Biomedical subjects
T P Green
Publications and source records attributed to T P Green.
The treatment of acute respiratory failure in children: a historical examination of landmark advances.
Explore the source record for details and available documents.
What is best for patients is best for the intensive care unit.
Explore the source record for details and available documents.
Dexamethasone reduces the inflammatory response to cardiopulmonary bypass in children.
BACKGROUND: A randomized, prospective, double-blind study of 29 children was performed to evaluate the hypothesis that dexamethasone administration prior to cardiopulmonary bypass would decrease the inflammatory mediator release and improve the postoperative clinical course. METHODS: Fifteen children received dexamethasone (1 mg/kg intravenously) and 14 (controls) received saline solution 1 hour prior to CPB. Serial blood analyses for interleukin-6, tumor necrosis factor-alpha, complement component C3a, and absolute neutrophil count were performed. Postoperative variables evaluated included temperature, supplemental fluids, alveolar-arterial oxygen gradient, and days of mechanical ventilation. RESULTS: Dexamethasone caused an eightfold decrease in interleukin-6 levels and a greater than threefold decrease in tumor necrosis factor-alpha levels after CPB (p < 0.05). Complement component C3a and absolute neutrophil count were not affected by dexamethasone. The mean rectal temperature for the first 24 hours postoperatively was significantly lower in the group given dexamethasone than in the controls (37.2 degrees +/- 0.4 degrees C versus 37.7 degrees +/- 4 degrees C; p = 0.007). Dexamethasone-treated patients required less supplemental fluid during the first 48 hours (22 +/- 28 mL/kg versus 47 +/- 34 mL/kg; p = 0.04). Compared with controls, dexamethasone-treated children had significantly lower alveolar-arterial oxygen gradients during the first 24 hours (144 +/- 108 mm Hg versus 214 +/- 118 mm Hg; p = 0.02) and required less mechanical ventilation (median duration, 3 days versus 5 days; p = 0.02). CONCLUSIONS: Dexamethasone administration prior to CPB in children leads to a reduction in the postbypass inflammatory response as assessed by cytokine levels and clinical course.
Oncology patients in the pediatric intensive care unit: room for optimism?
Explore the source record for details and available documents.
Randomised, prospective study comparing cemented and cementless total knee replacement: results of press-fit condylar total knee replacement at five years.
Early implants for total knee replacement were fixed to bone with cement. No firm scientific reason has been given for the introduction of cementless knee replacement and the long-term survivorship of such implants has not shown any advantage over cemented forms. In a randomised, prospective study we have compared cemented and uncemented total knee replacement and report the results of 139 prostheses at five years. Outcome was assessed both clinically by independent examination using the Nottingham knee score and radiologically using the Knee Society scoring system. Independent statistical analysis of the data showed no significant difference between cemented and cementless fixation for pain, mobility or movement. There was no difference in the radiological alignment at five years, but there was a notable disparity in the radiolucent line score. With cemented fixation there was a significantly greater number of radiolucent lines on anteroposterior radiographs of the tibia and lateral radiographs of the femur. At five years, our clinical results would not support the use of the more expensive cementless fixation whereas the radiological results are of unknown significance. Longer follow-up will determine any changes in the results and conclusions.
Education, physician presence, and the quality of care in pediatric intensive care units.
Explore the source record for details and available documents.
Sustained loading generates stress concentrations in lumbar intervertebral discs.
STUDY DESIGN: Cadaveric motion segment experiment. Measurements on each specimen were compared before and after creep loading. OBJECTIVES: To show how sustained "creep" loading affects stress distributions inside intervertebral discs. SUMMARY OF BACKGROUND DATA: The central region of an intervertebral disc acts like a hydrostatic "cushion" between adjacent vertebrae. However, this property depends on the water content of the tissues and may be lost or diminished after creep. METHODS: Twenty-seven lumbar motion segments consisting of two vertebrae and the intervening disc and ligaments were loaded to simulate erect standing postures in life. The distribution of compressive stress in the disc matrix was measured by pulling a miniature pressure transducer through the disc in the midsagittal plane. Profiles of vertical and horizontal compressive stress were repeated after each specimen had been creep loaded in compression for 2-6 hours. RESULTS: Creep reduced the hydrostatic pressure in the nucleus by 13-36%. Compressive stresses in the anulus were little affected when the profiles were measured at 1 kN, but at 2 kN, localized peaks of compressive stress appeared (or grew in size) in the posterior anulus after creep. CONCLUSIONS: Increased loading of the apophysial joints causes an overall reduction in intradiscal stresses after creep. In addition, water loss from the nucleus causes a transfer of load from nucleus to anulus. Stress concentrations may lead to pain, structural disruption, and alterations in chondrocyte metabolism. Disc mechanics depend on loading history as well as applied load.
The impact of extracorporeal membrane oxygenation on survival in pediatric patients with acute respiratory failure. Pediatric Critical Care Study Group.
OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency in the treatment of acute respiratory failure in pediatric patients. Our objective in this study was to test the hypothesis that ECMO improves outcome in pediatric patients with acute respiratory failure. DESIGN: Multicenter, retrospective cohort analysis. SETTING: Forty one pediatric intensive care units participated in the study under the auspices of the Pediatric Critical Care Study Group. PATIENTS: All pediatric patients admitted to the participating institutions with acute respiratory failure during 1991 were included. Patients with congenital heart disease, contraindications to ECMO, or incomplete data were excluded, yielding a data set of 331 patients from 32 hospitals. INTERVENTIONS: Conventional mechanical ventilation, high-frequency ventilation, and extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Multivariate logistic regression analysis was used to identify factors associated with survival. In a second analysis, pairs of ECMO and non-ECMO patients, matched by severity of disease and respiratory diagnosis, were compared. The use of ECMO (p = .0082), but not the use of high-frequency ventilation, was associated with a reduction in mortality. Other factors independently associated with mortality included oxygenation index (p < .0001), Pediatric Risk of Mortality score (PRISM) (p < .0001) and the Paco2 (p = .045). In 53 diagnosis- and risk-matched pairs, there was a significantly lower mortality rate (26.4% vs. 47.2%; p < .01) in the ECMO-treated patients. When all patients were stratified into mortality risk quartiles on the basis of oxygenation index and PRISM score, the proportion of deaths among ECMO-treated patients in the 50% to 75% mortality risk quartile was less than half the proportion in the non-ECMO treated patients (28.6% vs. 71.4% p < .05)> No effect was seen in the other quartiles. CONCLUSIONS: The use of ECMO was associated with an improved survival in pediatric patients with respiratory failure. The lack of association of outcome with treatment in the ECMO-capable hospital or with another tertiary technology (i.e. high-frequency ventilation) suggests that ECMO itself was responsible for the improved outcome. Further studies of this procedure are warranted but require broad-based multi-institutional participation to provide sufficient statistical power and sensitivity to demonstrate efficacy.
Quality of care and mortality in pediatric intensive care units.
Explore the source record for details and available documents.
Probability of survival after prolonged extracorporeal membrane oxygenation in pediatric patients with acute respiratory failure. Extracorporeal Life Support Organization.
OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency for respiratory failure that is unresponsive to conventional therapy. We examined the relationship between duration of ECMO and outcome to understand whether prolonged ECMO (duration of the procedure for > 14 days) was more commonly associated with futile therapy or eventual recovery. DESIGN: A cohort study of all patients reported to the Pediatric ECMO Registry for Acute Respiratory Failure of the Extracorporeal Life Support Organization. SETTING: Tertiary hospitals (n = 83) capable of providing extracorporeal support for pediatric patients. PATIENTS: Children (n = 382) between the ages of 1 wk and 18 yrs of age with severe respiratory failure. INTERVENTIONS: Extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: The death or live hospital discharge of ECMO-treated patients, together with the post-ECMO mechanical ventilation course, were examined as a function of duration of ECMO and of pre-ECMO respiratory status. The occurrence of complications and the causes of death were also noted. The criteria used to initiate ECMO, as well as the determination of the futility of further ECMO, were determined by local practice at individual centers. There were 382 patients treated with ECMO, of whom 184 (48%) survived. The proportional survival in the patients treated for the longest duration was similar to the overall group. The cause of death was given for 168 patients: 32 neurologic deaths; nine deaths due to ECMO complications; and 30 deaths due to nonpulmonary organ failure. There were 97 deaths due to elective ECMO termination; 80 of these deaths occurred after the determination of the futility of anticipating pulmonary recovery. The latter deaths occurred at widely varying durations of ECMO, with a median of 282 hrs. However, at that same duration, 47 eventual survivors (26% of all survivors) continued to receive ECMO. By discriminant analysis, the survival rate was independently related (r2 = .18; p < .0001) to peak ventilator inspiratory pressure before ECMO and duration of intubation before ECMO, patient age, and the occurrence of several complications. CONCLUSIONS: While the survival rate in pediatric patients receiving ECMO appears related to the severity of lung disease and to the occurrence of ECMO complications, the survival rate in patients treated with ECMO courses of > 2 wks was similar to the survival rate of patients treated for shorter periods of time. ECMO was terminated in some patients for pulmonary futility at durations of ECMO associated with survival in substantial numbers of patients in whom ECMO was continued.
Spondylolysis. Bending of the inferior articular processes of lumbar vertebrae during simulated spinal movements.
STUDY DESIGN: This was a cadaveric lumbar motion segment experiment. OBJECTIVES: To measure bending about the pars interarticularis during simulated flexion and extension movements, with and without high compressive forces. This was designed to indicate which activities are most likely to cause spondylolysis. SUMMARY OF BACKGROUND DATA: The mechanical etiology of spondylolysis is controversial. METHODS: Motion segments were loaded to simulate: A, full flexion; B, full extension; C, high compression in flexed posture, and D, high compression in lordotic posture. Bending of the inferior articular processes about the pars was measured in the sagittal plane, using a two-dimensional "MacReflex" infrared motion analysis system. RESULTS: In full flexion, tension in the intervertebral ligaments bent the processes forward and down (by 3.25 degrees +/- 3.07 degrees), whereas in the loading conditions B, C, and D, inter-facet compressive forces caused the processes to bend backward and upward, by 2.24 +/- 2.48 degrees, 0.40 +/- 0.23 degrees, and 0.74 +/- 0.56 degrees respectively. CONCLUSIONS: Activities that involve alternating flexion and extension movements cause large stress reversals in the pars and pose the greatest threat of spondylolysis. Compressive loading has little effect.
The strength in anterior bending of lumbar intervertebral discs.
STUDY DESIGN: This was a motion segment experiment. OBJECTIVES: To determine the strength in bending of lumbar intervertebral discs. METHODS: Eighteen "motion segments" consisting of two vertebrae and the intervening disc and ligaments were loaded to simulate forward bending movements in life. The range of flexion and the resistance to bending of each specimen was compared before and after removal of the posterior elements. Nine of the discs were tested after the intradiscal pressure had been reduced by damaging the vertebral end plate in compression. RESULTS: The posterior elements restricted the disc to 80% of its full range of flexion. The strength in anterior bending of isolated discs decreased with age and was 33 Nm on average. Reducing intradiscal pressure did not affect the discs' strength in bending. CONCLUSIONS: Disc failure in bending occurs through overstretching of the outer anulus in the vertical direction. In life, the posterior elements may not adequately protect the posterior anulus from fatigue damage.
Congenital diaphragmatic hernia in Minnesota. Impact of antenatal diagnosis on survival.
OBJECTIVE: We characterized the natural history and true mortality of congenital diaphragmatic hernia (CDH) in newborn patients by identifying all infants born with this condition in a fixed geographic region over a 2-year period. We examined this population to determine the frequency of intrauterine diagnosis, the outcome of prenatally diagnosed infants, and the impact of deaths in infants with an unsuspected diagnosis (the "hidden mortality") on the overall outcome of this condition. DESIGN: This was a retrospective population survey of all infants born with CDH in Minnesota between June 1988 and June 1990. SETTING: All Minnesota birth and death records were reviewed to identify patients with the diagnosis of CDH. A separate survey of all level 3 intensive care nurseries was conducted and the record of each identified patient was reviewed. Extracorporeal membrane oxygenation was available throughout the study period. MAIN OUTCOME MEASURE: Survival to hospital discharge and short-term morbidity were examined for each patient. RESULTS: Survival was 60% (29/48). Eleven of 19 deaths occurred in patients born prematurely and/or with coexisting major anomalies. Eight percent (4/48) of patients died within the first hour of life prior to diagnosis (hidden mortality). Intrauterine diagnosis of CDH was made in 15 patients. Survival was 60% (9/15) in infants whose conditions were diagnosed in utero, a rate identical to that for infants whose conditions were diagnosed in the postnatal period (61% [20/33]). There was no relationship between age at fetal diagnosis and mortality. CONCLUSIONS: The hidden mortality of CDH was low. Almost half of the total mortality for CDH was associated with coexisting, additional anomalies. Patients who were not offered extracorporeal membrane oxygenation owing to prematurity, other major anomalies, or birth at a center that did not offer extracorporeal membrane oxygenation accounted for 84% (16/19) of deaths. These data will be useful for determining the impact of new therapeutic strategies on the mortality of CDH.
Quaternary structure of the native GABAA receptor determined by electron microscopic image analysis.
In the transmitter-gated ion channel class of receptors, the members of which are all believed to be heterooligomers, the number and arrangement of the subunits are only known with any certainty for the nicotinic acetylcholine receptor from Torpedo electric fish. That receptor has been shown to possess a pentameric rosette structure, with five homologous subunits (alpha 2, beta gamma delta) arranged to enclose the central ion channel. The data were obtained by electron image analysis of two-dimensional receptor arrays, which form as a consequence of that receptor's exceptionally high abundance in the Torpedo membranes and are therefore not attainable for other receptors. We have applied another direct approach to determine the quaternary structure of native ionotropic GABA receptors. We have purified those receptors from porcine brain cortex and analysed the rotational symmetry of isolated receptors visualized by electron microscopy. The results show the receptor to have a pentameric structure with a central water-filled pore, which can now be said to be characteristic of the entire superfamily.
Predictors of outcome of severe respiratory syncytial virus-associated respiratory failure treated with extracorporeal membrane oxygenation.
OBJECTIVE: To examine the Extracorporeal Life Support Organization registry data base for all infants and children with respiratory syncytial virus-associated respiratory failure managed with extracorporeal life support, to delineate predictors of outcome. DESIGN: Retrospective cohort study. SETTING: Extracorporeal Life Support Organization data registry. PATIENTS: All pediatric patients treated in the United States with extracorporeal life support for severe pediatric respiratory syncytial virus-associated respiratory failure reported to the registry, from 1982 through June 1992. INTERVENTIONS: Venoarterial or venovenous extracorporeal life support. MEASUREMENTS AND MAIN RESULTS: As of June 1992, fifty-three pediatric patients meeting study entry criteria were reported to the Pediatric Respiratory Failure Registry (n = 412) as having received extracorporeal membrane oxygenation (ECMO) for severe respiratory syncytial virus infection with pulmonary failure. Forty-nine percent (26/53) were successfully managed and survived to hospital discharge. The mean patient age was 5.0 +/- 8.6 months. Duration of mechanical ventilation before institution of extracorporeal life support was 8.1 +/- 6.2 days. Multivariate logistic regression analysis found four variables to be associated with patient nonsurvival at the p < 0.05 level: male gender, longer duration of mechanical ventilation before ECMO, higher peak inspiratory pressure, and lower ratio of arterial oxygen tension to fraction of inspired oxygen. Era of treatment was not associated with outcome. Receiver operator characteristic curve analysis of this multivariate model resulted in cutoff points of r = 0.5 and 0.1 that resulted in 92% sensitivity and 81% specificity (false-positive ratio 19%) and 96% sensitivity and 73% specificity (false-positive ratio 27%), respectively. CONCLUSIONS: Predictors of outcome of severe respiratory failure caused by respiratory syncytial virus infection managed with ECMO exist, and multivariate predictive models with high sensitivity and low false-positive risk are possible. Similar mathematical models may be helpful in establishing criteria for future trials of ECMO versus conventional respiratory support.
Severity of illness correlates with alterations in energy metabolism in the pediatric intensive care unit.
OBJECTIVE: To evaluate the correlations between severity of illness scoring systems and biochemical markers of physiologic stress. SETTING: Tertiary care pediatric ICU in a university hospital. DESIGN: A prospective, clinical study. PATIENTS: Twelve patients aged 2 to 120 months (four patients aged less than 12 months) with varying diagnoses including sepsis, cardiovascular surgery, respiratory failure. INTERVENTIONS: Oxygen consumption (VO2), daily total urinary nitrogen, and the branch chain to aromatic amino acid ratio were correlated with the Physiologic Stability Index, Pediatric Risk of Mortality score, and Therapeutic Intervention Scoring System. Linear regression analysis and multivariate stepwise regression analysis were used to analyze the data. MEASUREMENTS AND MAIN RESULTS: Pediatric Risk of Mortality score and Physiologic Stability Index correlated with VO2 (r2 = .69, p less than .001 and r2 = .52, p less than .01, respectively) and with daily total urinary nitrogen excretion (r2 = .66, p less than .001 and r2 = .62, p less than .01, respectively). The Therapeutic Intervention Scoring System correlated with the total urinary nitrogen excretion (r2 = .69, p less than .001) and branch chain to aromatic amino acid ratio (r2 = .49, p less than .01). Correlations existed between Pediatric Risk of Mortality score and Physiologic Stability Index (r2 = .88, p less than .001) and Pediatric Risk of Mortality score and Therapeutic Intervention Scoring System (r2 = .48, p less than .01). CONCLUSIONS: The correlations were independent of diagnostic category, suggesting that the alterations in biochemical variables were most directly related to the overall severity of illness as measured by the scoring system.