Gene delivery to dendritic cells by orally administered recombinant Saccharomyces cerevisiae in mice.

DNA vaccination has caught the attention of many for triggering humoral as well as cellular immune responses. And delivering DNA into the antigen presenting cells (APCs) in order to induce efficient immunoresponse has become the backbone of this field. It has been confirmed that Saccharomyces cerevisiae, though non-pathogenic, is being engulfed by the dendritic cells and macrophages and delivers not only proteins, but also DNA materials (already confirmed in vitro). In this research, S. cerevisiae is used to deliver green fluorescent protein (GFP) reporter gene controlled under cytomegalovirus (CMV) promoter in living organism (mice). The recombinant yeast, transfected with the plasmid containing the GFP gene, was heat killed and orally administered to mice. After 60 h of yeast administration, mice were sacrificed and intestine was separated, washed and frozen in liquid nitrogen. Tissues were cut at the size of 10 µm using Cryostat machine, and GFP expression was successfully detected under a fluorescence microscope. After 45 days Western blot was able to detect GFP antibody in the blood of mice. These results imply that S. cerevisiae, being non-pathogenic, cheap, and easy to culture could be a good candidate to deliver DNA materials to the immune cells for vaccination.

PGE2 suppresses NK activity in vivo directly and through adrenal hormones: effects that cannot be reflected by ex vivo assessment of NK cytotoxicity.

Surgery can suppress in vivo levels of NK cell cytotoxicity (NKCC) through various mechanisms, including catecholamine-, glucocorticoid (CORT)-, and prostaglandin (PG)-mediated responses. However, PGs are synthesized locally following tissue damage, driving proinflammatory and CORT responses, while their systemic levels are often unaffected. Thus, we herein studied the role of adrenal factors in mediating in vivo effects of PGs on NKCC, using adrenalectomized and sham-operated F344 rats subjected to surgery or PGE(2) administration. In vivo and ex vivo approaches were employed, based on intravenous administration of the NK-sensitive MADB106 tumor line, and based on ex vivo assessment of YAC-1 and MADB106 target-line lysis. Additionally, in vitro studies assessed the kinetics of the impact of epinephrine, CORT, and PGE(2) on NKCC. The results indicated that suppression of NKCC by epinephrine and PGE(2) are short lasting, and cannot be evident when these compounds are removed from the in vitro assay milieu, or in the context of ex vivo assessment of NKCC. In contrast, the effects of CORT are long-lasting and are reflected in both conditions even after its removal. Marginating-pulmonary NKCC was less susceptible to suppression than circulating NKCC, when tested against the xenogeneic YAC-1 target line, but not against the syngeneic MADB106 line, which seems to involve different cytotoxicity mechanisms. Overall, these findings indicate that elevated systemic PG levels can directly suppress NKCC in vivo, but following laparotomy adrenal hormones mediate most of the effects of endogenously-released PGs. Additionally, the ex vivo approach seems limited in reflecting the short-lasting NK-suppressive effects of catecholamines and PGs.

Compromising bradycardia: management in the emergency department.

AIM OF THE STUDY: Bradycardia may represent a serious emergency. The need for temporary and permanent pacing is unknown. METHODS: We analysed a registry for the incidence, symptoms, presenting rhythm, underlying mechanism, management and outcome of patients presenting with compromising bradycardia to the emergency department of a university hospital retrospectively during a 10-year period. RESULTS: We identified 277 patients, 173 male (62%), median age 68 (IQR 58-78), median ventricular rate 33 min(-1) (IQR 30-40). The leading symptoms were syncope [94 (33%)], dizziness [61 (22%)], collapse [46 (17%)], angina [46 (17%)] and dyspnoea/heart failure [30 (11%)]. The initial ECG showed high grade AV block [134 (48%)], sinus bradycardia/AV block [46 (17%)], sinuatrial arrest [42 (15%)], bradycardic atrial fibrillation [39 (14%)] and pacemaker-failure [16 (6%)]. The underlying mechanisms were primary disturbance of cardiac automaticity and/or conduction [135 (49%)], adverse drug effect [58 (21%)], acute myocardial infarction [40 (14%)], pacemaker failure [16 (6%)], intoxication [16 (6%)] and electrolyte disorder [12 patients (4%)]. In 107 (39%) patients bed rest resolved the symptoms. Intravenous drugs to increase ventricular rate were given to 170 (61%) patients, 54 (20%) required additional temporary transvenous/transcutaneous pacing. Two severely intoxicated patients could be stabilised only by cardiopulmonary bypass. A permanent pacemaker was implanted in 137 patients (50%). Mortality was 5% at 30 days. CONCLUSION: In our cohort, about 20% of the patients presenting with compromising bradycardia required temporary emergency pacing for initial stabilisation, in 50% permanent pacing had to be established.

Major bleeding complications after cardiopulmonary resuscitation: impact of thrombolytic treatment.

OBJECTIVE: The risk of bleeding complications caused by thrombolysis in patients with cardiac arrest and prolonged cardiopulmonary resuscitation is unclear. We evaluate the complication rate of systemic thrombolysis in patients with out-of-hospital cardiac arrest caused by acute myocardial infarction, especially in relation to duration of cardiopulmonary resuscitation. DESIGN: The study was designed as retrospective cohort study, the risk factor being systemic thrombolysis and the end-point major haemorrhage, defined as life-threatening and/or need for transfusion. Over 10.5 years, emergency cardiac care data, therapy, major haemorrhage and outcome of 265 patients with acute myocardial infarction admitted to an emergency department after successful cardiopulmonary resuscitation were registered. RESULTS: We observed major haemorrhage in 13 of 132 patients who received thrombolysis (10%, 95% confidence interval 5-15%), five of these survived to discharge, none died because of this complication. Major haemorrhage occurred in seven of 133 patients in whom no thrombolytic treatment had been given (5%, 95% confidence interval 1-9%), two of these survived to discharge. Taking into account baseline imbalances between the groups, the risk of bleeding was slightly increased if thrombolytics were used (odds ratio 2.5, 95% confidence interval 0.9-7.4) but this was not significant (P = 0.09). There was no clear association between duration of resuscitation and bleeding complications (z for trend = 1.52, P = 0.12). Survival was not significantly better in patients receiving thrombolysis (odds ratio 1.6, 0.9-3.0, P = 0.12). CONCLUSIONS: Bleeding complications after cardiopulmonary resuscitation are frequent, particularly in patients with thrombolytic treatment, but do not appear to be related to the duration of resuscitation. In the light of possible benefits on outcome, thrombolytic treatment should not be withheld in carefully selected patients.

Spontaneous subarachnoid haemorrhage as a cause of out-of-hospital cardiac arrest.

OBJECTIVE: Spontaneous subarachnoid haemorrhage as a cause of out-of-hospital cardiac arrest is poorly evaluated. We analyse disease-specific and emergency care data in order to improve the recognition of subarachnoid haemorrhage as a cause of cardiac arrest. DESIGN: We searched a registry of cardiac arrest patients admitted after primarily successful resuscitation to an emergency department retrospectively and analysed the records of subarachnoid haemorrhage patients for predictive features. RESULTS: Over 8.5 years, spontaneous subarachnoidal haemorrhage was identified as the immediate cause in 27 (4%) of 765 out-of-hospital cardiac arrests. Of these 27 patients, 24 (89%) presented with at least three or more of the following common features: female gender (63%), age under 40 years (44%), lack of co-morbidity (70%), headache prior to cardiac arrest (39%), asystole or pulseless electric activity as the initial cardiac rhythm (93%), and no recovery of brain stem reflexes (89%). In six patients (22%), an intraventricular drain was placed, one of them (4%) survived to hospital discharge with a favourable outcome. CONCLUSIONS: Subarachnoid haemorrhage complicated by cardiac arrest is almost always fatal even when a spontaneous circulation can be restored initially. This is due to the severity of brain damage. Subarachnoid haemorrhage may present in young patients without any previous medical history with cardiac arrest masking the diagnosis initially.

Pulmonary embolism as a cause of cardiac arrest: presentation and outcome.

BACKGROUND: Pulmonary embolism (PE) is a possible noncardiac cause of cardiac arrest. Mortality is very high, and often diagnosis is established only by autopsy. METHODS: In a retrospective study, we analyzed clinical presentation, diagnosis, therapy, and outcome of patients with cardiac arrest after PE admitted to the emergency department of an urban tertiary care hospital. RESULTS: Within 8 years, PE was found as the cause in 60 (4.8%) of 1246 cardiac arrest victims. The initial rhythm diagnosis was pulseless electrical activity in 38 (63%), asystole in 19 (32%), and ventricular fibrillation in 3 (5%) of the patients. Pronounced metabolic acidosis (median pH, 6.95, and lactate level, 16 mmol/L) was found in most patients. In 18 patients (30%), the diagnosis of PE was established only postmortem. In 42 (70%) it was diagnosed clinically, in 24 of them the diagnosis of PE was confirmed by echocardiography. In 21 patients, 100 mg of recombinant tissue-type plasminogen activator was administered as thrombolytic treatment, and 2 (10%) of these patients survived to hospital discharge. Comparison of patients of the thrombolysis group (n = 21) with those of the nonthrombolysis group (n = 21) showed a significantly higher rate of return of spontaneous circulation (81% vs 43%) in the thrombolysis group (P=.03). CONCLUSIONS: Mortality related to cardiac arrest caused by PE is high. Echocardiography is supportive in determining PE as the cause of cardiac arrest. In view of the poor prognosis, thrombolysis should be attempted to achieve return of spontaneous circulation and probably better outcome.

Acute renal infarction. Clinical characteristics of 17 patients.

We analyzed the medical records of patients with an established diagnosis of acute renal infarction to identify predictive parameters of this rare disease. Seventeen patients (8 male) who were admitted to our emergency department between May 1994 and January 1998 were diagnosed by contrast-enhanced computed tomography (CT) as having acute renal infarction (0.007% of all patients). We screened the records of the 17 patients for a history with increased risk for thromboembolism, clinical symptoms, and urine and blood laboratory results known to be associated with acute renal infarction. A history with increased risk for thromboembolism with 1 or more risk factors was found in 14 of 17 patients (82%); risk factors were atrial fibrillation (n = 11), previous embolism (n = 6), mitral stenosis (n = 6), hypertension (n = 9), and ischemic cardiac disease (n = 7). All patients reported persisting pain predominantly from the flank (n = 11), abdomen (n = 4), and lower back (n = 2). On admission, elevated serum lactate dehydrogenase was found in 16 (94%) patients, and hematuria was found in 12 (71%) of 17 patients. After 24 hours all patients showed an elevated serum lactate dehydrogenase, and 14 (82%) had a positive test for hematuria. Our findings suggest that in all patients presenting with the triad--high risk of a thromboembolic event, persisting flank/abdominal/lower back pain, elevated serum levels of lactate dehydrogenase and/or hematuria within 24 hours after pain onset--contrast-enhanced CT should be performed as soon as possible to rule out or to prove acute renal infarction.

Causes and outcome of syncope.

BACKGROUND: Little is known about the frequency of patients presenting to the emergency department with syncope. Regarding mortality and predictors of outcome the literature remains inconclusive. AIMS: The aims of the study were to determine the frequency of patients presenting with syncope to an emergency department, to assess mortality among these patients and to determine potential predictors of poor outcome. METHODS: Data of all consecutive patients who were treated at our emergency department between January 1st 1994 and September 1st 1997 following syncope were collected retrospectively. The presumptive causes of syncope were classified into six categories (cardiogenic, neurogenic, autonomic dysfunction, psychiatric, toxic/alcoholic, idiopathic/unexplained). Patients were followed until December 31st, 1997. RESULTS: 701 patients (0.35% of all emergency department visits) were treated for this reason. 507 patients were eligible for the study. During follow-up 8% (n = 38) of the patients died. Three patients died within the first 28 days, all with a known severe underlying disease (congestive heart failure, malignancy, ischemic cerebral infarction). Non-survivors more frequently had a cardiogenic (34%) or neurogenic (13%) cause of syncope (p < 0.01). Age > 60 years, syncope due to neurogenic cause and abnormal ECG findings were independent predictors of increased mortality. CONCLUSIONS: Patients with syncope only comprise a small proportion of those seen at the emergency department. Mortality among these patients is 8%. Clinical history and ECG findings are major determinants of risk stratification: Age > 60 years, syncope due to neurogenic causes and abnormal ECG are independent predictors of poor outcome.

Accuracy and impact of presumed cause in patients with cardiac arrest.

BACKGROUND: International guidelines recommend differentiation between cardiac and noncardiac causes of cardiac arrest. The aim of this study was to find the rate of agreement between primarily postulated and definitive causes of cardiac arrest. METHODS AND RESULTS: We retrospectively analyzed the primarily presumed cause of cardiac arrest as determined by the emergency room physician on admission in all patients admitted to the emergency department of one urban tertiary care hospital. This was compared with the definitive cause as established by clinical evidence or autopsy. Within 4 years, the initially presumed cause was unclear in 24 (4%) of 593 patients. In the remaining 569 patients, the presumed cause was correct in 509 (89%) and wrong in 60 (11%) cases. Cardiac origin was presumed in 421 (71%) and the definitive cause in 408 (69%) cases. Noncardiac origin was presumed in 148 (25%) and the definitive cause in 185 (31%) patients. Presumed cardiac cause was sensitive (96%) but less specific (77%). Noncardiac causes such as pulmonary embolism, cerebral disorders, or exsanguination were those most frequently overlooked. Asystole occurred significantly more often in patients in whom presumed cause remained undetermined or differed from the definitive cause. CONCLUSIONS: Cause of cardiac arrest is not as easily recognized as anticipated, especially when the initial rhythm is different from ventricular fibrillation. This might affect comparability of study results, therapeutic strategies, prognosis, and outcome. Patients in whom the presumed cause was confirmed as being correct had significantly better survival and neurological outcome.

Successful automatic external defibrillator operation by people trained only in basic life support in a simulated cardiac arrest situation.

OBJECTIVE: To show whether in an in-hospital cardiac arrest, early defibrillation can also be performed by hospital staff trained only in basic life support. BACKGROUND: The International Liaison Committee on Resuscitation (ILCOR) endorses the concept that in many settings non-medical individuals should be allowed and encouraged to use defibrillators. METHODS: Five different groups of hospital staff were evaluated whether they were able to correctly operate an automatic external defibrillator in a simulated sudden cardiac arrest situation without any prior instruction. The participants were assigned either to the 'basic life support-trained' group (BLS, n = 40, or to the 'advanced life support-trained' group (ALS, n = 40). RESULTS: All persons of the 'only BLS-trained' group delivered the three sequential ('stacked') shocks with the automatic external defibrillator when persistent ventricular fibrillation was simulated. The 'ALS-trained' persons successfully delivered the three shocks with the automatic external defibrillator in 98% of the cases. When this group used a conventional defibrillator, only 88% were able to deliver the three shocks, however they were able to do it significantly more quickly. CONCLUSION: Using an automatic defibrillator without any prior instruction, even persons trained only in BLS were able to deliver three sequential shocks in a simulated persistent ventricular fibrillation cardiac arrest.

Analysing calls by lay persons reporting cardiac arrest.

Prior to establishing a protocol for pre-arrival instructions for cardio-pulmonary resuscitation in the Vienna emergency medical system dispatch centre, a study was performed to determine whether any problems exist which may compromise guidance for basic life-support on the telephone. To evaluate the feasibility of prearrival instructions, a retrospective analysis of cardiac arrest calls was performed. We reviewed the Vienna emergency medical services dispatch centre tape recordings, ambulance run sheets and the hospital charts of 114 patients suffering from atraumatic cardiac arrest. Analysis showed that in 59 cases the arrest occurred in the victim's home. The telephone and the patient were either in the same or in adjoining rooms in 55% of the calls. We did not experience any technical or language difficulties. The caller and victim were related in 51 cases. The callers were completely calm in 77% and fairly calm in an additional 15%. Not one caller was distraught. Our data show that most objections to the feasibility of pre-arrival instructions can be refuted. We conclude that in Vienna the setting and location of arrest will impose few problems on the performance of bystander-cardio-pulmonary resuscitation using pre-arrival instructions given by dispatchers.

Conservative management of foreign bodies in the gastrointestinal tract.

There are at present no clear guidelines whether foreign body ingestion in the gastrointestinal tract should be managed conservatively, endoscopically or surgically. Retrospectively we have, therefore, analyzed 78 foreign body ingestion's in 42 patients (age 15-72 years) admitted to the Emergency Department of the University Hospital in Vienna. Our intention was to assess the value of a conservative management, defined as daily follow-up visits until the foreign body spontaneously appeared in the feces and to find criteria when endoscopic or surgical management is required. Of 78 foreign bodies, 67 (86%) passed the gastrointestinal tract spontaneously without complications, 9 (11%) were removed endoscopically, and only 2 (3%) required surgery. There were no gastrointestinal perforations. Even foreign bodies with a maximal length of 13.5 cm appeared in the feces spontaneously within a few days. Our data suggests that more than 80% of adults with foreign body ingestion can be managed safely as outpatients by means of conservative treatment. Endoscopic or surgical removal is only indicated in very rare circumstances.

Arterial blood pressure after human cardiac arrest and neurological recovery.

BACKGROUND AND PURPOSE: In animal cardiac arrest studies, outcome has been improved by inducing arterial hypertension early after return of spontaneous circulation. The aim of our study was to evaluate whether arterial blood pressure within the first minutes and hours after return of spontaneous circulation influences neurological recovery in human cardiac arrest survivors. METHODS: Of 136 retrospectively evaluated patients after sudden cardiac death, two groups were defined: group 1, mean arterial blood pressure (MABP) within 5 minutes after return of spontaneous circulation above 100 mm Hg; group 2, MABP of 100 mm Hg or less. Thereafter MABP was measured every 5 minutes until 2 hours after return of spontaneous circulation. The groups were compared in regard to age, sex, in/out of hospital, witnessed/not witnessed, first electrocardiographic rhythm, time from cardiac arrest to beginning of life support and to return of spontaneous circulation, cumulative epinephrine dose administered, and best neurological outcome within 6 months. RESULTS: In group 1 (n = 54) good neurological recovery was observed in 63% and in group 2 (n = 82) in 55% (chi 2 = 0.87, P = NS). Both groups exhibited comparable baseline values except that time intervals from beginning of life support to return of spontaneous circulation were shorter in group 1. After we controlled for this difference with Spearman's partial rank correlation (rs), there was no association between MABP measured within the first 5 minutes and outcome (rs = -.023; P = NS). Good neurological recovery was independently and directly related to MABP measured during 2 hours after return of spontaneous circulation (rs = .26; P < .01). CONCLUSIONS: In human cardiac arrest survivors, good functional neurological recovery was independently and positively associated with arterial blood pressure during the first 2 hours after human cardiac arrest but not with hypertensive reperfusion within the first minutes after return of spontaneous circulation.

Oxygen application: when and how?

Airway management, including oxygen application, is of prime importance in any emergency. This article explains the causes of hypoxemia and the importance of, equipment for, and techniques of oxygen administration. To readily cope with emergencies in the dental office, proper equipment must be maintained and staff members must be fully trained in emergency response mechanisms.

[Molecular biology in diagnosis and detection of deletion in Duchenne muscular dystrophy]. / Molekularbiologische Diagnostik und Deletionsnachweis bei Duchennescher Muskeldystrophie.

For the purpose of carrier identification and genetic counselling we investigated deletions of the Duchenne muscular dystrophy (DMD) gene in three families of patients with Duchenne muscular dystrophy. Using a limited number of probes of the DMD cDNA in Southern blots, we detected a deletion in only one patient. Additional methodology is necessary to warrant reliable identification of carriers and exact prenatal diagnosis.