Chloroform, a halogenated hydrocarbon, causes central nervous system depression, cardiac arrhythmias, and hepatotoxicity. We describe a case of chloroform ingestion with a confirmatory serum level and resultant hepatotoxicity successfully treated with intravenously administered N-acetylcysteine (NAC). A 19-year-old man attempting suicide ingested approximately 75 mL of chloroform. He was unresponsive and intubated upon arrival. Intravenously administered NAC was started after initial stabilization was complete. His vital signs were normal. Admission laboratory values revealed normal serum electrolytes, AST, ALT, PT, BUN, creatinine, and bilirubin. Serum ethanol level was 15 mg/dL, and aspirin and acetaminophen were undetectable. The patient was extubated but developed liver function abnormalities with a peak AST of 224 IU/L, ALT of 583 IU/L, and bilirubin level reaching 16.3 mg/dL. NAC was continued through hospital day 6. Serum chloroform level obtained on admission was 91 μg/mL. The patient was discharged to psychiatry without known sequelae and normal liver function tests. The average serum chloroform level in fatal cases of inhalational chloroform poisoning was 64 μg/mL, significantly lower than our patient. The toxicity is believed to be similar in both inhalation and ingestion routes of exposure, with mortality predominantly resulting from anoxia secondary to central nervous system depression. Hepatocellular toxicity is thought to result from free radical-induced oxidative damage. Previous reports describe survival after treatment with orally administered NAC, we report the first use of intravenously administered NAC for chloroform ingestion. Acute oral ingestion of chloroform is extremely rare. Our case illustrates that with appropriate supportive care, patients can recover from chloroform ingestion, and intravenously administered NAC may be of benefit in such cases.
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Mary K. Robinson;
Samuel P. Caudill;
David D Koch;
James C Ritchie;
Glen Hortin;
John H. Eckfeldt;
Sverre Sandberg;
Desmond Williams;
Gary Myers;
W. Greg Miller
Background: Adsorption of albumin onto urine collection and analysis containers may cause falsely low concentrations. Methods: We added 125 I-labeled human serum albumin to urine and to phosphate buffered solutions, incubated them with 22 plastic container materials and measured adsorption by liquid scintillation counting. Results: Adsorption of urine albumin (UA) at 5-6. mg/l was < . 0.9%; and at 90. mg/l was < . 0.4%. Adsorption was generally less at pH. 8 than pH. 5 but only 3 cases had p. < . 0.05. Adsorption from 11 unaltered urine samples with albumin 5-333. mg/l was < . 0.8%. Albumin adsorption for the material with greatest binding was extrapolated to the surface areas of 100. ml and 2. l collection containers, and to instrument sample cups and showed < . 1% change in concentration at 5. mg/l and < . 0.5% change at 20. mg/l or higher concentrations. Adsorption of albumin from phosphate buffered solutions (2-28%) was larger than that from urine. Conclusions: Albumin adsorption differed among urine samples and plastic materials, but the total influence of adsorption was < . 1% for all materials and urine samples tested. Adsorption of albumin from phosphate buffered solutions was larger than that from urine and could be a limitation for preparations used as calibrators.
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R. Todd Stravitz;
Michelle Gottfried;
Valerie Durkalski;
Robert J. Fontana;
A. James Hanje;
David Koch;
Bilal Hameed;
Daniel Ganger;
Ram Subramanian;
Stan Bukofzer;
William R. Ravis;
Kristen Clasen;
Averell Sherker;
Lanna Little;
William M. Lee
Cerebral edema remains a significant cause of morbidity and mortality in patients with acute liver failure (ALF) and has been linked to elevated blood ammonia levels. l-ornithine phenylacetate (OPA) may decrease ammonia by promoting its renal excretion as phenylacetylglutamine (PAGN), decreasing the risk of cerebral edema. We evaluated the safety, tolerability, and pharmacokinetics of OPA in patients with ALF and acute liver injury (ALI), including those with renal failure. Forty-seven patients with ALI/ALF and ammonia ≥60 μM were enrolled. Patients received OPA in a dose escalation scheme from 3.3 g every 24 hours to 10 g every 24 hours; 15 patients received 20 g every 24 hours throughout the infusion for up to 120 hours. Plasma phenylacetate (PA) concentrations were uniformly below target (<75 μg/mL) in those receiving 3.3 g every 24 hours (median [interquartile range] 5.0 [5.0] μg/mL), and increased to target levels in all but one who received 20 g every 24 hours (150 [100] μg/mL). Plasma [PAGN] increased, and conversion of PA to PAGN became saturated, with increasing OPA dose. Urinary PAGN clearance and creatinine clearance were linearly related (r = 0.831, P < 0.0001). Mean ammonia concentrations based on the area under the curve decreased to a greater extent in patients who received 20 g of OPA every 24 hours compared with those who received the maximal dose of 3.3 or 6.7 g every 24 hours (P = 0.046 and 0.022, respectively). Of the reported serious adverse events (AEs), which included 11 deaths, none was attributable to study medication. The only nonserious AEs possibly related to study drug were headache and nausea/vomiting. Conclusion: OPA was well-tolerated in patients with ALI/ALF, and no safety signals were identified. Target [PA] was achieved at infusion rates of 20 g every 24 hours, leading to ammonia excretion in urine as PAGN in proportion to renal function. Randomized, controlled studies of high-dose OPA are needed to determine its use as an ammonia-scavenging agent in patients with ALF. (Hepatology 2018;67:1003–1013).
Aims
To compare the utility of metabolic syndrome (MetS) to random plasma glucose (RPG) in identifying people with diabetes or prediabetes.
Methods
RPG was measured and an OGTT was performed in 1,155 adults. Test performance was measured by are under the receiver-operating-characteristic curve (AROC).
Results
Diabetes was found in 5.1% and prediabetes in 20.0%. AROC for MetS with FPG was 0.80 to detect diabetes, and 0.76 for diabetes or prediabetes – similar to RPG (0.82 and 0.72). However, the AROC for MetS excluding fasting plasma glucose (FPG) was lower: 0.69 for diabetes (p<0.01 vs. both RPG and MetS with FPG), and 0.69 for diabetes or prediabetes. AROCs for MetS with FPG and RPG were comparable and higher for recognizing diabetes in blacks vs. whites, and females vs. males. MetS with FPG was superior to RPG for identifying diabetes only in subjects with age <40 or BMI <25.
Conclusions
MetS features can be used to identify risk of diabetes, but predictive usefulness is driven largely by FPG. Overall, to identify diabetes or prediabetes in blacks and whites with varying age and BMI, MetS is no better than RPG – a more convenient and less expensive test.
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Zhen Zhao;
Attila Kumanovics;
Tanzy Love;
Stacy EF Melanson;
Qing H Meng;
Alan HB Wu;
Joesph Wiencek;
Fred S Apple;
Caitlin R Ondracek;
David Koch;
Robert H Christenson;
Yan Victoria Zhang
Objectives: The objective of this prospective study was to investigate the role of adaptive immunity in response to SARS-CoV-2 vaccines. Design and Methods: A cohort of 677 vaccinated individuals participated in a comprehensive survey of their vaccination status and associated side effects, and donated blood to evaluate their adaptive immune responses by neutralizing antibody (NAb) and T cell responses. The cohort then completed a follow-up survey to investigate the occurrence of breakthrough infections. Results: NAb levels were the highest in participants vaccinated with Moderna, followed by Pfizer and Johnson & Johnson. NAb levels decreased with time after vaccination with Pfizer and Johnson & Johnson. T cell responses showed no significant difference among the different vaccines and remained stable up to 10 months after the study period for all vaccine types. In multivariate analyses, NAb responses (<95 U/mL) predicted breakthrough infection, whereas previous infection, the type of vaccine, and T cell responses did not. T cell responses to viral epitopes (<0.120 IU/mL) showed a significant association with the self-reported severity of COVID-19 disease. Conclusion: This study provides evidence that NAb responses to SARS-CoV-2 vaccination correlate with protection against infection, whereas the T cell memory responses may contribute to protection against severe disease but not against infection.
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Stacy EF Melanson;
Zhen Zhao;
Attila Kumanovics;
Tanzy Love;
Qing H Meng;
Alan HB Wu;
Fred Apple;
Caitlin R Ondracek;
Karen M Schulz;
Joseph R Wiencek;
David Koch;
Robert Christenson;
Victoria Y Zhang
Importance: Most healthcare institutions require employees to be vaccinated against SARS-CoV-2 and many also require at least one booster. Objective: We determine the impact of vaccine type, demographics, and health conditions on COVID-19 vaccine side effects in healthcare professionals. Design: A COVID-19 immunity study was performed at the 2021 American Association for Clinical Chemistry Annual Scientific meeting. As part of this study, a REDCap survey with cascading questions was administered from September 9, 2021 to October 20, 2021. General questions included participant demographics, past and present health conditions, smoking, exercise, and medications. COVID-19 specific questions asked about SARS-CoV-2 vaccine status and type, vaccine-associated side effects after each dose including any boosters, previous infection with COVID-19, diagnostic testing performed, and type and severity symptoms of COVID-19. Results: There were 975 participants (47.1% male, median age of 50 years) who completed the survey. Pfizer was the most commonly administered vaccine (56.4%) followed by Moderna (32.0%) and Johnson & Johnson (7.1%). There were no significant differences in vaccine type received by age, health conditions, smoking, exercise, or type or number of prescription medications. Side effects were reported more frequently after second dose (e.g., Moderna or Pfizer) (54.1%) or single/only dose of Johnson & Johnson (47.8%). Males were significantly more likely to report no side effects (p < 0.001), while females were significantly more likely to report injection site reactions (p < 0.001), fatigue (p < 0.001), headache (p < 0.001), muscle pain (p < 0.001), chills (p = 0.001), fever (p = 0.007), and nausea (p < 0.001). There was a significant upward trend in participants reporting no side effects with increasing age (p < 0.001). There were no significant trends in side effects among different races, ethnicities, health conditions, medications, smoking status or exercise. In multivariate logistic regressions analyses, the second dose of Moderna was associated with a significantly higher risk of side effects than both the second dose of Pfizer and the single dose of Johnson & Johnson. Conclusions and relevance: Younger people, females, and those receiving the second dose of Moderna had more COVID-19 vaccine side effects that per self-report led to moderate to severe limitations. As reported in other studies, the increase in side effects from Moderna may be explained by higher viral mRNA concentrations but be associated with additional protective immunity.
Context
Laboratory medicine is an integral component of patient care. Approximately 60% to 70% of medical decisions are based on laboratory results. Physicians in specialties that order the tests are teaching medical students laboratory medicine and test use with minimal input from laboratory scientists who implement and maintain the quality control for those tests.
Objective
To develop, implement, and evaluate a 1.5-day medical student clinical laboratory experience for fourth-year medical students in their last month of training.
Design
The experience was devised and directed by laboratory scientists and included a panel discussion, laboratory tours, case studies that focused on the goals and objectives recently published by the Academy of Clinical Laboratory Physicians and Scientists, and medical-student presentations highlighting salient points of the experience. The same knowledge quiz was administered at the beginning and end of the experience and 84 students took both quizzes.
Results
A score of 7 or more was obtained by 16 students (19%) on the initial quiz, whereas 34 (40%) obtained the same score on the final quiz; the improvement was found to be statistically significant (P = .002; t = 3.215), particularly in 3 out of the 10 questions administered.
Conclusions
Although the assessment can only measure a small amount of knowledge recently acquired, the improvement observed by fourth-year medical students devoting a short period to learning laboratory medicine principles was encouraging. This medical student clinical laboratory experience format allowed teaching of a select group of laboratory medicine principles in 1.5 days to an entire medical school class.
OBJECTIVE
Age, BMI, and race/ethnicity are used in National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and American Diabetes Association (ADA) guidelines to prompt screening for pre-diabetes and diabetes, but cutoffs have not been evaluated rigorously.
RESEARCH DESIGN AND METHODS
Random plasma glucose (RPG) was measured and 75-g oral glucose tolerance tests were performed in 1,139 individuals without known diabetes. Screening performance was assessed by logistic regression and area under the receiver operating characteristic curve (AROC).
RESULTS
NIDDK/ADA indicators age >45 years and BMI >25 kg/m2 provided significant detection of both diabetes and dysglycemia (both AROCs 0.63), but screening was better with continuous-variable models of age, BMI, and race and better still with models of age, BMI, race, sex, and family history (AROC 0.78 and 0.72). However, screening was even better with RPG alone (AROCs 0.81 and 0.72). RPG >125 mg/dl could be used to prompt further evaluation with an OGTT.
CONCLUSIONS
Use of age, BMI, and race/ethnicity in guidelines for screening to detect diabetes and pre-diabetes may be less important than evaluation of RPG. RPG should be investigated further as a convenient, inexpensive screen with good predictive utility.