Noninvasive determination of cardiac output using single breath CO2 analysis

OBJECTIVE: To examine the utility of single breath CO2 analysis as a noninvasive measure of cardiac output. SETTING: An animal laboratory in a university-affiliated medical center. DESIGN: A prospective, animal cohort study comparing 21 parameters derived from single breath CO2 analysis with cardiac output determined by an ultrasonic flow probe. SUBJECTS: Six healthy adult sheep. METHODS: The single breath CO2 analysis station consists of a mainstream capnometer, a variable orifice pneumotachometer, a signal processor, and computer software with capability for both on- and off-line data analysis. Twenty-one derived components of the CO2 expirogram were evaluated as predictors of cardiac output. Cardiac output was manipulated by successive injections of a hydraulic constrictor placed around the inferior vena cava. MEASUREMENTS AND MAIN RESULTS: Thirty-four measurements of cardiac output were available for comparison with derived variables from the CO2 expirogram. Stepwise linear regression identified two variables that were most predictive of cardiac output: a) the angle between the slope lines for phase II and III of the CO2 expirogram divided by the volume of CO2 per breath (angle/mL CO2); and b) the slope of phase II. The multivariate equation was highly statistically significant and explained 94% of the variance (adjusted r2 = .94, p < .0001). The bias and precision of the calculated cardiac output were .00 and .23, respectively. The mean percent difference for the cardiac output estimate derived from the single breath CO2 analysis station was 0.36%. CONCLUSIONS: Our data indicate that analysis of the CO2 expirogram can yield accurate information about the cardiovascular system. Specifically, two variables derived from a plot of expired CO2 concentration vs. expired volume predict changes in cardiac output in healthy adult sheep with an adjusted coefficient of determination of .94. Prospective application of this technology in the setting of lung injury and rapidly changing physiology will be essential in determining the clinical usefulness of the technique.     

Cellular mechanisms of intestine regeneration in the sea cucumber, Holothuria glaberrima Selenka (Holothuroidea:Echinodermata)

Echinoderms are the deuterostome group with the most striking capacity to regenerate lost body parts. In particular, members of the class Holothuroidea are able to regenerate most of their internal organs following a typical evisceration process. Such formation of new viscera in an adult organism provides a unique model to study the process of organogenesis. We have studied this process in the sea cucumber Holothuria glabberrima by describing the spatial and temporal pattern of cellular events that occur during intestine regeneration following chemically induced evisceration. Regeneration begins as a thickening of the mesenteries that supported the autotomized organs to the body wall. The mesenterial thickening consists of tissues where most of the cellular populations found in the normal intestine are already present. However, the cell numbers differ, particularly those of hemocytes and amoebocytes, suggesting that some of these cells play an important role in the formation of the solid rod of hypertrophic mesentery that characterizes the intestinal primordia. The appearance of the luminal epithelium, together with the formation of the lumen, occurs during the second week of regeneration by proliferation and extensive migration of cells from the esophagus and cloacal ends into the thickenings. At this stage all tissue layers are present, but it takes an additional week for them to exhibit the proportions typical of the normal organ. Cell division, as determined by BrdU labeling, mainly occurs in the coelomic epithelia of the hypertrophic mesentery and in the regenerating luminal epithelium. Our study provides evidence that the process of new organ formation in holothurians can be described as an intermediate process showing characteristics of both epimorphic and morphallactic phenomena.     

Seminar planning guidelines. As I see it

Small local chapter groups can present quality cost effective regional seminars. Key components are dedication of members, teamwork, and a sense of direction. The following guidelines and information can provide a framework for planning and coordinating a seminar.     

The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM

In addition to triggering the activation of B- or T-cell antigen receptors, the binding of a ligand to its receptor at the cell surface can sometimes determine the physiological outcome of interactions between antigen-presenting cells, T and B lymphocytes. The protein SLAM (also known as CDw150), which is present on the surface of B and T cells, forms such a receptor-ligand pair as it is a self-ligand. We now show that a T-cell-specific, SLAM-associated protein (SAP), which contains an SH2 domain and a short tall, acts as an inhibitor by blocking recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region. The gene encoding SAP maps to the same area of the X chromosome as the locus for X-linked lymphoproliferative disease (XLP) and we found mutations in the SAP gene in three XLP patients. Absence of the inhibitor SAP in XLP patients affects T/B-cell interactions induced by SLAM, leading to an inability to control B-cell proliferation caused by Epstein-Barr virus infections.     

A mutation spectra database for bacterial and mammalian genes: 1998

This database consists of over 24 000 mutations in 18 viral, bacterial, yeast or mammalian genes. The data are grouped as sets of DNA base sequence changes or spectra caused by a particular mutagen under defined conditions. The spectra are available on the World Wide Web at http://info.med.yale.edu/mutbase/ in two formats; in text format that can be browsed on-line or downloaded for use with a text editor and in dBASEIII format for use, after downloading, by relational database programs or by spreadsheets. Researchers are encouraged to submit DNA sequence changes to a suitable mutation database such as ours. A data entry program, MUTSIN, can be retrieved from this site. MUTSIN diagrams each mutation on the computer screen and alerts the user to any discrepancies.     

NMDA receptors mediate peripheral chemoreceptor afferent input in the conscious rat

N-methyl-D-aspartate (NMDA) glutamate receptors mediate critical components of cardiorespiratory control in anesthetized animals. The role of NMDA receptors in the ventilatory responses to peripheral and central chemoreceptor stimulation was investigated in conscious, freely behaving rats. Minute ventilation (VE) responses to 10% O2, 5% CO2, and increasing intravenous doses of sodium cyanide were measured in intact rats before and after intravenous administration of the NMDA receptor antagonist MK-801 (3 mg/kg). After MK-801, eupcapnic tidal volume (VT) decreased while frequency increased, resulting in a modest reduction in VE. Inspiratory time (TI) decreased, whereas expiratory time remained unchanged. The VE responses to hypercapnia were qualitatively similar in control and MK-801 conditions, with slight reductions in respiratory drive (VT/TI) after MK-801. In contrast, responses to hypoxia were markedly attenuated after MK-801 and were primarily due to reduced frequency changes, whereas VT was unaffected. Sodium cyanide doses associated with significant VE increases were 5 and 50 microg/kg before and after MK-801, respectively. Thus 1-log shift to the right of individual dose-response curves occurred with MK-801. Selective carotid body denervation reduced VE during hypoxia by 70%, and residual hypoxic ventilatory responses were abolished after MK-801. These findings suggest that, in conscious rats, carotid and other peripheral chemoreceptor-mediated hypoxic ventilatory responses are critically dependent on NMDA receptor activation and that NMDA receptor mechanisms are only modestly involved during hypercapnia.     

Mechanical distraction for treatment of severe knee flexion contractures

Ten patients (14 knees) with severe knee flexion contractures were treated by gradual mechanical distraction using either the Ilizarov or Orthofix external fixator. Range of motion improved from an average flexion contracture of 60 degrees before surgery to 16 degrees at the follow-up evaluation. Range of motion results were graded good or excellent in five knees, fair in two knees, and poor in three knees. Average total arc of motion remained essentially unchanged when comparing the preoperative (59 degrees) with the follow-up results (63 degrees). However, the functional position of this arc improved significantly. Problems encountered included a "rebound" phenomena after frame removal, with loss of the temporarily increased total arc of motion. The role of hamstring tenotomy and radical posterior knee release remains unclear.     

Tenth anniversary of chapter Falcon's: notes for the history of the Venezuelan Association for the Advancement of Science (AsoVAC)]

Chapter Falcón of the Venezuelan Association for the Advancement of Science (AsoVAC) was chartered in 1984. In this essay we outline and analyze the circumstances and elements that made possible the establishment of this chapter. The key factors probably were a tight relation with Universidad Nacional Experimental Francisco de Miranda (UNEFM), which allowed to advance several common projects; the selection of realistic projects that could be "read" as organizational muscle; setting of goals that could be achieved with the resources at hand; and taking advantage of some of the psychological traits of Falcón State inhabitants. This chapter's future is pondered under the light of the unusual responsibilities that it will face during this year: mainly the organization of the AsoVAC annual convention, which will be held in Falcón for the first time.     

The Benchmarking Effort for Networking Children's Hospitals (BENCHmark)

BACKGROUND: In 1992, 12 large children's hospitals established the Benchmarking Effort for Networking Children's Hospitals (BENCHmark). The goal was for the BENCHmark effort to supplement the hospitals' continuous quality improvement (CQI) programs and to speed adoption of best practices from peer institutions. For three years, the hospitals have been comparing data on cost, quality, and speed indicators. Also, "best practice" groups have met to share information on how processes can be improved. RESULTS: The BENCHmark hospitals have experienced significant process improvement in areas such as emergency department waiting time and admitting process time. EXAMPLE: The BENCHmark hospitals selected admitting as one of the first best practice groups to meet. Interdisciplinary staff from all BENCHmark hospitals met three times over the course of a year to define their indicator and share information on best practices. St Louis Children's Hospital, as a result, instituted a pre-arrival team and cross-trained staff, with the result being a reduction of admitting processing time from 58 minutes to 19 minutes. Same-day surgery patients now bypass the admitting department and go directly to the surgical floor. Patient and surgeon satisfaction has increased greatly. CONCLUSIONS: Hospitals that are planning to benchmark are encouraged to reach consensus on project goals and to focus on indicators that provide a clear business advantage. Physician involvement is key to improving performance and physicians will only be engaged if the hospitals against whom they are benchmarked are considered peers. Being willing to share initial data openly seems to be a key factor in determining successful integration of the BENCHmark process into hospital CQI efforts. The BENCHmark project has been so successful that a second group of 12 comparable pediatric institutions, known as the Network II, has been established.