Protein kinase A-dependent neuronal nitric oxide synthase activation mediates the enhancement of baroreflex response by adrenomedullin in the nucleus tractus solitarii of rats.

BACKGROUND: Adrenomedullin (ADM) exerts its biological functions through the receptor-mediated enzymatic mechanisms that involve protein kinase A (PKA), or neuronal nitric oxide synthase (nNOS). We previously demonstrated that the receptor-mediated cAMP/PKA pathway involves in ADM-enhanced baroreceptor reflex (BRR) response. It remains unclear whether ADM may enhance BRR response via activation of nNOS-dependent mechanism in the nucleus tractus solitarii (NTS). METHODS: Intravenous injection of phenylephrine was administered to evoke the BRR before and at 10, 30, and 60 min after microinjection of the test agents into NTS of Sprague-Dawley rats. Western blotting analysis was used to measure the level and phosphorylation of proteins that involved in BRR-enhancing effects of ADM (0.2 pmol) in NTS. The colocalization of PKA and nNOS was examined by immunohistochemical staining and observed with a laser confocal microscope. RESULTS: We found that ADM-induced enhancement of BRR response was blunted by microinjection of NPLA or Rp-8-Br-cGMP, a selective inhibitor of nNOS or protein kinase G (PKG) respectively, into NTS. Western blot analysis further revealed that ADM induced an increase in the protein level of PKG-I which could be attenuated by co-microinjection with the ADM receptor antagonist ADM22-52 or NPLA. Moreover, we observed an increase in phosphorylation at Ser1416 of nNOS at 10, 30, and 60 min after intra-NTS administration of ADM. As such, nNOS/PKG signaling may also account for the enhancing effect of ADM on BRR response. Interestingly, biochemical evidence further showed that ADM-induced increase of nNOS phosphorylation was prevented by co-microinjection with Rp-8-Br-cAMP, a PKA inhibitor. The possibility of PKA-dependent nNOS activation was substantiated by immunohistochemical demonstration of co-localization of PKA and nNOS in putative NTS neurons. CONCLUSIONS: The novel finding of this study is that the signal transduction cascade that underlies the enhancement of BRR response by ADM in NTS is composed sequentially of cAMP/PKA and nNOS/PKG pathways.

Bajiaolian poisoning-a poisoning with high misdiagnostic rate.

BACKGROUND: One of the oldest Chinese herbal medicine, bajiaolian is widely used in traditional therapy. In Taiwan, bajiaolian is the fifth highest cause of poisoning among herbal medicines. The diagnosis is difficult because physicians are unfamiliar with this medicine's multiple presentations in different stages of intoxication. PROCEDURES: The records of 4 major poison centers in Taiwan were searched for all bajiaolian intoxication from July 1985 (the opening of first poison center) to March 2003. Two emergency physicians with toxicologic training reviewed the admission charts and visited case patients for follow-up. FINDINGS: Seventeen patients were identified, of which 15 (88.2%) had been misdiagnosed initially. In the beginning of their medical care, 14 cases were diagnosed as acute gastroenteritis. CONCLUSION: Bajiaolian intoxication is probably misdiagnosed because of early gastrointestinal symptoms followed by neurologic symptoms. A detailed patient history should be taken, and symptoms should be reviewed systemically to improve diagnostic accuracy.

Urine output and performance of runners in a 12-hour ultramarathon.

OBJECTIVE: To understand the urination pattern and to determine the relationships between urine output and performance of ultramarathon runners. DESIGN: Prospective observational study. SETTING: The 2005 Soochow University international ultramarathon, in which each athlete ran for 12 hours. PARTICIPANTS: All entrants in the 12-hour race were invited to participate in the study. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Athletes were weighed immediately before and after the race. Urine samples were collected during the race and immediately after the race. RESULTS: There was a trend toward better performance of the group with less urination (LU), although the difference was not statistically significant. Further analysis of hourly running distances between groups showed better performance in the group with LU during the first 11 hours of the competition. Comparison of athletes in 3 levels of running distance (tertiles) showed statistically significant differences between groups in total urine output. The fastest tertile had lower prerace body weight and greater body weight change than the slowest and intermediate tertiles, but the differences were not statistically significant. Linear regression analysis using the stepwise method showed that total urine output and prerace body weight were negatively associated with performance. CONCLUSIONS: Runners with LU had better performance during the first 11 hours of the competition. Linear regression analysis showed that total urine output and prerace body weight were negatively associated with performance.

Cessation of nail growth following Bajiaolian intoxication.

Bajiaolian (Dysosma pleianthum), a species in the Mayapple family (Podophyllum pelatum), has been widely used as a traditional Chinese herbal medication for the remedies of snake bite, tumor growth, post-partum recovery, and acne. It has also been used in western medicine, especially topically for various skin lesions. Both oral ingestion and dermal application may result in severe toxicity. The clinical presentations reported after Bajiaolian poisoning include nausea, vomiting, diarrhea, abdominal cramps, tachycardia, orthostatic hypotension, paralytic ileus, urinary retention, hepatorenal dysfunction, leukocytosis followed by leukopenia, thrombocytopenia, prolonged areflexia, prolonged paraethesia and sensory ataxia, dizziness, fever, memory impairment, hallucinations, paranoia, convulsion, fainting, and coma. There are no previous reports in the literature about the cessation of nail growth as a clinical presentation following Bajiaolian poisoning. We present a case of nail growth that was halted for more than seven years after a single case of Bajiaolian poisoning.

Glycated hemoglobin level is an independent predictor of major adverse cardiac events after nonfatal acute myocardial infarction in nondiabetic patients: A retrospective observational study.

The effect of glycemic control on the prognosis of nondiabetic patients after acute myocardial infarction (AMI) remains uncertain. We investigated whether glycated hemoglobin (HbA1c) is associated with adverse outcomes after AMI in nondiabetic patients. In this observational study, we enrolled nondiabetic patients with AMI in the emergency department of 2 medical centers from January 2011 to September 2014. All patients received primary percutaneous coronary intervention and were divided into 4 groups according to the interquartile range of average HbA1c level (Group I, ≤5.6%; Group II, 5.6%-5.8%; Group III, 5.8%-6.0%; and Group IV, >6.0%). Multivariate logistic analysis was performed to estimate the correlation of HbA1c with major adverse cardiac events (MACEs) after AMI. In total, 267 eligible patients were enrolled; 48 patients (18%) developed MACEs within a median follow-up of 178 days. Univariate analysis showed HbA1c > 6.0%, with a higher risk of MACEs in Group IV than in Group I (odds ratio [OR]: 2.733; 95% confidence interval [CI]: 1.123-6.651 vs OR: 1.511; 95% CI: 0.595-3.835). Multivariate analysis revealed an approximately 3.8 times higher risk of MACEs in Group IV than in Group I (OR: 3.769; 95% CI: 1.30-10.86). The HbA1 level is a significant predictor of MACEs after AMI in nondiabetic patients.

Coenzyme q10 confers cardiovascular protection against acute mevinphos intoxication by ameliorating bioenergetic failure and hypoxia in the rostral ventrolateral medulla of the rat.

Coenzyme Q10 (CoQ10, ubiquinone) is a highly mobile electron carrier in the mitochondrial respiratory chain that also acts as an antioxidant. We evaluated the cardiovascular protective efficacy of CoQ10 at the rostral ventrolateral medulla (RVLM), a medullary site where sympathetic vasomotor tone originates and where the organophosphate poison mevinphos (Mev) acts to elicit cardiovascular intoxication. Experiments were carried out in adult male Sprague-Dawley rats that were maintained under propofol anesthesia. Microinjection bilaterally of Mev (10 nmol) into the RVLM induced progressive hypotension and minor bradycardia, alongside significant depression of the activity of NADH cytochrome c reductase (enzyme marker for Complexes I and III) or cytochrome c oxidase (enzyme marker for Complex IV) in the mitochondrial respiratory chain, reduction in ATP concentration, or tissue hypoxia in the RVLM. On the other hand, the activity of succinate cytochrome c reductase (enzyme marker for Complexes II and III) remained unaltered. The Mev-induced hypotension, bioenergetic failure, or hypoxia was significantly reversed when CoQ10 (4 microg) was coadministered bilaterally into the RVLM with the organophosphate poison. We conclude that CoQ10 confers cardiovascular protection against acute Mev intoxication by acting on the RVLM, whose neuronal activity is intimately related to the "life-and-death" process. We also showed that amelioration of the selective dysfunction of respiratory enzyme Complexes I and IV in the mitochondrial respiratory chain, the reduced ATP level, and the induced tissue hypoxia in the RVLM are among some of the underlying mechanisms for the elicited protection.

Depression of mitochondrial respiratory enzyme activity in rostral ventrolateral medulla during acute mevinphos intoxication in the rat.

We investigated possible changes in bioenergetics at the rostral ventrolateral medulla (RVLM), a medullary site where sympathetic vasomotor tone originates and where the organophosphate poison mevinphos (Mev) acts to elicit cardiovascular intoxication. In Sprague-Dawley rats maintained under propofol anesthesia, microinjection bilaterally of Mev (10 nmol) into the RVLM induced progressive hypotension that was accompanied by an early augmentation (80-100 min post-Mev; Phase I), followed by a decrease (>100 min post-Mev; Phase II) in the power density of the vasomotor components (0-0.8 Hz) in systemic arterial pressure (SAP) signals. Enzyme assay revealed that local application of Mev into the RVLM also significantly and progressively depressed the activity of NADH cytochrome c reductase (marker for Complexes I and III) and cytochrome c oxidase (marker for Complex IV) in the mitochondrial respiratory chain of the RVLM, but not the heart. On the other hand, the activity of succinate cytochrome c reductase (marker for Complexes II and III) remained unaltered. Both the cardiovascular consequences and depression of mitochondrial respiratory chain enzymes elicited by Mev were significantly antagonized on comicroinjection of atropine (3.5 or 7 nmol) bilaterally into the RVLM. We conclude that Mev adversely effects cardiovascular control by acting as a cholinesterase inhibitor in the RVLM, whose neuronal activity is intimately related to the death process. The resulting accumulation of acetylcholine and prolonged activation of muscarinic receptors in the RVLM is manifested by a selective dysfunction of respiratory enzyme Complexes I and IV in the mitochondrial respiratory chain that underlies cardiovascular toxicity associated with organophosphate poisons such as Mev.

Acute mountain sickness in Jade Mountain climbers of Taiwan.

BACKGROUND: Although there are more than 200 peaks higher than 3000 m in the Taiwan Alps, no data on the incidence of acute mountain sickness (AMS) are available. This study investigated the incidence of AMS in Jade Mountain climbers. METHODS: The study was performed at the entrance of Jade Mountain, the highest peak (3952 m) in Taiwan. A standardized form was used to collect information. All the recorders had previously been trained in the management of high altitude illness. The Lake Louise consensus was used for the diagnosis of AMS. RESULTS: There were 93 trekkers (18 females and 71 males) who were surveyed. Four records with incomplete data were excluded, leaving 89 records for analysis. The ages ranged from 20-68 yr, with an average age of 41.1 +/- 11.2 SD. All subjects had a home residence below 1 km. The most common high altitude symptoms were headaches. Some 25 trekkers (28%) [corrected] met the diagnoses of AMS. The most common site of the AMS cases feeling their worst symptoms was in the midway overnight hut, and not on the summit. The lower the O2 saturation recorded at the entrance (2659 m) of Jade Mountain, the higher the score of the Lake Louise Acute Mountain Sickness Score (LLAMSS). CONCLUSIONS: Acute mountain sickness is a common problem in Taiwan summit climbers. In our study, 28% [corrected] of the Jade Mountain trekkers met the diagnosis of AMS; however, the incidence of AMS was lower than that of other studies at similar altitudes.

Seroprevalence of antibodies to pandemic (H1N1) 2009 influenza virus among hospital staff in a medical center in Taiwan.

BACKGROUND: The pandemic (H1N1) 2009 influenza emerged in April 2009 and spread rapidly and broadly all over the world. In addition to specific antiviral agents, massive vaccination is thought to be the most effective way of controlling the transmission. To understand the prevaccination status of certain risk groups, this study compared the baseline sero-prevalence of antibodies to the pandemic (H1N1) 2009 influenza virus among hospital staff with different contact risks and that of the general population. METHODS: A total of 295 serum samples from hospital staff and 244 control serum samples from people who came for physical check-up (control group) were collected between October 2009 and November 2009 before the massive vaccination campaign. The hospital staff was divided into first-line risk personnel (group 1) and second-line risk personnel (group 2) according to their potential contact risks. Hemagglutination-inhibition (HI) tests were conducted to determine the individual serological status. The seropositive rate (SPR, defined as the proportion with HI titer >/= 1:40) of antibodies to H1N1 influenza virus and its geometric mean titer (GMT) were calculated and compared among the different groups. RESULTS: The mean ages and sex ratio (% male) of the hospital staff and control groups were 36.9 +/- 10.6 years and 52.0 +/- 12.6 years, and 24.4% and 57.6%, respectively. The SPR of the antibodies to H1N1 influenza virus of the hospital staff was significantly higher than that of the control group (20.0%vs. 2.9%, p < 0.001). Furthermore, the SPR antibodies to H1N1 influenza virus of group 1 were significantly higher than that of group 2 (30.8%vs. 12.6%, p < 0.001). However, the GMT of antibodies to H1N1 influenza virus of the hospital staff was not significantly different from that of the control group (p = 0.925). CONCLUSION: The SPR of antibodies against the pandemic (H1N1) 2009 virus in the hospital staff was higher than that in the general population, reflecting a higher contact risk. Prevaccination surveillance of the immune status of different risk groups may help to prioritize which groups should be vaccinated first.

Features and prognostic factors for elderly with acute poisoning in the emergency department.

BACKGROUND: Elderly persons with acute poisoning in the emergency department (ED) and prognostic factors of outcomes have not been well addressed in previous research. This study aimed to investigate the characteristics of elderly patients with acute poisoning visiting the ED, and to identify the possible predictive factors of mortality. METHODS: Patients aged > or = 65 years with acute poisoning who visited the ED in Taipei Veterans General Hospital from January 1, 2006 through to September 30, 2008 were enrolled in the study. We collected demographic information on underlying diseases, initial presentations, causes and toxic substances, complications, dispositions, and outcomes. Analyses were conducted among different groups categorized according to age, suicide attempt, and outcome. Multiple logistic regression was applied to identify possible predictive clinical factors influencing mortality in the elderly with acute poisoning. RESULTS: A total of 250 patients were enrolled in the study, with a mean age of 77 years and male predominance. The most common cause of intoxication was unintentional poisoning. Medication accounted for 57.6% of poisonous substances, of which benzodiazepine was the most common drug, followed by warfarin. The overall mortality rate was 9.6%. The average length of stay in the ED increased significantly in the old (65-74 years), very old (75-84 years) and extremely old (> or = 85 years) groups. Suicide attempt patients experienced more complications including respiratory failure, aspiration pneumonia, hypotension and mortality. Three clinical predictive factors of mortality were identified: herbicide poisoning, hypotension and respiratory failure upon presentation. CONCLUSION: Our results demonstrated that elderly patients with acute poisoning had a mortality rate of 9.6%. Suicide attempts resulted in more serious complications. The risk factors for mortality were herbicide intoxication, hypotension and respiratory failure.

Diffuse Cerebral Cortex, Cerebellar Cortex and Basal Ganglia Injury: a Rare MR Imaging Manifestation of Heat Stroke.

We present a case of heat stroke with rare magnetic resonance (MR) imaging manifestations. In addition to abnormal high signals in bilateral cerebellum and basal ganglia seen on T2-weighted MR images (T2WI), the case showed diffuse cerebral cortical high signals on T2WI and diffusion-weighted images (DWI). Heat stroke with diffuse hypoperfusion to the brain due to diversion of blood circulation was hypothesized as the cause of brain injury, including the cerebral cortex.

The feasibility of full computerization in the ED.

For understanding the feasibility of full computerization of an emergency department (ED), we investigated the completion rate performed by doctors, nurses, or registration clerks since the implementation of full computerization in our ED. We evaluated the changing style of chart-recording, from hand-writing pattern to full computer recording, by recording the execution rate of different information keyed by doctors, nurses, or registration clerks according to their work in ED. We recorded and analyzed different monthly reports of the execution rate in the 18-month period of study. Statistical analysis was performed using Wilcoxon rank-sum test or Kruskal-Wallis one-way ANOVA. The average monthly census was 4570.1 +/- 580.7 (95% confidence interval [CI] for mean: 4281.3, 4858.9). The average execution rate for mode of arrival and triage classification were 97.1 +/- 4.1% (95% CI for mean: 95.1%, 99.1%) and 97.2 +/- 4.1% (95% CI for mean: 95.2%, 99.2%), respectively. In comparison with the execution rate for disposition status between the period of the first 10 months (keying data by nurses) and the late 8 months (keying data by clerks), it showed 72.0 +/- 33.2% v 96.7 +/- 2.0%; 66.7 +/- 35.0% v 95.8 +/- 1.9%; 57.5 +/- 32.0% v 88.2 +/- 8.2% in nontrauma, trauma and pediatric section, respectively, with statistic significance (P <.01). To compare the rate of execution performed by physicians, we divided the study period into 3 phases (phase 1: first 6 months, phase 2: 7-12 months, phase 3: 13-18 months of the study period). The results were statistically significant (P =.004) in phase 3 (83.4 +/- 5.3%) with higher execution rate than phase 1 (69.7 +/- 7.7%) and phase 2 (75.2 +/- 4.9%) in trauma physician. In the pediatric section, it was also significantly higher in phase 3 than phase 2 (88.2 +/- 7.7% v 70.7 +/- 5.9%, P =.012). We concluded that it is efficient to key in data by registration clerks instead of nurses, and it takes time to persuade and educate most physicians to cooperate in using the computer while seeing patients.

Acute urinary retention in the elderly: an unusual presentation of appendicitis with a high perforation risk.

BACKGROUND: Urological manifestations are rare in acute appendicitis. Although acute urinary retention (AUR) is more commonly found in elderly patients, any previous cases reported have been under the age of 30. OBJECTIVE: The aim of this study was to investigate the incidence, clinical presentation, and results of adult appendicitis patients presenting with AUR. AUR is defined as the sudden inability to urinate with obstructive symptoms. METHODS: A retrospective case note review of 480 adult patients (>/=18 years) with appendicitis, diagnosed at the Veterans General Hospital-Taipei over a 3-year period, was carried out. RESULTS: Six patients (1.3% of the adults or 3.9% of the elderly patients), 5 men and 1 woman averaging 71.5 years of age, presented with AUR. Associated existing diseases were benign prostatic hyperplasia in 2 of the males and surgical repair for uterine prolapse in the only female. The mean duration from initial gastrointestinal symptoms to AUR was 1.7 days. The quantity of residual urine ranged from 180 to 450 ml. All patients had persistent right lower quadrant tenderness and hematuria. Five (83.3%) were found to have a perforated appendix at operation, and their average hospital stay was 14.7 (8-29) days. CONCLUSIONS: AUR may occur as an initial presentation in acute complicated appendicitis in the elderly. It has been reported that the prolonged hospital stay might be related to the delayed diagnosis and resulting complications arising in these patients. Primary care physicians need to be reminded that this common genitourinary complaint may arise in patients with acute appendicitis. When confronted with a geriatric patient presenting with AUR, one should entertain an alternative diagnosis and a reexamination of the patient is mandatory.

A simple, safe, and efficient way to treat severe fluoride poisoning--oral calcium or magnesium.

PURPOSE: To examine the efficacy and safety of administration of calcium and magnesium orally and intraperitoneally to treat severe sodium fluoride intoxication. MATERIALS AND METHODS: Mice were initially gavaged a lethal dose of sodium fluoride (NaF) or water. Then, mice were treated with water or varying concentrations of calcium chloride (CaCl2) or magnesium sulfate (MgSO4) via intraperitoneal (IP) route or via oral route. Mice were monitored for 24 h, and the time of death was recorded. RESULTS: IP injections of large amounts of CaCl2 or MgSO4 were dangerous. All mice gavaged with water and then treated with oral CaCl2 or MgSO4 survived and displayed normal activity during the experiment. The survival rate of mice gavaged with a lethal dose of NaF and then treated with a high dose of oral CaCl2 or MgSO4 was significantly higher than those of using low dose. CONCLUSION: Oral administration of a high dose of CaCl2 or MgSO4 is a simple, safe, and effective adjunctive method for treating severe oral fluoride poisoning.