for the susceptibilities given (29%) and some "usually" or "always" preferred using the most broad-spectrum empiric antimic...

Qualitative and Quantitative Assessment of Daily Cleaning of High-Touch Environmental Surfaces in Hospital Patient Rooms

Open Forum Infectious Diseases

Knowledge, Attitudes, and Practices of Environmental Service Workers Related to Environmental Cleaning and Healthcare-Associated Infections (HAI)

Open Forum Infectious Diseases

Quantitative Assessment of the Cleanliness of High-Touch Environmental Surfaces and Shared Equipment in the Hospital

Open Forum Infectious Diseases

Open Forum Infectious Diseases

Open Forum Infectious Diseases

Rate of nephrotoxicity was 43% with once daily vs. 22% with twice daily dosing Once daily dosing ... more Rate of nephrotoxicity was 43% with once daily vs. 22% with twice daily dosing Once daily dosing was not an independent predictor of nephrotoxicity Nephrotoxicity was multifactorial Risk factors included PMB longer duration, higher doses, and receiving >2 other nephrotoxic agents concomitantly Nephrotoxicity was reversible as most patients recovered their renal function to baseline Need further confirmation of our results in a prospective study with matched cohorts # 1804 Background: Nephrotoxicity is a known adverse effect of PMB. Animal data suggests that once daily dosing may be associated with decreased rate, severity and more gradual onset of nephrotoxicity compared to divided dosing. Clinical data evaluating the effect of PMB dosing frequency on nephrotoxicity is limited. Objective: Compare rate of acute kidney injury (AKI) with PMB once vs. twice daily dosing. Methods: In a single center, retrospective study we evaluated adult patients with Creatinine Clearance (CrCl) ≥30 mL/min who received ≥48h of PMB therapy. Nephrotoxicity was defined as development of AKI using RIFLE criteria. Results: A total of 173 patients were included (once daily n=141, twice daily n=32). Median age was 68 years (IQR 56-79), CrCl was 65 mL/min (IQR 44-91), mAPACHE II score was 14 (12-16), PMB duration of therapy was 6 days (IQR 4-11), 59% of patients received concomitant nephrotoxic agents, and these were comparable between once and twice daily dosing. Overall, rate of AKI was 43% with once vs. 22% with twice daily dosing, P=0.04 with most cases being Risk category by RIFLE (18 vs. 16%, P=0.9). No patients met ESRD. In-hospital mortality was 19% with once vs. 28% with twice daily dosing, P=0.4. Time to AKI onset (7 vs. 8 days) and peak serum creatinine (SCr) (8 vs. 8 days) was similar with once vs. twice daily dosing. In multivariate model, severe sepsis (OR 4.2, 95% CI 1.6-11.3, P=0.005), receipt of >2 concomitant nephrotoxic agents (OR 2.6, 95% CI 1.0-6.7, P=0.045), PMB duration of therapy >10 days (OR 2.6, 95% CI 1.0-4.5, P=0.02) and total dose >1,500,000 units/day (OR 2.1, P=0

Understanding Barriers to Optimal Cleaning and Disinfection in Hospitals: A Knowledge, Attitudes, and Practices Survey of Environmental Services Workers

Infection control and hospital epidemiology, Dec 13, 2016

In this study, we used an online survey to assess knowledge, attitudes, and practices related to ... more In this study, we used an online survey to assess knowledge, attitudes, and practices related to environmental cleaning and other infection prevention strategies among environmental services workers (ESWs) at 5 hospitals. Our findings suggest that ESWs could benefit from additional education and feedback as well as new strategies to address workflow challenges. Infect Control Hosp Epidemiol 2016;1-4.

Antimicrobial Agents and Chemotherapy, 2015

There is significant variation in the use of polymyxin B (PMB), and optimal dosing has not been d... more There is significant variation in the use of polymyxin B (PMB), and optimal dosing has not been defined. The purpose of this retrospective study was to evaluate the relationship between PMB dose and clinical outcomes. We included patients with bloodstream infections (BSIs) due to carbapenem-resistant Gram-negative rods who received ≥48 h of intravenous PMB. The objective was to evaluate the association between PMB dose and 30-day mortality, clinical cure at day 7, and development of acute kidney injury (AKI). A total of 151 BSIs were included. The overall 30-day mortality was 37.8% (54 of 151), and the median PMB dosage was 1.3 mg/kg (of total body weight)/day. Receipt of PMB dosages of <1.3 mg/kg/day was significantly associated with 30-day mortality (46.5% versus 26.3%;P= 0.02), and this association persisted in multivariable analysis (odds ratio [OR] = 1.58; 95% confidence interval [CI] = 1.05 to 1.81;P= 0.04). Eighty-two percent of patients who received PMB dosages of <1.3...

Fontana JF, Eiras D and Salvatore M. Human Influenza Virus Infections in ‘Human Respiratory Viral Infections’ Taylor & Francis Group, S K. Singh, Editor, 2014 pp 404-436

Cutaneous Leishmaniasis: Current Treatment Practices in the USA for Returning Travelers

Current Treatment Options in Infectious Diseases, 2015

Leishmaniasis, a protozoal infection transmitted by sandfly bite, produces a clinical spectrum of... more Leishmaniasis, a protozoal infection transmitted by sandfly bite, produces a clinical spectrum of disease ranging from asymptomatic infection to ulcerative skin and mucosal lesions to visceral involvement. Leishmaniasis is endemic in regions of Africa, the Middle East, south Asia, southern Europe, northern South America, and Central America. There has been an increase in imported leishmaniasis into developed, non-endemic countries due to increasing global travel. While pentavalent antimonials have been the mainstay of antileishmanial treatment for decades, newer therapeutic options have become available for all forms of infection, including liposomal amphotericin B, miltefosine, fluconazole, and ketoconazole. For the returning traveler with cutaneous leishmaniasis in the USA, treatment approaches are determined based on infecting species, initial presentation, extent and progression of disease, the advantages and drawbacks of available parenteral and oral drugs, and clinician-consultant experience.

Human Influenza Virus Infections

Human Respiratory Viral Infections, 2014

Hematological Oncology, 2010

Introduction: Classical Hodgkin's Lymphoma (cHL) has been frequently associated with Epstein-Barr... more Introduction: Classical Hodgkin's Lymphoma (cHL) has been frequently associated with Epstein-Barr virus (EBV), which can be found in a latent pattern in Reed-Sternberg (RS) cells. However, the impact of the presence of EBV in RS cells and its prognosis are still controversial. We analysed the presence of EBV in RS cells and its influence in the clinical evolution of patients with cHL treated in two public hospitals in the city of São Paulo, Brazil. Materials and Methods: We selected 97 patients with cHL from 1994 to 2004. Patients were only included in this study if they had (1) >18 years, (2) negative HIV serology, (3) undergone similar chemotherapy protocols, (4) paraffin blocks available with enough material for systematic review and histological reclassification and for detection of EBV in RS cells by in situ hybridization and immunohistochemistry and (5) clinical, epidemiological and laboratorial parameters available after a thorough chart review. Results: EBV was identified in 52.5% of the cases. Mixed cellularity (MC) subtype was more common in EBV-related tumours (25.5%) ( p ¼ 0.005). There was no difference on age, gender, stage and the presence of B symptoms between the two groups. The presence of EBV did not influence event free survival (EFS) ( p ¼ 0.38) or overall survival (OS) ( p ¼ 0.80) with a median follow-up of 80 months. Conclusion: We demonstrate that the prevalence of EBV-related cHL in this Brazilian population is 52.5% and, that, the presence of EBV does not change the clinical evolution and OS of patients treated with similar chemotherapy protocols.

Role of IL-6 in an IL-10 and IL-4 Double Knockout Mouse Model Uniquely Susceptible to Acetaminophen-Induced Liver Injury †

Chemical Research in Toxicology, 2007

Drug-induced hepatitis remains a challenging problem for drug development and safety because of t... more Drug-induced hepatitis remains a challenging problem for drug development and safety because of the lack of animal models. In the current work, we discovered a unique interaction that makes mice deficient in both IL-10 and IL-4 (IL-10/4-/-) highly sensitive to the hepatotoxic effects of acetaminophen (APAP). Male C57Bl/6 wild type (WT) and mice deficient in one or more cytokines were treated with 120 mg/kg APAP. Within 24 h after WT, IL-10-/-, IL-4-/-, or IL-10/4-/- mice were administered APAP, 75% of the IL-10/4-/- mice died of massive hepatic injury while all other genotypes were resistant to liver toxicity at this dose of APAP. The unique susceptibility of IL-10/4-/- mice was associated with reduced levels of liver glutathione and remarkably high serum levels of IL-6 and several proinflammatory factors including TNF-alpha, IFN-gamma, macrophage inflammatory protein-1alpha (MIP-1alpha), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), and osteopontin (OPN) as well as nitric oxide (NO). IL-6 appeared to have a causal role in controlling the unique susceptibility of IL-10/4-/- mice to APAP-induced liver disease (AILD) because IL-6 neutralizing antibody reversed the high sensitivity of these mice to AILD. Moreover, IL-10/4/6-/- mice were also resistant to the enhanced susceptibility to AILD and expressed relatively low levels of most proinflammatory factor genes that were elevated in the IL-10/4-/- mice. In conclusion, liver homeostasis following AILD appears to be highly dependent on the activities of both IL-10 and IL-4, which together help prevent overexpression of IL-6 and other potential hepatotoxic factors.

Healthcare Disparities in the Treatment of Acute Chest Pain

Academic Emergency Medicine, 2007

American Journal of Infection Control, 2006

Inappropriate use of antibiotics contributes to antimicrobial resistance worldwide. In Latin Amer... more Inappropriate use of antibiotics contributes to antimicrobial resistance worldwide. In Latin America, antibiotics are easily obtained over the counter. In the United States, the Latino population is the largest and fastest growing immigrant group. Hence, it is necessary to understand Latino cultural practices in regards to antibiotic use to develop effective interventions that reduce inappropriate antibiotic use among this population. We conducted a systematic review of descriptive and intervention studies measuring knowledge, attitudes, and practices of antibiotic use among Latinos in the United States. The search yielded only 11 descriptive studies and no interventions. The literature suggests that many Latinos in the United States self-prescribe antibiotics because of financial and sociocultural barriers and inaccurately believe that antibiotics help treat viral infections. Increased access to health care and appropriate culturally tailored interventions specific to Latinos are needed to promote judicious antibiotic use among Latinos. (Am J Infect Control 2006;34:495-502.)