Byeong Jo Chun

Disruption of protein kinase A localization using a trans-activator of transcription (TAT)-conjugated A-kinase-anchoring peptide reduces cardiac function.

Localization of protein kinase A (PKA) via A-kinase-anchoring proteins (AKAPs) is important for cAMP responsiveness in many cellular systems, and evidence suggests that AKAPs play an important role in cardiac signaling. To test the importance of AKAP-mediated targeting of PKA on cardiac function, we designed a cell-permeable peptide, which we termed trans-activator of transcription (TAT)-AKAD for TAT-conjugated A-kinase-anchoring disruptor, using the PKA binding region of AKAP10 and tested the effects of this peptide in isolated cardiac myocytes and in Langendorff-perfused mouse hearts. We initially validated TAT-AKAD as a PKA localization inhibitor in cardiac myocytes by the use of confocal microscopy and cellular fractionation to show that treatment with the peptide disrupts type I and type II PKA regulatory subunits. Knockdown of PKA activity was demonstrated by decrease in phosphorylation of phospholamban and troponin I after β-adrenergic stimulation in isolated myocytes. Treatment with TAT-AKAD reduced myocyte shortening and rates of contraction and relaxation. Injection of TAT-AKAD (1 μm), but not scrambled control peptide, into the coronary circulation of isolated perfused hearts rapidly (<1 min) and reversibly decreased heart rate and peak left ventricular developed pressure. TAT-AKAD also had a pronounced effect on developed pressure (−dP/dt), consistent with a delayed relaxation of the heart. The effects of TAT-AKAD on heart rate and contractility persisted in hearts pretreated with isoproterenol. Disruption of PKA localization with TAT-AKAD thus had negative effects on chronotropy, inotropy, and lusitropy, thereby indicating a key role for AKAP-targeted PKA in control of heart rate and contractile function.

Acute endosulfan poisoning: a retrospective study.

Endosulfan is a widely used insecticide that is associated with a high fatality rate in humans when ingested accidentally or with the aim of suicide. However, the literature concerning human endosulfan exposure is limited to case reports. Thus, we sought to 1) describe the clinical features of patients with acute endosulfan poisoning and 2) identify independent factors to predict patients’ outcome. Fifty-two patients who presented with acute endosulfan poisoning between January 2001 and January 2007 were enrolled in this retrospective study. Sixteen (30.7%) of the 52 patients died, and 48 patients experienced seizures. Endosulfan poisoning caused the hypotension and the abnormalities on electrocardiogram at presentation. Over half of the patients developed complications, such as rhabdomyolysis, hepatic toxicity, and hypotension. These complications resolved without sequelae in the survival group. Refractory status epilepticus was the most common cause of death in this series (75.0%). Amount ingested being greater than 35 g of endosulfan was the most found to be an independent variable that predicted patient mortality. Patients with this risk factor must be treated aggressively during the early stage of endosulfan poisoning.

The value of initial lactate in patients with carbon monoxide intoxication: in the emergency department.

Patients with carbon monoxide (CO) poisoning have been found to have a correlation between initial clinical severity on admission and blood lactate levels. Recently, it is suggested that the lactate level may be a useful prognostic factor in cases study. The purpose of this study was to determine whether lactate levels were associated with the short-term outcome of patients with CO poisoning and identify the characteristics of patients with high initial lactate levels. Eighty patients that presented to the Chonnam National University Hospital after CO poisoning, over 5 years, were enrolled in this retrospective study. Fifty-six (70.0%) patients had high lactate (>2.1 mmo/L) on admission. Thirty-three (41.3%) patients had medical complications and one patient (1.3%) died. The patients with high initial lactate had an altered mental status more frequently, higher WBC, glucose and carboxyhemoglobin (COHb), and lower base deficit on admission. The multivariate analysis showed that lactate was an independent factor associated with serious complications and the need for intensive medical treatment, along with advanced age, WBC, and altered mental status on admission. The results of this study show that the initial lactate was useful for patient prognosis after CO poisoning.Patients with carbon monoxide (CO) poisoning have been found to have a correlation between initial clinical severity on admission and blood lactate levels. Recently, it is suggested that the lactate level may be a useful prognostic factor in cases study. The purpose of this study was to determine whether lactate levels were associated with the short-term outcome of patients with CO poisoning and identify the characteristics of patients with high initial lactate levels. Eighty patients that presented to the Chonnam National University Hospital after CO poisoning, over 5 years, were enrolled in this retrospective study. Fifty-six (70.0%) patients had high lactate (>2.1 mmo/L) on admission. Thirty-three (41.3%) patients had medical complications and one patient (1.3%) died. The patients with high initial lactate had an altered mental status more frequently, higher WBC, glucose and carboxyhemoglobin (COHb), and lower base deficit on admission. The multivariate analysis showed that lactate was an independent factor associated with serious complications and the need for intensive medical treatment, along with advanced age, WBC, and altered mental status on admission. The results of this study show that the initial lactate was useful for patient prognosis after CO poisoning.

The efficacy of high doses of vitamin C in patients with paraquat poisoning.

Paraquat (PQ) poisoning is an extremely difficult condition to manage clinically because of the lack of effective treatments. The purpose of this study was to assess the effect of high doses of vitamin C in combination with anti-inflammatory and immunosuppressant therapy in patients with PQ poisoning. The medical records of 134 patients who presented to the emergency department within 24 hours after PQ poisoning were reviewed retrospectively. The 57 patients presented between January 2004 and September 2005 were group 1; they received pulse therapy, which included cyclophosphamide and methylprednisolone, followed by the administration of dexamethasone over 2 weeks. The 77 patients that presented between October 2005 and January 2008 were group 2; they received the above-mentioned therapy and high-dose vitamin C for 2 weeks. There was no difference in the distribution of baseline variables between the 2 groups. However, group 2 showed a significant reduction in acute kidney injury related to PQ. Furthermore, a multivariate logistic regression analysis showed that the addition of vitamin C to the treatment was significantly associated with an increased survival of the patients. Larger trials will be needed to verify the effect of high-dose vitamin C on survival in patients with PQ poisoning.Paraquat (PQ) poisoning is an extremely difficult condition to manage clinically because of the lack of effective treatments. The purpose of this study was to assess the effect of high doses of vitamin C in combination with anti-inflammatory and immunosuppressant therapy in patients with PQ poisoning. The medical records of 134 patients who presented to the emergency department within 24 hours after PQ poisoning were reviewed retrospectively. The 57 patients presented between January 2004 and September 2005 were group 1; they received pulse therapy, which included cyclophosphamide and methylprednisolone, followed by the administration of dexamethasone over 2 weeks. The 77 patients that presented between October 2005 and January 2008 were group 2; they received the above-mentioned therapy and high-dose vitamin C for 2 weeks. There was no difference in the distribution of baseline variables between the 2 groups. However, group 2 showed a significant reduction in acute kidney injury related to PQ. Furthermore, a multivariate logistic regression analysis showed that the addition of vitamin C to the treatment was significantly associated with an increased survival of the patients. Larger trials will be needed to verify the effect of high-dose vitamin C on survival in patients with PQ poisoning.

FENTANYL INTOXICATION CAUSED BY ABUSE OF TRANSDERMAL FENTANYL

Fentanyl has an analgesic effect 100 times greater than that of morphine; therefore, transdermal administration of fentanyl has been widely used to control pain. Due to misconceptions regarding the proper use of fentanyl, its simple method of administration, and the absence of regulatory rules regarding its use, both medical providers and non-medical providers have abused fentanyl. We report on three cases of fentanyl intoxication and suggest solutions to prevent its abuse in the future. Three patients were intoxicated by transdermal fentanyl, which resulted in respiratory depression. Two of these cases were attributed to non-medical use of the drug and the other occurred while using fentanyl as directed by medical personnel. Physicians should use transdermal fentanyl only to control chronic pain, and rules should be established to prevent abuse of fentanyl that occurs due to its ease of use and the absence of any established policy regarding the prescription and disposal of this drug.

Can Early Hemodialysis Affect the Outcome of the Ingestion of Glyphosate Herbicide

The ingestion of small amounts of glyphosate herbicide usually causes only mild symptoms. However, when large volumes of concentrates are ingested intentionally, it can generate potentially fatal symptoms that are refractory to treatment. It also is well known that the treatment for glyphosate poisoning is primarily of a supportive nature. We report two patients who intentionally ingested glyphosate herbicide, and both exhibited cardiovascular collapse and complicated renal failure despite the use of aggressive supportive therapy. Hemodialysis was conducted and the results were satisfactory; both patients were discharged without any sequelae. After analyzing these cases, we suggest that hemodialysis might have contributed to the favorable outcomes of our patients, and that there are several mechanisms that might justify the use of hemodialysis in these patients. In conclusion, physicians may wish to consider the early use of hemodialysis to improve the prognosis of patients exhibiting refractory hypotension and oliguria, despite vigorous supportive treatment in glyphosate herbicide intoxication.The ingestion of small amounts of glyphosate herbicide usually causes only mild symptoms. However, when large volumes of concentrates are ingested intentionally, it can generate potentially fatal symptoms that are refractory to treatment. It also is well known that the treatment for glyphosate poisoning is primarily of a supportive nature. We report two patients who intentionally ingested glyphosate herbicide, and both exhibited cardiovascular collapse and complicated renal failure despite the use of aggressive supportive therapy. Hemodialysis was conducted and the results were satisfactory; both patients were discharged without any sequelae. After analyzing these cases, we suggest that hemodialysis might have contributed to the favorable outcomes of our patients, and that there are several mechanisms that might justify the use of hemodialysis in these patients. In conclusion, physicians may wish to consider the early use of hemodialysis to improve the prognosis of patients exhibiting refractory hypotension and oliguria, despite vigorous supportive treatment in glyphosate herbicide intoxication.

Predicting the complicated neutropenic fever in the emergency department

Objectives: The purpose of this study was to identify independent factors that can be used to predict whether febrile neutropenic patients who appear healthy at presentation will develop subsequent complications, using variables that are readily available in the emergency department (ED). Method: The medical records of 192 episodes in which the patients presented to the ED with neutropenic fever resulting from chemotherapy, with an alert mental state and haemodynamic stability were retrospectively reviewed. Endpoints examined were fever response to administered antibiotics, death or severe medical complications during hospitalisation. Results: Thirty-eight episodes of neutropenic fever with complicated outcomes were identified from among a total of 192 episodes. Three parameters emerged as independent factors for the prediction of neutropenic fever with complications in the multivariate regression analysis: platelet count (130−450 × 103 cells/mm3) <50 000 cells/mm3, serum C-reactive protein (CRP, 0.1–1 mg/dl) >10 mg/dl and pulmonary infiltration on chest x ray. Conclusions: Platelet count, CRP and pulmonary infiltration on chest x ray at presentation could be used to identify febrile neutropenic patients who will develop complications, and these factors may be useful in making treatment-related decisions in the ED.

Symptomatic epidural pneumorrhachis associated with an occult pneumomediastinum due to minor trauma.

Study Design. A case report and review of the literature. Objective. To discuss the significance of identifying symptomatic epidural pneumorrhachis associated with an occult pneumomediastinum in the absence of pneumothorax and subcutaneous emphysema after minor trauma. Summary of Background Data. Pneumorrhachis is defined as the presence of air in the epidural space or subarachnoid space. Previous reports have suggested that traumatic epidural pneumorrhachis was usually asymptomatic and a combination of pneumothorax, pneumomediastinum, and subcutaneous emphysema following major trauma and managed by conservative treatment. Methods. A 53-year-old man was admitted to the emergency department after the traffic collision. He presented with diffuse pain ranging from the neck to back, and complained of radiating shoulder pain. Results. The lateral cervical spine radiograph revealed an air shadow in the anterior cervical space. Axial image of cervical spine computed tomography (CT) revealed epidural pneumorrhachis. The sagittal reconstruction image of neck CT showed a small amount of air in the posterior mediastinum, and scattered air in the anterior cervical spinal canal. Our patient was treated conservatively and had a complete and uneventful recovery. Conclusion. To our knowledge, this is the first case in which symptomatic traumatic epidural pneumorrhachis was associated with an occult pneumomediastinum in the absence of pneumothorax and subcutaneous emphysema. These findings may be useful in alerting trauma specialists to carefully evaluate the associated pathologies leading to pneumorrhachis enabling adequate therapy.

Active surveillance of the trachea or throat for MRSA is more sensitive than nasal surveillance and a better predictor of MRSA infections among patients in intensive care.

Background Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of infection in the intensive care unit (ICU). Although surveillance culture for MRSA is recommended for ICU patients, no comparative study investigating the optimal sites and frequency of culture has been performed in this population. Methods A prospective observational cohort study was performed in an 18-bed emergency intensive care unit (EICU) in a tertiary teaching hospital. A total of 282 patients were included. Samples for MRSA detection were obtained at the time of admission, 48 h after admission, and then weekly thereafter. All subjects were routinely monitored for the development of MRSA infection during their stay in the ICU. Results MRSA colonization was detected in 129 (46%) patients over the course of the study. The sensitivity of MRSA surveillance culture was significantly higher in throat or tracheal aspirates (82%; 106/129) than in anterior nares (47%; 61/129) (P<0.001). The sensitivity of MRSA surveillance culture for subsequent MRSA infection and MRSA pneumonia was also higher in the throat/trachea (69 and 93%, respectively) than in the anterior nares (48 and 50%, respectively). The area under the curve for subsequent MRSA infection was higher in trachea/throat (0.675) than in the anterior nares (0.648); however, this difference was not significant (P>0.05). The area under the curve for MRSA pneumonia was significantly higher in trachea/throat (0.791; 95% CI, 0.739-0.837) than anterior nares (0.649; 95% CI, 0.590-0.705) (P = 0.044). Conclusion MRSA colonization was more common in the trachea/throat than in the anterior nares in ICU patients. Cultures from throat or tracheal aspirates were more sensitive and predictive of subsequent MRSA pneumonia than cultures from the anterior nares in this population.

The promoter of brain‐specific angiogenesis inhibitor 1‐associated protein 4 drives developmentally targeted transgene expression mainly in adult cerebral cortex and hippocampus

Restricting transgene expression to specific cell types and maintaining long‐term expression are major goals for gene therapy. Previously, we cloned brain‐specific angiogenesis inhibitor 1‐associated protein 4 (BAI1‐AP4), a novel brain‐specific protein that interacts with BAI1, and found that it was developmentally upregulated in the adult brain. In this report, we isolated 5 kb of the 5′ upstream sequence of the mouse BAI1‐AP4 gene and analyzed its promoter activity. Functional analyses demonstrated that an Sp1 site was the enhancer, and the region containing the transcription initiation site and an AP2‐binding site was the basal promoter. We examined the ability of the BAI1‐AP4 promoter to drive adult brain‐specific expression by using it to drive lacZ expression in transgenic (TG) mice. Northern blot analyses showed a unique pattern of β‐galactosidase expression in TG brain, peaking at 1 month after birth, like endogenous BAI1‐AP4. Histological analyses demonstrated the same localization and developmental expression of β‐galactosidase and BAI1‐AP4 in most neurons of the cerebral cortex and hippocampus. Our data indicate that TG mice carrying the BAI1‐AP4 promoter could be a valuable model system for region‐specific brain diseases.