[Characteristics of ERG, Fli-1, CD34, CD31 and Fâ §RAg expression in hepatic malignant vascular tumors].

Objective: To investigate the expression of ERG, Fli-1, CD34, CD31 and factor Ⅷ-related antigen(FⅧRAg) in hepatic malignant vascular tumors. Methods: A retrospective analysis was conducted on 63 cases of primary hepatic malignant vascular tumors and 31 cases of hepatic other malignant spindle cell tumors collected during January 1986 to January 2014. EnVision method was used to detect the expression of ERG, Fli-1, CD34, CD31, FⅧRAg. Results: Sixty-three cases of malignant vascular tumors, including 24 cases of angiosarcoma, 38 cases of epithelioid hemangioendothelioma and 1 case of hepatic Kaposi's sarcoma. All of the cases were positive for ERG(100.0%, 63/63). Positive rate of Fli-1, CD34, CD31, FⅧRAg was 96.8% (61/63), 87.3% (55/63), 81.0% (51/63) and 41.3% (26/63), respectively. In other hepatic malignant spindle cell tumors, the positive rate of ERG, Fli-1, CD34, CD31 and FⅧRAg was 3.2% (1/31), 19.4% (6/31), 19.4% (6/31), 9.7%(3/31) and 3.2%(1/31), respectively.The sensitivity of ERG, Fli-1, CD34, CD31, FⅧRAg was 100.0%, 96.8%, 87.3%, 81.0% and 41.3%, respectively.The specificity was 96.8%, 80.6%, 80.6%, 90.3% and 96.8%, respectively. Conclusion: ERG is a more sensitive and specific diagnostic marker for hepatic malignant vascular tumors in comparison to Fli-1, CD34, CD31 and FⅧRAg.

Acute hydrofluoric acid exposure reported to Taiwan Poison Control Center, 1991-2010.

BACKGROUND: Hydrofluoric acid (HF) is a dangerous chemical that can cause severe cutaneous burns as well as possible systemic toxicity. METHODS: We retrospectively analyzed all human HF exposure cases reported to the National Poison Control Center of Taiwan between 1991 and 2010. RESULTS: In this 20-year survey, 324 calls were identified, with a majority of dermal exposure (84%). Occupational exposure accounted for 80% of all cases, with workers in semiconductor industry (61%), cleaning industry (15%), chemical or metal industry (13%), and other industries (11%). Electrolyte imbalances were uncommon, hypocalcemia, hypomagnesemia, and hypokalemia were recorded in 8.6%, 1.2%, and 1.5% of all cases, respectively. Most cases (64%) of dermal exposure received antidotal treatment. Treatment modalities of dermal exposure included calcium gluconate soaking, 49.8%; intravenous calcium, 20.6%; and topical use of calcium gluconate gel, 13.9%. Twenty patients (7%) received surgery. Following HF exposure, the majority of patients presented with mild (56.5%) or moderate (36.7%) toxic effects. However, four patients were severely intoxicated; two patients died of HF-related dysrhythmia and shock. CONCLUSIONS: Significant symptomology may occur following HF exposure, and most of the HF exposure required hospitals evaluation. Calcium gluconate soaks appear to be effective in reducing local pain and tissue damage. Hyperkalemia should not be overemphasized as a common finding in HF exposure, hypokalemia tends to occur in cases of severe HF poisoning.

Toxic epidermal necrolysis after extensive dermal use of realgar-containing (arsenic sulfide) herbal ointment.

BACKGROUND: Realgar (arsenic sulfide) is thought to be safe with few reports on toxicities or adverse effects and has been used in Traditional Chinese Medicine for many centuries. Serious realgar poisoning is rare, and we report a fatal case resulted from short-term use of realgar-containing herbal medicine through dermal route. CASE DETAILS: A 24-year-old man with atopic dermatitis had received 18 days of oral herbal medicine and realgar-containing herbal ointments over whole body from a Traditional Chinese Medicine (TCM) practitioner. Seven days after the herbal use, he had diminished appetite, dizziness, abdomen discomfort, itching rash, and skin scaling. He later developed generalized edema, nausea, vomiting, decreased urine amount, diarrhea, vesico-edematous exanthems, malodorous perspiration, fever, and shortness of breath. He was taken to the hospital on Day 19 when the dyspnea became worse. Toxic epidermal necrolysis complicated with soft tissue infection and sepsis was noted, and he later died of septic shock and multiple organ failure. The post-mortem blood arsenic level was 1225 µg/L. Herbal analysis yielded a very high concentration of arsenic in three unlabeled realgar-containing ointments (45427, 5512, and 4229 ppm). CONCLUSION: Realgar-containing herbal remedy may cause severe cutaneous adverse reactions. The arsenic in realgar can be absorbed systemically from repeated application to non-intact skin and thus should not be extensively used on compromised skin.

Sesamol attenuates oxidative stress-mediated experimental acute pancreatitis in rats.

Acute pancreatitis is a potentially fatal disease with no known cure. The initial events in acute pancreatitis may occur within the acinar cells. We examined the effect of sesamol on (i) a cerulein-induced pancreatic acinar cancer cell line, AR42J, and (ii) cerulein-induced experimental acute pancreatitis in rats. Sesamol inhibited amylase activity and increased cell survival. It also inhibited medium lipid peroxidation and 8-hydroxydeoxyguanosine in AR42J cells compared with the cerulein-alone groups. In addition, in cerulein-treated rats, sesamol inhibited serum amylase and lipase levels, pancreatic edema, and lipid peroxidation, but it increased pancreatic glutathione and nitric oxide levels. Thus, we hypothesize that sesamol attenuates cerulein-induced experimental acute pancreatitis by inhibiting the pancreatic acinar cell death associated with oxidative stress in rats.

The role of toll-like receptors 2 and 4 in acute allograft rejection after liver transplantation.

Toll-like receptors (TLRs) are germline-encoded receptors expressed on antigen-presenting cells (APCs) that identify a variety of microbial and endogenous ligands and activate the innate immune responses to the presence of danger. However, their role in the development of allograft rejection after liver transplantation remains unknown. In this study, we used flow cytometry to assess TLR-4 and TLR-2 expression among circulating CD14+ monocytes in 64 liver transplant patients and 24 healthy volunteers. We demonstrated significantly higher TLR-2 and TLR-4 expression on circulating monocytes among conditioned liver transplantation recipients with acute rejection compared with those in clinically stable with normal liver function. Steroid pulse therapy significantly reduced the expression of TLR-4 and TLR-2 on the monocytes of recipients with acute rejection. Based on these data, we have suggested that activation of innate immunity in liver transplant recipients through TLR-4 and TLR-2 contributes to the development of acute allograft rejection after liver transplantation. The reduced expression of TLR-4 and TLR-2 may be one of the mechanisms by which steroid pulse therapy inhibits the development of acute rejection. Estimation of TLR expression on APCs may be predictive of in acute rejection after liver transplantation.

Determination of tetrodotoxin in human urine and blood using C18 cartridge column, ultrafiltration and LC-MS.

Six fishermen were victims (including one death) of food poisoning from unknown fish on their boat in central Taiwan Strait, in April 2001. The symptoms were like those of tetrodotoxin (TTX) poisoning. As there was no remaining fish, a new protocol was developed to determine TTX in the urine and blood of the victims. The urine and blood samples were cleansed using a C18 Sep-Pak cartridge column, and the toxin was extracted by methanol. The eluate was filtered through a microcentrifuge filter. The filtrate was freeze-dried, dissolved in distilled water, and determined by LC-MS. The recovery was more than 88.9%. The detection limit was 15.6 nM. A linear relationship between response and concentration was obtained between 93.75 and 9375 nM of TTX. It was shown that the urine and blood of the victims contained TTX. The range of TTX was 4.5-40.6 nM in blood and 47-344 nM in urine. Judging from the symptoms of the victims and the experimental data, the causative agent of the food poisoning was identified as TTX.

Severe acute respiratory syndrome (SARS): knowledge, attitudes, practices and sources of information among physicians answering a SARS fever hotline service.

In June 2003, Taiwan introduced a severe acute respiratory syndrome (SARS) telephone hotline service to provide concerned callers with rapid access to information, advice and appropriate referral where necessary. This paper reports an evaluation of the knowledge, attitude, practices and sources of information relating to SARS among physicians who staffed the SARS fever hotline service. A retrospective survey was conducted using a self-administered postal questionnaire. Participants were physicians who staffed a SARS hotline during the SARS epidemic in Taipei, Taiwan from June 1 to 10, 2003. A response rate of 83% was obtained. All respondents knew the causative agent of SARS, and knowledge regarding SARS features and preventive practices was good. However, only 54% of respondents knew the incubation period of SARS. Hospital guidelines and news media were the major information sources. In responding to two case scenarios most physicians were likely to triage callers at high risk of SARS appropriately, but not callers at low risk. Less than half of all respondents answered both scenarios correctly. The results obtained suggest that knowledge of SARS was generally good although obtained from both medical and non-medical sources. Specific knowledge was however lacking in certain areas and this affected the ability to appropriately triage callers. Standardized education and assessment of prior knowledge of SARS could improve the ability of physicians to triage callers in future outbreaks.

Acetylcholinesterase inhibition and the extrapyramidal syndrome: a review of the neurotoxicity of organophosphate.

Organophosphate poisonings are not uncommon, and are the leading cause of death in suicide patients in Taiwan. Acute cholinergic crisis caused by the inhibition of synaptic acetylcholinesterase is the major manifestation of organophosphate poisoning and may cause death within minutes. Delayed neurotoxicities include intermediate syndrome and delayed polyneuropathy have also been described. However, these symptoms may not characterize the complete picture of organophosphate poisoning. Among the 633 patients ever admitted to our hospital with organophosphate poisoning, three patients were found exhibiting impermanent neuromuscular dysfunction, including blepharoclonus, oculogyric crisis, intermittent dystonia, rigidity, and tremor, with two of them developing mask face, dyskinesia and akathisia later, following acute cholinergic crisis. The symptoms appeared within 4 days with the duration ranging from 25 days to 2 months. Other causes of the extrapyramidal syndrome noted on these patients have been excluded, and we consider the extrapyramidal syndrome a possible neurotoxic manifestation of organophosphate poisoning, which is transient, needs no treatment, and may be missed because of the critical condition, in a minority of patients. The mechanism remains to be identified, but may be related to the impediment of the function of acetylcholinesterase to modify nigrostriatal dopaminergic system, which is independent of hydrolyzing acetylcholine. More detailed observation for organophosphate poisoned patients and more studies for the biological functions of acetylcholinesterase including the influence on the nigrostriatal dopaminergic system are needed.

Rhabdomyolysis: an unusual feature with mushroom poisoning.

Rhabdomyolysis resulting from mushroom poisoning previously has been unreported in the literature. We present an outbreak of Russula subnigricans poisoning with rhabdomyolysis. The most severely ill patient presented with rhabdomyolysis, severe electrolyte disturbance (hyperkalemia, hypocalcemia), respiratory failure, acute renal failure, pulmonary edema, ventricular tachycardia, and circulatory shock. Mycotoxin may be the cause of rhabdomyolysis. In areas where mushroom gathering is common, mushroom poisoning should be included in the differential diagnosis of rhabdomyolysis.

Food poisoning due to methamidophos-contaminated vegetables.

BACKGROUND: Organophosphate poisoning is well known for its characteristic symptoms and signs, but food poisoning caused by pesticide-contaminated food is seldom reported. CASE REPORT: We report three incidents of food poisoning that resulted from exposure to the organophosphate insecticide methamidophos in vegetables. These outbreaks caused a cholinergic syndrome in 4 patients. The cholinergic overactivity led as to suspect organophosphate food poisoning. All patients recovered well following appropriate therapy. The clinical diagnosis of organophosphate poisoning was confirmed by reduced levels of erythrocytes and plasma cholinesterase and the presence of methamidophos in the vegetable leftovers. The implicated vegetables and levels of methamidophos were: Ipomoea batatas 255 ppm, Gynura bicolor 110 ppm, and red cabbage 26.3 ppm. Since methamidophos is normally applied to vegetables during planting, improper selection and/or overuse of pesticide or improper harvest times may explain the occurrence of these high residue levels of methamidophos.

Acute toxicities of betel nut: rare but probably overlooked events.

BACKGROUND: Betel nut chewing has long been a social habit in Taiwan and other Asian and tropical countries. It produces various autonomic and psychoneurologic effects including tachycardia, flushing, warmth, cholinergic activation, alertness, and euphoria. Although the oral carcinogenic effects are well known, data concerning its acute toxicity are few. To better understand the toxicity of betel nut, cases reported to the Taiwan Poison Control Center as probable or possible betel nut-related toxicity (January 1988-June 1998) were reviewed. In the 17 cases suitable for review (14 males, 3 females, age 21 to 60 years), the most common manifestations were tachycardia/palpitations (7); tachypnea/dyspnea (6); hypotension and sweating (5); vomiting, dizziness, and chest discomfort (4); abdominal colic, nausea, numbness, and coma (3); and acute myocardial infarction and related manifestations (2). The reported quantity of betel nut used was low (1 to 6 nuts), except an extract of 100 betel nuts was used in 1 case and 66 chewed in another. Most cases recovered within 24 hours after the exposure. One patient developed probable acute myocardial infarction and ventricular fibrillation and died despite repeated cardiac defibrillation. Although betel nut chewing is widespread, significant toxicity as reported to a poison center is rare. Because most betel nut-related effects are transient and mild in nature, the incidence of such events is likely to be underreported. Nevertheless, betel nut chewing can produce significant cholinergic, neurological, cardiovascular, and gastrointestinal manifestations. It is possible that it may aggravate cardiac diseases in susceptible patients but this hypothesis must be further investigated. Treatment is symptomatic. With timely support, rapid and complete recovery is anticipated but a small risk of major complications cannot yet be discounted.

A case of jellyfish sting.

Jellyfish sting may result in a wide range of symptoms from common erythematous urticarial eruptions to the rare box-jelly induced acute respiratory failure. In Taiwan, with the increasing frequency of international travel, cases of jellyfish sting to foreigners are on the rise. We report a case of jellyfish sting with the rare presentation of painless contact dermatitis. A 38-y-o man accidentally stepped on a sea urchin with his right foot during scuba diving in a beach in Thailand. Traditional therapy with vinegar was applied on the lesion. However, when he returned to Taiwan, erythematous patches on the left thigh with linear radiations to the leg were discovered. The skin lesions had bizzare shapes and showed progressive change. No pain or numbness was noticed. Jellyfish stingwas suspected, topical medications were applied, and the patient recovered without complication. Jellyfish stings usually result in a painful erythematous eruption. In this case, though the lesion involved a large surface, there was no pain. Delayed diagnosis of jellyfish sting was due to the atypical presentation and the physician's unfamiliarity to the Thai jellyfish sting. Awareness to the wide spectrum of jellyfish sting symptoms should be promoted.

Identification of cyprinol and cyprinol sulfate from grass carp bile and their toxic effects in rats.

To elucidate the responsible toxic components of grass carp bile, the bile salt 5 alpha-cyprinol sulfate and its desalted form 5 alpha-cyprinol from grass carp bile were purified and identified by analyses of infrared spectrum, (1)H-, (13)C-nuclear magnetic resonance spectra and mass spectrum. The toxicity of grass carp bile powder, butanol extract of grass carp bile powder, 5 alpha-cyprinol and 5 alpha-cyprinol sulfate in rats were further determined. The kidney and liver functions were significantly affected by grass carp bile powder, butanol extract and 5 alpha-cyprinol sulfate. However, 5 alpha-cyprinol also significantly affected the kidney function, but the toxic effect was less.

Cholestatic hepatitis caused by acute gold potassium cyanide poisoning.

INTRODUCTION: Poisoning after oral ingestion of gold potassium cyanide is rarely reported. A case of suicidal ingestion of gold potassium cyanide (potassium dicyanoaurate; CAS# 13967-50-5) is described. CASE REPORT: A 27-year-old man attempted suicide by ingesting 5 mL gold potassium cyanide solution. He developed vomiting, hyperamylasemia, and hepatic dysfunction. Cyanide poisoning was not detected but acute gold toxicity was noted. Pathologic findings of the liver showed centrilobular cholestasis with eosinophilic degeneration. The whole blood and serum gold were 4361 and 6011 microg/L, respectively, and the 24-hour urine gold was 429 microg/d in samples obtained on day 4. CONCLUSION: Gold-induced hepatotoxicity has been seen infrequently in patients receiving gold therapy. Reported agents include sodium aurothiomalate, sodium aurothiopropranol sulfonate, aurothioglucose, aurothiopolypeptide (Auro-detoxin), auric sulfide, and gold thiosulfate, our report adds gold potassium cyanide.

Pancytopenia, hyperglycemia, shock, coma, rhabdomyolysis, and pancreatitis associated with acetaminophen poisoning.

It is well recognized that acetaminophen overdose can cause severe hepatic injury. However, extra-hepatic manifestations may also develop following inappropriate use or ingestion of large amounts of acetaminophen. We present a 44-y-o female who manifested coma, metabolic acidosis, shock, hypothermia, hyperglycemia, rhabdomyolysis, hepatotoxicity, and renal insufficiency after suicidal ingestion of an unknown amount of acetaminophen. Although her consciousness and hemodynamic status gradually improved after treatment with N-acetylcysteine and other supportive measures, she was found to have pancytopenia, pancreatitis and hepatorenal failure during the hospitalization and eventually died 18 d post-admission. Review of relevant literature reports and the clinical findings in our patient suggests that direct toxic effects mediated by acetaminophen or its metabolites were most likely responsible for most of the observed clinical features.

Acute ethylene chlorohydrin poisoning: experience of a poison control center.

BACKGROUND: Ethylene chlorohydrin (CAS 107-07-3), a chemical once used in hastening grape vine sprouting in Taiwan, has caused severe toxicity upon acute exposure. Although such use of ethylene chlorohydrin is now prohibited in Taiwan, poisoning still occurs following its illegal use. Since data concerning human ethylene chlorohydrin poisoning remain rare, we report our experience in treating acute ethylene chlorohydrin-poisoned patients. METHODS: A retrospective analysis was conducted to evaluate patients with ethylene chlorohydrin poisoning reported to Taiwan Poison Control Center during 1985-1998. RESULTS: Seventeen patients with ethylene chlorohydrin poisoning were identified. There were 11 male and 6 female patients, ranging in age from 2 to 70 years (median 53 years). The intent of exposure was suicide in 5, accident in 9, and occupational exposure in 3 patients. Oral ingestion was the most common route of exposure (14 patients). Seven out of the 17 patients died within 24 hours due to metabolic acidosis and respiratory failure. Ethanol therapy, used in 2 patients, had no apparent benefit. Moderate or mild poisoning was characterized by gastrointestinal effects only and an uneventful recovery. CONCLUSIONS: Ethylene chlorohydrin can result in severe metabolic acidosis, respiratory failure, coma, and death after acute exposure.

Relative bioavailability of salmon calcitonin given intramuscularly.

BACKGROUND: Salmon calcitonin, a polypeptide hormone, is used in the treatment of osteoporosis, hypercalcemia and Paget's disease. The purpose of this study was to evaluate the pharmacokinetics and relative bioavailability of two salmon calcitonin products, Miacalcic (Novartis Pharmaceuticals, Basle, Switzerland) and Calcinin (Purzer Pharmaceuticals, Taipei, Taiwan). METHODS: This was a randomized, single-dose, crossover study conducted under fasting conditions with a washout period of 1 week between doses. Ten healthy male subjects were enrolled in this study. Each subject received a 100 IU dose (20 micrograms; 50 IU/ampule x 2) of salmon calcitonin intramuscularly (i.m.) followed by collection of blood samples at specified time intervals. Serum salmon calcitonin concentrations were measured using a validated radioimmunoassay method with a detection limit of 15.0 pg/ml. Values for the area under the serum concentration from time zero to last time and infinity curve (AUC0-t and AUC0-infinity), peak concentration (Cmax), time to peak concentration, terminal first order rate constant, terminal half-life, mean residence time, total clearance divided by absolute bioavailability, onset time, maximal effect and duration were compared for each product. RESULTS: The 90% confidence intervals for AUC0-t, AUC0-infinity and Cmax after logarithmic transformation were 93.2% to 113.1%, 97.2% to 114.9% and 84.9% to 108.0%, respectively. CONCLUSIONS: Based on the two one-sided tests procedure, we conclude that Miacalcic and Calcinin are bioequivalent.