Biomedical subjects
Publications and source records attributed to C S Cox.
Placement of a transpyloric feeding tube is a common procedure done through a previous gastrostomy site. Conventional fluoroscopic and endoscopic methods can be tedious because of the difficulty in cannulating the pylorus. Described here is a simplified method to place a transpyloric feeding tube under fluoroscopy.
Nonoperative management of blunt abdominal trauma is widely accepted in pediatric patients. There are few factors prospectively available to predict reliably which children will not respond to nonoperative treatment. Computed tomography scans demonstrating a vascular contrast blush are associated with arterial bleeding and the failure of nonoperative management of splenic injuries in adults. The authors describe five hemondynamically stable pediatric patients who have intraabdominal injury and a characteristic vascular contrast blush who acutely did not respond to nonoperative treatment. Vascular blush may be an indication for early laparotomy in pediatric trauma patients.
In order to evaluate prophylaxis and therapy for individuals infected with pathogens by the airborne route, we have designed and built a simple apparatus in which small laboratory animals may be exposed to aerosols of infectious microorganisms. Animals are kept in a chamber closed by a HEPA filter and exposed to the pathogen aerosolized using a Collison nebulizer. Air in the exposure chamber may be sampled to show that the infectious agent is present but the dose of agent must be expressed as 50% effective doses determined by titration. An effective dose may be defined by whatever criteria are chosen to judge disease. Using this apparatus we have shown that St Louis encephalitis (SLE) virus is infectious for mice by the airborne route. These data support the idea that there may be significant hazard to personnel exposed to aerosols of infectious SLE after a laboratory accident.
OBJECTIVE: The purpose of this study was to evaluate the accuracy of abdominal ultrasonography (US) for screening and grading pediatric splenic injury. SUMMARY BACKGROUND DATA: The use of abdominal US has increased rapidly as a method of evaluating organ damage after blunt abdominal trauma. Despite US's increasing use, little is known about its accuracy in children with splenic injury. METHODS: Children (N = 32) suffering blunt abdominal trauma who were diagnosed with splenic injury by computerized tomography (CT) scan prospectively were enlisted in this study. Degree of splenic injury was evaluated by both CT and US. The ultrasounds were evaluated by an initial reading as well as by a radiologist who was blinded as to the results of the CT. RESULTS: Twelve (38%) of the 32 splenic injuries found on CT were missed completely on the initial reading of the US. When the ultrasounds were graded in a blinded fashion, 10 (31%) of the splenic lacerations were missed and 17 (53%) were downgraded. Seven (22%) of the 32 splenic fractures were not associated with any free intraperitoneal fluid on the CT scan. CONCLUSIONS: This study has shown that US has a low level of sensitivity (62% to 78%) in detecting splenic injury and downgrades the degree of injury in the majority of cases. Reliance on free intraperitoneal fluid may be inaccurate because not all patients with splenic injury have free intra-abdominal fluid. Based on these findings, US may be of limited use in the initial assessment, management, and follow-up of pediatric splenic trauma.
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BACKGROUND: Pulmonary contusion (PC) is a common sequelae of blunt trauma in adults and children; previous reports suggest that children have more favorable outcomes because of differences in mechanisms of injury, associated injury, and physiologic response. Our objective was to determine whether children who sustain PC have different outcomes compared with similarly injured adults. STUDY DESIGN: Our Level I Trauma Registry was reviewed for a 4-year period and identified 251 consecutive patients who sustained PC. Their charts were reviewed retrospectively for demographics, injury mechanism, injury severity scores, associated injuries, and outcomes (measured by the need for intubation, ventilation days, pneumonia, acute respiratory distress syndrome, and death). Data are expressed as the mean +/- SEM. The Student's t-test was used to compare the groups. A p value less than 0.05 was considered significant. RESULTS: Of the study patients, 41 (16%) were children (ages 2-16, mean 10 years) and 210 (84%) were adults (ages 17-80, mean 34 years). The most common injury mechanisms in children were motor vehicle accidents (56%) and auto-pedestrian accidents (39%), but in adults, motor vehicle accidents (80%, p = 0.02) predominated. Injury severity score was not significantly different between groups (children, 26 +/- 2 and adults 25 +/- 1). Similarly, the incidence of associated injuries was not different between children and adults: head 78% versus 62%, abdomen 59% versus 43%, and skeletal fractures 41% versus 29%, respectively. Neither need for intubation, ventilator days, pneumonia, acute respiratory distress syndrome, or death differed significantly between groups. CONCLUSIONS: Although children and adults differ in regard to injury mechanism, their overall injury severity, associated injuries, and outcomes are quite similar. Thus, contrary to previous reports, children do not have a more favorable outcome after PC.
OBJECTIVES: The NHANES I Epidemiologic Followup Study (NHEFS) is a longitudinal study that uses as its baseline those adult persons 25-74 years of age who were examined in the first National Health and Nutrition Examination Survey (NHANES I). NHEFS was designed to investigate the association between factors measured at baseline and the development of specific health conditions. The three major objectives of NHEFS are to study morbidity and mortality associated with suspected risk factors, changes over time in participants' characteristics, and the natural history of chronic disease and functional impairments. METHODS: Tracing and data collection in the 1992 Followup were undertaken for the 11,195 subjects who were not known to be deceased in the previous surveys. No additional information was collected in the 1992 NHEFS for the 3,212 subjects who were known to be deceased before the 1992 NHEFS data collection period. RESULTS: By the end of the 1992 NHEFS survey period, 90.0 percent of the 11,195 subjects in the 1992 Followup cohort had been successfully traced. Interviews were conducted for 9,281 subjects. An interview was conducted for 8,151 of the 8,687 surviving subjects; 551 interviews were administered to a proxy respondent because the subject was incapacitated. A proxy interview was conducted for 1,130 of the 1,392 decedents identified in the 1992 NHEFS. In addition, 10,535 facility stay records were collected for 4,162 subjects reporting overnight facility stays. Death certificates were obtained for 1,374 of the 1,392 subjects who were identified as deceased since last contact. Approximately 32 percent of the NHEFS cohort is known to be deceased with a death certificate available for 98 percent of the 4,604 NHEFS decedents.
To address the controversy regarding the relationship between cognitive impairment (lowering of IQ) and magnetic resonance imaging (MRI) characteristics (T2-weighted hyperintensities or unidentified bright objects [UBOs]) in children with neurofibromatosis-1 (NF-1), we used a pairwise NF-1/ sibling design; we set out to predict the lowering of IQ in each child with NF-1 as a discrepancy from the IQ of an unaffected sibling (D-SIQ). Our multiple regression model included the age of the child with NF-1, familial or sporadic nature of the NF-1, number of locations in the child's brain occupied by T2-weighted hyperintensities (UBOs), and the volumetric percentage of brain tissue occupied by T2-weighted hyperintensities (UBOs). Only the number of locations occupied by UBOs accounted for IQ lowering (D-SIQ) in children with NF-1 (42% of the variance in D-SIQ). This is the first report to confirm that a continuum of lowered IQs in NF-1-affected children exists in relation to the distribution of UBOs (range 0-7), not just presence (vs. absence) of any UBOs.
There is evidence of increased oxygen free radical activity after smoke inhalation with and without concomitant burn injury. We determined the effects of manganese superoxide dismutase (Mn SOD) on lung fluid balance as measured by lung microvascular permeability coefficient (sigma), filtration coefficient (Kf), and lymph flow. Merino breed ewes (n = 6/group) were surgically prepared. The SOD group (SOD) received Mn SOD (9,000 U/kg) as an intravenous bolus and was insufflated with smoke. The control group (CON) received saline and smoke. sigma and Kf were determined 24 h before and 24 h after smoke injury. Lymph flow, arterial O2-to-inspired O2 fraction ratio, systemic hemodynamics, and pulmonary arterial and capillary pressures were measured. The sigma was significantly (P < 0.05) higher after smoke insufflation in SOD compared with CON (0.71 +/- 0.03 vs. 0.53 +/- 0.05). Kf was significantly lower after smoke insufflation in SOD compared with CON (0.038 +/- 0.010 vs. 0.061 +/- 0.010). Lymph flows were significantly lower during the 24 h after smoke insufflation in SOD compared with CON (33 +/- 7 vs. 55 +/- 8 ml/h at 24 h). Arterial O2-to-inspired O2 fraction ratio was significantly improved at 6 and 12 h after smoke insufflation in SOD compared with CON at the same time points. Mn SOD meliorates the lung microvascular permeability changes associated with smoke inhalation injury.
IVOX (intravenous oxygenator and CO2 removal device) augments venous gas exchange in patients with severe respiratory failure. Controlled hypoventilation with permissive hypercapnia reduces airway pressures during mechanical ventilation and augments CO2 exchange through the IVOX. To quantify the additive effects of gradual permissive hypercapnia and IVOX on gas exchange and reduction of airway pressures, 13 adult sheep underwent tracheostomy and severe smoke inhalation injury. Seven were mechanically ventilated alone (control), and six had mechanical ventilation, systemic anticoagulation, and implantation of IVOX (size 7 with 0.21-m2 surface area) (IVOX group). Both groups were anesthetized and paralyzed for 24 hr. In the IVOX group, minute ventilation was decreased in a stepwise fashion to produce a gradual increase in PaCO2, from 30 to 95 mm Hg, over 12 hr, and then sustained for an additional 12 hr. Sodium bicarbonate was given intravenously as necessary to keep arterial pH above 7.25. There were no significant differences in mean arterial pressure, cardiac output, or pulmonary artery pressure between the two groups. In the IVOX/permissive hypercapnia group, IVOX CO2 removal increased as a linear function of PaCO2 (y = 0.87x + 8.99, R2 = 0.80). IVOX CO2 removal was only 40 ml/min at normocapnia (40 mm Hg) but increased to 91 ml/min when PaCO2 was 95 mm Hg. Both peak inspiratory pressure and minute ventilation of the IVOX/permissive hypercapnia group were significantly lower than the control group, 30 +/- 4 mm Hg vs 51 +/- 3 mm Hg and 3.9 +/- 0.3 liters vs 8.4 +/- 0.5 liters (P < 0.05) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Since 1973, 7667 neonates have been treated with extracorporeal membrane oxygenation for severe respiratory failure and their cases reported to the Extracorporeal Life Support Organization Registry. The overall survival was 81% in these neonates, who were thought to have a survival of 20% without extracorporeal membrane oxygenation. A total of 4322 mechanical complications (0.56 +/- 0.84 per case) and 13,827 patient complications (1.80 +/- 2.12 per case) were reported overall. The most common mechanical complications included clots in the circuit (19%), cannula placement (9%), oxygenator failure (4%), and others (9%). Common patient complications included cardiopulmonary (43%), neurologic (35%), bleeding (35%), metabolic (32%), renal (25%), and renal (25%), and infectious (9%). From the initial experience to 1988 the average number of mechanical complications per case was 0.27 per case and this significantly increased during 1990 to 1992 to 0.75 per case (p < 0.05). Likewise, from 1973-1985 to 1988 the average patient complications per case were 1.44 per case and this significantly increased during 1990 to 1992 to 2.10 per case. During the same periods, patient survival significantly decreased from 84% (1973-1985 to 1988, n = 2463) to 80% (1990 to 1992, n = 4005). Venovenous double-lumen single cannula extracorporeal membrane oxygenation had a higher survival than venoarterial extracorporeal membrane oxygenation (91% versus 81%) and a lower rate of major neurologic complications. The incidence and survival with seizures (6% and 89% venovenous versus 13% and 61% venoarterial) or cerebral infarction (9% and 69% venovenous versus 14% and 46% venoarterial) was significantly lower with the venovenous method and appeared to have a substantial impact on overall survival. The correlation of patient complication rate and total complication rate with survival was highly significant, however, causality cannot be established. Explanations for the increase in complications, relative to a decrease in survival, despite a growing nationwide experience include (1) increased complexity of cases as many programs expand entry criteria (more premature infants, infants with grade 1 or 2 intracranial hemorrhage, and complex congenital diaphragmatic hernia), (2) a growing number of programs with fewer cases per program, yet greater accessibility, (3) less reluctance to report complications encountered during extracorporeal membrane oxygenation as group experience grows, and (4) changes in the Extracorporeal Life Support Organization data form to be more inclusive of more minor complications.
In addition to water, microbes mainly comprise lipids, carbohydrates, proteins and nucleic acids. Their structure and function singularly and conjointly is affected by water activity. Dessication leads to dramatic lipid phase changes whereas carbohydrates, proteins and nucleic acids initially suffer spontaneous, reversible low activation energy Maillard reactions forming products that more slowly re-arrange, cross-link etc. to give non-native states. While initial products spontaneously may reverse to native states by raising water activity, later products only do so through energy consumption and enzymatic activity eg. repair. Yet, native states of lipid membranes and associated enzymes are required to generate energy. Consequently, good reserves of high energy compounds (e.g. ATP) and of membrane stabilisers (e.g. trehalose) may be expected to enhance survival following drying and rehydration (e.g. anhydrobiotic organisms).
OBJECTIVE: To evaluate the hypothesis that heparin administration increases cardiac output and improves oxygenation in experimental hyperdynamic sepsis in sheep. DESIGN: Prospective trial. SETTING: Laboratory at a large university-affiliated medical center. SUBJECTS: A total of 14 sheep weighing 28 to 44 kg. INTERVENTIONS: All 14 chronically instrumented sheep received a continuous infusion of Escherichia coli endotoxin (10 ng/kg/min) over 24 hrs. Seven sheep received a fixed bolus of beef lung heparin (5000 units) every 4 hrs intravenously. The other seven sheep served as controls. MEASUREMENTS AND MAIN RESULTS: The heparinized animals showed a triphasic cardiovascular response. Cardiac index increased (p < .05), and systemic vascular resistance index decreased (p < .05) at 2 hrs after the start of the endotoxin infusion (early phase, 0 to 2 hrs). Both variables returned to approximately baseline levels at 4 hrs (second period, 2 to 4 hrs). A hyperdynamic state (in terms of an increased cardiac index), a decreased systemic vascular resistance index, and a decreased mean arterial pressure (MAP) (p < .05 for all) was observed in the third phase (8 to 24 hrs). In the control group, cardiac index, systemic vascular resistance index, and MAP showed no changes in the first period, but a slight decrease in cardiac index and a slight increase in systemic vascular resistance index in the second period. The onset of the hyperdynamic state was less pronounced in the control group and cardiac index was lower (p < .05); likewise, systemic vascular resistance index was increased (p < .05) when compared with heparinized animals. Both groups developed pulmonary hypertension during the endotoxin infusion. The gas exchange in the heparin group was significantly impaired in the first and second periods, but returned to baseline levels in the hyperdynamic phase, whereas the oxygenation of the nonheparinized animals showed only minor changes in the first and second phases, but deteriorated significantly during the third phase of endotoxemia. CONCLUSIONS: In this experimental model of hyperdynamic sepsis, heparin significantly influenced the cardiopulmonary performance. Heparin preserved gas exchange and increased cardiac output but lowered systemic vascular resistance and MAP in the hyperdynamic state.
Noncardiogenic edema fluid often contains high levels of plasma proteins, which may inhibit the function of the lung surfactant complex and thus decrease interstitial hydrostatic pressures. We questioned whether, in the awake and standing animal, displacement of the alveolar surface lining would alter the permeability of the thin and sparsely supported pulmonary capillaries. Sheep prepared with lung lymph fistulae were given an aerosolized detergent (Det) to displace the lung surfactant complex. After the sheep were given Det, protein flux was significantly increased (P < 0.05). To validate the suggested permeability increase, pulmonary vein occluders were surgically implanted and experiments repeated with pulmonary arterial pressures elevated 10 mmHg above baseline. After 2 h of elevated pulmonary arterial pressure, lung lymph increased fivefold. At this time, lymph-to-plasma total protein concentration ratios for air and saline-plus-ethanol vehicle were significantly lower (P < 0.01) than baseline ratios (0.26 +/- 0.06 and 0.34 +/- 0.07, respectively). No significant difference could be shown in lymph-to-plasma ratios after the sheep were given Det. We conclude that disruption of the alveolar lining can cause a detectable increase in protein flux due, in part, to an increase in microvascular permeability.
An ovine model was used to study the pathophysiology of smoke inhalation injury treated with extracorporeal membrane oxygenation (ECMO). Smoke inhalation is characterized by leukocyte-oxygen free-radical mediated acute lung injury. Treatment with ECMO was by extracorporeal venoarterial or venovenous perfusion using a venous drainage reservoir, roller pump, heat exchanger, and membrane lung oxygenator capable of oxygen delivery to and carbon dioxide removal from a patient. Blood-foreign surface interactions are known to occur during ECMO. We examined the effects of ECMO on circulating leukocytes, oxygen free-radical activity, thromboxane release, and gas exchange after smoke inhalation injury. Animals treated with smoke and ECMO had significantly increased circulating thromboxane B2 levels and oxygen free-radical activity compared with sham-treated animals and animals treated with smoke and mechanical ventilation (MV). Likewise, there was a significant increase in lung wet-to-dry weight ratios in animals treated with smoke and ECMO compared with those treated with smoke and MV. These data may account for the initial deterioration in native lung function after the initiation of ECMO and imply that ECMO may potentiate the pathophysiology of smoke inhalation injury.
Inhalation injury is one of the main causes of mortality in burn victims. The tracheobronchial epithelium sloughs and combines with a protein rich exudate to form casts of the airways that can lead to obstruction. We studied the effects of a continuous infusion of heparin on the acute pulmonary injury that occurs after smoke inhalation injury in sheep. Twelve ewes with vascular catheters received a standardized smoke inhalation injury and mechanical ventilation according to protocol for 72 hours. The heparin group (n = 6) received a 400 unit per kilogram bolus of heparin followed by a continuous infusion to maintain the activated clotting time between 250 to 300 seconds. The control group (n = 6) received a saline solution vehicle. Hemodynamics, blood gases and plasma samples for conjugated dienes were taken every six hours. At necropsy, pulmonary tissue was collected for histologic findings, polymorphonuclear neutrophil leukosequestration, wet-to-dry weight ratios and conjugated dienes. PaO2 to FIO2 ratios were improved in the heparin group compared with the control group at 12 to 72 hours after injury, and peak airway pressures were higher in the control group compared with the heparin group. Positive end expiratory pressure requirements were higher in the control group compared with the heparin group. There were significantly fewer airway tracheobronchial casts as determined by our tracheobronchial casts scoring system (2.4 +/- 0.4 versus 0.67 +/- 0.21) and confirmed by histologic examination. Pulmonary blood-free wet-to-dry weight ratios were higher in the control group compared with the heparin group (6.4 +/- 0.5 versus 5.2 +/- 0.1; p < 0.05). There were no differences in pulmonary tissue or plasma conjugated dienes; likewise, pulmonary leukosequestration was unaffected by heparin. Heparin decreases tracheobronchial cast formation, improves oxygenation, minimizes barotrauma and reduces pulmonary edema in an ovine model of severe smoke inhalation injury. Heparin does not reduce oxygen free radical activity after smoke inhalation injury.
Pressure limited ventilation or "lung rest" may prevent further exacerbation of acute lung injury from high airway pressures. A therapeutic goal of an intracorporeal oxygenation and carbon dioxide removal device (IVOX) is reduction of airway pressures. We noted increased IVOX CO2 removal as mixed venous CO2 increased in experimental animals. However, we recognize the limited clinical utility of removing approximately 30% of venous CO2. Therefore, intentional hypoventilation to limit airway pressures (mild permissive hypercapnia) was used in 5 patients with respiratory failure, and again we noted improved CO2 removal with increasing mixed venous CO2 concentrations. Preliminary calculations demonstrate that a CO2 gradient of approximately 70 mm Hg is needed to remove 100 ml CO2/min. The use of more aggressive permissive hypercapnia protocols with IVOX may permit further reduction in airway pressure without problems of severe respiratory acidosis.
Extracorporeal membrane oxygenation (ECMO) has been a successful treatment (82% survival) in over 5000 neonates with severe respiratory failure (80% predicted mortality without ECMO). ECMO is prolonged extracorporeal cardiopulmonary bypass achieved by extrathoracic vascular cannulation using a modified heart-lung machine. ECMO is currently the treatment of choice for full-term newborns with severe respiratory failure. The report summarizes indications, resulting complications, and future applications of neonatal ECMO.