Identification of an optimal CPR chest compression protocol.

In this study, we used a high-fidelity integrated computational model of the respiratory and cardiovascular systems to investigate cardiopulmonary resuscitation (CPR) after cardiac arrest in a virtual healthy subject. For the purpose of this work, a newly developed thoracic model has been integrated to the current model, to study the influence of external chest compressions upon the arrested circulation during CPR. We evaluated the chest compression (CC) parameters, namely, end compression force, compression rate, and duty cycle to optimize the coronary perfusion pressure and the systolic blood pressure, using a genetic algorithm. While the sternal displacement associated with the CC force agreed with the ERC guidelines, the CC rate and duty cycle were respectively higher and lower than the ones recommended by the ERC guidelines. The effect of these CC parameters on cardiac output (CO) were also assessed. The end compression force was the parameter with the largest impact on CO, while the compression rate and duty cycle scarcely influence it.Relevance- Our results may aid in understanding the underlying pathophysiology of cardiac arrest and help guide research into the refinement of CPR strategies, without sacrificing animals or conducting clinical trials, which are difficult to undertake in crisis scenarios.

Computer simulation clarifies mechanisms of carbon dioxide clearance during apnoea.

BACKGROUND: Apnoeic oxygenation can come close to matching the oxygen demands of the apnoeic patient but does not facilitate carbon dioxide (CO2) elimination, potentially resulting in dangerous hypercapnia. Numerous studies have shown that high-flow nasal oxygen administration prevents hypoxaemia, and appears to reduce the rate of increase of arterial CO2 partial pressure (PaCO2), but evidence is lacking to explain these effects. METHODS: We extended a high-fidelity computational simulation of cardiopulmonary physiology to include modules allowing variable effects of: (a) cardiogenic oscillations affecting intrathoracic gas spaces, (b) gas mixing within the anatomical dead space, (c) insufflation into the trachea or above the glottis, and (d) pharyngeal pressure oscillation. We validated this model by reproducing the methods and results of five clinical studies on apnoeic oxygenation. RESULTS: Simulated outputs best matched clinical data for model selection of parameters reflecting: (a) significant effects of cardiogenic oscillations on alveoli, both in terms of strength of the effect (4.5 cm H2O) and percentage of alveoli affected (60%), (b) augmented gas mixing within the anatomical dead space, and (c) pharyngeal pressure oscillations between 0 and 2 cm H2O at 70 Hz. CONCLUSIONS: Cardiogenic oscillations, dead space gas mixing, and micro-ventilation induced by pharyngeal pressure variations appear to be important mechanisms that combine to facilitate the clearance of CO2 during apnoea. Evolution of high-flow oxygen insufflation devices should take advantage of these insights, potentially improving apnoeic gas exchange.

Segmental colonic dilation is associated with premature termination of high-amplitude propagating contractions in children with intractable functional constipation.

BACKGROUND: Colonic dilation is common in children with intractable functional constipation (FC). Our aim was to describe the association between segmental colonic dilation and colonic dysmotility in children with FC. METHODS: We performed a retrospective study on 30 children with intractable FC (according to the Rome III criteria) who had undergone colonic manometry and contrast enema within a 12-month time period. Colonic diameter was measured at 5 cm intervals from the anal verge up to the splenic flexure. Moreover, the distance between the lateral margins of the pedicles of vertebra L2 was measured to provide a ratio (colonic diameter or length/distance between the lateral margins; "standardized colon size" [SCS]). All manometry recordings were visually inspected for the presence of high-amplitude propagating contractions (HAPCs); a parameter for colonic motility integrity. The intracolonic location of the manometry catheter sensors was assessed using an abdominal X-ray. KEY RESULTS: Colonic segments with HAPCs had a significantly smaller median diameter than colonic segments without HAPCs (4.08 cm vs 5.48 cm, P<.001; SCS 1.14 vs 1.66, P=.001). Children with prematurely terminating HAPCs had significantly larger SCS ratios for colonic diameter than children with fully propagating HAPCs (P=.008). SCS ratios for the length of the rectosigmoid and the descending colon and the SCS ratio for sigmoid colon diameter were significantly larger in children with FC compared to a previously described normative population (P<.0001, P<.0001 and P=.0007 respectively). CONCLUSIONS & INFERENCES: Segmental colonic dilation was associated with prematurely terminating HAPCs and may be a useful indicator of colonic dysmotility.

High PEEP in acute respiratory distress syndrome: quantitative evaluation between improved arterial oxygenation and decreased oxygen delivery.

BACKGROUND: Positive end-expiratory pressure (PEEP) is widely used to improve oxygenation and prevent alveolar collapse in mechanically ventilated patients with the acute respiratory distress syndrome (ARDS). Although PEEP improves arterial oxygenation predictably, high-PEEP strategies have demonstrated equivocal improvements in ARDS-related mortality. The effect of PEEP on tissue oxygen delivery is poorly understood and is difficult to quantify or investigate in the clinical environment. METHODS: We investigated the effects of PEEP on tissue oxygen delivery in ARDS using a new, high-fidelity, computational model with highly integrated respiratory and cardiovascular systems. The model was configured to replicate published clinical trial data on the responses of 12 individual ARDS patients to changes in PEEP. These virtual patients were subjected to increasing PEEP levels during a lung-protective ventilation strategy (0-20 cm H2O). Measured variables included arterial oxygenation, cardiac output, peripheral oxygen delivery, and alveolar strain. RESULTS: As PEEP increased, tissue oxygen delivery decreased in all subjects (mean reduction of 25% at 20 cm H2O PEEP), despite an increase in arterial oxygen tension (mean increase 6.7 kPa at 20 cm H2O PEEP). Changes in arterial oxygenation and tissue oxygen delivery differed between subjects but showed a consistent pattern. Static and dynamic alveolar strain decreased in all patients as PEEP increased. CONCLUSIONS: Incremental PEEP in ARDS appears to protect alveoli and improve arterial oxygenation, but also appears to impair tissue oxygen delivery significantly because of reduced cardiac output. We propose that this trade-off may explain the poor improvements in mortality associated with high-PEEP ventilation strategies.

Validation and invalidation of systems biology models using robustness analysis.

Robustness, the ability of a system to function correctly in the presence of both internal and external uncertainty, has emerged as a key organising principle in many biological systems. Biological robustness has thus become a major focus of research in Systems Biology, particularly on the engineering-biology interface, since the concept of robustness was first rigorously defined in the context of engineering control systems. This review focuses on one particularly important aspect of robustness in Systems Biology, that is, the use of robustness analysis methods for the validation or invalidation of models of biological systems. With the explosive growth in quantitative modelling brought about by Systems Biology, the problem of validating, invalidating and discriminating between competing models of a biological system has become an increasingly important one. In this review, the authors provide a comprehensive overview of the tools and methods that are available for this task, and illustrate the wide range of biological systems to which this approach has been successfully applied.

A systems engineering approach to validation of a pulmonary physiology simulator for clinical applications.

Physiological simulators which are intended for use in clinical environments face harsh expectations from medical practitioners; they must cope with significant levels of uncertainty arising from non-measurable parameters, population heterogeneity and disease heterogeneity, and their validation must provide watertight proof of their applicability and reliability in the clinical arena. This paper describes a systems engineering framework for the validation of an in silico simulation model of pulmonary physiology. We combine explicit modelling of uncertainty/variability with advanced global optimization methods to demonstrate that the model predictions never deviate from physiologically plausible values for realistic levels of parametric uncertainty. The simulation model considered here has been designed to represent a dynamic in vivo cardiopulmonary state iterating through a mass-conserving set of equations based on established physiological principles and has been developed for a direct clinical application in an intensive-care environment. The approach to uncertainty modelling is adapted from the current best practice in the field of systems and control engineering, and a range of advanced optimization methods are employed to check the robustness of the model, including sequential quadratic programming, mesh-adaptive direct search and genetic algorithms. An overview of these methods and a comparison of their reliability and computational efficiency in comparison to statistical approaches such as Monte Carlo simulation are provided. The results of our study indicate that the simulator provides robust predictions of arterial gas pressures for all realistic ranges of model parameters, and also demonstrate the general applicability of the proposed approach to model validation for physiological simulation.

Robustness analysis of biochemical network models.

Biological systems that have been experimentally verified to be robust to significant changes in their environments require mathematical models that are themselves robust. In this context, a necessary condition for model robustness is that the model dynamics should not be sensitive to small variations in the model's parameters. Robustness analysis problems of this type have been extensively studied in the field of robust control theory and have been found to be very difficult to solve in general. The authors describe how some tools from robust control theory and nonlinear optimisation can be used to analyse the robustness of a recently proposed model of the molecular network underlying adenosine 3',5'-cyclic monophosphate (cAMP) oscillations observed in fields of chemotactic Dictyostelium cells. The network model, which consists of a system of seven coupled nonlinear differential equations, accurately reproduces the spontaneous oscillations in cAMP observed during the early development of D. discoideum. The analysis by the authors reveals, however, that very small variations in the model parameters can effectively destroy the required oscillatory dynamics. A biological interpretation of the analysis results is that correct functioning of a particular positive feedback loop in the proposed model is crucial to maintaining the required oscillatory dynamics.

Dynamic ultrasound findings of bilateral anterior tibialis muscle herniation in a pediatric patient.

Muscular hernias represent focal muscular protrusions through an acquired or congenital fascial defect. The anterior tibialis muscle is most frequently affected. The ultrasound (US) findings in a pediatric patient with bilateral anterior tibialis muscle herniation are presented. US examination performed following exercise enhanced sonographic visualization of the fascial defect and the associated muscular herniation.

Ultrasound diagnosis of the anterior urethral valve.

We present a neonate with an obstructing anterior urethral valve depicted by longitudinal transpenile ultrasound. Voiding images are recommended to identify the obstructing valve tissue. Ultrasound depiction of the anterior urethral valve tissue is identical to that seen in posterior urethral valves.

Congenital urethroperineal fistula.

PURPOSE: To characterize the radiographic appearances of congenital urethroperineal fistula and to distinguish it from urethral duplication of the hypospadiac type. MATERIALS AND METHODS: The authors examined four patients with congenital urethroperineal fistula in whom radiographic examinations were performed to define the pathologic anatomy. RESULTS: Congenital urethroperineal fistula mimics the hypospadiac form of urethral duplication, except the normally positioned dorsal channel is the normal urethra. Patients with congenital urethroperineal fistula have normal micturition. Both a normal dorsal penile urethra and a ventral urethroperineal fistula can be observed during radiographic and cystoscopic examination. The dorsal urethra is the functionally normal channel. Excision of the ventral channel is simple and curative. This contrasts starkly with congenital urethral duplication of the hypospadiac type, where excision of the ventral channel may be catastrophic. CONCLUSION: Although it resembles the hypospadiac form of urethral duplication, congenital urethroperineal fistula should be classified as a separate entity.

Patellar sleeve fracture: demonstration with MR imaging.

PURPOSE: To demonstrate the magnetic resonance (MR) imaging characteristics of patellar sleeve fracture, a cartilaginous avulsion from the lower pole of the patella occurring during forceful contraction of the quadriceps muscle against a partially flexed knee. MATERIALS AND METHODS: The authors evaluated radiographs and MR images from three children with suspected sleeve fractures. RESULTS: Radiographs showed small bone fragments avulsed from the lower patella in two children and no bone abnormality in one. MR imaging demonstrated separation of most of the cartilaginous lower patella in all children, definite intraarticular extension in one, and possible intraarticular extension in another. CONCLUSION: MR imaging can help determine the need for surgery by depicting the extent of cartilaginous injury and displacement of fracture fragments.

Preventing nuclear war: what physicians can achieve.

On its fifth anniversary, the International Physicians for the Prevention of Nuclear War was awarded the Nobel Peace Prize. The organization was conceived by two Boston cardiologists who joined with some Soviet colleagues to create an international forum for considering the medical consequences of and means for preventing nuclear war. This article by the organization's archivist documents its difficult progress yet remarkable growth. Overcoming serious obstacles has added to its strength and credibility: now involving organizations with 145,000 members in 41 countries, IPPNW has become the international voice of medicine's concern about nuclear war.