Hexavalent chromium intoxication induces intrinsic and extrinsic apoptosis in human renal cells.

Hexavalent chromium [Cr(VI)], is a well­known toxic form of the heavy metal chromium in the natural environment. Clinical evidence has indicated that exposure to Cr(VI) can cause severe renal damage. The production of reactive oxygen species (ROS) due to intracellular reduction of Cr(VI) is the main mechanism underlying the induction of cellular dysfunction and apoptosis. The present study aimed to investigate in detail the apoptotic pathways induced by Cr(VI)­exposure in a human immortalized proximal tubular epithelial cell line HK­2, in order to understand the mechanism involved therein. Exposure to 10 µM potassium dichromate (K2Cr2O7), a toxic compound of Cr(VI), significantly decreased cell viability after 24 and 48 h of incubation and induced intracellular ROS generation. The expression levels of markers that activate the apoptotic pathway including cleaved caspase­3 and poly (ADP­ribose) polymerase were significantly upregulated in K2Cr2O7­exposed HK­2 cells. In addition, the induction of intrinsic and extrinsic apoptotic markers was detected in K2Cr2O7­exposed HK­2 cells. In summary, the present study described for the first time the novel apoptotic mechanism of Cr(VI)­toxicity in human renal cells which may be beneficial in designing optimal clinical treatment for renal damage caused by acute Cr(VI) toxicity.

Optimal Regimen of N-Acetylcysteine on Chromium-Induced Renal Cell Damage.

Chromium (Cr) is a well-known heavy metal that can cause renal damage. The production of reactive oxygen species (ROS) due to chromium-induced toxicity induces cell dysfunction, apoptosis, and death. N-acetylcysteine (NAC) is an antioxidant used as an antidote for chromium-induced toxicity. However, the optimal regimen and protective mechanisms of NAC are not fully understood in human renal cells. Our results showed that exposure to 10 µM K2Cr2O7, a toxic Cr(VI) compound, induced apoptosis and production of intracellular ROS in the human proximal tubular epithelial cell line HK-2. Supplements of 600 or 1000 µg/mL NAC inhibited intracellular ROS in HK-2 cells exposed to Cr(VI) and significantly increased cell viability within 2 h of Cr(VI)-induced cytotoxicity. Moreover, Cr(VI) induced the expression of apoptosis markers, including cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerase, cleaved-caspase 8, and cleaved-caspase 9, and altered the expression ratio of Bax/Bcl-xL. Expression of apoptosis markers within 2 h of Cr(VI)-induced cytotoxicity in cells treated with 600 µg/mL NAC was significantly suppressed. However, delayed treatment with NAC at 4 h and 8 h after exposure to Cr did not suppress the activation of apoptotic pathways. In summary, our study reports the optimum timing and dose of NAC for the protection of human renal proximal tubular cells from Cr(VI)-induced cell death. The NAC treatment strategy described could be applied in clinical practice to suppress renal cell apoptosis, which in turn could rescue renal function.

Optimal dosage and early intervention of L-ascorbic acid inhibiting K2Cr2O7-induced renal tubular cell damage.

Chromium poisoning can cause renal failure and death. Chromium intoxication may be managed using L-ascorbic acid (vitamin C) therapy. However, the evidence supporting the effectiveness of this treatment is insufficient, and the mechanism of action has not been clarified in renal cells. In this study, our results showed that the optimal regimen of L-ascorbic acid therapy in human epithelial renal proximal tubule cells, HK-2 cells, was 30 µg/mL. Supplementation of L-ascorbic acid with 30 µg/mL and within 8 h of chromium intoxication (K2Cr2O7, Cr6+) was effective to inhibit renal tubular cell damage by blocking generation of free radicals, cell apoptosis, and autophagy. Intracellular chromium concentrations were estimated using electrothermal atomic absorption spectrometry. Treatment of L-ascorbic acid within 8 h of chromium intoxication significantly decreased the entry of chromium into the cells. Moreover, concomitant administration of L-ascorbic acid with repeatedly dosing at 8-hourly intervals had a better protective effect at lower concentration of L-ascorbic acid when compared to single dosing of L-ascorbic acid at an early time point of chromium intoxication. These findings might help physicians develop effective therapy strategies in renal failure.

Spontaneous hemopneumothorax simulating acute abdominal affections.

Spontaneous hemopneumothorax (SHP) is a rare potentially life-threatening condition that occurs in predominantly young adolescents. The resultant massive hemorrhage leading to hypovolemic shock can be a surgical emergency. It constitutes 1-12% of all spontaneous pneumothoraces and presents with two cardinal features, chest pain and dyspnea. However, the pain of SHP may be confined to the abdomen secondary to the irritation of diaphragmatic pleura, which produces signs simulating an acute abdomen. SHP masquerading as an abdominal affection is apparently regarded as extremely rare. We present a case of a 16-year-old male with SHP presenting features simulating acute gallbladder disease. After prompt diagnosis with appropriate surgical intervention, he had an uneventful recovery. Our experience emphasizes the importance of careful and thorough chest examination for each child with atypical pictures for abdominal pain to exclude possible extra-abdominal lesions, even rare as SHP.

Water extract of Pueraria lobata Ohwi has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines.

Human respiratory syncytial virus (HRSV) infects all age groups and causes bronchiolitis, pneumonia, and acute respiratory distress syndrome with a significant mortality rate. To date, only ribavirin has been used to manage HRSV infection. However, ribavirin is expensive with an only modest effect. Furthermore, ribavirin has several side effects, which means it has limited clinical benefit. Pueraria lobata Ohwi (P. lobata) is a common ingredient of Ge-Gen-Tang (Kakkon-to) and Sheng-Ma-Ge-Gen-Tang (Shoma-kakkon-to), which are prescriptions of Chinese traditional medicine proven to have antiviral activity against HRSV. Therefore, it was hypothesized that P. lobata might be effective against HRSV. To find a cost-effective therapeutic modality, both human upper (HEp-2) and lower (A549) respiratory tract cell lines were used to test the hypothesis that P. lobata could inhibit HRSV-induced plaque formation. Results showed that the water extract of P. lobata was effective (p < 0.0001) against HRSV-induced plaque formation. P. lobata was more effective when given prior to viral inoculation (p < 0.0001) by inhibiting viral attachment (p < 0.0001) and penetration (p < 0.0001). However, supplementation with P. lobata could not stimulate interferon secretion after HRSV infection. In conclusion, P. lobata has antiviral activity against HRSV-induced plaque formation in airway mucosa mainly by inhibiting viral attachment and internalization. Further identification of effective constituents could contribute to the prevention of HRSV infection.

Posterior Reversible Encephalopathy Syndrome in Children: Case Series and Systematic Review.

To study presentations and outcome of posterior reversible encephalopathy syndrome in children, we retrospectively analyzed 14 patients admitted to our pediatric intensive care unit. We further assessed 94 additional pediatric cases from a systematic review. Our patients had a mean age of 11.6 years. Their precipitating factors were hypertension (100%), immunosuppressants (71%), antineoplastic agents (21%), and hemodialysis (14%). Initial neurologic manifestations included seizures (100%), mental change (100%), headache (79%), and visual disturbance (57%). After prompt diagnosis by magnetic resonance imaging (MRI) with intensive management, all patients had complete clinical recovery with subsequent radiologic resolution. Systemic literature review indicated that seizures (90%), hypertension (85%), and atypical neuroimaging findings (80%) are common presentations in childhood posterior reversible encephalopathy syndrome. We conclude that in children presenting with seizures and hypertension, a pediatric neurologist should consider posterior reversible encephalopathy syndrome within a comprehensive differential diagnosis of acute encephalopathy. Early recognition and intensive care are essential to ensure complete neurologic recovery in children with posterior reversible encephalopathy syndrome.

Anti-viral activity of water extract of Paeonia lactiflora pallas against human respiratory syncytial virus in human respiratory tract cell lines.

Paeonia lactiflora Pallas (P. lactiflora, Ranunculaceae) is a common ingredient of Sheng-Ma-Ge-Gen-Tang (SMGGT; Shoma-kakkon-to) and Ge-Gen-Tang (GGT; kakkon-to). SMGGT and GGT are different prescriptions of traditional Chinese medicine with different ingredients designed for airway symptoms. Both SMGGT and GGT have anti-viral activity against human respiratory syncytial virus (HRSV). Therefore, P. lactiflora was hypothesized to be the effective ingredient of both SMGGT and GGT against HRSV. However, P. lactiflora does not have any proven antiviral activity. This study used both human upper (Human larynx epidermoid carcinoma cell line, HEp-2) and lower (human lung carcinoma cell line, A549) respiratory tract cells to test the hypothesis that a hot water extract of P. lactiflora could effectively inhibit plaque formation induced by HRSV infection. The ability of P. lactiflora to stimulate anti-viral cytokines was evaluated by enzyme-linked immunosorbent assay (ELISA). The results showed that P. lactiflora was time-dependently and dose-dependently effective against HRSV in HEp-2 and A549 cells, particularly supplemented before viral inoculation (p < 0.0001). 10 µg/ml P. lactiflora had a comparable anti-HRSV activity with 10 µg/ml ribavirin, a broad-spectrum antiviral agent. P. lactiflora was dose-dependently effective against viral attachment (p < 0.0001), with a better effect on A549 cells (p < 0.0001). P. lactiflora was time-dependently (p < 0.0001) and dose-dependently (p < 0.0001) effective against viral penetration. Moreover, P. lactiflora stimulated IFN-ß secretion without any effect on TNF-α secretion. Therefore, P. lactiflora could be beneficial at preventing HRSV infection by inhibiting viral attachment, internalization, and stimulating IFN secretion.

Transient hyperammonemia associated with postictal state in generalized convulsion.

Previous studies revealed that transient hyperammonemia was noted after generalized convulsion. This study was undertaken to analyze the association between postictal state and serum ammonia levels. Adult patients presenting to the emergency department with seizures were included. Serum ammonia and other blood tests were compared between patients with full recovery of consciousness after generalized convulsion and those who had not completely regained consciousness. Patients who had not completely regained consciousness (7 of 7, 100%) had higher rate (p=0.035) of hyperammonemia compared with patients who had fully regained consciousness (4 of 10, 40%) and higher level of serum ammonia (246 ± 96 µg/dL vs. 102 ± 99 µg/dL, p=0.006). All patients who showed postictal consciousness level impairment on arrival at the emergency department had elevated serum ammonia at that time. Transient hyperammonemia is associated with postictal confusion.

Characteristics of undiagnosed liver abscesses on initial presentation at an emergency department.

Liver abscesses often present with nonspecific symptoms and laboratory examination abnormalities, resulting in missed diagnoses at emergency departments (ED). The purpose of this study was to determine if there are differences in presentation and prognosis between patients in whom liver abscess is diagnosed at an ED or once the patient has been transferred to a ward. Patients with a liver abscess who were discharged from our hospital between 2005 and 2007 were retrospectively reviewed. We compared the clinical characteristics between patients with liver abscess diagnosed at an ED or in a ward. Patients with liver abscess diagnosed at an ED had more abdominal pain (73.4%vs. 42.9%, p < 0.001), longer duration of symptoms before hospitalization (5.5 days vs. 3.8 days, p = 0.034) and fewer respiratory tract symptoms (12.5%vs. 24.5%, p = 0.05). Fewer cases with abnormal chest X-rays also existed for these patients (4.7%vs. 14.7%, p = 0.048). Cases not diagnosed at ED had delayed diagnoses for 4.41 +/- 3.16 days. Rates of mortality (6.3%vs. 8.2%, p = 0.740), shock (19.5%vs. 20.4%, p = 0.896), and length of hospital stay (19.6 days vs. 22.4 days, p = 0.173) were not significantly different between the patients diagnosed at an ED and those diagnosed later in a ward. Most information collected at the ED could not be used to aid diagnosis. Only abdominal pain was highly associated with liver abscess diagnosed at the ED. Undiagnosed liver abscess presented less abdominal pain and more symptoms or examination abnormalities related to infection of the respiratory and urinary tracts. Abdominal sonography should be performed more frequently at EDs to exclude liver abscess from differential diagnosis. However, further diagnosis and treatment while the patient with liver abscess is attending a ward does not affect prognosis.

Postictal transient hyperammonemia as an indicator of seizure disorder.

BACKGROUND AND PURPOSE: Transient hyperammonemia can occur after episodes of seizure. To verify that transient hyperammonemia is a unique finding in seizure patients, we compared the change in blood ammonia concentration during the postictal period with that of other patients who suffered consciousness disturbances due to other disorders. METHODS: We compared the results of a biochemical examination, including serum ammonia levels, between adult patients sent to the emergency department (ED) with seizure and those with other causes of consciousness disturbance. RESULTS: Nineteen out of 31 patients with generalized epileptic seizures showed hyperammonemia at initial data measurement. Seventeen of these patients showed transient hyperammonemia. Only 10 patients with hepatic encephalopathy showed hyperammonemia, while none of the patients suffering from other causes of consciousness disturbance showed transient hyperammonemia within hours of arrival at the ED. CONCLUSION: Transient hyperammonemia was observed in the majority of generalized tonic-clonic seizure patients examined in this study but not in those with other causes of consciousness disturbance. Because ammonia is checked in patients presenting with transient consciousness disturbance to the ED, with or without witness, transient hyperammonemia could be an indicator of recent epileptic seizure.

[Hospital response and medical management in toxic chemical substance disasters].

A hazardous material is defined as any item or agent which has the potential to cause harm to humans, animals, or the environment, either by itself or through interaction with other factors. Toxic chemical substance events are increasingly common events in our modern world. The numerous variables and special equipment involved make effective response to toxic chemical events an especially critical test of hospital emergency response and patient rescue mechanisms. Inadequacies in management could result in disaster - even when only a simple event and minimal error are involved. This article introduces the general medical management algorithm for toxic chemical substance injury and the hospital incident command systems (HICS) developed and currently used by Taiwanese hospitals. Important steps and frequent mistakes made during medical management procedures are further described. The goal of medical care response and emergency units is to prevent catastrophic disasters in the emergency room and their subsequent results. This article further emphasizes correct patient management not only in terms of medical unit effort, but also in terms of cooperation between various relevant organizations including factory-based industrial health and safety systems, multi-factory union defense systems, coordination centers, fire protection and disaster rescue systems, the Environmental Protection Administration and national defense system in order to achieve the most appropriate management. Such coordination, in particular, requires reinforcement in order to ensure readiness for future response needs.

Intravenous thiamylal and local anesthetic infiltration for pediatric facial repair procedures performed in emergency departments.

Thiamylal is widely used for procedural sedation in emergency departments (ED); however, there are limited safety data for doses of thiamylal > 5 mg/kg in children. We investigated whether intravenous thiamylal in combination with local anesthetics is safe and effective for pediatric procedural sedation in the ED and to identify the association between increasing doses thiamylal and adverse events. Between July 2004 and June 2008, 227 children who underwent procedural sedation met the inclusion criteria, including 105 males (46.3%) and 122 females (53.7%). Facial laceration was the most common indication for procedural sedation. All children received an intravenous injection of thiamylal, with a loading dose of 5 mg/kg. Eighty-one children (35.7%) received a supplemental dose of 2.5 mg/kg thiamylal because of inadequate sedation. Of these, 27 (11.9%) received a second supplemental dose of 2.5 mg/kg because of inadequate sedation. Sixty-six patients (29.1%) experienced 75 mild and self-resolving adverse events, and most of which (15/75; 20%) were drowsiness. Four (1.8%) patients experienced oxygen saturation below 96%, which was related to the supplemental dose of thiamylal (p = 0.002). No children suffered from any lasting or potentially serious complications. Our results indicate that intravenous thiamylal in combination with local anesthetic infiltration is a well tolerated for therapeutic procedures in the ED. Thiamylal offers rapid onset of sedation without compromising the patient's cardiorespiratory function during pediatric procedural sedation.

Acute multiple organ failure with imidacloprid and alcohol ingestion.

Imidacloprid [1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine] belongs to a relatively new class of insecticidal chemistry, the chloronicotinyl neonicotinoid compounds. Animal studies indicate relatively low toxicity to mammals due to nicotinic receptor resistance. Human poisoning is usually mild, and reports are quite limited. Here, we report a case of ingestion of alcohol with an insecticide containing imidacloprid. Clinical manifestation included mild disorientation, followed by bradycardia, ventricular arrhythmia, and cardiopulmonary arrest. Acute multiple organ failure, including oliguric kidney injury, acute lung injury, hypotension, and metabolic acidosis developed within hours of ingestion. Renal replacement therapy, including intermittent hemodialysis and continuous venovenous hemodialysis, quickly corrected the metabolic acidosis with better blood pressure. Despite original belief that imidacloprid has low mammalian toxicity, there is increasing evidence that imidacloprid may cause heart, kidney, and other organ damages and even death besides gastrointestinal irritation and neurological symptoms. The role of aldehyde oxidase, imidacloprid metabolites, and ethanol alcohol consumption in the pathogenesis of imidacloprid toxicity needs further study.

Common toxidromes of plant poisonings in Taiwan.

OBJECTIVE: To describe the toxidromes associated with plant poisonings in Taiwan. METHODS: Retrospective review of acute single-plant exposures with clinical signs and symptoms reported between January 1987 and December 2006 by hospitals to the network of Taiwan Poison Control Centers. Recorded data included demographic data, intent of exposures, exposure routes, clinical findings, and therapeutic strategies. RESULTS: There were 389 cases that met the criteria. Each case was placed into one of the expected toxidromes: anticholinergic, mucosal inflammation, gastroenteritis, acute multisystem organ failure, delayed multisystem organ failure, cholinergic, cardiac dysrhythmia, hepatotoxicity, dermatitis, seizures, and dyspnea. Anticholinergic poisoning was the most common toxidrome. CONCLUSION: Plant poisonings can be classified into recognizable toxicologic syndromes. These toxidromes may guide a clinician's evaluation and management before a botanist can confirm the actual plant identity.

Acute quadriparesis caused by spinal arteriovenous malformation: a case report.

Arteriovenous malformations (AVMs) in the spinal cord are relatively rare lesions, especially in the cervical region. Here we report a case of cervical spinal AVM with hemorrhage in a young man who developed acute quadriparesis during exercise. For spinal AVM, emergent spinal magnetic resonance imaging (MRI) is a useful screening tool, and angiography can provide the most important diagnostic information. The emergency physician should have a high index of suspicion for diagnosis and appropriate management of this rare condition. Early diagnosis and management is essential to preserve neurologic functioning.

Epidemiology of organophosphate pesticide poisoning in Taiwan.

INTRODUCTION: The nationwide epidemiology of organophosphate pesticide (OP) poisoning has never been reported in detail for Taiwan. METHODS: This study retrospectively reviewed all human OP exposures reported to Taiwan's Poison Control Centers (PCCs) from July 1985 through December 2006. RESULTS: There were 4799 OP exposures. Most OP exposures were acute (98.37%) ingestions (74.50%) of a single OP (80.37%) to attempt suicide (64.72%) in adults (93.25%). Males were the most common gender (64.95%). Most patients (61.97%) received atropine and/or pralidoxime. The mortality rate for all 4799 OP exposures was 12.71%. Exposures to single OPs without co-intoxicants caused 524 deaths; of these, 63.36% were due to dimethyl OPs. CONCLUSION: Dimethyl OPs cause the majority of deaths in Taiwan.

Characteristics of febrile patients with normal white blood cell counts and high C-reactive protein levels in an emergency department.

Fever is one of the more common chief complaints of patients who visit emergency departments (ED). Many febrile patients have markedly elevated C-reactive protein (CRP) levels and normal white blood cell (WBC) counts. Most of these patients have bacterial infection and no previous underlying disease of impaired WBC functioning. We reviewed patients who visited our ED between November 2003 and July 2004. The WBC count and CRP level of patients over 18 years of age who visited the ED because of or with fever were recorded. Patients who had normal WBC count (4,000-10,000/L) and high CRP level (> 100 mg/L) were included. The data, including gender, age and length of hospital stay, were reviewed. Underlying diseases, diagnosis of the febrile disease and final condition were recorded according to the chart. Within the study period, 54,078 patients visited our ED. Of 5,628 febrile adults, 214 (3.8%) had elevated CRP level and normal WBC count. The major cause of febrility was infection (82.24%). Most of these patients were admitted (92.99%). There were 32 patients with malignant neoplasm, nine with liver cirrhosis, 66 with diabetes mellitus and 11 with uremia. There were no significant differences in age and gender between patients with and those without neoplasm. However, a higher inhospital mortality rate and other causes of febrility were noted in patients with neoplasm. It was not rare in febrile patients who visited the ED to have a high CRP level but normal WBC count. These patients did not necessarily have an underlying malignant neoplasm or hematologic illness. Factors other than malignant neoplasm or hematologic illness may be associated with the WBC response, and CRP may be a better indicator of infection under such conditions.

Pre-hospital and in-hospital delays after onset of acute ischemic stroke: a hospital-based study in southern Taiwan.

The biggest hurdle for early hospital presentation is the narrow therapeutic window after stroke. The aims of our study were to investigate the time lags and the factors causing pre-hospital and emergency department (ED) delay during acute ischemic stroke attack. Between June 2004 and October 2005, we prospectively studied 129 acute ischemic stroke patients who presented to the ED of the study hospital within 4 hours after symptom onset. Chi-square testing for trend, univariate and multiple logistic regression analyses was performed to evaluate the factors influencing delays in the ED presentation of acute ischemic stroke patients. The median time from symptom onset to ED arrival was 71 (mean +/- SD, 82.7 +/- 57.7) minutes. The median times from ED arrival to neurologic consultation, computed tomography scan, electrocardiogram, and laboratory data completion were 10 (11.3 +/- 9.9) minutes, 17 (9.6 +/- 11.3) minutes, 14 (23.3 +/- 55) minutes, and 39 (44.4 +/- 24.5) minutes, respectively. Univariate and multiple logistic regression models revealed that age < 65 years, illiteracy and awakening with symptoms were the most significant factors related to a delay in ED presentation. This study indicates that 2 hours of pre-hospital delay is the cutoff point for thrombolytic therapy. Organization of a stroke team and standardized stroke pathways may help to shorten in-hospital time consumption. Educational efforts should not only focus on the public, but also on the training of ED physicians and other medical personnel.

An unusual presentation of metastatic gastric adenocarcinoma--acute onset of right neck swelling.

Central venous thrombosis is an uncommon problem associated with malignancy. We present here a 53-year-old male who visited the emergency room because of right neck swelling. Fluid accumulation over deep neck space led to the diagnosis of suspected hemorrhage, and central venous thrombosis was found by computed tomography. This patient had no other precipitating cause. Autoimmune disorders, hypercoagulation and malignancy surveys were performed during hospitalization. Elevated serum tissue polypeptide antigen and CA130 were noted, and multiple liver metastases were found by another computed tomography. Subsequently, gastric adenocarcinoma was confirmed after gastroendoscopy. Gastric adenocarcinoma with distal metastases was finally diagnosed. This case reminds us that central venous thrombosis is a sign of many diseases. Malignancy, including gastric adenocarcinoma, is one of the causes that should be considered.