[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.

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.

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.

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.

Prolonged severe withdrawal symptoms after acute-on-chronic baclofen overdose.

INTRODUCTION: Baclofen is frequently used to treat muscle spasticity due to spinal cord injury and multiple sclerosis. Baclofen overdose can lead to coma, respiratory depression, hyporeflexia, and flaccidity. An abrupt decrease in the dose of baclofen due to surgery or a rapid tapering program may result in severe baclofen withdrawal syndrome manifesting hallucinations, delirium, seizures, and high fever. Severe baclofen withdrawal syndrome secondary to intentional overdose, however, has not received mention. CASE REPORT: A 42-year-old male receiving chronic baclofen therapy, 20 mg/d, attempted suicide by ingesting at least 800 mg of baclofen. He was found in coma 2 hours postingestion with depressed respirations, areflexia, hypotonia, bradycardia, and hypotension. Treatment with intravenous fluids, atropine, dopamine, and hemodialysis was associated with restoration of consciousness within 2 days but disorientation, hallucinations, fever, delirium, hypotension, bradycardia, and coma developed during the following week. Baclofen withdrawal syndrome was not diagnosed until hospital day 9, when reinstitution of baclofen rapidly stabilized his condition. Oral overdosage of baclofen causes severe neurological and cardiovascular manifestations due to its GABA and dominant cholinergic effects. Severe baclofen withdrawal syndrome is manifest by neuropsychiatric manifestations and hemodynamic instability. Caution should be exercised after a baclofen overdose in patients receiving chronic baclofen therapy.

Continuous flumazenil infusion in preventing complications arising from severe benzodiazepine intoxication.

A prospective, randomly controlled study was conducted to test the effect of continuous flumazenil infusion in preventing complications arising from severe benzodiazepine (BZ) intoxication. Patients who were believed to be suffering benzodiazepine intoxication and whose Glasgow Coma Scale (GCS) score was below 10 were enrolled after showing a clear-cut response to flumazenil 0.5 or 1 mg (an improvement by 4 or more on the GCS). The patients were consecutively enrolled and randomized into two groups: a continuous infusion group (CI, n = 50) who were immediately given flumazenil 0.5 mg/h for 5 hours, and a control group (CIN, n = 50). Age, sex, incidence of underlying disease, GCS score at several time points, and complication rate were compared in the two groups. Although the CI group had a higher GCS score at most time points, the complication rate did not significantly differ between the two groups (14 of 36 in the CI group v 12 of 38 in the CIN group, P = .684). A greater incidence of underlying disease and an older age seemed to contribute to the higher complication rates in both groups. Several patients (in both groups) resedated into deeper coma after showing an initial response to flumazenil or after the cessation of flumazenil infusion. For severe BZ intoxication, treatment with flumazenil infusion should still be considered skeptically and should not be recommended as routine management BZ-intoxicated patients with an underlying disease, an older age, and resedation into a deep comatose state after showing an initial response to flumazenil should be treated in an intensive care unit.

Outbreak of obstructive ventilatory impairment associated with consumption of Sauropus androgynus vegetable.

BACKGROUND: Forty four individuals, suffering from temporary insomnia and poor appetite followed by progressive difficulty breathing after four weeks or more ingestion of the Sauropus androgynus or Sabah vegetable, were reported to the National Poison Center of Taiwan by physicians between August 23, 1994 and August 25, 1995. OBJECTIVE: A telephone questionnaire survey was designed and conducted to collect demographic data, information about use of the vegetable, past medical history and clinical presentation. Laboratory data were obtained from their physicians as available. RESULTS: Forty one patients, predominantly women, 43 +/- 11 years old, were identified in our survey. They reported a variety of sources and preparation methods for the vegetable. Difficulty breathing, identified in 36 cases, was the clinical hallmark. Twenty people gave a history of dyspnea delayed until 44 +/- 40 days after discontinuing vegetable consumption. Laboratory evidence of obstructive ventilatory impairment (FEV1/FVC 56 +/- 12%, FEV1 31 +/- 6%, PaO2 71 +/- 15%) was observed in 12 cases tested. An open lung biopsy performed in a demonstration case disclosed bronchiolitis obliterans organizing pneumonia. CONCLUSION: In this case series of 41 victims, we have identified a severe pulmonary effect and hypothesize that it is related to consumption of sauropus androgynus vegetable. Papaverine has been previously identified in this vegetable but is unlikely to be responsible for the full range of toxicity seen.

Severe rhabdomyolysis mimicking transverse myelitis in a heroin addict.

Heroin addiction is known to cause various medical and neurological complications. We report here a case of rhabdomyolysis following heroin abuse, in which a neurological lesion mimicking transverse myelitis was also noted. A 29-year-old man was found comatose in a kneeling position one day after a heroin overdose. On admission, he was awake, yet with total paralysis of his lower legs. Physical examination revealed marked swelling and tenderness of the four limbs, especially the lower extremities. Deep tendon reflexes and positional sense were absent in both legs; however, pin-prick sense was preserved. Transverse myelitis or spinal cord vasculitis was the initial working diagnosis. Laboratory tests disclosed significantly elevated creatinine kinase of 146289 U/L. Though suffering transient acute renal failure, his neurological abnormalities gradually improved over four weeks and a left foot drop was the only residual lesion at discharge. Rhabdomyolysis, a well defined complication following heroin use, may also cause concomitant neurological symptoms, for which careful differential diagnosis is warranted. With the increasing number of heroin addicts in Taiwan, more cases with rhabdomyolysis-induced neurological symptoms may be observed in the future.

Experimental podophyllotoxin (bajiaolian) poisoning: I. Effects on the nervous system.

Bajiaolian, one of the species in the Mayapple family (Podophyllum pelatum), has been widely used as a traditional Chinese herbal medicine for the remedies of snake bites, general weakness, poisons, condyloma accuminata, lymphadenopathy, and certain tumors in China. In Western medicine, Podophyllum was first used medically as a laxative in the early 19th century. Since 1940, the resin of podophyllum has also been used topically for various skin lesions, such as warts and condyloma. Human poisonings have been reported. An animal model was established to investigate the neurotoxic effects of Bajiaolian. Podophyllotoxin, the major active ingredient in Podophyllum, was injected (ip) to young adult male rats at doses of 0, 5, 10, or 15 mg.kg-1 b.w.. The animals were sacrificed 72 h after injection. Neuronal changes were readily observable in animals treated with 10 or 15 mg.kg-1 of the toxin. Edematous changes of the anterior horn motoneurons were observed in the spinal cord. No neuronal necrosis was found. The type of neuronal swelling is believed to be only a transient change and would probably subside with time if no further assaults occur. More serious and perhaps longer term of changes were found in the dorsal ganglion neurons and the nerve fibers (axons) in the central and peripheral nervous system. Severe depletion of the Nissl substance (RNA/polyribosomes) was observed in the dorsal root ganglion neurons. Alterations in these sensory neurons would give rise to and correlate with the sensory disturbances experienced by the patients. Bodian staining also revealed a dose-related increase in the coarseness (thickness) of the nerve fibers (axons) in the cerebellum, cerebral cortex, brainstem, and spinal cord. This is the first scientific study showing the neurotoxicity of Bajiaolian, a commonly used Chinese herbal medicine. Toxicities on other organ systems by this drug certainly exist. Caution should be exercised in the dispensing and usage of this medicine.

Podophyllotoxin intoxication: toxic effect of Bajiaolian in herbal therapeutics.

Bajiaolian (Dysosma pleianthum), one species in the Mayapple family, has been widely used as a general remedy and for the treatment of snake bite, weakness, condyloma accuminata, lymphadenopathy and tumours in China for thousands of years. However, the textbooks of traditional Chinese medicine mention little about the toxicity of Bajiaolian. Within 1 year, the authors saw five people who manifested nausea, vomiting, diarrhoea, abdominal pain, thrombocytopenia, leucopenia, abnormal liver function tests, sensory ataxia, altered consciousness and persistant peripheral tingling or numbness after drinking infusions made with Bajiaolian. The herb was recommended by either traditional Chinese medical doctors or herbal pharmacies for postpartum recovery and treatment of a neck mass, hepatoma, lumbago and dysmenorrhoea. Podophyllotoxin is one of the main ingredients of the Bajiaolian root. The clinical manifestations observed in our patients were consistent with podophyllum intoxication. Podophyllotoxin intoxication usually results from the accidental ingestion or topical application of podophyllum resin. However, these cases of Bajiaolian intoxication were iatrogenic and results from 'therapeutic doses' of Bajiaolian cited in the textbooks of traditional Chinese medicine.

Renal cell cancer among paperboard printing workers.

A physician's alert prompted us to investigate workers' cancer risk at a paperboard printing manufacturer. We conducted a retrospective cohort mortality study of all 2,050 persons who had worked at the facility for more than 1 day, calculated standardized incidence ratios (SIRs) for bladder and renal cell cancer, and conducted a nested case-control study for renal cell cancer. Standardized mortality ratios (SMRs) from all causes [SMR = 1.0, 95% confidence interval (CI) = 0.9-1.2] and all cancers (SMR = 0.6, 95% CI = 0.3-1.0) were not greater than expected. One bladder cancer and one renal cell cancer were included in the mortality analysis. Six incident renal cell cancers were observed, however, compared with less than two renal cell cancers expected (SIR = 3.7, 95% CI = 1.4-8.1). Based on a nested case-control analysis, the risk of renal cell cancer was associated with overall length of employment but was not limited to any single department or work process. Although pigments containing congeners of dichlorobenzidine and o-toluidine had been used at the plant, environmental sampling could not confirm any current exposure. Several limitations and a potential selection bias limit the inferences that can be drawn.

Characterisation of respiratory health and exposures at a sintered permanent magnet manufacturer.

Sintered permanent magnets are made from the powdered metals of cobalt, nickel, aluminium, and various rare earths. During production, exposure to respirable crystalline silica and asbestos may also occur. Reported here is a cross sectional study of 310 current and 52 retired hourly employees who worked 10 or more years making sintered magnets. Each participant had a chest radiograph, spirometry, and completed a respiratory questionnaire. Illness logs were also reviewed to calculate the incidence of recorded respiratory disorders. The prevalences of abnormalities in pulmonary function and respiratory symptoms were not higher than found in an external referent population. Although the prevalence of diffuse parenchymal opacities consistent with pneumoconiosis (four workers) was similar to the referent population, one worker had radiographic findings consistent with silicosis and two workers had profusion scores of 1/2 or above, not seen in the referent group. The incidence of reported respiratory conditions in the log, including asthma, was 10 times that of other manufacturers in the same industrial classification category. Excessive exposures to cobalt, nickel, and respirable silica were shown by environmental measurements.

Reduction in caffeine toxicity by acetaminophen.

A patient who allegedly consumed 100 tablets of an over-the-counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms/mL) reduced the CNS toxicity of caffeine. Studies in DBA/2J mice showed that: 1) pretreatment with acetaminophen (100 mg/kg) increased the interval between the administration of caffeine (300 to 450 mg/kg IP) and the onset of fatal convulsions by a factor of about two; and 2) pretreatment with acetaminophen (75 mg/kg) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12.5 to 75 mg/kg IP). The frequency of sound-induced seizures after 12.5 or 25 mg/kg caffeine was reduced from 50 to 5% by acetaminophen. In the absence of caffeine, acetaminophen (up to 300 mg/kg) did not modify the seizures induced by maximal electroshock and did not alter the convulsant dose of pentylenetetrezol in mice (tests performed by the Anticonvulsant Screening Project of NINCDS). Acetaminophen (up to 150 micrograms/mL) did not retard the incorporation of radioactive adenosine into ATP in slices of rat cerebral cortex. Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown.