Being overweight or obese as a risk factor for acute liver injury secondary to acute acetaminophen overdose

Purpose

Increased incidences of hepatotoxicity have been observed in obese patients with acute acetaminophen overdose. We evaluate whether the status of being overweight or obese is associated with increase in the development of hepatotoxicity and acute liver injury (ALI) in patients with acute acetaminophen overdose.

Methods

This was a retrospective cohort study comparing the risk of hepatotoxicity and ALI between overweight or obese patients (body mass index [BMI] ≥ 25) and normal BMI patients (BMI ≤ 24.9) presenting with acute acetaminophen overdose at Siriraj Hospital during January 2004 to June 2012. All patients were treated with intravenous N‐acetylcysteine. Psi parameters were calculated. High psi was defined as psi of ≥5.0 mM‐hour. Data were analyzed using multinomial logistic regressions, odds ratio (OR), stratified OR, and 95% confidence interval (CI).

Results

There were 197 patients who fulfilled the criteria for analysis, 35 (17.8%) were obese, 24 (12.2%) were overweight, and 138 (70%) were normal BMI cases. Hepatotoxicity and ALI developed in 25 (12.7%) and 40 (20.3%) cases, respectively. Multinomial logistic regression revealed that the overweight‐obesity status and log₁₀(psi value) were significant risk factors of ALI, with OR (95% CI) of 2.68 (1.21‐5.95) and 1.74 (1.27‐2.38), respectively, while only log₁₀(psi) was a significant risk factor of hepatotoxicity with OR (95% CI) 378.51 (39.49‐3627.99). From stratification, overweight‐obesity had significant odds ratios for ALI in strata with low acetaminophen concentration, early initiation of N‐acetylcysteine and low psi.

Conclusion

We conclude that being overweight or obese is an independent risk factor of ALI in acute acetaminophen overdoses.     

Combined therapy for cancer of the anal canal: A follow-up report

Summary We believe this preoperative combined therapy is highly effective in treating squamous-cell carcinoma of the anal canal, and that a subsequent larger cooperative study with controls is indicated. This pilot study suggests that some individuals may be spared abdominoperineal resection when treated in the manner described. Department of Oncology Department of Surgery Department of Radiotherapy Supported in part by Clinical Cancer Research Center Grant CA-07177 from the National Cancer Institute, United States Public Health Service.     

A rat model for studying colonic cancer: Effect of cholestyramine on induced tumors

Summary Dimethylhydrazine, azoxymethane, and methylazoxymethanol are highly efficient intestinal carcinogens in the rat. Azoxymethane is the best, producing tumors in all rats. The lesions occurred in significant numbers in the small intestine when given at high dosage levels over a period of six months or more. The tumors tend to occur more in the proximal halves of both segments of the intestine. When the animals are fed a 2 per cent cholestyramine diet, there is a marked increase in the tumor yield and the increase is, for the most part, in the large intestine, especially its distal half. Investigations of the mechanisms whereby cholestyramine enhances tumor formation in the large intestine of the rat are continuing. We conclude that the rat given azoxymethane subcutaneously at weekly intervals while on a 2 per cent cholestyramine diet is an excellent experimental model for studies of colonic cancer. Read at the meeting of the American Proctologic Society, New York N. Y., June 11 to 14, 1972. Supported by Matilda R. Wilson Fund.     

Predicting acute acetaminophen hepatotoxicity with acetaminophen-aminotransferase multiplication product and the Psi parameter

Context. Prediction of potential hepatotoxicity is important for individualizing therapy with N-acetylcysteine (NAC) in patients with acute acetaminophen overdose. Acetaminophen-aminotransferase multiplication product (APAP × AT) and the Psi Parameter (Psi) have been reported to be the predictors of acetaminophen hepatotoxicity. Objective. To determine the validity of APAP × AT and Psi in predicting hepatotoxicity secondary to acute acetaminophen overdose. Materials and methods. We retrospectively reviewed acute acetaminophen overdose cases who were treated with NAC at Siriraj Hospital, Thailand during January 2004–June 2012. The patients’ ages were 12 years or more. Initial acetaminophen concentration (mg/L) and aminotransferase (IU/L) were multiplied to obtain APAP × AT. Psi were derived from initial acetaminophen concentrations (mg/L) and lag time (hours) to NAC therapy. The cut-off values for APAP × AT and Psi were 1500 mg?IU/L² and 5 mM?h, respectively. Hepatotoxicity (defined as aspartate or alanine aminotransferase (ALT) greater than 1000 IU/L) was the outcome of interest. Results. A total of 255 patients were included, 32 of whom developed hepatotoxicity. APAP × AT had sensitivity, specificity, and negative likelihood ratio of 90.6%, 62.8%, and 0.2, respectively. The sensitivity of Psi, specificity, and negative likelihood ratio were 96.9%, 91.5%, and 0.0, respectively. The areas under the curve of the receiver operating characteristic (ROC) curve for APAP × AT and Psi were 0.82 and 0.96, respectively, with a statistically significant difference between the two methods (p = 0.002). APAP × AT showed higher specificity (92.5%) in patients who presented 8–24 h after the overdose. Discussion and conclusion. Psi and APAP × AT are valid clinical tools in predicting hepatotoxicity secondary to acute acetaminophen overdose in adults. APAP × AT is useful in predicting a low likelihood of hepatotoxicity after standard NAC therapy among late-presenting patients.     

Prognostic significance of p53 gene mutations in laryngeal cancer

OBJECTIVE/HYPOTHESIS: We examined whether p53 gene mutations were predictive of clinical behavior in laryngeal cancer. STUDY DESIGN: Retrospective study of 45 patients with laryngeal cancer from 1985 to 1997. METHODS: DNA was extracted from tumor tissue and subject to polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) as well as DNA sequencing. The clinical outcome was correlated to the presence or absence of a p53 mutation. RESULTS: The p53 gene was analyzed by direct DNA sequencing and was found to be mutated in 33% (15/45) of patients. The presence of a p53 mutation was associated with a significant improvement in overall survival (80% vs. 43%, P < .03) and a trend toward improved disease-free survival (87% vs. 60%, P = .08). When other prognostic factors were adjusted, multivariate analysis revealed a trend toward improvement in overall survival as well as disease-free survival. CONCLUSION: Depending on the location of a p53 mutation, the suppressive functions or clinical outcome may or may not be affected. Fifty-three percent of mutations were detected in nonconserved regions as opposed to 17% as reported in colon cancer. In colon cancer, mutations in conserved regions of the p53 gene predicted a poorer survival, whereas nonconserved gene mutations were not predictive. In our group of patients. p53 mutations predicted a better prognosis, which may be due to a large proportion of mutations that lie within nonconserved areas. The predictive power of p53 gene mutations may depend on functional loss and inactivation of highly conserved areas and must be tested in a prospective trial.     

Histamine poisoning from insect consumption: an outbreak investigation from Thailand

Background: Insect consumption is a common practice in the Asian culture and all over the world. We are reporting an outbreak investigation of histamine poisoning from ingestion of fried insects.

Methods: On 24 July 2014, a group of students at a seminar presented to Angthong Provincial Hospital, Thailand, with pruritic rash after ingesting snacks consisting of fried insects from a vendor. We initiated an outbreak investigation with retrospective cohort design and collected samples of remaining foods for analyses. Attack rates, relative risks and their confidence intervals (CI) were calculated.

Results: Out of 227 students, 28 developed illnesses that were consistent with our case definition which included, flushing, pruritus, urticarial rashes, headache, nausea, vomiting, diarrhea, dyspnea and bronchospasm. Two children were hospitalized for progressive bronchospasm overnight without serious complications. The types of food ingested included a lunch that was provided at the seminar for all students and snacks that 41 students bought from the only vendor in the vicinity. The snacks included fried grasshoppers, silkworm pupae, common green frogs, bamboo borers, crickets and meat balls. The attack rates were highest (82.6 and 85.0%) among students who ingested fried grasshoppers and silkworm pupae and lowest (4.4 and 5.3%) among those who did not ingest them, with relative risk of 18.7 (95% CI 9.6–36.4) for grasshoppers and 16.0 (95% CI 8.8–29.3) for silkworm pupae. Histamine concentrations in the fried grasshoppers and silkworm pupae were 9.73 and 7.66?mg/100g, respectively.

Discussion and conclusion: Through epidemiological analysis and laboratory confirmation, we have illustrated that histamine poisoning can occur from ingestion of fried insects. We postulate that histidine, which is present in high concentration in grasshoppers and silkworm pupae, is decarboxylated by bacteria to histamine, a heat stable toxin. The ingestion of histamine is responsible for the clinical pictures being reported.