Kyu-Yoon Hwang

Predictors of survival after acute paraquat poisoning.

Acute paraquat poisoning is often fatal. Many studies have investigated successful treatment modalities, but no standard treatment yet exists. The purpose of this study was to determine the predictors of survival after acute paraquat poisoning in 602 patients. The paraquat exposure was assessed based on the amount of ingested paraquat and a semiquantitative measure of the urine level of paraquat. Initial clinical parameters including vital signs, hemoglobin, white-blood-cell count, pH, PaCO2, PaO2, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, total bilirubin, amylase, and glucose were obtained at the time of arrival at the emergency room. Outcomes after acute paraquat poisoning were categorized as survivors and nonsurvivors. Multiple logistic regression analysis was applied to assess the predictors of survival after acute paraquat poisoning. Some patients (55.5%) survived after oral ingestion of paraquat, whereas all those exposed to paraquat percutaneous or inhalational route survived. The amount of paraquat (24.5% concentrate of 1,1′-dimethyl-4,4′-bipyridium dichloride) ingested was 45.69 / 74.1 mL (mean9 / SD). In addition to degree of paraquat exposure, survival after acute paraquat poisoning was associated with age, respiratory rate, pH, PaCO2, hemoglobin, white-blood-cell count, blood urea nitrogen, amylase, and the number of failed organs in multiple logistic regression analysis. In conclusion, young age, percutaneous or inhalational route, exposure to less paraquat, and lesser degrees of leukocytosis, acidosis, and renal, hepatic, and pancreatic failures on admission are good prognostic factors of survival after acute paraquat poisoning.

Associations between laboratory parameters and outcome of paraquat poisoning

Paraquat, a non-selective herbicide, is a known fatal substance in humans, and intentional ingestion of paraquat is increasing among Korean suicides. In 1999, 147 subjects admitted to the Institute of Pesticide Poisoning, Soonchunhyang Chunan Hospital, Korea ingested paraquat. Initial routine laboratory tests were conducted and the outcome of paraquat poisoning was categorized as survivor and fatality. Mean amount (S.D.) of ingestion was 54.5 (104.9) ml, and the overall fatality rate was 44.2%. Abnormal liver function (GOT and GPT), renal dysfunction (BUN and creatinine), metabolic acidosis (pH and PaCO(2)), and abnormal urine analysis (RBC, WBC, and protein) had significant odds ratios (ORs) for paraquat fatality (P<0.05). In multiple logistic regression, subjects with liver or renal dysfunction or metabolic acidosis had significant risks of the fatality. Our results determined that initial routine laboratory parameters could be used to predict the outcome of paraquat poisoning and recommended that evaluation of acid-base status and renal and liver function should be conducted and evaluated before intensive therapy.

Paraquat intoxication in Korea

Abstract In this study, the authors explored acute paraquat intoxication and determined potential factors related to paraquat fatalities. During 1999, 154 patients with paraquat intoxication were admitted to the Institute of Pesticide Poisoning at the Soonchunhyang University Chunan Hospital. The authors assessed paraquat exposure by quantifying the amount of ingested paraquat and by semiquantitative assay of paraquat in urine. Outcomes of paraquat intoxication were categorized as recovery or death. Among all the patients, 139 (90.3%) were transferred from other medical facilities to the Institute of Pesticide Poisoning following a mean exposure time of 20.1 hr (standard deviation = 2.6 hr). Intentional ingestion of paraquat accounted for 73.4% (113/154 patients) of all paraquat poisonings, and it represented a significantly higher fatality rate (53.2%) than did accidental ingestion (19.1 % [p < .001]). The overall paraquat fatality was 43.8%. Multiple logistic-regression analysis revealed that the risk of fatality increased significantly with (1) the quantity of paraquat ingested and (2) a positive urinary paraquat test. The results indicated that paraquat is potentially lethal in humans, and the risk of fatality is directly related to the amount ingested and absorbed.

Effect of vitamin C on plasma total antioxidant status in patients with paraquat intoxication

This study was conducted to evaluate whether vitamin C (VC) was associated with total antioxidant status (TAS) in human plasma and to determine the usefulness of VC on TAS in the treatment of patients with paraquat poisoning. VC and TAS were measured in 56 healthy subjects. Then, various concentrations (1-100 mg/dl) of VC in pooled plasma from 10 volunteers were constructed in vitro and TAS was measured. The VC and TAS were measured in vivo at 0.5, 1, 2, 3, 5, 7, 9, and 11 h after injection of VC (50 mg/kg) in seven volunteers and pharmacokinetic data were calculated. Finally, various amounts of VC (100, 500, 1000, 3000 mg/day, and 3000 mg/8 h) were given to 10 paraquat-poisoned patients for 5 consecutive days, and blood was taken for TAS 1 h after each injection. The means (SD) of VC and TAS in healthy subjects were 2.22 (0.16) mmol/l and 0.48 (0.10) mg/dl, respectively. Positive correlation between VC and TAS was observed in both in vitro and in healthy volunteers. The pharmacokinetic results in vivo were as follows: means (SD) of distribution volume, area under curve, plasma clearance, half life, C(max), and T(max) were 32.0 (4.4) l, 36.4 (11.3) mg h/dl, 2.13 (1.36) l/h, 10.2 (7.8) h, 17.1 (7.1) mg/dl, and 0.64 (0.24) h, respectively. Estimated loading and maintenance doses of VC were 2278 mg and 146 mg/h, respectively. The means of TAS were increased over 5 consecutive days as 2.26, 2.76, 2.81, 3.18, and 3.58 mmol/l in paraquat patients. All patients were recovered within mean (SD) 21.2 (5.4) admission days. Our data suggested that VC was a significant antioxidant as TAS in human plasma and that increased TAS by high doses of VC could be useful as a free radical scavenger for paraquat poisoned patients.

Isolation, identification, and quantitation of urinary glycosaminoglycans.

Background: Substantial amounts of glycosaminoglycans (GAGs) are present in the urine of healthy individuals, but the concentration in the serum is very low. This finding suggests that urinary GAGs come from the glomerulus and may reflect the turnover of GAGs in the glomerulus. Hypothesis: However, little is known about the physiologic regulation of the urinary GAGs in humans, and so investigations are needed to evaluate the effects of age and sex on urinary GAGs in normal individuals. Methods: Eighty-seven healthy subjects were included in this study. Urinary GAGs were isolated and quantified at the nanogram level by combined azure A-silver staining in agarose gels. Results: The level of urinary GAGs peaked at 10–19 years in both sexes. The proportion of chondroitin sulfate decreased with age, but the proportion of heparan sulfate increased with age. Conclusion: The total amount of GAGs and the proportions of chondroitin sulfate, heparan sulfate, and dermatan sulfate appear to change with age. Therefore, investigations in which urinary GAG is used as a parameter of glomerular GAG turnover should ensure that control groups are precisely matched for age. Changes in the proportions of each GAG may be more informative than their absolute levels.

The methylenetetrahydrofolate reductase gene polymorphism in Koreans with coronary artery disease

Hyperhomocysteinemia is a known risk factor of cardiovascular diseases. Methylenetetrahydrofolate reductase (MTHFR), involved in folate-dependant metabolism, is associated with homocysteine levels. We studied the associations among MTHFR genotypes, coronary artery disease (CAD), and homocysteine levels in 85 patients with CAD and 152 healthy subjects. The MTHFR genotypes and plasma homocysteine levels were determined. No significant difference in mutation of the MTHFR gene between two groups was observed (P>0.05). While the homozygous mutant genotype (V/V) had the highest homocysteine levels compared to wild (A/A) and heterozygous mutant (A/V) genotypes, there were no significant differences in homocysteine levels among the MTHFR genotype groups. Homocysteine was significantly and inversely related to folate levels, the significant association in V/V genotype (beta coefficient=-1.954, P=0.04). Our data suggested that MTHFR polymorphism was not associated with homocysteine levels, implying no association between gene polymorphism and CAD in Koreans.

Chronic lead nephropathy with excessive body lead burden

A 50-yr-old man, a secondary lead smelting worker, was examined because of persistent renal insufficiency and intermittent gouty arthritis. Four yr earlier, his serum creatinine had fluctuated between 2.1 and 2.5 mg/dl, and creatinine clearance and serum uric acid levels were 40 to 54 ml/min/1.73 m and 9.9 to 12.3 mg/dl, respectively. He had worked intermittently at several lead-smelting plants for approximately 17 yr between 1968 and 1994. Air lead monitoring in 1993–94 at his work site showed it in excess of the threshold limit value (TLV) for lead in Korea (0.05 mg/m). The man was completely removed from further exposure after he was diagnosed as having lead poisoning by a regular special health examination in September 1994. We had examined his health condition by regular health check-up annually since 1988, but no specific symptoms and abnormal screening findings related to renal function were observed until 1994. He presented with fatigue, dizziness, numbness, facial edema, and polyarthralgia for several years before admission. However, he denied headache, wrist drops, and abdominal pain. The remainder of his medical and familial histories were non-contributory. On physical examination, his blood pressure was 120/80 mmHg, and other vital signs were normal. He had a slightly pale face, mild edema on both legs, and reddish nodules on the left ankle and great toe. Results of laboratory studies showed the following values: normocytic normochromic anemia (hemoglobin, 10.7 g/dl) with basophilic stippling of erythrocytes; albumin, 4.2 mg/dl; total cholesterol, 225 mg/dl; sodium, 140 mEq/L; potassium, 5.0 mEq/L; C3, 140 mg/dl; C4, 50 mg/dl; IgG/IgA/IgM, 1,520/220/165 mg/dl; blood lead, 62.0 μg/dl; and zinc protoporphyrin, 218 μg/dl. Renal sonography revealed bilateral normalsized kidneys. Renal biopsy showed focal moderate atrophy or loss of proximal tubules with prominent interstitial fibrosis. Also, 22% of glomeruli showed global sclerosis and arterioles exhibited patchy hyaline deposits (Fig. 1-A). An ultra-structural study revealed an absence of immune complex depositions. The schedule of the lead mobilization test (LMT) is summarized in Table 2. Baseline urinary excretion of lead was 106 μg/d, and after the first LMT with an intravenous infusion of 1 g calcium disodium ethylenediamine tetraacetic acid (CaEDTA), urine lead increased to 3,934 μg/d (Table 1). Cortical bone lead was assessed (in units of μg Pb/g bone mineral) after 30 min of measurement at the left mid-tibia shaft using Cd K-shell X-ray fluorescence (K-XRF) . Tibial bone lead level was 337 μg Pb/g bone mineral. At present, after treatment with 50 g CaEDTA over 11 months, serum creatinine has fallen to less than 2.0 mg/dl (about 1.5 to 1.9 mg/dl) and CaEDTA chelatable lead has decreased to 3,028 μg/d. However, blood lead has been sustained at a high level (59.3 μg/dl).