Optimal Response to Cardiac Arrest study: defibrillation waveform effects.

INTRODUCTION: Advances in early defibrillation access, key to the "Chain of Survival", will depend on innovations in defibrillation waveforms, because of their impact on device size and weight. This study compared standard monophasic waveform automatic external defibrillators (AEDs) to an innovative biphasic waveform AED. MATERIAL AND METHODS: Impedance-compensated biphasic truncated exponential (ICBTE) and either monophasic truncated exponential (MTE) or monophasic damped sine (MDS) AEDs were prospectively, randomly assigned by date in four emergency medical services. The study design compared ICBTE with MTE and MDS combined. This subset analysis distinguishes between the two classes of monophasic waveform, MTE and MDS, and compares their performance to each other and to the biphasic waveform, contingent on significant overall effects (ICBTE vs. MTE vs. MDS). Primary endpoint: Defibrillation efficacy with < or =3 shocks. Secondary endpoints: shock efficacy with < or =1 shock, < or =2 shocks, and survival to hospital admission and discharge. Observations included return of spontaneous circulation (ROSC), refibrillation, and time to first shock and to first successful shock. RESULTS: Of 338 out-of-hospital cardiac arrests, 115 had a cardiac aetiology, presented with ventricular fibrillation, and were shocked by an AED. Defibrillation efficacy for the first "stack" of up to 3 shocks, for up to 2 shocks and for the first shock alone was superior for the ICBTE waveform than for either the MTE or the MDS waveform, while there was no difference between the efficacy of MTE and MDS. Time from the beginning of analysis by the AED to the first shock and to the first successful shock was also superior for the ICBTE devices compared to either the MTE or the MDS devices, while again there was no difference between the MTE and MDS devices. More ICBTE patients achieved ROSC pre-hospital than did MTE patients. While the rates of ROSC were identical for MTE and MDS patients, the difference between ICBTE and MDS was not significant. Rates of refibrillation and survival to hospital admission and discharge did not differ among the three populations. CONCLUSIONS: ICBTE was superior to MTE and MDS in defibrillation efficacy and speed and to MTE in ROSC. MTE and MDS did not differ in efficacy. There were no differences among the waveforms in refibrillation or survival.

Localization of SRY by primed in situ labeling in XX and XY sex reversal.

Primed in situ labeling (PRINS) can be used to localize DNA segments too small to be detected by fluorescence in situ hybridization. By PRINS we identified the SRY gene in two XX males, a woman with XY gonadal dysgenesis, and an azoospermic male with Xp-Yp interchange. Because PRINS has been used generally in the study of repetitive sequences, we modified the technique for study of the single copy 2. 1-kb SRY sequence. SRY signals were identified at band Yp11.31p11.32 in normal XY males and in the woman with XY gonadal dysgenesis. SRY signals were identified on Xp22 in one XX male but not in the other. They were identified in the corresponding region (Xp22) of the der(X) in the azoospermic male with Xp-Yp interchange. SRY signals were not observed in normal XX females. Presence of SRY in DNA samples from the various subjects was confirmed by polymerase chain reaction. We conclude that PRINS is ideal for rapid localization of single copy genes and small DNA segments in general.

Multicenter, randomized, controlled trial of 150-J biphasic shocks compared with 200- to 360-J monophasic shocks in the resuscitation of out-of-hospital cardiac arrest victims. Optimized Response to Cardiac Arrest (ORCA) Investigators.

BACKGROUND: In the present study, we compared an automatic external defibrillator (AED) that delivers 150-J biphasic shocks with traditional high-energy (200- to 360-J) monophasic AEDs. METHODS AND RESULTS: AEDs were prospectively randomized according to defibrillation waveform on a daily basis in 4 emergency medical services systems. Defibrillation efficacy, survival to hospital admission and discharge, return of spontaneous circulation, and neurological status at discharge (cerebral performance category) were compared. Of 338 patients with out-of-hospital cardiac arrest, 115 had a cardiac etiology, presented with ventricular fibrillation, and were shocked with an AED. The time from the emergency call to the first shock was 8.9+/-3.0 (mean+/-SD) minutes. CONCLUSIONS: The 150-J biphasic waveform defibrillated at higher rates, resulting in more patients who achieved a return of spontaneous circulation. Although survival rates to hospital admission and discharge did not differ, discharged patients who had been resuscitated with biphasic shocks were more likely to have good cerebral performance.

Hypomelanosis of ito and a 'mirror image' whole chromosome duplication resulting in trisomy 14 mosaicism.

We describe a female infant with multiple congenital anomalies including unusual hyperpigmentation, tetralogy of Fallot, absent corpus callosum and wide prominent nasal bridge. The infant was initially seen for genetic consultation on day one after birth. Chromosome analysis from cultured lymphocytes showed a normal 46,XX karyotype. However, cultured skin fibroblasts showed mosaicism with 46,XX,add(14)(q32).ish psu dic dup(14)(q32p13)(wcp14+)/46,XX complements. A review of the published report with chromosome mosaicism and hypomelanosis of Ito (HMI) is included. We suggest that the trisomy 14 mosaicism seen in fibroblast cultures has importance in the expression of pigmentation dysplasias in this patient. Pigmentary anomaly may be due to loss or gain of specific genes that influence pigmentation located on the long arm of chromosome 14 in this patient.

Chromosome duplications and deletions and their mechanisms of origin.

Duplications and deletions of the same gene loci or chromosome regions are known to produce different clinical manifestations and are significant factors in human morbidity and mortality. Extensive cytogenetic and molecular cytogenetic studies with cosmid and YAC probes in two patients with unique mosaicism for reciprocal duplication-deletion allowed us to further understand the origin of these abnormalities. The first patient's mosaic karyotype was 46,XX, inv dup(11) (q23q13)/46,XX,del(11)(q13q23). The second patient had a 46,XY,dup(7)(p11.2p13)/46,XY,del(7)(p11.2p13)/46,XY karyotype. Fluorescence in situ hybridization studies on the first patient placed the two breakpoints near the folate-sensitive fragile sites FRA11A and FRA11B. The presence of repeated sequences responsible for these fragile sites may have been involved in the patient's duplication-deletion. Our investigation leads us to conclude that, in addition to known mechanisms (such as unequal crossovers between homologs, unequal sister chromatid exchanges, excision of intrachromatid loops, and meiotic recombination within a single chromatid), duplication-deletion can also arise by the formation of an overlying loop followed by an uneven crossover at the level of the DNA strand.

Rapid identification of marker chromosomes using primed in situ labeling (PRINS).

Primed in situ labeling (PRINS) is a relatively new technology with wide-ranging applications in clinical cytogenetics. Using PRINS, we have identified the chromosomal origin of marker chromosomes in three patients. In the first patient with primary amenorrhea, we were able to confirm the marker chromosome as originating from an X. In the second (prenatal) case, PRINS allowed us to determine rapidly the origin of the marker as a Y chromosome. In the third patient with minor anomalies, the marker was identified as derived from a chromosome 18. In all three cases, application of PRINS permitted us to characterize the marker chromosomes within 1 hour after the slides were prepared. The methodology is simple, has added advantages over conventional fluorescence in situ hybridization (FISH), and can be used as a viable and effective alternative to FISH in clinical cytogenetic diagnosis.

Hypertrichosis, pigmentary retinopathy, and facial anomalies: a new syndrome?

We report on a 22-month-old male with congenital hypertrichosis of the face, arms, legs, shoulders, back, and buttocks, abnormal facial appearance, dolichocephaly, and pigmentary retinopathy. Symmetrical hyperpigmentation is present on the sideburn areas of his face, and hyperpigmented streaks are seen on arms and legs. Biopsy of the hyperpigmented' skin showed many separate bundles of smooth muscles in the dermis. No relative had hypertrichosis or other birth defects. To our knowledge, the syndrome of facial anomalies, pigmentary retinopathy, and congenital hypertrichosis has not been reported previously.

Atraumatic cardiac arrest in apparently healthy young women.

Sudden non-traumatic death in young people (< 30 years old) has been discussed both in systematic studies and anecdotal reports. After presenting three remarkable cases, a global survey of the incidence with special reference to the Belgian CPCR database, ethiopathogenesis and prognosis of sudden non-traumatic death in this specific age group is given. The atherosclerotic coronary artery disease (CAD) related and especially the non-CAD related causes are extensively discussed as well as the role of intoxication and increasing drug and substance abuse. After conventional cardiopulmonary resuscitation with restoration of spontaneous circulation and a favourable neurological outcome, a thorough search for the underlying disease is mandatory. The involvement of drugs or other toxins has to be excluded in the first place. Apart from transoesophageal echocardiography and coronary angiography, electrophysiological testing, serological exams, myocardial biopsy and magnetic resonance imaging should be considered.

Transplacental needle passage in early amniocentesis and pregnancy loss.

OBJECTIVE: To determine whether transplacental needle passage affects the frequency of pregnancy loss in early amniocentesis. METHODS: We reviewed 380 consecutive cases of amniocentesis performed before 14.9 weeks' gestation because of advanced maternal age (at least 35 years old). Procedure and pregnancy outcome data were obtained from reviews of patients' charts and telephone contact with patients or referring physicians. RESULTS: Transplacental needle passage occurred in 147 cases (38.7%). Pregnancy loss rates were similar in the transplacental and nontransplacental groups. Only the frequency of bloody taps was significantly increased among women undergoing early transplacental amniocentesis. CONCLUSION: Transplacental needle passage in cases of amniocentesis performed before 14.9 weeks' gestation does not appear to increase the risk of pregnancy loss. Therefore, deferring early amniocentesis to a later time at which nontransplacental amniocentesis may be performed should be reserved only for cases complicated by placental vessels, placental vascular lacuna ("placental lakes"), or subchorionic hematomas that should not be traversed by a needle.

Characterization of an unbalanced de novo rearrangement by microsatellite polymorphism typing and by fluorescent in situ hybridization.

Unbalanced de novo rearrangements, difficult to characterize by conventional cytogenetic techniques, may be elucidated by molecular approaches. By dinucleotide repeat polymorphism typing and fluorescence in situ hybridization (FISH), we have defined the composition of an unbalanced de novo translocation (46,XX,15p+) in a child with multiple congenital anomalies. Use of a microsatellite repeat D5S208 (localized to 5p15) and polymerase chain reaction (PCR) analysis confirmed that the extra segment originated from the short arm of chromosome 5. Amplification of the patient's DNA with primers for dinucleotide repeats D5S350 and D5S118 showed that the entire 5p (from 5pter to 5q11) was present in 3 copies. FISH confirmed the trisomic status of 5p, and further revealed the presence of centromeres of both chromosomes 5 and 15 on the rearranged chromosome thus delineating its dicentric nature. This information allowed us to redefine the de novo rearrangement in this patient as 46,XX,dic der(15)t(5;15)(q11;p11).

Further prospective evidence of a circadian variation in the frequency of call for sudden cardiac death. Belgian Cardiopulmonary Cerebral Resuscitation Study Group.

OBJECTIVE: To determine whether in a larger data base call for sudden cardiac death exhibits a specific circadian rhythm similar to that recently demonstrated by Levine et al. DESIGN AND SETTING: The time of the day of calls received for out-of-hospital cardiac arrests (OOHCA) prospectively registered between 1983 and '90 by 7 major Belgian pre-hospital EMS-MICU services. Chrono-biologic assessment was made by two-harmonic linear regression analysis of the data tabulated by hour of the day. The hourly distribution of calls for OOHCAs was subjected to Fourier transformation resulting in a periodogram. PATIENTS: 3471 OOHCAs with presumed cardiac etiology and age of more than 18 years versus 2007 inpatients registered in the same period. MEASUREMENTS AND RESULTS: Significant and remarkably similar circadian patterns were found (R-square = 0.84) for the cardiac origin OOHCAs and the ventricular fibrillation OOHCAs. There is a low incidence during the night and an increased incidence from 6 a.m. until noon with an additional early afternoon-peak. The data were always better fitted when applying sinusoids with periods of 8 and 24 h instead of 12 and 24 h. Our observed circadian distribution resembles the reported circadian variation of ischaemic episodes, ventricular tachycardia and acute myocardial infarction in the awake hours. The time distribution of OOHCA (cardiac origin) differs significantly from OOHCA (non-cardiac origin) and from in-hospital cardiac arrests. The in-hospital CA pattern shows less deviation. The age dependent variation in the incidence of cardiac origin OOHCAs, was not obvious for the ventricular fibrillation subgroup. CONCLUSION: Knowledge about the cyclical nature of incidence of cardiac arrests is useful to improve intersystem comparisons and make sound decisions about prophylaxis, treatment and allocation of resources.

A comparison of two different European EMS centers (Brugge and Göttingen) using the same electronic 'cardiopulmonary-cerebral-resuscitation' registration program: a preliminary report.

A preliminary comparison of out-of-hospital cardiac arrest (CA) data registered with a common software program (Utstein style) in two different European EMS centers is presented. Rather than attempting independently several small-scale trials, we prefer to develop in a committed effort a coordinated program of active and passive surveillance. Hopefully, this will allow us to determine the true European profile and outcome of our out-of-hospital CA victims.

A sudden infant death like syndrome possibly induced by a benzodiazepine in breast-feeding.

The cause of the 'sudden infant death syndrome' (SIDS) remains unknown. We describe a case in which a benzodiazepine unadvisedly taken by a mother might have been at least in part responsible for the death of her breast-fed 'at risk' daughter. Moreover, in this case, home monitoring as a preventive measure was not effective.

Near-death-experiences in out-of-hospital cardiac arrest survivors. Meaningful phenomena or just fantasy of death?

Frequent criticism concerning the investigation of near-death-experiences (NDEs) has been the lack of uniform nomenclature and the failure to control the studied population with an elimination of interfering factors such as administration of sedatives and nonspecific stress responses. Greyson's NDE Scale is a 16-item questionnaire developed to standardize further research into mechanisms and effects of NDEs. Using this scale, we interviewed good out-of-hospital cardiac arrest survivors, with documented time-intervals between call for help and restoration of spontaneous circulation, yet without obvious brain damage or known, psychiatric history. The incidence of such experiences appeared to be extremely low among survivors of genuine cardiac arrest events. Alteration of information processing under the influence of hypoxia and hypercarbia only occurs after several minutes of brain ischaemia. International multicentric data collection within the framework for standardized reporting of cardiac arrest events will be the only satisfying method to address this fascinating and intriguing issue.

Influence on outcome after cardiac arrest of time elapsed between call for help and start of bystander basic CPR. The Belgian Cerebral Resuscitation Study Group.

The exact impact of the 'interval between cardiac arrest (CA) and the start of basic cardiopulmonary resuscitation (CPR) performed by bystanders' on outcome is not fully established. We retrospectively evaluated data with regard to response intervals of 1195 out-of-hospital CA interventions where bystander CPR was performed and continued by the eight mobile intensive care units (MICUs) participating in the Belgian Cerebral Resuscitation Registry between 1982 and 1990. Partial correlations between time elapsed from CALL to CPR by lay public and outcome were determined when the effect of response times of 1st and 2nd tier were removed. The following groups were studied: ventricular fibrillation (VF), asystole and electromechanical dissociation (EMD), non-witnessed and witnessed. Good outcome was represented by initial restoration of spontaneous circulation (ROSC successes) and by prolonged survival (CPR successes) being 22.7 and 9.7%, respectively. The mean time +/- S.E.M. between CALL and CPR initiated by lay people for the studied population (n = 1195) was 2.5 +/- 0.1 min. The partial correlation coefficient between prolonged survival and time passed between CALL and bystander CPR was negative for all types of CA, yet significance was reached only in the non-witnessed group. Using ROSC as the endpoint significance is achieved in all groups except the VF patients, where the intervention times were shorter. In our population, prolonged survival was independently and negatively influenced by a delay between CALL and any CPR in the non-witnessed CA group (n = 421).