Computed tomographic grading of splenic injury.
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Humans↗
Biomedical subjects
J W Davis
Publications and source records attributed to J W Davis.
The effects of left heart assist on right ventricular muscle mechanics and ventricular coupling in the injured heart.
So that we could better characterize the effects of left heart assist on right ventricular myocardial muscle mechanics and ventricular mechanical coupling in the injured heart, nine dogs underwent 30 minutes of global cardiac ischemia supported by cardiopulmonary bypass followed by randomly varied levels of left heart assist at 0, 1.0, and 2.0 L/min (0, 37 +/- 4, and 74 +/- 7 ml/kg per minute). A centrifugal pump with left ventricle-to-aorta bypass was used with the intent to cause left ventricular volume unloading but without complete left ventricular pressure unloading. Right ventricular regional free wall and septal-free wall dimensions were measured by a sonomicrometer and right ventricular pressure by a micromanometer. Pressure and dimension data were acquired over a range of preloads produced by transient vena caval occlusion and at steady state at an initial control point and after ischemia at each level of left heart assist. Right ventricular regional early diastolic function was assessed by percent segmental relaxation during the first third of diastole, end-diastolic compliance by the end-diastolic pressure-dimension relationship, systolic contractile performance by the slope (Mw) and dimension axis intercept (Lw) of the linear preload recruitable stroke work relationship, and right ventricular isovolumic relaxation by the pressure decay time constant. Ischemia reduced Mw of both the free wall (38.3 +/- 16.1 to 16.4 +/- 4.2 erg.cm-3 x 10(3), p < 0.01) and septal free wall (30.2 +/- 12.7 to 13.4 +/- 4.9 erg.cm-3 x 10(3), p < 0.01) and shifted Lw rightward (1.3 +/- 0.3 to 1.4 +/- 0.3 mm, p < 0.01, and 2.8 +/- 0.8 to 3.0 +/- 0.9 mm, p < 0.01), which confirmed myocardial ischemic injury. There were no effects of left heart assist on free wall or septal-free wall systolic contractile performance assessed by Mw and Lw or on early diastolic relaxation assessed by percent segmental relaxation during the first third of diastole in either right ventricular region (all p = not significant). There were also no observed characteristic alterations of free wall or septal-free wall end-diastolic pressure-dimension relationships with left heart assist. The pressure decay time constant decreased with increasing levels of left heart assist (51 +/- 14, 49 +/- 16, and 43 +/- 11 msec, p < 0.05), which indicated an improvement in right ventricular isovolumic relaxation attributable to left heart assist. These data demonstrate that mechanical ventricular interactive effects during left heart assist are beneficial, but limited to isovolumic relaxation in the injured heart.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Interactions between pyruvate carboxylase and other mitochondrial enzymes.
Although pyruvate carboxylase associated with both mitochondrial aspartate aminotransferase and malate dehydrogenase, it had a higher affinity for the amino-transferase. Furthermore, the aminotransferase enhanced dissociation of malate dehydrogenase from pyruvate carboxylase. Glutamate dehydrogenase did not associate with pyruvate carboxylase alone, but it apparently associated with the pyruvate carboxylase-aminotransferase complex, and malate dehydrogenase associated with the resulting ternary complex. Citrate synthase and other proteins tested did not associate with pyruvate carboxylase. However, citrate synthase associated with the pyruvate carboxylase-malate dehydrogenase complex. Apparently as a consequence of these heteroenzyme interactions, the rate of the pyruvate carboxylase reaction was slightly greater when coupled with malate dehydrogenase or both malate dehydrogenase and citrate synthase than when coupled with citrate synthase alone. In addition, in the presence of both coupling enzymes, the rate of conversion of pyruvate to citrate was higher than predicted on the basis of the Michaelis-Menten relationship of the two coupling enzymes. Therefore, binding of malate dehydrogenase to pyruvate carboxylase enhances pyruvate carboxylase activity. Association of citrate synthase with the malate dehydrogenase-pyruvate carboxylase binary complex does not alter activation of pyruvate carboxylase but results in citrate synthase being more reactive than free citrate synthase with oxalacetate.
Animals↗
The epidemiology of traumatic death. A population-based analysis.
Despite the proliferation of trauma systems, there are no population-based data describing the epidemiology of traumatic death. To provide these data, we reviewed all trauma deaths occurring in San Diego (California) County during 1 year. There were 625 traumatic deaths during the study (27.3 deaths per 100,000 population per year). Motor vehicle trauma was the most common cause of injury leading to death (N = 344 [55.2%]; 15.0 annual deaths per 100,000 population). Central nervous system injuries were the most common cause of death (48.5%, or 13.2 deaths per 100,000 population per year). Sepsis was responsible for only 2.5% of the overall mortality. Based on life-table data, traumatic death resulted in an annual loss of 1091 years of life per 100,000 and an annual loss of 492 years of productivity per 100,000. Injury continues to account for an enormous loss of life despite improvements in survival wrought by trauma systems.
Accidents, Traffic↗
A new method for vertebral fracture diagnosis.
A number of methods have been proposed for estimating the prevalence of vertebral fractures. Most methods are based on the distribution of normal vertebral dimensions in the population. However, these methods fail to identify a significant proportion (20-30% or more) of fractures documented on serial radiographs. This may occur because vertebral size varies between individuals as a result of differences in body size (and possibly other factors), and a normal range based on population reference data may be too large. In this paper, a new method is described for identifying vertebral fractures that are missed using diagnostic criteria based on vertebral dimension distributions of the population. This new method is based on calculating the average vertebral size, and statistical confidence limits, for the individual. The average vertebral size method was evaluated by testing its ability to identify incident fractures (which were identified from changes in dimensions compared to previous radiographs), using only the final film. The new method correctly identified most (81% of crush and 83% of wedge) incident fractures on the final radiograph. In contrast, criteria based on population distributions correctly identified only 53% of crush and 72% of wedge incident fractures. Using prospective data, prevalent fractures identified using both population-based and individual size-based criteria predicted the risk of incident fractures. Furthermore, incident fractures identified using both methods (population- and individual-based criteria) were associated with increased back pain. These data suggest that both types of prevalent deformities are important indicators of disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Regional geometry and function during myocardial ischemia and recovery.
To define the effects of altered left ventricular (LV) geometry on regional myocardial function during ischemia and recovery, regional and global LV geometry and transmural pressure (P) were measured in seven conscious dogs with sonomicrometry and micromanometry. Data were obtained at steady state and during rapid vena caval occlusion (VCO) under control conditions, after 15 min of left anterior descending occlusion, and after 1, 4, and 24 hr of reperfusion. Regional midwall minor axis (MA) Lagrangian strain (epsilon) and stress (sigma) were calculated from measured MA segment length (L), MA midwall radius, and wall thickness. Unstressed regional geometry was quantified using L0, the value of L at P = 0 during maximal VCO. Conventional (SWL) and normalized (SW sigma epsilon) regional MA stroke work were calculated for each cardiac cycle as the area of P vs L and sigma vs epsilon relationships, respectively. Regional Frank-Starling mechanisms corrected for changes in unstressed LV geometry were quantified as the slope (M sigma epsilon) of the linear end diastolic epsilon vs SW sigma epsilon relationship for data obtained during VCO (mean r = 0.98). M sigma epsilon returned to baseline levels within 1 h of reperfusion (P = 0.314 vs control). In contrast, 15 min of ischemia increased L0 by 15.2 +/- 2.5% (P < 0.05), which remained increased 5.7 +/- 1.7% above control values after 1 hr of reperfusion (P < 0.05). Both steady-state SWL and SW sigma epsilon decreased with ischemia and slowly returned towards baseline, remaining 28.7 +/- 7.5% and 26.4 +/- 6.3% below control values after 1 hr of reperfusion (both P < 0.05). Therefore, late functional recovery from reversible ischemic injury is primarily correlated with reversal of changes in regional geometry, specifically the reversal of diastolic creep. As a result, adequate quantification of postischemic regional myocardial performance requires characterization of changes in regional geometry as well as indicators of Frank-Starling mechanisms.
Animals↗
Predicting vertebral fracture incidence from prevalent fractures and bone density among non-black, osteoporotic women.
We evaluated the ability of bone density and vertebral fractures at baseline to predict vertebral fracture incidence in a cohort of postmenopausal women with osteoporosis. The study population was 380 postmenopausal women (mean age 65 years) treated for osteoporosis in a randomized, placebo-controlled, clinical trial of the bisphosphonate etidronate at seven geographic centers in the United States. Baseline measurements of bone mineral density were obtained in 1986 by quantitative computed tomography at the spine and dual-photon absorptiometry at the lumbar spine and hip. Vertebral fractures were documented on serial spine radiographs. Proportional hazards models were used to evaluate the ability to predict the risk of subsequent fractures during an average of 2.9 years of follow-up. Presence of one or two fractures increased the rate of new vertebral fractures 7.4-fold (95% confidence interval = 1.0 to 55.9). Additional fractures at baseline further increased the fracture rate. A decrease of 2 standard deviations in spinal bone density by absorptiometry was associated with a 5.8-fold increase in fracture rate (95% confidence interval = 2.9 to 11.6). The lowest and highest quintiles of bone density had absolute fracture rates of 120 and 6 cases per 1000 patient-years, respectively. In general, the simultaneous use of two predictors (bone density and prevalent fractures or two bone density measurements) improved fracture prediction, compared with the use of a single predictor. We conclude that both bone density and prevalent vertebral fractures are strong, complementary predictors of vertebral fracture risk. The results suggest that physicians can use bone density and prevalent vertebral fractures, individually or in combination, as risk factors to identify patients at greatest risk of new fractures.
Aged↗
Bone mass and beyond: risk factors for fractures.
Numerous prospective studies have demonstrated a strong relationship between bone mass and fracture risk. The fact that the bone mass distributions of fracture and nonfracture cases overlap does not necessarily indicate a shortcoming of bone mass, but might instead be due to the sporadic nature of falls and the influence of other fracture risk factors. The recent finding that prevalent fractures are strong predictors of fracture risk, independent of bone mass, suggests (but does not prove) that there may be other, potentially measurable fracture risk factors that complement, and act independently of, bone mass. This paper reviews possible mechanisms by which prevalent fractures might serve as etiologic risk factors, or as surrogate indicators of other risk factors. Potential risk factors other than bone mass and prevalent fractures are also considered. Whether or not etiologic fracture risk factors other than bone mass can be identified, it appears that treatments that influence bone will be most effective if begun early, before bone strength becomes impaired and fractures begin to occur.
Absorptiometry, Photon↗
Effects of chlorhexidine during immunosuppressive chemotherapy. A preliminary report.
Immunosuppressive chemotherapy and bone marrow transplantation are increasingly used to treat and, in some cases, cure numerous malignant conditions. The systemic sequelae as a result of these immunosuppressive techniques lead to a host of oral and dental complications. The direct and indirect stomatotoxic effects lead to development of ulcerative, hemorrhagic, or infectious complications that potentially can lead to increased mortality and morbidity. Chlorhexidine was studied to evaluate its broad spectrum antimicrobial properties and to evaluate its effect on immunosuppression-induced mucositis. Our double-blind randomized study revealed that chlorhexidine versus controls had considerable effect in the bone marrow transplant cohort. Patients who received chlorhexidine while undergoing bone marrow transplantation were found to exhibit fewer and less painful mucositis lesions. This study supports prophylactic use of chlorhexidine in patients who undergo bone marrow transplantation.
Antineoplastic Agents↗
Declining bone loss rate variability with increasing follow-up time.
Bone loss rates are believed to vary substantially among post-menopausal women. The belief, however, might be largely based upon comparisons of loss rates measured with considerable error. This issue arises because the precision of the bone mass instrumentation (1-2% errors in measuring bone mass) is similar in magnitude to the loss rate (typically 1-2% of bone mass per year). The 'true' variability in loss rates, however, can be estimated by adjusting for instrument errors. An equation is presented which estimates the true variability in loss rates from a study sample. The adjustment was examined using a cohort of post-menopausal, Japanese-American women living in Hawaii. The study examined the calcaneus, distal, and proximal radius sites. The results suggest that measurement errors did not markedly inflate the bone loss variability. Even after adjustment for measurement errors considerable variability in loss rates remained. The variability was examined for various follow-up durations. Both the observed and adjusted loss rates had smaller standard deviations over long intervals than over short intervals. This result suggests that the more extreme rates of change in bone mass over a year or two were often not sustained. The implications of this finding for sample size calculations in longitudinal studies are examined. The results also indicate that the length of follow-up and instrument precision should be taken into consideration when comparing the proportion of fast losers between populations.
Absorptiometry, Photon↗
The etiology of missed cervical spine injuries.
Missed or delayed diagnosis of cervical spine (C-spine) injuries may lead to extension of those injuries and subsequent preventable mortality or morbidity. Previous reports examining the incidence of missed C-spine injuries have not determined the nature of the causal clinical errors made or the extent to which these errors are avoidable. This study was undertaken to (1) determine the incidence of delayed or missed diagnosis of C-spine injuries and the consequences of those missed injuries; (2) define the clinical errors leading to the delays; and (3) to determine if these errors are the result of fundamental problems or a lack of advanced diagnostic skills or equipment. Between August 1985 and February 1991, 32,117 trauma patients were admitted to one of the six trauma centers in San Diego county. Cervical spine injuries were identified in 740 patients and the diagnosis was delayed or missed in 34 patients (4.6%). Ten of the 34 patients (29%) developed permanent sequelae as a result of these delays. The single most common error was the failure to obtain an adequate series of C-spine roentgenograms. Delayed diagnosis could have been avoided in at least 31 of 34 injuries by the appropriate use of a standard three-view C-spine series and careful interpretation of those roentgenograms. Patients at risk for C-spine injuries require a technically adequate three-view C-spine series and skilled radiographic interpretation. Cervical spine precautions should be maintained, particularly in high risk patients, until appropriate and expert review of the cervical spine roentgenograms can be obtained.
Adolescent↗
Physiology of cardiac tamponade and paradoxical pulse in conscious dogs.
The physiological mechanism of paradoxical pulse in cardiac tamponade remains controversial. In eight conscious dogs with intact pericardia, ultrasonic dimension transducers assessed biventricular geometry and volumes, while micromanometers measured right ventricular (RV), left ventricular (LV), pleural, and pericardial pressures. With normal inspiration, peak LV pressure fell by 7.7 +/- 1.3 mmHg at control and by 20.3 +/- 3.7 mmHg during tamponade (P < 0.001), consistent with the development of paradoxical pulse. At peak inspiration during tamponade, RV filling increased, the interventricular septum shifted leftward, transeptal pressure became negative, and LV septal arc length (l theta) became smaller than its respective unpreloaded value at maximal vena caval occlusion (l(o)). Analysis of stroke work (SW)-end-diastolic volume (EDV) and end-systolic pressure-volume coordinates at peak inspiration during tamponade revealed that end-systolic pressure was 19.1 +/- 10.2 mmHg below the baseline end-systolic pressure-volume curve (P < 0.01), and SW was 24.2 +/- 8.8% below the baseline SW-EDV curve (P < 0.01), indicating transient inspiratory LV dysfunction. It is proposed that inspiratory leftward interventricular septal shifting at low LV EDV during tamponade completely unloads the septum (l theta < l o), eliminates the septal contribution to global LV SW, results in transient inspiratory LV dysfunction, and contributes to the phenomenon of paradoxical pulse.
Animals↗
The effect of sulfinpyrazone on treadmill exercise-induced angina pectoris.
Suspecting that platelet thromboemboli could play a role in the pathogenesis of myocardial ischemia, we have done a random-order, double-blind, crossover study of the effect of the platelet-active drug sulfinpyrazone on treadmill exercise-induced angina pectoris in 30 men with coronary artery disease. The mean duration of exercise before onset of angina was 43 s longer after taking sulfinpyrazone than before and 11 s shorter after taking placebo than before. Analysis of variance for crossover design showed that the mean difference between the values obtained before and after sulfinpyrazone was significantly different (p < 0.01) from the mean difference between the values before and after placebo. Sulfinpyrazone had no effect on the mean heart rate-blood pressure product at onset of angina, change in ST segment during exercise, or preexercise platelet aggregate ratio and bleeding time. Exercise until angina occurred did not affect the platelet aggregate ratio.
Angina Pectoris↗
Cigarette-smoking affects platelets and endothelium in chronic hemodialysis patients.
Previous work has shown that cigarette-smoking affects platelets and endothelium in men and women without renal failure. The present study compared 10 male habitual smokers receiving maintenance hemodialysis for chronic renal failure with 11 healthy male habitual smokers before and after controlled cigarette-smoking after a 12-hour period of abstinence. Collagen-induced platelet aggregation was not significantly different in the two groups of men before smoking. The platelet aggregate ratio was lower and the plasma concentration of platelet factor 4 was higher in the dialysis patients than in the healthy men (p < 0.05). Mean or median values before and after cigarette smoking by the dialysis patients were 42 and 62 chart units for collagen-induced platelet aggregation, 0.88 and 0.77 for the platelet aggregate ratio, 6.2 and 8.5 ng/ml for the plasma concentration of platelet factor 4, 0.8 and 1.7 per counting chamber for the endothelial cell count and 4 and 37 ng/ml for the plasma nicotine concentration (each p < 0.01). None of the changes which occurred in the dialysis patients was statistically significantly different from those in the healthy men. We conclude that cigarette-smoking has similar effects on platelets and endothelium in patients receiving maintenance hemodialysis and in healthy controls.
Adult↗
Kinetics and regulation of hepatoma mitochondrial NAD(P) malic enzyme.
Kinetic studies of Morris 7777 hepatoma mitochondrial NAD(P) malic enzyme were consistent with an ordered mechanism where NAD adds to the enzyme before malate and dissociation of NADH from the enzyme is rate-limiting. In addition to its active site, malate apparently also associates with a lower affinity with an activator site. The activator fumarate competes with malate at the activator site and facilitates dissociation of NADH from the enzyme. The ratio of NAD(P) malic enzyme to malate dehydrogenase activity in the hepatoma mitochondrial extract was found to be too low, even in the presence of known inhibitors of malate dehydrogenase, to account for the known ability of NAD(P) malic enzyme to intercept exogenous malate from malate dehydrogenase in intact tumor mitochondria (Moreadith, R.W., and Lehninger, A.L. (1984) J. Biol. Chem. 259, 6215-6221). However, NAD(P) malic enzyme may be able to intercept exogenous malate because according to the present results, it can associate with the pyruvate dehydrogenase complex, which could localize NAD(P) malic enzyme in the vicinity of the inner mitochondrial membrane. The activity levels of some key metabolic enzymes were found to be different in Morris 7777 mitochondria than in liver or mitochondria of other rapidly dividing tumors. These results are discussed in terms of differences among tumors in their ability to utilize malate, glutamate, and citrate as respiratory fuels.
Animals↗
Relationship between bone mass and rates of bone change at appendicular measurement sites.
The rate of bone change among postmenopausal women may vary depending upon the initial bone mass. Examining this possibility is difficult, however, because of a negative statistical bias that occurs when change is regressed against the initial value of the same variable. In this article, four statistical methods were applied to measure the association between bone mass and the rate of bone change. The study population was Japanese-American women, who were monitored for approximately 5 years. Bone changes were determined for the calcaneus and the distal and proximal radius. The results were consistent across the bone sites but differed between statistical methods. Three of the four methods indicated that the women with the greater bone mass had the greater loss rates. The fourth method did not support this association. Possible reasons for the discordant results are discussed. Using the "best" estimate of the relationship, a gradual convergence of bone mass was projected over time toward the population mean. The convergence occurred because women with higher bone mass had a somewhat faster loss rate than women with lower bone mass. Overall, however, the variation in bone mass between individuals was large compared to the rate of convergence.
Absorptiometry, Photon↗
Renal excretion of perfluorooctanoic acid in male rats: inhibitory effect of testosterone.
There is a marked sex difference in the whole-body elimination of perfluorooctanoic acid (PFOA) in rats, with females excreting the perfluorinated acid much more rapidly (half life [t1/2] less than 1 day) than males (t1/2 = 15 days). Our objective was to determine if androgens or estrogens are involved in causing this sex difference in PFOA elimination. Castration of males greatly increased the elimination of [1-14C]PFOA (9.4 mumol/kg, i.p.) in urine, demonstrating that a factor produced by the testis was responsible for the slow elimination of PFOA in male rats. Castration plus 17 beta-estradiol had no further effect on PFOA elimination whereas castration plus testosterone replacement at the physiologic level reduced PFOA elimination to the same level as rats with intact testes. Thus, in male rats, testosterone exerts an inhibitory effect on renal excretion of PFOA. In female rats, neither ovariectomy nor ovariectomy plus testosterone affected the PFOA urinary elimination, demonstrating that the inhibitory effect of testosterone on PFOA renal excretion is a male-specific response. Probenecid decreased the high rate of PFOA renal excretion in castrated males but had no effect on male rats with intact testes. We conclude that testosterone is a key determinant of the sex difference in PFOA elimination in rats.
Alpha-Globulins↗
Ability of vertebral dimensions from a single radiograph to identify fractures.
It has been proposed that vertebral dimensions be used to objectively identify vertebral fractures, permitting standardization of methodology for comparisons between studies. In this report, we evaluate the ability of various vertebral dimensions and ratios to identify "abnormal" vertebrae. As no "gold standard" exists for prevalent vertebral fractures, we examined the ability of cross-sectional dimensions (at a single point in time) to detect fractured vertebrae that had been identified from changes in dimensions compared with previous radiographs. Theoretically, a cutoff of 3 SD below the mean will rarely misclassify normal vertebrae as fractured (specificity = 99.9%). However, we found that this cutoff correctly identified only about 70% of the incident fractures. A less stringent criterion (2 SD below the mean; theoretical specificity = 97.7%) identified about 85-90% of true fractures. Dividing by stature or other vertebral heights sometimes yielded marginal improvements in the ability of the anterior or posterior height dimensions to diagnose fractures. The results suggest that the true fracture prevalence may sometimes be substantially higher than suggested by cross-sectional vertebral measurements.
Bone and Bones↗