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The relevance of the development of developing experience and methodological support of the constituent entities of the Russian Federation. To organize activities to provide activities aimed at the development of the direction, the experience of St. Petersburg, as a subject of the leader in the Russian Federation in the development of technologies for accompanied accommodation, was studied and analyzed. The study was conducted on the basis of the results of the annual monitoring study of materials submitted by the executive authorities of 85 constituent entities of the Russian Federation on the organization of technologies for accompanied accommodation.As a result of the study, the main activities in the development of this direction in St. Petersburg were identified: expanding the regional list of social services provided by social service providers; assigning disabled people of working age with intellectual disabilities to a separate social group; developing recommended individual social service programs, including: for disabled people of working age with intellectual disabilities when living in social apartments, development of industry-specific technological regulations for the provision of measures to support disabled people, creation of equal opportunities to enter the social services market for both state and non-state social service organizations, implementation of infrastructure measures, identification of financial sources, etc. The use by the constituent entities of the Russian Federation of recommendations on reforming the regional regulatory legal framework and the implementation of key events will allow introducing the best practices of St. Petersburg in organizing various forms of accompanied residence.

Nine cross-cutting issues which could foster or impede food and nutrition security are discussed. These are the concept of the right to food; gendering food security; land tenure; population growth pressure on land and water resources; empowerment and resilience through access to factors of production; food security governance; government capacity to formulate, implement, and institutionalize change and reform; food sovereignty; and climate change.

Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are involved in a variety of physiologic growth and development and pathophysiologic inflammatory conditions. We hypothesized that 1) MMP-2 and -9 plasma activities and TIMP-1 and -2 plasma concentrations in preterm and term neonates were dependent on the gestational and postnatal age; and 2) the respective MMP and their inhibitors were deranged in the development of bronchopulmonary dysplasia (BPD) and intraventricular hemorrhage (IVH) in preterm neonates. From 1998 to 1999, blood samples were collected from preterm neonates (25-36 wk gestation) with or without BPD and/or IVH as well as from healthy term (37-40 wk gestation) neonates during the first 28 d of life. MMP-2 and MMP-9 plasma activities were measured by zymography; TIMP-1 and TIMP-2 plasma concentrations were determined by ELISA. In neonates without BPD or IVH (n = 50), MMP-2 and MMP-9 plasma activities both appeared to be gestational age dependent, with the highest levels observed in neonates of 33-36 wk gestation. TIMP-1 plasma concentration was highest in term neonates but no gestational difference was found in TIMP-2. Only MMP-9 showed a 50% decrease after d 1 in the first postnatal month. Twelve preterm infants with BPD and/or IVH had significantly lower MMP-2 but higher MMP-9 activity and higher TIMP-1 concentration than those of corresponding neonates without BPD or IVH. These findings show the gestational age-dependent expression of plasma MMP activities and their inhibitors. MMP and TIMP may be involved in the feto-neonatal development and may contribute to the pathogenesis of BPD and/or IVH in critically ill preterm neonates.

BACKGROUND Activated neutrophils have been implicated in reperfusion injury of the myocardium; leukocyte depletion at the time of reperfusion may contribute to better myocardial protection after cardiac surgery. In the present study, we examined whether leukocyte depletion as an adjunct to terminal blood cardioplegia attenuates reperfusion injury. METHODS Porcine hearts that had undergone 60 minutes of normothermic ischemia with cardioplegia and 60 minutes of reperfusion under cardiopulmonary bypass were divided into four groups according to the methods of 15 min of controlled initial reperfusion: whole blood reperfusion (n = 6), leukocyte-depleted reperfusion (n = 6), secondary blood cardioplegia (n = 6) and leukocyte-depleted secondary blood cardioplegia (n = 6). At 60 min of reperfusion, hemodynamic recovery, release of malondialdehyde (MDA) as a marker for free oxygen radicals, CK-MB-isoenzyme from the coronary sinus, recovery of adenosine triphosphate, and myocardial water content were evaluated. RESULTS The group with leukocyte-depleted secondary blood cardioplegia showed the best hemodynamic recovery (Emax and total dp/dt), lowest levels of MDA, CK-MB and myocardial water content, and highest adenosine triphosphate recovery. CONCLUSIONS These results suggest that controlled reperfusion with leukocyte-depleted secondary blood cardioplegia attenuated severe damage of the myocardium as compared to whole blood reperfusion.

During lung development, the extracellular matrix undergoes dynamic remodeling. Matrix metalloproteinases (MMPs), and tissue inhibitors of matrix metalloproteinases (TIMPs), are important enzymes that participate in regulating tissue remodeling. There is an abnormal balance of the synthesis and degradation of collagen and elastin in perinatal lung associated with congenital diaphragmatic hernia (CDH). This study was designed to (1) determine the expression and gelatinolytic activity patterns of MMPs 2 and 9 and TIMPs 1 and 2 in rat lungs during the perinatal period, and (2) to test the hypothesis that they are abnormal in nitrofen-induced CDH. Measurements were made using reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and zymography. The mRNA expression and activity of MMP 2 did not change significantly from embryonic day 16 to postnatal day 14. The most striking feature found was the rapid increase in the expression of MMP 9 soon after birth. Measurements were repeated on lung tissue isolated from embryonic rats with nitrofen-induced CDH. The expression and activity of MMPs and TIMPs were similar to control values and thus we conclude that these proteins appear not to be responsible for the altered extracellular matrix and morphological abnormalities noted in CDH lungs at birth.

In this review, we discuss recent advances in the study of the pathogenesis of congenital diaphragmatic hernia (CDH). Much of the research has involved the use of an animal model of CDH in which diaphragmatic defects are produced in fetal rats by administering the herbicide nitrofen to dams during mid-gestation. The animal model is described and the relevance to the human condition is discussed. The data derived from the animal studies are critically assessed in the context of commonly cited hypotheses proposed for the pathogenesis of CDH. Finally, experimental strategies are proposed for systematically examining the normal and pathological formation of the pleuroperitoneal fold. We conclude that a malformation of the primordial diaphragm, the pleuroperitoneal fold, underlies the muscle defects associated with CDH.

Arteriovenous malformations of the Vein of Galen continue to present diagnostic and therapeutic challenges in the neonatal period. Approximately 40-50% of all malformations of the Vein of Galen present in the neonatal period, usually with congestive heart failure. These neonates represent the most severe cases and are also the most difficult to manage. We report a case of a neonate with a Vein of Galen Malformation who presented with cyanosis, a cardiac murmur, and severe persistent pulmonary hypertension of the newborn. Cardiac failure developed later in the patient's course. The degree of pulmonary hypertension on echocardiography was used to time endovascular embolization of the Vein of Galen Malformation. Following embolization, his pulmonary hypertension subsided dramatically. We speculate that pulmonary hypertension associated with Vein of Galen Malformations has been underestimated in the morbidity and demise of these neonates, and should be more aggressively monitored and treated.

We previously reported on the presence of respiratory pacemaker cells that are highly sensitive to CO(2), in a region of the medulla oblongata in the fetal rat, 2 mm rostral to the obex. We now report on the CO(2) dose responses of these cells, as well as their responsiveness to certain chemical agents known to affect breathing in the fetus. Twenty-day-old fetal Sprague Dawley rats were block-dissected, and the cells of target areas were dissociated as previously described. Neuronal cells were plated on a medullary background and placed in the incubator with 10% CO(2) for 2-3 weeks. Cells were then studied using patch-clamp techniques. Pacemaker cells with single or bursting potentials showed responsiveness to CO(2) starting with pulses of 10 msec. Irregular beating or silent cells had poor or absent responsiveness to CO(2). Pacemaker cells responded to norepinephrine with increased firing potential; this action was blocked by metropolol. PGE(2) had no effect on pacemaker-cell activity, but indomethacin increased the spike frequency from 336+/-41 to 384+/- 65 spikes/min. Morphine stimulated the pacemaker cells from 205+/-25 to 272+/-29 spikes/min; this was blocked by naloxone. Finally, a placental extract, which inhibited breathing in the unanesthetized fetal sheep preparation, increased the activity of pacemaker cells from 301+/-35 to 452+/-52 spikes/min. In all of the above, irregular beating cells responded poorly and silent cells did not respond. The findings indicate that these pacemaker cells are uniquely designed to respond to CO(2) and have some properties which allow them to respond to certain chemical mediators in a manner similar to that of the whole respiratory system in vivo.

The timing and magnitude of airway narrowing in central apneas is unknown. We have developed a method of apnea classification that relies on the transmission of cardiac airflow oscillation to indicate airway patency. Using a theoretical model, we showed that the amplitude of the cardiac airflow oscillation is proportional to airway diameter for small lumens. While in the majority of central apneas the amplitude of the cardiac airflow oscillation remains nearly constant, in a subset of events the waveform decreases with time, suggesting airway narrowing. We hypothesized that this is not a random occurrence but reflects a critical period of airway instability during central apnea. To test this hypothesis we studied 41 preterm infants. Of 4,456 central apneas, 585 had a decrease in the amplitude of the cardiac oscillation. The amplitude of the cardiac airflow oscillation during an apnea was recorded to provide a dynamic measure of changes in airway diameter with time. To allow for comparisons between patients the amplitude of each cardiac airflow oscillation was expressed as a proportion of the maximum amplitude observed in each infant. We then compared the amplitude at multiple successive 0.5 s intervals with the amplitude of the cardiac airflow oscillation observed at the apnea outset using ANOVA. We found a significant decrease in cardiac airflow oscillation after only 1 s irrespective of the apnea duration (3 to 16 s). We conclude that airway narrowing during central apnea is not a random occurrence but appears shortly after the onset of the apnea. We speculate that the phenomenon is secondary to passive airway relaxation.

We describe a neonate with tricuspid atresia, absent pulmonary valve, right ventricular hypoplasia, small venrricular septal defect, left ventricular ourflow tract obstruction and a patent arterial duct. These finding were diagnosed by echocardiography and confirmed by cardiac catherterization and postmortem examination. This is a unique report of a functionally single ventricle variant of absent pulmonary valve syndrome and biventricular outlet obstuction.

Inhaled nitric oxide (iNO) is a potent local vasodilator. Numerous case reports describe its efficacy in treating persistent pulmonary hypertension of the newborn (PPHN). This report describes experience at the authors' institution with iNO therapy in 10 consecutive infants with PPHN of a number of etiologies. Infants received iNO at doses of 0.2 to 80 ppm for 1 to 481 h. Five infants were classified as responders (20 torr or greater rise inPaO2) and one as a partial responder (PaO2rise of 10 to 19 torr). The remaining four did not respond. Overall observed mortality was three of 10, with two of four of nonresponders and the only partial responder dying. Survivors required ventilation for 18±18 days and oxygen for 29±30 days, and they remained in hospital 40±30 days (mean ± SD). Although improvement in oxygenation with iNO was primarily due to reduction in pulmonary pressure, in selective patients, changes in ventilation-perfusion relationships could account for some of the increase in oxygenation. The presence of significant methemoglobinemia in two patients (7% and 4.5%) when the infants' iNO dose was increased to 80 ppm highlights the importance of careful monitoring for toxicity. Further studies are needed to define the best dosage and duration of iNO. While iNO shows great promise in the treatment of PPHN, randomized controlled trials are needed to delineate in which infants iNO use is indicated.

Apnea of prematurity (AOP) is frequently managed with nasal continuous positive airway pressure (NCPAP). Nasal cannula (NC) are used at low flows (Objective. To determine the NC flow required to generate PDP equal to that provided by NCPAP at 6 cm H2O and to assess the effectiveness of HFNC as compared NCPAP in the management of AOP.Method. Forty premature infants, gestation 28.7 ± 0.4 weeks (mean ± standard error of mean), postconceptual age at study 30.3 ± 0.6 weeks, birth weight 1256 ± 66 g, study weight 1260 ± 63 g who were being managed with conventional NCPAP for at least 24 hours for clinically significant apnea of prematurity, were enrolled in a trial of ventilator-generated conventional NCPAP versus infant NC at flows of up to 2.5 L/min. End expiratory esophageal pressure was measured on NCPAP and on NC, and the gas flow on NC was adjusted to generate an end expiratory esophageal pressure equal to that measured on NCPAP. Two 6-hour periods were continuously recorded and the data were stored on computer.Results. The flow required to generate a comparable PDP with NC varied with the infant's weight and was represented by the equation: flow (L/min) = 0.92 + 0.68x, x = weight in kg,R = 0.72. There was no difference in the frequency and duration of apnea, bradycardia or desaturation per recording between the 2 systems.Conclusion. NC at flows of 1 to 2.5 L/min can deliver PDP in premature neonates. HFNC is as effective as NCPAP in the management of AOP.

The biopotency of single-chain analogs of human hFSH, human chorionic gonadotropin (hCG), and a dually active gonadotropin construct (FcCGβα) was examined. Sheep (bwt=61.4±1.1 kg; n=6 ewes/treatment) received a single injection (5 IU/kg, i.v.) of the hFSH analog (Fcα), the hCG analog (CGβα), FcCGβα, or Fcα and CGβα. Control animals received conditioned media. Ovulation was induced 3 days after analog administration using hCG (1000 IU, i.v.). Basal serum concentrations of estradiol (E2) were maintained in control animals. Neither Fcα nor CGβα alone induced significant E2 production during the pre-hCG period. Conversely, serum concentrations of E2 were increased (P4 concentrations were maintained at basal levels in control animals, significant increase was noted in all other treatment groups during the post-hCG period. Final ovarian weight was significantly increased (P2 production. Conversely, the construct that incorporates β-domains from both CG and FSH has dual activity. The long-lived nature of the single-chain constructs suggests that these recombinant gonadotropins may be effective alternatives to pituitary- or placenta-derived gonadotropins in out-of-season breeding and/or superovulation protocols.

A 61-year-old man presented with aortic valve stenosis, coronary artery disease in combination with rheumatic arthritis, peri-aortic inflammation and fibrosis with aortitis. In the pathological literature this has been termed chronic periaortitis, while in the surgical literature, non-aneurysmal dilatation of the aorta associated with atherosclerosis and inflammation has been described as aortitis. The name chronic periarteritis refers to the associated involvement of coronary arteries. Although different terminologies have been used, it is suggested that all of them most likely represent the same disease entity.

Paraplegia after an open heart operation in a neonate is a rare complication. We report a case of a infant in whom paraplegia developed after a successful arterial switch operation for transposition of the great arteries. The infant was monitored and resuscitated in the preoperative period with umbilical arterial and venous catheter tips located in the midthoracic region. He likely suffered a clinically silent thromboembolic event predisposing him to a localized hemorrhagic infarction during the repair.

We report a female patient with mitral valve replacement and preservation of subvalvular apparatus in which parts of the papillary muscle ruptured postoperatively. During systole the ruptured papillary muscle prolapsed through the native aortic valve. Echocardiographic documentation and operative procedure were demonstrated.

The goal of this study was to determine when fetal breathing movements (FBMs) commence in the rat and to characterize age-dependent changes of FBMs in utero. These data provide a frame of reference for parallel in vitro studies of the cellular, synaptic, and network properties of the perinatal rat respiratory system. Ultrasound recordings were made from unanesthetized Sprague-Dawley rats from embryonic (E) day 15 (E15) to E20. Furthermore, the effects of respiratory stimulants (doxapram and aminophylline) and hypoxia on FBMs were studied. Single FBMs, occurring at a very low frequency (approximately 8 FBMs/h), commenced at E16. The incidence of single FBMs increased to approximately 80 FBMs/h by E20. Episodes of clustered rhythmic FBMs were first observed at E18 (approximately 40 FBMs/h). The incidence of episodic clustered FBMs increased to approximately 300 FMBs/h by E20, with the duration of each episode ranging from approximately 40 to 180 s. Doxapram, presumably acting to stimulate carotid body receptors, did not increase FBMs until E20, when the incidence of episodic clustered FBMs increased twofold. Aminophylline, a central-acting stimulant, caused an increase in episodic clustered FBMs after E17, reaching significance at E20 (3-fold increase). Exposing the dam to 10% O(2) caused a rapid, marked suppression of FBMs (5-fold decrease) that was readily reversed on exposure to room air.

The goals of this study were to further our understanding of diaphragm embryogenesis and the pathogenesis of congenital diaphragmatic hernia (CDH). Past work suggests that the pleuroperitoneal fold (PPF) is the primary source of diaphragmatic musculature. Furthermore, defects associated with an animal model of CDH can be traced back to the formation of the PPF. This study was designed to elucidate the anatomic structure of the PPF and to determine which regions of the PPF malform in the well-established nitrofen model of CDH. This was achieved by producing three-dimensional renderings constructed from serial transverse sections of control and nitrofen-exposed rats at embryonic day 13.5. Renderings of left- and right-sided defects demonstrated that the malformations were always limited to the dorsolateral portions of the caudal regions of the PPF. These data provide an explanation of why the holes in diaphragmatic musculature associated with CDH are characteristically located in dorsolateral regions. Moreover, these data provide further evidence against the widely stated hypothesis that a failure of pleuroperitoneal canal closure underlies the pathogenesis of nitrofen-induced CDH.

Purpose: The aim of this study was to determine whether recirculation could be quantified by a thermodilution technique during venovenous (VV) extracorporeal membrane oxygenation (ECMO) in a rabbit model. Methods: Five New Zealand white rabbits, mean weight, 4.5 (range, 3.7 to 5.7) kg, were anesthetized, instrumented, cannulated with a double-lumen catheter, and placed on VV ECMO. Serial injections of ice-cold saline were performed at the arterial arm of the circuit, and the resultant temperature change at various pump flows was measured at the venous arm of the circuit using a thermistor-tipped catheter and a cardiac output computer. Results were compared with the respective 100% recirculation measured with all the circuit flow passing through the bridge. Results: Using linear regression, recirculation percentage could be calculated as: 19 + 0.1 × pump flow (R 2 = 0.81, P Conclusions: Recirculation can be quantified during VV ECMO by measuring the change in temperature in the venous arm using a cardiac output computer after injection of a known quantity of ice-cold saline in the arterial side of the circuit. The effect of interventions to reduce recirculation can be assessed conveniently and reliably. J Pediatr Surg 35:1411-1414. Copyright © 2000 by W.B. Saunders Company.

In this review, we discuss recent advances in the study of the pathogenesis of congenital diaphragmatic hernia (CDH). Much of the research has involved the use of an animal model of CDH in which diaphragmatic defects are produced in fetal rats by administering the herbicide nitrofen to dams during mid-gestation. The animal model is described and the relevance to the human condition is discussed. The data derived from the animal studies are critically assessed in the context of commonly cited hypotheses proposed for the pathogenesis of CDH. Finally, experimental strategies are proposed for systematically examining the normal and pathological formation of the pleuroperitoneal fold. We conclude that a malformation of the primordial diaphragm, the pleuroperitoneal fold, underlies the muscle defects associated with CDH.

A 55-year-old woman who was admitted to hospital with acute chest pain as a case of emergency suffered from an acute anteroseptal myocardial infarction. Four weeks later coronary angiography revealed a long dissection of the left anterior descending artery (LAD) as well as a significant stenosis of the left main and the proximal circumflex. Cardiovascular surgery was done subsequently. In addition to myocardial revascularization using coronary artery bypass grafts a readaptation of the dissecting artery walls and a proximal ligation of the LAD before anastomosis were performed. Clinical data, pathogenesis, and indications for medical and surgical treatment of spontaneous artery dissection are presented.

Atrial fibrillation (AFib) is a frequent complication of coronary artery bypass grafting (CABG). Its cause, however, is unknown. As the adrenergic system is involved in some types of AFib, we hypothesized that a change in guanine nucleotide-binding protein (G protein) expression plays a role in the development of post-CABG AFib. In 28 patients undergoing CABG surgery, the G(s alpha)/G(i alpha) ratio (stimulatory/inhibitory G protein alpha) at the protein (Western blotting) and mRNA (reverse transcription polymerase chain reaction) levels was measured before and after surgery. As a suitable test system allowing multiple analysis mononuclear leukocytes (MNL) were chosen. The perioperative change of the G(s alpha)/G(i alpha) ratio of protein and mRNA was significantly different in patients who subsequently developed AFib (eight patients) and in patients who did not (20 patients; P

Airway closure during mixed apneas in preterm infants may be due to lack of tone in the upper airway followed by collapse and obstruction or diaphragmatic action inducing obstruction. We examine whether respiratory efforts are necessary for airway closure using a new method of detecting airway obstruction, based on the disappearance of an amplified cardiac pulse observed on the respiratory flow tracing. We analyzed 198 episodes of mixed apnea of various lengths (or = 3 seconds) observed in 33 preterm infants (birth weight, 1.4 +/- 0.1 kg [mean +/- SEM]; study weight, 1.7 +/- 0.1 kg; gestational age, 29 +/- 1 weeks; post-natal age, 33 +/- 4 days). The great majority of these episodes (88%) had a central, followed by an obstructive, component. Infants were studied by using a nosepiece and a flow-through system. Respiratory efforts (abdominal and chest movements) were recorded. Of the apneas, 20 were5 seconds; 78, 5 to10 seconds; 45, 10 to15 seconds; 27, 15 to20 seconds; and 28,or = 20 seconds. Of the 198 mixed apneas, 151 (76%) occurred in the absence of any respiratory effort; 43 (22%) showed a simultaneous cessation of the cardiac oscillation and respiratory effort; and 4 (2%) showed diaphragmatic activity appearing after cessation of the cardiac oscillation (airway occlusion). Respiratory efforts never preceded the cessation of the cardiac oscillation. The findings suggest that diaphragmatic action is not needed to occlude the airway in mixed apneas. The simultaneous cessation of cardiac oscillations (airway occlusion) and onset of respiratory efforts may indicate that such effort contributes to closure or is induced by the same stimulus that closes the airway. We speculate that the mechanism for airway closure in mixed apneas is most likely a lack of upper airway tone, which normally occurs with the cessation of a central drive to breathe.

We tested the hypothesis that in preterm infants, prolonged apneas (apneas > or = 20 sec) are not random events but are preceded by frequent and progressively longer respiratory pauses associated with changes in ventilatory variables. We studied 36 preterm infants with apnea [birth weight 1190 +/- 60 g (mean +/- SEM), study weight 1300 +/- 60 g, gestational age 28 +/- 1 weeks, and postnatal age 23 +/- 2 days]. A nosepiece with a flow-through system was used to measure ventilation and alveolar gases. Throughout the monitoring period for each infant we established 10-min moving "window of observation" followed by a 1-min interval examined for the detection of a prolonged apnea. Within the 10-min window, three variables were defined: the number of apneic episodes, the maximum length of a single apneic episode, and the total duration of apneic time. During the following minute (eleventh) the presence or absence of a prolonged apnea was determined. Chi-square test for a linear-trend in the rate of prolonged apnea and multiple logistic regression analysis showed that the relative risk of a prolonged apnea increases significantly from preceding periods without apnea to preceding periods containing the potential predictors of prolonged apnea. The strongest predictor was total duration of apneic time in the previous 10 min. When the 1 min before prolonged apnea was compared with the 1 min of similar sleep state not having prolonged apnea, minute ventilation decreased, primarily due to a decrease in respiratory frequency. Oxygen saturation decreased and alveolar PCO2 did not change. These findings suggest that prolonged apnea is not a random event but is preceded by a disturbance of the respiratory control system characterized by (1) frequent apneas of progressive duration, (2) decrease in respiratory minute volume and frequency, and (3) decreased O2 saturation.

Arterial access for blood sampling and continuous blood pressure monitoring is the cornerstone of modern neonatal intensive care. Although umbilical arterial catheters have traditionally been utilized for arterial access, they are associated with potentially devastating complications. Consequently, there has been an increase in the use of peripheral arterial catheters. Unfortunately, these catheters have a limited useful lifespan secondary to vasospasm, intimal damage and/or thrombus formation. In this report, we describe the use of tolazoline (0.02 to 0.2 mg/kg/h) to counteract local arterial vasospasm in five critically ill neonates, where arterial access was vital for care but difficult to maintain.

Currently the classification of neonatal apnea relies upon an inference of airway closure based upon the presence of breathing efforts against such an obstruction. In this study we evaluate a new method of classification which utilizes the presence or absence of cardiac airflow oscillation to detect airway closure. Specifically, this evaluation consisted of an examination of the transmission characteristics of an artificially produced airflow oscillation through discrete airway narrowing in a model system; a confirmation that voluntary upper airway occlusion in adult volunteers uniformly induces complete loss of the oscillation; and a comparison of the cardiac oscillation method with the traditional method of apnea classification in a cohort of 4,309 apneas in 32 infants. We determined that the amplitude of the oscillation is negatively correlated with resistance (r = 0.97) and positively with the radius (r = 0.98) of narrowing in a model system, and that voluntary airway obstruction in adult subjects uniformly results in loss of transmitted cardiac oscillations. Moreover, although there was similarity in the frequency distribution of central, obstructive, and mixed apneas in our infants, there were statistically significantly greater obstructive events detected by the cardiac oscillation method. In addition, the cardiac oscillation method had the additional advantage of providing information regarding the timing of airway obstruction during apnea.

Differentially expressed cDNA clones were isolated from salt-adapted Aspergillus nidulans (FGSC #359). Poly (A)+ RNA from adapted mycelia was used to construct a lambda Uni-ZAP cDNA library. The library was screened with mixed subtracted cDNA probes. Three-hundred and fifty-seven positive plaques were isolated in the primary screening. Sixty-two randomly selected plaques were purified and placed into eight different cross-hybridization groups. A representative cDNA from each group was used to study expression under unadapted, salt-adapted and salt-shock conditions. These clones, representing eight different genes, displayed enhanced expression under salt stress. Exploratory nucleotide sequencing was performed, and the predicted amino-acid sequence was compared with known gene sequences in the data-bank. Five of the cDNA clones were identified as a mitochondrial (mt) ATPase beta subunit, a mt ATPase subunit 9, a mt transport protein, a ubiquitin-extension protein and a ribosomal protein. Three cDNA clones could not be identified due to lack of adequate homology with known sequences. These results suggest that at least five genes with known function in cellular processes like ATP generation and protein synthesis, and three other genes of unknown identity, are greatly induced in salt-adapted conditions.

We report a newborn infant with extensive aplasia cutis congenita of the flanks and thighs, associated with a co-twin fetus papyraceus. DNA restriction fragment polymorphism analysis of the twins proved dizygosity. The association of these two conditions in twins is reviewed.

Zur Erklarung der unterschiedlichen Verteilung von Herz-Kreislauf-Erkrankungen in der Bevolkerung hat sich in der Epidemiologie das sog. Risikofaktorenkonzept, man kann durchaus sagen weltweit durchgesetzt. Wenn auch die dort ausgewiesenen Risikofaktoren „Hypercholesterinamie“, „Hypertonie“, „Zigarettenrauchen“ und (flankierend) „Ubergewicht“ und „Bewegungsmangel“ in ihrer Bedeutung im Verhaltnis zu den jeweils anderen unterschiedlich eingeschatzt wurden, so haben doch alle Faktoren ihr „Killerimage“ beibehalten. Zusammen werden sie fur einen betrachtlichen Teil aller Todesfalle verantwortlich gemacht, die in industrialisierten Gesellschaften eintreten. Behauptet wird auch, die schon lange bekannte und beobachtete sozialgrup-penspezifisch unterschiedliche Verteilung der Morbiditat und der Mortalitat sei durch Unterschiede in den Neigungen, risikoreich zu leben, begrundet, also auch personlich verantwortet (Stammler, 1979).

Gesundheitliche Beeintrachtigungen konnen durch arbeitsbedingte Belastungen und Gefahrdungen direkt bedingt sein. Dies gilt beispielsweise fur Arbeitsunfalle wie auch fur die anerkannten Berufskrankheiten. Hier mus im Regelfall die Schadigung eindeutig identifizierbar und monokausale Verursachungszusammenhange zwischen Exposition am Arbeitsplatz und Krankheitsgeschehen durch arbeitsmedizinische Verfahren und Untersuchungen belegt sein.

Klinische und epidemiologische Studien zeigen, das — neben anderen Determinanten — sowohl die soziookonomische Lage als auch physiologische und psychosoziale Belastungsmerkmale, nicht zuletzt im Rahmen der Berufstatigkeit, die Blutdruckwerte beeinflussen konnen. Neben anderen Risikofaktoren fur Herz-Kreislauf-Erkrankungen kommt auch ein erhohtes Blutdruckniveau bei Erwachsenen mit eingeschrankter beruflicher Qualifikation und damit einem niedrigen sozialen Status haufiger als im Bevolkerungsdurchschnitt vor [10]. Unter den teilweise mit einem niederen Sozialstatus korrelierenden Belastungsmerkmalen wurden im Zusammenhang mit dem Blutdruckniveau untersucht: Arbeitsplatzunsicherheit und Arbeitslosigkeit, Umgebungsbelastungen (z.B. Larm, Hitze, Schadstoffe), Merkmale des Arbeitsvollzugs (z.B. korperliche Schwerarbeit), Stres durch Uberforderung (z.B Tempo, Konzentration), Monotonie, Dequalifizierung und Fremdbestimmung [3].

Mit der Erfassung und Entdeckung physiologischer Risikofaktoren fur haufige Zivilisationskrankheiten kommen auf die Medizin immer mehr Aufgaben zu, die uber die blose Kuration hinausgehen. Die Behandlung solcher Risikofaktoren — nach ihrer Entdeckung, z.B. durch Screening-Programme — wird als ein zentraler Teil der Praventivmedizin angesehen (Borgers, 1983). Vor allem im Zusammenhang mit der Gesundheitsreform und den jetzt eingefuhrten Gesundheits-Checkups durfte sich dieser Aufgabenbereich deutlich ausweiten; grose Teile der Bevolkerung werden sich, sofern sie sich den Checkups unterziehen, danach als behandlungsbedurftig herausstellen, weil sie erhohte Risikofaktorenwerte auf weisen (Kramer, 1989).

Dem Bereich der Primarpravention im Gesundheitssicherungssystem kommt eine zunehmende Bedeutung zu. Eine Vielzahl von Einrichtungen, Organisationen, kommerziellen Institutionen bieten eine Fulle von Masnahmen zur Gesundheitsforderung an. Diesen Angeboten liegen teilweise jedoch kaum fundierte Analysen gesundheitlicher Problemsituationen der anzusprechenden Zielgruppe zugrunde, vielmehr wird haufig nach dem Motto verfahren: wir mussen auch einmal etwas tun. Der generellen Zielsetzung von Pravention, die Gesundheitsqualitat der Bevolkerung zu verbessern, bzw. Bevolkerungsgruppen, die besonderen gesundheitlichen Belastungen ausgesetzt sind, wie beispielsweise untere Sozialgruppen, problemadaquate Handlungsalternativen zu vermitteln, wird dadurch haufig eine eher nachgeordnete Prioritat zugunsten organisationsspezifischer Zielsetzung zugewiesen.

Noninvasive Quantification of Recirculation during Double Lumen Venovenous Extracorporeal Membrane Oxygenation (ECMO)

Characterization of Matrix Metalloproteinase-2 Activity in Lung Tissue in the Nitrofen Rat Model of Congenital Diaphragmatic Hernia (CDH)

In Search of the Respiratory Center: Medullary Pacemaker Cells and Their Response to Neurotransmitters

When are Follow-Up Sleep Studies Necessary in Preterm Infants Discharged Home on Theophylline?

Charaterization of Pacemaker Cells Uniquely Responsive to CO 2 : Effects of Neuromediators and a Placental Extract ♦ 1731

We have previously found that brief infusion (2 minutes) of a placental extract into the carotid artery inhibited spontaneous fetal breathing in sheep; in 50% of the infusions, the electrocortical activity (ECoG) switched from low voltage (LV) to high voltage (HV). The action was primarily found in the 1-10 kD subfraction and was tissue specific. In the present study we determined the effects of a more prolonged infusion of the 1-10 kD subfraction(over 3 hr) to see if the inhibition of breathing was independent of changes in ECoG and whether it persisted throughout the infusion. Infusion of the 1-10 kD subfraction (40 cc/hr) into the carotid artery of the fetal sheep (139± 2 days of gestation), induced a decrease in the incidence of breathing from 58% (baseline) to 43%, 27%, and 7% during the first, second, and third hour of infusion respectively (p

We have previously found specific pacemaker cells, highly sensitive to CO2, in the areas of the nucleus ambiguus (NA) and nucleus tractus solitarius (NTS), 2 mm rostral to the obex, in the fetal rat (J. Neurosci. Res., 33:590-597, 1992 & 33:579-589, 1992). We now report on the dose response evaluation of these cells as well as on their responsiveness to neurotransmitters. Twenty days old fetuses of pregnant Dawley rats were block dissected and the cells of the target areas were dissociated as previously described. Neuronal cells were plated in medullary background and placed in the incubator with 10% CO2 for 2 or 3 weeks. Cells were then studied using patch-clamp techniques. Pacemaker cells with single or bursting potentials showed responsiveness to CO2 starting with pulses of 10 msec(n=28 cells; 16 NA and 12 NTS). Irregularly beating or silent cells show either absent or poor responsiveness to CO2 (50 cells; 23 NA, 27 NTS). Pacemaker cells responded to norepinephrine (n=11) with an increase in firing potential, in a dose- response manner; this action was blocked by prazosin. Irregular beating cells (n=5) responded to norepinephrine poorly; silent cells(n=18) did not respond. Pacemaker cells responded to carbachol (n=18) with an increase in activity. Irregular beating cells responded poorly and silent cells did not respond; atropine blocked these effects. There were no differences in response related to the NA or NTS areas of the medulla. The findings suggest: 1) there is a very specific group of pacemaker cells in the most crucial respiratory area of the upper medulla which responds uniquely to CO2 in a dose-dependent manner. This property is not shared by non- pacemaker neurons; and 2) the responses to norepinephrine and carbachol are in agreement with respiratory responses observed in brainstem sectioned fetal lambs. We speculate that these pacemaker cells have been specifically designed for central CO2 chemoreception and may be involved in the generation of breathing.

VV ECMO is not widely used. A recent collaborative multicenter trial of neonatal ECMO showed that only 25% of the patients received VV ECMO (Lancet 1996;348:75-82). We retrospectively reviewed the charts of all neonatal ECMO candidates admitted to the NICU at the RAH since the introduction of VV ECMO in March 1993 to December 1996. Sixty-five near-term and term neonates were supported with ECMO during this period. Fifty-seven (88%) were initially supported by VV ECMO and 8 (12%) by venoarterial (VA) ECMO. Five (9%) of those initially supported by VV ECMO required conversion to VA ECMO for myocardial dysfunction. Six of the 8 VA ECMO neonates were placed on VA ECMO due to cannulation failure (small jugular vein) and the other two because of myocardial dysfunction. The neonates placed on VV ECMO were unstable with an oxygenation index of 89 ± 40 (mean ± SD), and requiring inotropic support of dopamine at 18 ± 7 mcg/kg/min and epinephrine at 1.2 ± 1 mcg/kg/min. The following table compares survival between the RAH and the Extracorporeal Life Support Organization(ELSO) data (January 1996) according to diagnosis when only VV ECMO was used. Fisher's exact test was employed.

The exact mechanism for airway closure during mixed apneas in preterm infants is unknown. One possibility is that lack of tone in the upper airway is followed by collapse and obstruction; another possibility is that the diaphragmatic action sucks the upper airway in and induces obstruction. We took advantage of our new method of detecting airway obstruction, based on the disappearance of a magnified cardiac pulse observed on the respiratory flow, to examine whether respiratory efforts are necessary for airway closure. We analyzed 198 mixed apneas of various lengths (≥3 s) observed in 33 preterm infants [birthweight 1400±100 g (mean±SE), study weight 1745±120 g; gestational age 29±1 wk, postnatal age 33±4 d]. The great majority of these apneas (88%) had a central followed by an obstructive component. The infants were studied using a nosepiece and a flow-through system. Respiratory efforts (abdominal and chest movements, diaphragmatic EMG) were recorded. Of the apneas, 20 were less than 5 second duration; 78, 5 to 10 seconds; 45, 10 to 15 seconds; 27, 15 to 20 seconds; and 28 greater than 20 seconds. Of the 198 mixed apneas, 151 occurred in the absence of any respiratory effort; 43 showed a simultaneous cessation of the cardiac oscillation and respiratory effort; and 4 showed diaphragmatic activity appearing after cessation of the cardiac oscillation. There was never any evidence of respiratory efforts preceding the cessation of the cardiac oscillation. The findings suggest 1) the diaphragmatic action is not needed to occlude the airway in mixed apneas, since most of them occlude without diaphragmatic activity, and in some such activity follows the closure of the airway; and 2) the simultaneous occlusion of the airway with the beginning of respiratory efforts in 43 apneas may indicate that such effort contributes to closure or is induced by the same stimulus that closes the airway. We speculate that the mechanism for airway closure in mixed apneas is most likely a lack of upper airway tone, which normally occurs simultaneously with the cessation of a central drive to breathe.Supported by the Children's Hospital of Winnipeg Research Foundation.

INCREASED INCIDENCE OF CLINICALLY SILENT OBSTRUCTIONS DURING APNEA IN PRETERM INFANTS WHO HAVE FAILED THEOPHYLLINE AND DOXAPRAM. 1335

Airway obstruction can be defined by the complete absence of a transmitted cardiac airflow oscillation in the flow tracing during an apnea. It may be further classified as overt or silent depending on the presence or absence of breathing efforts against the obstruction. Many patients manifest both types of obstructive apnea during an apnea study. We hypothesized that the presence or absence of a breathing effort response to obstruction is reflected in differences in oxygenation and/or ventilation in the minute prior to the apnea. To test this, we examined 3056 apneas of ≥ 3 s duration in 24 infants [birth weight 2100±190 g (mean±SE), study weight 2765±220 g, gestational age 33±1 wk, postnatal age 35±5 d] studied on 27 occasions, yielding 51 overt and 45 silent obstructive apneas. Although there was a significant difference in apnea duration between overt and silent types (13.0±1.25 vs 7.2±0.55s, p < 0.005), we detected no differences in oxygen saturation (97±0.7 vs 91±4.8), minute ventilation (0.249±0.011 vs 0.240±0.017 L·min-1·kg-1), respiratory rate (35±2 vs 37±2 breaths per minute), tidal volume (7.3±0.4 vs 6.6±0.4 ml·kg-1) and PACO2 (38±4 vs 35±1 Torr) in the minute preceding the apneas. These findings suggest that 1). The presence or absence of breathing efforts which defines overt and silent obstructive apnea respectively, is not attributable to differences in either oxygenation or ventilation in the minute prior to the apnea; and 2). the observed difference in apnea length between silent and overt obstructions, and the fact that no apneas have ever contained elements of both obstruction types, supports the idea that overt and silent obstructions have different underlying pathophysiologic mechanisms. Supported by the Canadian Lung Association, & Children's Hospital of Winnipeg Research Foundation.

With the advent of new technologies, it has become routine to offer supplemental oxygen to neonates via nasal prongs rather than by increasing the ambient oxygen in the incubator. The rationale for use of nasal prongs is that it provides more constant inspired O2 concentration whereas ambient oxygen is subject to fluctuations due to opening of the incubator doors. Nasal prongs, however, have significant disadvantages including i) nasal trauma, ii) increased restlessness, and iii) increased upper airway resistance with increased work of breathing. It remains subject to inspired O2 fluctuation due to prong dislodgement, which is common. Furthermore, we observed substantial clinical improvement in two preterm infants who had fewer apneas and appeared more comfortable after removing the nasal prongs and increasing the ambient O2 concentration. We hypothesized, therefore, that infants would have less apnea, less desaturation and less bradycardia with increased ambient O2 concentration compared with the nasal canulae. To test this hypothesis we studied 8 preterm infants[birthweight 1160±587g (mean ± SE), study weight 1240±534g, gestational age 28±3wk, postnatal age 28 + 4 d] on 9 occasions. Each study consisted of two consecutive 4 hour epochs where FiO2, hypopharyngeal O2, episodes of desaturation 10 s duration were measured while the infant was given O2 by either nasal prongs or into the isolette to maintain saturations at about 95%. Hypopharyngeal FiO2 was measured using a 10F suction catheter inserted via the nares and through which a 60 cc sample of gas was aspirated and its FiO2 measured with a Miniox O2 analyzer. Although hypopharyngeal O2 concentrations were similar (24 ± 4 vs 23 ± 5%, p = 0.55), we observed significantly greater number of apneas 13.2 ± 3 vs 2.8 ± 7 (p < 0.008) and desaturations 14 ± 3 vs 9 ± 3 (p < 0.008) when using nasal prongs. There was no difference in the number of bradycardias. We conclude that administration of O2 into the isolette is associated with fewer apneas and less desaturations and, for this reason, it may be a superior method of O2 administration in preterm infants. Supported by Children's Hospital Research Foundation & Canadian Lung Association.

We have developed a method of apnea classification which relies on the transmission of cardiac airflow oscillation to indicate airway patency. Using a theoretical model we have previously shown that the amplitude of the cardiac airflow oscillation is proportional to airway diameter for small lumens. While in the majority of central apneas, the amplitude of the cardiac airflow oscillation remains constant, there is a subset of events where the waveform decreases with time. We hypothesized that this is not a random occurrence but reflects a critical period of airway instability during a central apnea. To test this we examined 212/1257 central apneas in 12 infants [birth weight 1625±240 g (mean±SE), study weight 2065±270 g, gestational age 30±1 wk, postnatal age 35±9 d] referred to our laboratory. The amplitude of the cardiac airflow oscillation produced by each individual heart beat during an apnea was measured and tabulated to provide a dynamic measure of changes in airway diameter with time. To allow for comparisons between patients the amplitude of each cardiac airflow oscillation was expressed as a proportion of the maximum amplitude observed in each infant. We then compared the amplitude at multiple successive 0.5 second intervals with the amplitude of the cardiac airflow oscillation observed at the apnea outset using an ANOVA. We found a significant decrease in cardiac airflow oscillation after only one second (initial=0.609±0.215, vs. 0.5s=0.611±0.213, p=0.53; vs. 1s=0.589±0.235, p≤0.01; vs. 2s=0.471±0.301, p≤0.001) irrespective of the apnea duration (3 to 16 s). We conclude that airway narrowing during central apnea is not a random occurrence but occur shortly after the onset of the apnea. We speculate that the phenomenon is secondary to passive airway relaxation. Supported by Canadian Lung Association and Children's Hospital of Winnipeg Research Foundation.