Shorter time until return of spontaneous circulation is the only independent factor for a good neurological outcome in patients with postcardiac arrest syndrome.

OBJECTIVE: Few studies have reported factors that result in a better neurological outcome in patients with postcardiac arrest syndrome (PCAS) following return of spontaneous circulation (ROSC). We investigated the factors affecting neurological outcome in terms of both prehospital care and treatments after arrival at hospital in patients with PCAS. METHODS: The study enrolled patients with cardiogenic cardiac arrest who were admitted to an intensive care unit after ROSC with PCAS. We investigated the association of the following factors with outcome: age, gender, witness to event present, bystander cardiopulmonary resuscitation (CPR) performed, ECG waveform at the scene, time interval from receipt of call to arrival of emergency personnel, time interval from receipt of call to arrival at hospital, prehospital defibrillation performed, special procedures performed by emergency medical technician, and time interval from receipt of call to ROSC, coronary angiography/percutaneous coronary intervention (PCI) and therapeutic hypothermia performed. RESULTS: The study enrolled 227 patients with PCAS. Compared with the poor neurological outcome group, the good neurological outcome group had a statistically significant higher proportion of the following factors: younger age, male, witness present, bystander CPR performed, first ECG showed ventricular fibrillation/pulseless ventricular tachycardia, defibrillation performed during transportation, short time interval from receipt of call to ROSC, coronary angiography/PCI and therapeutic hypothermia performed. Of these factors, the only independent factor associated with good neurological outcome was the short time interval from receipt of the call to ROSC. CONCLUSIONS: In the present study, shortening time interval from receipt of call to ROSC was the only important independent factor to achieve good neurological outcome in patients with PCAS.

A randomized, controlled, multicenter trial of the effects of antithrombin on disseminated intravascular coagulation in patients with sepsis.

INTRODUCTION: To test the hypothesis that the administration of antithrombin concentrate improves disseminated intravascular coagulation (DIC), resulting in recovery from DIC and better outcomes in patients with sepsis, we conducted a prospective, randomized controlled multicenter trial at 13 critical care centers in tertiary care hospitals. METHODS: We enrolled 60 DIC patients with sepsis and antithrombin levels of 50 to 80% in this study. The participating patients were randomly assigned to an antithrombin arm receiving antithrombin at a dose of 30 IU/kg per day for three days or a control arm treated with no intervention. The primary efficacy end point was recovery from DIC on day 3. The analysis was conducted with an intention-to-treat approach. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) scoring system. The systemic inflammatory response syndrome (SIRS) score, platelet count and global markers of coagulation and fibrinolysis were measured on day 0 and day 3. RESULTS: Antithrombin treatment resulted in significantly decreased DIC scores and better recovery rates from DIC compared with those observed in the control group on day 3. The incidence of minor bleeding complications did not increase, and no major bleeding related to antithrombin treatment was observed. The platelet count significantly increased; however, antithrombin did not influence the sequential organ failure assessment (SOFA) score or markers of coagulation and fibrinolysis on day 3. CONCLUSIONS: Moderate doses of antithrombin improve DIC scores, thereby increasing the recovery rate from DIC without any risk of bleeding in DIC patients with sepsis. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000000882.

Clinical evaluation of a new creatine kinase MB activity reagent abrogating the effect of mitochondrial creatine kinase.

BACKGROUND: Measuring creatine kinase (CK) MB activity using the immunoinhibition method remains useful in clinical laboratories. CK-MB activity is abnormally high when macro CK type 2 (mitochondrial creatine kinase, MtCK) is present in patient serum. In order to improve the accuracy of the CK-MB activity assay, we developed a new CK-MB activity method using highly specific anti-MtCK antibodies. We evaluated the clinical performance of the new method, which abrogates the effect of MtCK activity. METHODS: Receiver operating characteristic analysis, CK-MB activity range, cut-off, and CK-MB to CK activity ratio were investigated. RESULTS: Mean CK-MB activity in normal human serum was 2.5 U/L by our method, in contrast to 12.0 U/L by the current method. Approximately 80% of CK-MB activity determined using the current kit corresponds to MtCK activity, and ubiquitous mitochondrial creatine kinase activity constitutes approximately 90% of MtCK activity. The cut-off and CK-MB activity ratio of our method were 12 U/L and 3 to 20%, respectively, in contrast to 22 U/L and 5 to 23%, respectively, using the current CK-MB method. The areas under the curve of our method, current CK-MB, electrophoresis, and CK-MB mass were 0.976, 0.928, 0.967, and 0.991, respectively. Our new method was superior to the electrophoresis and CK-MB mass as well as the conventional method due to jts promptness, simplification, and low cost. CONCLUSIONS: The new kit will improve the clinical diagnosis of acute myocardial infarction. CK-MB activity assay was considered as a suitable alternative to conventional cardiac markers due to its superior diagnostic validity.

A case of traumatic hematoma in the basal ganglia that showed deterioration after arrival at the hospital.

A case of traumatic hematoma in the basal ganglia that showed deterioration after arrival at the hospital was reported. A 65-year-old man crashed into the wall while riding a motorcycle. His Glasgow coma scale was E3V4M6 and showed retrograde amnesia and slight right motor weakness. Because head CT in the secondary trauma survey showed subarachnoid hemorrhage in the right Sylvian fissure and multiple gliding contusions in the left frontal and parietal lobe, he was entered into the intensive care unit for diagnosis of diffuse brain injury. He showed complete muscle weakness of left upper and lower limbs 5 h after the accident. Head CT newly showed hematoma, 2 cm in diameter, in the right basal ganglia. The patient vomited following the CT scan, and so his consciousness suddenly deteriorated into a stupor. We performed head CT again. The hematoma had enlarged to 5 cm at the same lesion and partially expanded into midbrain. The patient died on the 13th day of trauma. Based on retrospective interpretation, we conclude that clinical examinations, follow-up CT scans and blood examinations should be performed frequently as part of ICU management for all TBI patients in the early phase after trauma.

Effects of bag-mask versus advanced airway ventilation for patients undergoing prolonged cardiopulmonary resuscitation in pre-hospital setting.

BACKGROUND: There is no evidence that the advanced airway ventilation (AAV) method improves patient outcome in the pre-hospital cardiac arrest setting. OBJECTIVE: The aim of this study was to estimate the effectiveness of AAV vs. bag-mask ventilation (BMV) for cardiopulmonary arrest (CPA) patients, when administered by a licensed emergency medical technician in the pre-hospital setting. METHODS: The study used the database of patients who suffered out-of-hospital cardiogenic CPA from 2006 to 2007 in our hospital. Patient records were searched for the method of pre-hospital airway management (BMV or AAV) and the patient's outcomes were compared between groups. The primary endpoint was a favorable neurological outcome; the secondary endpoints were rate of return of spontaneous circulation (ROSC) and rate of admission to the intensive care unit (ICU). RESULTS: A total of 355 CPA patients (156 BMV and 199 AAV) were retrospectively enrolled. There was no significant difference in demographics between the two groups. The transportation time exceeded 30 min in both groups. The overall ROSC rate and ICU admission rate were significantly higher in the AAV group (p = 0.0352 and p = 0.0089, respectively). The data showed that AAV (odds ratio 1.960; 95% confidence interval 1.015-3.785) resulted in a higher overall ROSC rate than BMV, but there were no significant differences in either the rate of pre-hospital ROSC or in favorable neurological outcome. CONCLUSION: AAV may yield advantages over BMV in the overall rate of ROSC in CPA patients, but both approaches for airway management in this study resulted in a comparably favorable neurological outcome. Earlier ROSC would be required for improved overall outcome.

Change in brain glucose after enteral nutrition in subarachnoid hemorrhage.

BACKGROUND: The alteration of brain extracellular glucose after enteral nutrition (EN) remains unclear. In this study, we used brain microdialysis methods to estimate whether the physiologic elevation of plasma glucose following EN affects brain glucose metabolism of aneurysmal subarachnoid hemorrhage (SAH) patients. METHODS: Brain extracellular glucose, lactate, glycerol, glutamate, and pyruvate were measured with a brain microdialysis probe in 12 patients (mean age: 60.0 y+/-7.8 y) after SAH. The EN was initially administered a mean of 3.2 d after the onset of SAH. All of the measured parameters were estimated before and after EN. RESULTS: Cerebral perfusion pressure did not significantly change after SAH during the study period. Plasma glucose rose significantly after EN (141.4+/-11.6mg/dL before EN versus 183.8+/-26.2mg/dL immediately after EN (P=0.0006), 177.7+/-30.2mg/dL at 2h after EN (P=0.0033)). The brain extracellular glucose before EN (2.5+/-0.92mmol/L) was significantly lower than the levels measured just after (3.49+/-1.0mmol/L, P=0.0186) and 2h after the end of EN (3.70+/-1.0mmol/L, P=0.0053). Brain extracellular concentrations of lactate, glutamate, pyruvate, and glycerol showed no significant changes. CONCLUSIONS: Brain extracellular glucose increased after the transient elevation of plasma glucose following EN. These results suggest that brief, physiologic elevations in plasma glucose after EN produced no changes in brain extracellular glutamate concentration or lactate/pyruvate ratio. These data may help determine the plasma glucose levels most effective for avoiding brain metabolic acidosis in patients after SAH. It remains unclear, however, how SAH itself influences these findings.

The peculiar processing of pancreatic hormone glucagon seen in traumatized patients.

BACKGROUND/AIM: The kinetics of the pancreatic hormone glucagon in traumatized patients has not been minutely investigated as well as that of insulin, despite its significant influence on energy metabolism. In the present study, we examined the kinetics of glucagon and glucagon-related peptides assessed by radioimmunoassay, and the molecular forms of these peptides using gel filtration chromatography. In addition, we discuss glucagon processes in the pancreas and intestine in traumatized patients in the early operative days. METHODOLOGY: Twelve traumatized patients who had undergone emergency surgery were enrolled in this study (group S). Ten healthy volunteers were also enrolled as normal control subjects (group C). The serum level of glucagon and glucagon-related peptides were assessed in the early morning fasting state in both groups, on the second postoperative day in group S, using the glucagon nonspecific N-terminal (glucagon-like immunoreactivity [GLI]) and specific C-terminal (immunoreactive glucagon [IRG]) radioimmunoassays. The molecular forms of these peptides were also estimated using the gel filtration chromatography method. RESULTS: Serum IRG in group S was significantly high compared with that of group C (P < .05). Serum GLI was not significantly different between both groups. In all 12 patients in group S, a peculiar glicentin-like peptide (GLLP: MW approximately 8000 Da) other than pancreatic glucagon was seen on gel filtration chromatography, which was not seen in group C. CONCLUSIONS: The kinetics and processing of glucagon in traumatized patients was different from those of healthy subjects. In traumatized patients, the peculiar processing of glucagon was processed in the intestine, which is different from the ordinary glucagon processing either in the pancreas or the intestine, generating a peculiar glicentin-like peptide (GLLP).

Supernormal Antithrombin Activity Is an Independent Predictor of In-Hospital Mortality in Patients With Sepsis: A Retrospective Observational Study.

Supernormal antithrombin (AT) activity is rare in patients with sepsis. This study compared mortality rate of patients with sepsis and supernormal AT activity with that of other patients. This retrospective study included patients with sepsis from 42 intensive care units (ICUs) in Japan. Patients were included if their AT activity was measured on ICU admission, and if they did not receive AT concentrate. They were categorized into low, normal, and supernormal with respective AT activity of ≤70%, >70% to ≤100%, and >100%. The primary outcome was hospital in-patient mortality. Nonlinear regression analysis showed that mortality risk gradually increased with AT activity in the supernormal range, but without statistical significance. Survival rate was significantly lower in low (67%) and supernormal (57%) AT groups than in the normal AT group (79%; P < .001 and P = .008, respectively). After adjusting for disease severity and AT activity on day 2, supernormal AT activity was the only independent predictor of mortality. Sepsis with supernormal AT activity associated with high mortality, independent of disease severity, might be a predictor of in-hospital mortality.

Acute subdural hematoma because of boxing.

BACKGROUND: To identify factors determining the clinical characteristics and prognosis of acute subdural hematoma (ASDH) arising from boxing injuries by comparing with ASDH due to any nonboxing cause. METHODS: Two groups were selected for this study: 10 patients with ASDH because of boxing injuries and 26 patients with nonboxer ASDH. All of the patients underwent neurologic examination by neurosurgeons. Primary resuscitation and stabilization as well as operative therapy were performed to all patients according to the European Brain Injury Consortium Guidelines. Two groups were compared in terms of age, the Glasgow Coma Scale at admission, neurologic findings, craniogram and brain computed tomography scan findings, operative findings, and prognosis. As potential prognostic indicators for boxers, the time interval until surgery, the Glasgow Outcome Scale, hematoma thickness, midline shift, and the site of bleeding were analyzed. RESULTS: The characteristics of patients because of boxing injuries are that patients were younger, had lucid interval, and had no cerebral contusion or contralateral brain injury. There was no significant difference in initial Glasgow Coma Scale, hematoma thickness, midline shift, and their prognosis. The most peculiar clinical presentation of boxers' ASDH was that all bleedings were limited from "bridging veins" or "cortical veins." The prognosis of boxers was most closely correlated with the site of bleeding (r2 = 0.81; p = 0.0001) and the midline shift (r2 = 0.67; p = 0.007). CONCLUSIONS: Our study shows that ASDH because of boxing is characterized by bleeding from bridging or cortical veins, and that the site of bleeding is a significant determinant of their prognosis.

Characterization of multicomponent crystal formed between indomethacin and lidocaine.

PURPOSE: Crystalline complex was formed between indomethacin (IDM) and lidocaine (LDC) at molar ratio 2:1 from ethanol solution. The purpose of this study was elucidation of an interactive manner between IDM and LDC in ethanol solution and mechanism of the complex formation through solid state as well as liquid state. METHODS: The chemical and physical nature of the complex was clearly elucidated by the alliance of powder X-ray diffractometry, differential scanning calorimetry, and infrared spectroscopy. The complex was also formed via solid-state reaction by cogrinding and heating treatment without any solvent. RESULTS: The complexation process was estimated to be as follows: (i) mixing and contact of two components, (ii) disorder of crystalline LDC by grinding or fusion, and then (iii) crystal growth by heating. In addition, 1H-NMR coupled with microchanneled cell for synthesis monitoring revealed that a primary interactive force between IDM and LDC molecule was coulomb energy.

Decreased activated protein C levels as a clinical predictor in patients with ST-elevation myocardial infarction.

BACKGROUND: Circulating markers that indicate atherosclerotic plaque instability may have diagnostic and prognostic value in patients with acute coronary syndromes. We evaluated activated protein C (APC), which has antithrombotic, anti-inflammatory, and profibrinolytic properties, as a possible clinical predictor in ST-elevation myocardial infarction (STEMI), including return of spontaneous circulation after sudden cardiac arrest. METHODS: Patients with STEMI whose APC level was measured upon arrival at the emergency room were enrolled in this study (n=335). The primary end point was inhospital death from any cause. RESULTS: The APC level ranged from 29% to 142% with a median of 80%. The unadjusted death rate increased in a stepwise fashion with decreasing APC levels (33.7% in quartile 1, 12.7% in 2, 6.0% in 3, and 3.6% in 4, P<.001). This association remained significant in subgroups of patients with STEMI only (P=.04) or with return of spontaneous circulation (P=.01). After adjusting for independent predictors of inhospital death, the odds ratio for death among those in the first quartile of APC levels was 9.4 (95% CI 1.1-81.6, P=.04). A cutoff APC level of 65% had the highest combined sensitivity and specificity in predicting death. CONCLUSIONS: Measuring APC levels provides predictive information for use in risk stratification across the STEMI spectrum. Decreased APC levels may be a unifying feature among patients at high risk for death after STEMI.

Hyperglycemia and lipopolysaccharide decrease depression effect of interleukin 8 production by hypothermia: an experimental study with endothelial cells.

OBJECTIVE: This study assessed whether hyperglycemia and lipopolysaccharide (LPS) decrease the depression effect of interleukin (IL) 8 production by hypothermia in endothelial cells. DESIGN AND SETTING: Laboratory study in a university laboratory. SUBJECTS: Human umbilical vein endothelial cells (HUVECs). INTERVENTIONS: HUVECs were cultivated in various concentrations of glucose (5.5 or 16.5mM = 100 or 300mg/dl) with or without LPS stimulation for 5, 12, or 24h at either 30 degrees or 37 degrees C. RESULTS: After culturing, IL-8 mRNA expressions and IL-8 levels were measured. At 37 degrees C, hyperglycemia significantly increased basal IL-8 mRNA at 12h and basal IL-8 at 24h. At 37 degrees C hyperglycemia significantly increased LPS-stimulated IL-8 mRNA at 12h and LPS-stimulated IL-8 at 12 and 24h. At 30 degrees C basal IL-8mRNA, basal IL-8, and LPS-stimulated IL-8 were significantly decreased by hypothermia, but these hypothermic effects were not observed in LPS-stimulated IL-8 mRNA. Furthermore even at 30 degrees C hyperglycemia significantly increased LPS-stimulated IL-8 mRNA at all time points and LPS stimulated IL-8 at 24h. CONCLUSIONS: Hypothermia (30 degrees C) decreases the production of IL-8 in HUVECs but does not decrease the expression of IL-8 mRNA. When hypothermia is followed by hyperglycemia and LPS stimulation, such a combination may expose the patients to a high risk of secondary tissue damage during therapeutic hypothermia.

[The progress of therapeutic hypothermia for patients with comatose survivors of out-of-hospital cardiac arrest this century].

Two randomized clinical trials were reported using mild therapeutic hypothermia following cardiac arrest in the 2002. One is the multicenter randomized clinical trial projected by The Hypothermia after Cardiac Arrest Study Group. The other one was performed by four centers in Australia. Two trials significantly showed better outcome in the hypothermia group compared with the normothermia group. There were some differences between Europe study and Australia study, although their outcome was doing very well. We will discuss cooling techniques (blanket or ice pack or cold saline intravenously), selection of patients (ventricular fibrillation or pulseless electrical activity or asystole), timing of cooling (as possible as earlier or within 3 hours or 6 hours) and monitoring in the hypothermia group in future. In addition, clinicians including cardiologists, intensivists, emergency physicians and neurologists, should work together to practice protocols for mild hypothermia treatment.

Inhibition of lipopolysaccharide stimulated interleukin-1beta production after subarachnoid hemorrhage.

PURPOSE: To identify the characteristics of cytokine production from peripheral blood mononuclear cells (PBMCs) in response to lipopolysaccharide (LPS) in patients with subarachnoid hemorrhage (SAH). METHODS: Blood samples were collected on the first day and 3 days after SAH (n = 12) to measure plasma concentrations of catecholamines, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-10. PBMCs from SAH patients or healthy volunteers were incubated with LPS (1 microg) for 24 hours. In the second phase, PBMCs from healthy volunteers (n = 6) were incubated with or without catecholamine (10 micromol/1) for 6 hours. After pre-treatment, the cells were treated with LPS (1 microg) for 18 hours. Supernatants were extracted and subjected to measurement by enzyme-linked immunosorbent assay. RESULTS: Plasma concentrations of epinephrine or dopamine prolong increased significantly 3 days after SAH, involved in elevation of plasma IL-10. In the PBMCs from the SAH patients, LPS-stimulated IL- 10 production was inhibited significantly. Pre-treatment with epinephrine or dopamine inhibited LPS-stimulated IL-1beta production significantly in the PBMCs from the healthy volunteers. CONCLUSIONS: The initial SAH involved in an impaired production of pro-inflammatory cytokines in response to LPS with an elevation of plasma epinephrine, dopamine and IL-10 after acute stressful conditions. This phenomenon may play an important role of an early immnosupression in patients with poor grade SAH.

The effects of neurotensin in the colon of patients with slow transit constipation.

BACKGROUND/AIMS: The cause of dysmotility in the colon of patients with slow transit constipation (STC) is still unknown. Neurotensin (NT) has recently been shown to be a neurotransmitter in the non-adrenergic non-cholinergic (NANC) excitatory nerves of the human alimentary tract. To clarify the physiological significance of NT in the colon of patients with STC, we examined the enteric nerve responses in lesional and normal bowel segments derived from patients with STC and patients who underwent colon resection for colonic cancers. METHODOLOGY: Twenty-eight preparations were taken from colonic lesions in 10 patients with slow transit constipation (2 men and 8 women, aged 23 to 70 years, mean 46.3 years). Forty-six preparations were taken from the normal colons of 16 patients with colonic cancer (8 men and 8 women, aged 40 to 66 years, mean 50.1 years). A mechanographic technique was used to evaluate in vitro muscle responses to electrical field stimulation (EFS) before and after treatment with various autonomic nerve blockers and NT. RESULTS: After blocking both the adrenergic and cholinergic nerves (Experiment 1), NT showed contraction reaction on both normal and STC colons in a concentration-dependent manner. The contraction reactions to NT in the normal colon were more dominant than those in the STC colon. There were significant differences between the frequency of contraction reactions to NT in normal colon strips and those in STC colon strips (P < 0.001). Following addition of tetrodotoxin (Experiment II), all muscle strips of normal and STC colons demonstrated contraction responses by NT. The effects of NT in the normal and STC colon muscle strips were essentially the same as in experiment 1, although the extent of contraction was somewhat diminished. CONCLUSIONS: Those results suggested that NT acts both via NANC excitatory nerves and also directly on the colonic smooth muscle. A decrease of NT mediates NANC excitatory nerves and plays an important role in the dysmotility observed in the colons of patients with STC.

Changes in glucagon kinetics and processing in patients with acute pancreatitis.

BACKGROUND/AIMS: The kinetics of the pancreatic hormone glucagon in patients with acute pancreatitis have not been investigated as carefully as those of insulin, in spite of its crucial influence on energy metabolism. In the present study, we studied the kinetics of glucagon and glucagon-related peptides assessed by radioimmunoassay. Furthermore, the molecular forms of these peptides were examined using gel filtration chromatography, and the glucagon processes in the pancreas and intestine in the early stage in patients with acute pancreatitis were investigated. METHODOLOGY: Fourteen patients with acute pancreatitis were enrolled in this study. Eight had severe pancreatitis (group S) and six had mild pancreatitis (group M). Ten healthy volunteers were also enrolled as the normal control (group C). Serum levels of glucagon and glucagon-related peptides were assessed on the second admission day in groups S and M, and in an early morning fasting state in group C, using glucagon non-specific N-terminal (glucagon-like immunoreactivity: GLI) and specific C-terminal (immunoreactive glucagon: IRG) radioimmunoassays. The molecular forms of these peptides were also estimated using gel filtration chromatography. We then discuss the glucagon processes based on these findings. RESULTS: Serum GLI and IRG in groups S and M were significantly higher than those of group C (P < 0.01), while those in group S were also significantly higher than those in group M (P < 0.05). In all patients in groups S and M, except for only three in group S, a peculiar glicentin-like peptide (GLLP: MW about 8000) other than pancreatic glucagon was observed in IRG gel filtration chromatography, which was clearly absent from group C. CONCLUSIONS: The kinetics and processing of glucagon in patients with acute pancreatitis were quite different from those of healthy subjects. In patients with acute pancreatitis, the peculiar processing of glucagon proceeded in the intestine quite differently from ordinary glucagon processing either in the pancreas or in the intestine, generating a peculiar GLLP.

Regulation of enteric nervous system in the proximal and distal parts of the normal human pyloric sphincter--in vitro study.

BACKGROUND/AIMS: The structure of the pyloric sphincter (PS) muscle has recently been shown to divide into two parts (proximal and distal parts). To clarify the functional differences in the human PS between proximal and distal parts, we investigated the enteric nerve responses in normal proximal and distal PS specimens. METHODOLOGY: Normal PS specimens derived from 20 patients with early gastric cancer (13 men and 7 women aged from 50 to 64 years, average 58.2 years) were used. These PS muscles were divided into 2 parts [1/2 oral site of PS; proximal part (PPS; n=26), 1/2 anal site of PS; distal part (DPS; n=24)]. A mechanographic technique was used to evaluate in vitro muscle strip responses to electrical field stimulation (EFS) before and after treatment with various autonomic nerve blockers. RESULTS: Findings were: (1) Response to EFS before blockade of the adrenergic and cholinergic nerves: Excitatory responses (contraction reaction) via cholinergic nerves in the PPS were regulated more predominantly than in the DPS. Inhibitory responses (relaxation reaction) via adrenergic nerves in the DPS were regulated more predominantly than in the PPS. (2) Response to EFS after blockade of the adrenergic and cholinergic nerves: Excitatory responses (contraction reaction) via non-adrenergic non-cholinergic (NANC) excitatory nerves in the PPS were regulated significantly more than in the DPS (P = 0.0439). Inhibitory responses (relaxation reaction) via NANC inhibitory nerves in the DPS were also regulated significantly more than in the PPS (P = 0.0439). (3) EFS response in the pylorus was blocked by tetrodotoxin. CONCLUSIONS: There are differences between the PPS and DPS in the regulation of the enteric nervous system. Contraction reaction via excitatory nerves, especially cholinergic nerves, was mainly involved in the regulation of enteric nerve responses to EFS in the PPS. Relaxation reaction via inhibitory nerves, especially NANC inhibitory nerves, was mainly involved in the regulation of enteric nerve responses to EFS in the DPS.

Changes in glucagon processing occurring in the intestines of surgically stressed patients.

BACKGROUND/AIMS: The kinetics of the pancreatic hormone glucagon in surgically stressed patients has not been investigated as thoroughly as that of insulin, despite its significant influence on energy metabolism in surgically stressed conditions. In the present study, we examined the kinetics of glucagon and glucagon-related peptides assessed by radioimmunoassay, and the molecular forms of these peptides using gel filtration chromatography, and in addition discuss glucagon processes in the pancreas and intestine in surgically stressed patients. METHODOLOGY: Ten patients who had undergone abdominal surgery for acute abdominal disorders were enrolled in this study (group S). Ten healthy volunteers were also enrolled as normal controls (group C). The serum level of glucagon and glucagon-related peptides were assessed in the early morning fasting state in both groups, on the second postoperative day in group S, using glucagon nonspecific N-terminal (glucagon-like immunoreactivity: GLI) and specific C-terminal (immunoreactive glucagon: IRG) radioimmunoassays. The molecular forms of these peptides were also estimated using the gel filtration chromatography method. RESULTS: Serum IRG in group S was significantly higher than that of group C (P < 0.05). Serum GLI was not significantly different between the two groups. In all patients except one in group S, a peculiar glicentin-like peptide (GLLP: MW about 8000) other than pancreatic glucagon was seen in gel filtration chromatography, which was not seen in group C. CONCLUSIONS: The kinetics and processing of glucagon in surgically stressed patients were quite different from those of healthy subjects. In surgically stressed patients, peculiar processing of glucagon occurred in the intestine, which was quite different from ordinary glucagon processing either in the pancreas or the intestine, generating GLLP.

The expression of the inducible nitric oxide synthase messenger RNA on monocytes in severe acute pancreatitis.

BACKGROUND/AIMS: Although there have been numerous studies that nitric oxide (NO) is produced in monocytes and macrophages in animal models, it still remains controversial whether NO is produced by human monocytes and macrophages. To clarify whether NO is produced by human monocytes in patients with systemic inflammatory response syndrome (SIRS), we examined the expression of inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) and constitutive nitric oxide synthase (cNOS) mRNA in cultured monocytes derived from severe acute pancreatitis patients complicated with SIRS. METHODOLOGY: Monocytes were harvested from peripheral blood of nine severe acute pancreatitis patients with SIRS (group S) and five mild acute pancreatitis patients with no SIRS (group M). Then we examined the expression of iNOS mRNA and cNOS mRNA in cultured monocytes using the reverse transcription PCR (RT-PCR) method. RESULTS: iNOS mRNA was expressed in the cultured monocytes derived from eight of the nine patients in group S, but not in any of the five patients in group M, while cNOS mRNA was not found in cultured monocytes derived from any patient in either group. CONCLUSIONS: Although it is still not clear whether NO is produced in human monocytes or not, these findings indicate that iNOS is induced in monocytes in severe acute pancreatitis patients with SIRS, but not in mild pancreatitis patients.

Reduced effectiveness of hypothermia in patients lacking the wave V in auditory brainstem responses immediately following resuscitation from cardiac arrest.

AIMS: Therapeutic hypothermia appears to improve the outcome of pre-hospital cardio-pulmonary arrest (CPA) in patients with an initial cardiac rhythm of ventricular fibrillation or nonperfusing ventricular tachycardia (VF/VT). Notwithstanding, the outcome of this procedure is certainly difficult to predict based solely on the initial rhythm. The aim of the present study was to predict the outcome using auditory brainstem responses (ABRs) in CPA patients treated with therapeutic hypothermia. DESIGN AND SETTING: A prospective observational study in the intensive care unit of a university hospital. PATIENTS: The study included 26 patients resuscitated from out-of-hospital CPA. INTERVENTIONS: Basic and advanced cardiac life support, intensive care and post-resuscitative hypothermia. MEASUREMENT AND RESULTS: ABRs were recorded immediately after the return of spontaneous circulation (ROSC). An ABR wave V was recorded in 16 patients. Among 8 patients with a favourable outcome, the initial rhythms were VF/VT in 6 patients and other rhythms in 2. All 10 patients without a detectable ABR wave V had an unfavourable outcome. The VF/VT as the initial arrest rhythm and the presence of wave V were significantly (p = 0.0095) correlated with a favourable outcome. The presence of wave V had a 100% sensitivity to a favourable outcome. CONCLUSION: The absence of the ABR wave V in the early phase after ROSC wave indicated a reduced effect of therapeutic hypothermia, even in cases that underwent hypothermia promptly after out-of-hospital CPA. Measurement of ABRs appears to be useful as a predictor of effectiveness and as a criterion for determining the indication for therapeutic hypothermia.