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Allele-specific down-regulation of MHC class I antigens in Burkitt lymphoma lines.

We have reported that Burkitt lymphomas (BL) that arise in HLA-A11 positive individuals are resistant to lysis by HLA-A11-specific and HLA-A11-restricted CTLs(10,11). Here we show that this phenomenon can be explained by a selective loss of the HLA-A11 polypeptide. The HLA-A11 negative phenotype is due to a regulatory phenomenon, rather than a structural defect, as proven by the ability to rescue expression of HLA-A11 in in vitro Epstein-Barr virus (EBV)-converted sublines of EBV negative BLs.

Alleles↗

Selective induction of allostimulatory capacity after 5-azaC treatment of EBV carrying but not EBV negative Burkitt lymphoma cell lines.

Epstein-Barr virus (EBV) negative and EBV carrying Burkitt lymphoma (BL) lines that remain phenotypically similar to the in vivo tumor cells (operationally defined group I BLs) express high levels of CD10 and CD77, and lack immunoblastic markers such as CD23 and CD39, and the cell adhesion molecules CD11a, CD18, CD54 and CD58. This cell phenotype is associated with poor stimulatory capacity in allogeneic mixed lymphocytes cultures (MLC) [Avila-Carino et al. Int. J. Cancer 40, 691-697 (1987)] EBV carrying BL lines tend to drift spontaneously towards an immunoblastic phenotype in parallel with up-regulation of six EBV-encoded nuclear antigens (EBNA-2 to -6) and two membrane proteins (LMP-1 and -2). These viral antigens are characteristically expressed in all EBV transformed lymphoblastoid cell lines (LCLs) of normal B cell origin and can be induced in group I BL lines by treatment with the DNA demethylating agent 5-azacytidine (5-azaC) [Masucci et al. J. Virol. 65, 1558-1567 (1989)]. We have now studied the effect of 5-azaC on the induction of allogenic T cell proliferation by three EBV negative (Ramos, BL28 and BL41) and four EBV carrying BL lines (Rael, Eli, Chep and Mutu) which stably express a group I phenotype. Pre-treatment with 4-15 microM 5-azaC had no effect on the EBV negative cells but increased the stimulatory capacity of all four EBV carrying lines. LMP-1 was the only viral antigen regularly induced suggesting that its expression may be required for the increase of allostimulation. This was corroborated by the observation that LMP-1 transfection increased 35-70-fold the stimulatory capacity of Rael cells. The cell adhesion molecule CD54 was the only cellular marker selectively up-regulated in all cell lines with increased stimulatory capacity.

Antigens, CD↗

Lymphokine gene transcription in CD4+CD8- T cells of a type III bare lymphocyte syndrome patient.

In this study we analyzed the impact of a MHC class-II-deficient environment on the differentiation of CD4+CD8- T lymphocytes into functional defined subsets of lymphokine-producing T-helper cells. To this end a CD4+CD8- T-cell line and CD4+CD8- T-cell clones, isolated from PBMCs of a type III BLS patient, were stimulated in vitro with anti-CD3 and PMA and assessed for lymphokine transcription patterns. The results of these analyses show that CD4+CD8- T cells that have matured in a MHC class-II-deficient environment display lymphokine transcription patterns that resemble those of MHC class-II-expressing family control-derived CD4+CD8- T cells.

CD4 Antigens↗

Bystander cardiopulmonary resuscitation (CPR) in out-of-hospital cardiac arrest. The Cerebral Resuscitation Study Group.

Prevalence of bystander CPR and effect on outcome has been evaluated on 3053 out-of-hospital cardiac arrest (CA) events. Bystander CPR was performed in 33% of recorded cases (n = 998) by lay people in 406 cases (family members 178, other lay people 228) and by bystanding health care workers in 592 cases (nurses 86, doctors 506). Family members and lay people mainly applied CPR in younger CA victims at public places, roadside or at the working place. Sudden infant death syndrome (SIDS) and drowning are highly represented. Health care workers performed CPR mainly in older patients, at public places or at the roadside and especially in case of cardiac or respiratory origin. CA caused by trauma/exsanguination and intoxication/metabolic origin received less bystander CPR (23% resp. 22%). Cardiac arrests receiving bystander CPR are more frequently witnessed and have a shorter access time to the emergency medical service (EMS) system and shorter response time of basic life support (BLS). Advanced life support (ALS) response time is significantly longer. In witnessed arrests of cardiac origin receiving bystander CPR a significantly better late survival was observed. In non-witnessed arrests of cardiac origin early and late survival are significantly higher in patients receiving bystander CPR. In CA events where response time of ALS exceeds 8 min, the beneficial effect of bystander CPR is most significant. Furthermore no deleterious effect of bad technique or inefficient bystander CPR can be demonstrated.

Adult↗

Early effects of nimodipine on intracranial and cerebral perfusion pressures in cerebral anoxia after out-of-hospital cardiac arrest.

Some calcium entry blockers seem to improve the neurological survival of anoxic comas. The early monitoring of intracranial pressure shows the frequency of intracranial hypertension. A calcium channel blocker has been shown to increase the cerebral blood flow which can potentially lead to deleterious increases of the intracranial pressure. This study presents 39 out-of-hospital cardiac arrests resuscitated with success. The intracranial pressures were registered by means of an extra dural screw set up as soon as possible. Nineteen patients received an early continuous 5 days nimodipine treatment (0.58 gamma/kg weight/min. after a 12.3 gamma/kg weight bolus). The other 20 patients did not receive any calcium entry blocker. The two groups were similar in terms of age, origin and electrical type of cardiac arrest, duration of cardiac arrest before BLS and before ACLS, principles of the treatment, initial neurological status and biological values. The maximum and mean intracranial pressures of the nimodipine group were always lower than the intracranial pressure of the control group. The cerebral perfusion pressure was never significantly different in both groups. If the nimodipine treatment proves to be efficient on neurological survival, it would be all the more interesting because it seems to limit the intracranial hypertension phenomenon which aggravates the neurological prognosis.

Cerebrovascular Circulation↗

Factors influencing variable outcomes after ventricular fibrillation cardiac arrest of 15 minutes in dogs.

Animal experiments with cardiac arrest and cardiopulmonary resuscitation (CPR) despite controlled insult and postinsult life support, have yielded variable individual outcomes. This report concerns 10 dog experiments with a standardized model of VF cardiac arrest with no flow for 10 min followed by CPR basic life support (BLS) from VF 10 to 15 min and then CPR advanced life support (ALS) with epinephrine at 15 min. Defibrillating countershocks began at 17 min, for restoration of spontaneous circulation. After controlled ventilation to 20 h and intensive care to 96 h, outcome was evaluated using the overall performance category (OPC) 1 (normal) (n5) vs. OPC 2-4 (impaired) (n5) (P less than 0.001). We searched for correlations between normal vs. impaired outcome in various prearrest, arrest and postarrest factors that are suspected to influence postarrest neurologic deficit. Prearrest variables were similar in the normal and impaired groups. Resuscitation variables were similar in both. Coronary perfusion pressure during CPR-ALS was higher in the normal outcome group (P = 0.03). Among postarrest variables, postarrest reperfusion pressure pattern (initial hypertensive bout), blood glucose, cardiac output, Hct, pHa, PaO2 and PaCO2 were the same. Our data support the importance of maximizing coronary perfusion pressure not only for restoration of heart beat but also as a possible predictor of improved cerebral outcome.

Animals↗

Knowledge, skills and counselling behaviour of Belgian general practitioners on CPR-related issues.

General practitioners (GP) can identify potential cardiac arrest victims. They have the opportunity to inform cardiac patients and their families about the risk of sudden cardiac death and can motivate family members to attend a CPR-course. To study actual counselling practices concerning basic CPR-training a questionnaire was mailed to a representative sample of Belgian GPs (n = 1119). The level of CPR-training of the GPs was fairly good: 67% had received BLS training on a manikin and 63% had already attended a cardiac arrest event. A discrepancy was observed between the positive attitude towards CPR and the counselling of family members to attend a CPR-course (9%). GPs feared to inflict additional stress to the patient (32%) or the family (43%) or did not know where CPR courses were organised (37%). GPs are a primary target group for CPR-training and should learn how to counsel potential bystanders of a cardiac arrest to attend a CPR-course without inflicting additional anxiety on the patient or his family.

Attitude of Health Personnel↗

The effect of global ischemia and reperfusion on the plasma levels of vasoactive peptides. The neuroendocrine response to cardiac arrest and resuscitation.

OBJECTIVE: Return of spontaneous circulation with CPR is a function of coronary perfusion pressure, which is determined by vasomotor tone and the force of compression. Vasomotor tone is affected by the relative stimulation of arterial vasoconstricting and vasorelaxing receptors by vasoactive substances. We measured the plasma levels of the endogenous vasoactive peptides arginine vasopressin (AVP) angiotensin II (ANG-II) and atrial natriuretic peptide (ANP) during cardiac arrest and resuscitation. DESIGN: A fibrillatory canine model of canine arrest was used. 'Down time' was greater than 10 min, during which no therapy, including BLS, was given. Standard ACLS was initiated at the end of the down time with manual external chest compression standardized to an esophageal pulse pressure of 50 mmHg. Blood samples were collected through an aortic catheter during spontaneous circulation and 3 min after initiation of ACLS. Peptide levels were measured using standard RIA techniques. Results are reported as the mean +/- S.D. in pg/ml. RESULTS: AVP levels increased from a baseline of 1.7 +/- 1.0 pg/ml during spontaneous circulation to 29.9 +/- 33.3 during cardiac arrest and CPR (P = 0.01). There was a moderate positive correlation between aortic pressure and circulating AVP levels after the first dose of epinephrine (R = 0.5). There was a trend towards higher AVP levels in animals with return of spontaneous circulation (P = 0.12). ANG-II levels increased from a baseline of 14.7 +/- 12.9 pg/ml during spontaneous circulation to 151 +/- 105 during cardiac arrest and CPR (P < 0.05). ANP levels increased from a baseline of 55 +/- 46 pg/ml during spontaneous circulation to 293 +/- 73 during cardiac arrest and CPR (P < 0.01). CONCLUSION: There were significant increases in the levels of these endogenous vasoactive peptides. This reflects the neuroendocrine response to global ischemia and CPR reperfusion. Plasma levels of these peptides may effect the vital organ perfusion pressures, response to exogenous vasopressors, and outcome of resuscitative efforts. Future therapies may be directed at enhancing or blocking the effect of these peptides so as to optimize perfusion pressure which is one of the principle determinants of outcome during CPR.

Angiotensin II↗

Early defibrillation by emergency physicians or emergency medical technicians? A controlled, prospective multi-centre study.

UNLABELLED: In a controlled, prospective multi-centre study, defibrillation by emergency medical technicians (EMTs) was compared with the current standard of care in Germany--defibrillation by emergency physicians (EPs)-in order to answer the following questions: can EMTs in a two-tiered emergency medical services (EMS) system with physicians in the field defibrillate earlier than, and as safely as EPs? Does defibrillation by EMTs (study group) affect survival rate and long-term prognosis of patients in ventricular fibrillation (VF), as compared with the current national standards in resuscitation (basic cardiopulmonary resuscitation (CPR) by EMTs, and defibrillation by physicians: control group? METHODS: Prior to the onset of the study, all EMTs completed retraining in basic life support (BLS). Randomly assessed EMTs were then trained to use semi-automatic defibrillators. With the help of on-line tape recordings, the complete resuscitation sequence was evaluated. Follow-up of the patients was carried out with the help of the Glasgow Coma Scale as well as Pittsburgh Cerebral and Overall Performance Categories. RESULTS: A total of 159 patients with VF were included in the study. In 121 cases, collapse was witnessed. Of the patients receiving defibrillation by EMTs 25% were discharged from hospital alive, compared to 24% of the patients defibrillated by EPs. Of the study patients 67% were defibrillated within 12 min, while the percentage of control patients was 46%. Study patients were defibrillated earlier (P < 0.01), the return of spontaneous circulation (ROSC) was achieved earlier (P < 0.05), and the rate of patients requiring no adrenalin during resuscitation was higher in the study group (P < 0.05). The total amount of adrenalin administered in the study group was lower (P < 0.05). No statistically significant differences were found concerning the neurologic long-term prognosis. CONCLUSIONS: In our study, EMT defibrillation was equally effective as defibrillation by EPs, but failed to improve survival rates or long-term outcome of patients in VF significantly, compared to EP defibrillation. Due to a reduction in the time intervals from collapse to defibrillation and to ROSC, as well as in adrenalin doses, by EMT-defibrillation, EMTs in Germany should defibrillate if they reach a patient prior to an EP, provided they have received continuous medical training and supervision.

Cardiopulmonary Resuscitation↗

A comparison of prolonged manual and mechanical external chest compression after cardiac arrest in dogs.

The effects of manual and a new mechanical chest compression device (Heartsaver 2000) during prolonged CPR with respect to haemodynamics and outcome were tested in a prospective, randomized, controlled experimental trial during ventricular fibrillation in 12 dogs of 9-13 kg body weight after 1 min of cardiac arrest. During the first 10 min of CPR the dogs were resuscitated according to the Basic Life Support (BLS) algorithm, followed by 20 min of Advanced Life Support (ALS) algorithm. After 30 min of CPR both manual and mechanical CPR groups were resuscitated following a standardized ALS protocol. During CPR, coronary perfusion pressure and end tidal CO2 were greater with mechanical CPR. All animals were successfully resuscitated and neurological deficit scores were not different. The CPR trauma score was less in the mechanical group. Mechanical external chest compression provided better haemodynamics than the manual technique, though outcome did not differ. Both optimally performed manual and mechanical techniques produce flow sufficient to maintain organ viability for 30 min of CPR after a 1 min arrest interval.

Animals↗

Multistep evolution of B-cell-derived tumors in humans and rodents.

At least three genetic changes are known to contribute to the genesis of Burkitt's lymphoma (BL): the Ig/myc translocation, the presence of Epstein-Barr virus (EBV) in the vast majority of the endemic and a minority of sporadic tumors, and a p53 mutation, present in approximately 60% of the BL-derived lines. Activation of c-myc by juxtaposition to Ig sequences is a universal common denominator in endemic and sporadic EBV positive and negative BLs. It acts by preventing the cell from leaving the cycling compartment and by facilitating immune escape. EBV probably acts by expanding the target cell population at risk and prolonging its life span. This, together with the malaria co-factor, would increase the risk of the translocation accident. The p53 mutation may be essential for the continued growth of the tumors where it occurs, since introduction of wild-type p53 leads to their apoptotic death.

Animals↗

Emergency cardiopulmonary bypass for resuscitation from prolonged cardiac arrest.

After cardiac arrest (no flow) of more than approximately 5 minutes' duration, standard external cardiopulmonary resuscitation (CPR) basic, advanced, and prolonged life support (BLS, ALS, PLS) do not reliably produce cerebral and coronary perfusion pressures to maintain viability and achieve stable spontaneous normotension; nor do they provide prolonged control over pressure, flow, composition, and temperature of blood. Since these capabilities are often needed to achieve conscious survival, emergency closed-chest cardiopulmonary bypass (CPB) by veno-arterial pumping via oxygenator is presented in this review as a potential addition to ALS-PLS for selected cases. In six dog studies by the Pittsburgh group (n = 221; 1982 through 1988), all 179 dogs that received CPB after prolonged cardiac arrest (no flow) or after CPR (low flow) states had restoration of stable spontaneous circulation. The use of CPB enhanced survival and neurological recovery over those achieved with CPR-ALS attempts only. With CPB and standard intensive care, it was possible to reverse normothermic ventricular fibrillation (VF) cardiac arrest (no flow) of up to 15 minutes and to achieve survival without neurologic deficit; VF of 20 minutes to achieve survival but with neurologic deficit; and VF of 30 minutes to achieve transient restoration of spontaneous circulation followed by secondary cardiac death. CPB could restore stable spontaneous circulation after ice water submersion of up to 90 minutes. Other groups' laboratory and clinical results agree with these findings in general. Clinical feasibility trials are needed to work out logistic problems and to meet clinical challenges. Future possibilities for emergency CPB require further research and development.

Animals↗

An evaluation of automated defibrillation and manual defibrillation by emergency medical technicians in a rural setting.

We show that automated external defibrillation training of emergency medical technicians (EMTs) is less time consuming than manual defibrillation training, and hypothesize that both improve survival from sudden cardiac death. Data on 91 cardiac arrests over 27 months among five basic life support services was collected before EMT-defibrillation (EMT-D) training. Subsequently, seven BLS services were trained in EMT-D using either manual difibrillation or automated external defibrillation technology, and 55 sudden cardiac death patients were entered after training. Manual defibrillation required 11 more hours per student in initial training. Survival to hospital discharge improved from two of 91 patients (2.2%) in the series before EMT-D training to nine of 55 patients (16.4%) after EMT-D training (P = .001). Improved survival was correlated with shorter prehospital defibrillation times, 8.84 minutes, when EMTs performed defibrillation versus 16.3 minutes before training when EMTs awaited advanced life support defibrillation (P < .001). To enhance equipment familiarity we allowed EMTs to apply three-lead electrode monitors to all medical/cardiac patients during transport (surveillance). There were six emergency medical service-witnessed "surveillance" arrests and three arrests survived to hospital discharge (50% survival). This group represented 33% of all survivors in the series. We recommend automated external defibrillation training for EMTs. Improved survival in sudden cardiac death cases in well-run emergency medical service systems should result from EMT-D training. Finally, we recommend that routine "surveillance" of high-risk patients during transport by defibrillation-capable EMTs be considered in EMT-D programs, rather than limiting EMT-D only to units capable of rapid "man-down" response.

Aged↗

Positioning of cervical carcinoma and Burkitt lymphoma translocation breakpoints with respect to the human papillomavirus integration cluster in FRA8C at 8q24.13.

Molecular cytogenetic analysis frequently shows human papillomavirus (HPV) integration near translocation breakpoints in cervical cancer cells. We have recently described a cluster of HPV18 integrations in the distal end of the common fragile site FRA8C at 8q24 in primary cervical carcinoma samples. Chromosome band 8q24 contains the MYC gene (alias c-MYC), FRA8C, and FRA8D. The MYC gene is frequently deregulated--usually by translocation or amplification--in various tumor types. In the present study, we performed a molecular cytogenetic analysis of HPV18 integration patterns and the 8q24 translocation in a primary cervical carcinoma and in HeLa cells using combined binary ratio-fluorescence in situ hybridization. Our aim was to determine how the chromosomal breaks involved in these events relate physically to the MYC gene; whether they map to the FRA8C site, the FRA8D site, or both; and how they correlate with the occurrence of DNA flexibility domains. The 8q24 translocation breakpoints mapped between stretches of integrated HPV18 sequences in the distal end of FRA8C. This region contained DNA helix flexibility clusters, several of which mapped in the vicinity of HPV integration sites and translocation breakpoints in cervical carcinomas. DNA helix flexibility clusters were also found near known MYC translocation breakpoints in Burkitt lymphomas (BL), but most BL breakpoints mapped clearly outside FRA8C. Our data revealed that FRA8C is involved in HPV integration and chromosomal translocations in cervical carcinoma; however, this fragile site is not involved in classical MYC translocations in most BLs. In the context of the familial nature of cervical cancer, FRA8C may be considered a candidate susceptibility region for cervical carcinoma.

Burkitt Lymphoma↗

Trace determination of beta-lactam antibiotics in surface water and urban wastewater using liquid chromatography combined with electrospray tandem mass spectrometry.

A sensitive and reliable method using liquid chromatography-electrospray tandem mass spectrometry has been developed and validated for the trace determination of beta-lactam antibiotics in natural and wastewater matrices. Water samples were enriched by solid-phase extraction. The analytes included amoxicillin (AMOX), ampicillin (AMP), oxacillin (OXA), cloxacillin (CLOX) and cephapirin (CEP). Average recoveries of beta-lactams (BLs) in fortified samples were generally above 75% (except amoxicillin) with the standard deviations lower than 10% in water matrices. Amoxicillin was not quantified due to poor recovery (less than 40%) in the investigated water matrices. Matrix effects were found to be minimal when measuring these compounds in water matrices. The accuracy, within- and between-run precision of the assay fell within acceptable ranges of 15% absolute. The method detection limit (MDL) was estimated to range between 8 and 10 ng/L in surface water, 13 and 18 ng/L in the influent and 8 and 15 ng/L in the effluent from a wastewater treatment plant. A large number of actual water samples were analyzed using this method in order to evaluate the occurrence of the beta-lactams in a river and a wastewater treatment plant in northern Colorado. Most of the samples were negative for all analytes. These compounds were found at 15-17 ng/L in the three influent samples and at 9-11 ng/L in three surface water samples out of a total of 200 samples. This indicates that contamination by beta-lactam antibiotics is of minor importance to the small mixed-watershed.

Anti-Bacterial Agents↗

Seeking an explanation for the poor uptake of in-hospital AED programs.

The automated external defibrillator (AED) has been adopted by emergency service personnel as a first-line intervention in the management of out-of-hospital cardiac arrest (OHCA). AED leads to more successful Advanced Cardiac Life Support; consequently, national resuscitation organisations worldwide have recommended that nurses and doctors also integrate AEDs as a component of their basic life-support response to cardiac arrest. Despite these recommendations, the implementation of AED programs within hospitals has been generally sporadic and isolated. A continuation of this situation will most likely disturb and perplex nurses and patients, as they are key stakeholders with respect to upholding recommended BLS practices. In the absence of any explanation from change agents within hospitals, this paper seeks, by way of a pilot study and a review of the literature, to identify the extent of the problem and identify factors contributing to the relatively slow uptake of this device. We argue that nurses and other first responders to in-hospital cardiac arrest (CA) have much to gain, in the context of Occupational Health Safety and Welfare (OHS and W), from ready access to AEDs. Cost factors are also considered, with initial cost of AED purchase likely to be a major concern for managers of hospital budgets. The issues we discuss in this paper clearly support the need for further research to (a) explain the nature of public hospital resistance to AEDs and (b) to consider whether AEDs will provide practical advantages to public hospitals from an occupational, social and economic perspective.

Australia↗

Modeling an emergency medical services system using computer simulation.

STUDY OBJECTIVES: In the emergency medical services (EMS) system, appropriate prehospital care can substantially decrease casualty mortality and morbidity. This study designed a simulation model, evaluated the existing EMS system, and suggested improvements. METHODS: The study focused on 23 networked EMS hospitals affiliated with 36 emergency response units (subgroups) to perform two-tier rescues (advanced life support [ALS] in addition to basic life support [BLS] services) in Taipei, Taiwan. Using the existing EMS model as a base, this research constructed a computer simulation model and explored several model alternatives to achieve the study's objectives. The virtual models varied with staffing level, number of assigned emergency network hospitals, and various two-tier rescue probabilities. RESULTS: Increasing the staffing to two teams for Hospital 22 lessened the call waiting probability (delay between rescue call and ambulance dispatch) by 50%, even if the dispatch rate of the two-tier rescue increased from the empirical 2% to a simulated 10 and 20%. Changing the two-tier rescue pattern so each EMS subgroup cooperated with two specific, preassigned network hospitals lowered the probability of patients having to wait for rescue dispatch to under 1%. CONCLUSION: The following alternatives provided the greatest combination of effectiveness, quality patient care, and cost-efficiency: (1) because of its unique location, increase Hospital 22's staffing level to two ALS teams. (2) Establish a specific rescue protocol for the two-tier system that preassigns two network hospitals to each of the 36 EMS subgroups along with a prearranged calling sequence. If implemented, this will improve EMS performance, streamline the system, reduce randomness, and enhance efficiency.

Computer Simulation↗

Diaminofurazan (DAF): Thermolysis and evaluation as ballistic modifier in double base propellant.

Diaminofurazan (DAF) is used as a precursor in the synthesis of many high performance insensitive high explosives. This paper reports the thermal studies on DAF and its evaluation as a ballistic modifier in double base propellant formulations. Differential scanning calorimetry (DSC) and differential thermal analysis (DTA) revealed that DAF shows two-stage decomposition, whereas the kinetics of initial stage of thermal decomposition of DAF evaluated from TG data gave activation energy (E(a)) of 67 kJ mol(-1). The evolution of gases containing species such as CN, NH, OH and oxides of nitrogen during thermal decomposition of DAF was also revealed by hyphenated TG-FTIR data. Evaluation of DAF as a ballistic modifier in RDX incorporated double base propellant formulations indicated that it brings down the pressure index to 0.20 compared to 0.70 for a control composition in the pressure range 6.9-8.8 MPa when used in combination with basic lead salicylate (BLS). It was observed that DAF does not have adverse effect on vulnerability and chemical stability of the propellant formulation.

Calorimetry, Differential Scanning↗