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Biomedical subjects

J W Davis

Publications and source records attributed to J W Davis.

At least 19 recordsLinked to original sources

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

Mechanical correlates of the third heart sound.

In seven chronically instrumented conscious dogs, micromanometers measured left ventricular pressure, and ultrasonic dimension transducers measured left ventricular minor-axis diameter; the latter recording was filtered to examine data between 20 and 100 Hz. Acceptable external heart sounds were recorded with a phonocardiographic microphone in four of the seven dogs. With each dog sedated, intubated and mechanically ventilated, data were obtained during hemodynamic alterations produced by volume loading, phenylephrine, calcium infusion and vena caval occlusion. Damped oscillations were noted consistently in the left ventricular diameter waveform toward the end of rapid ventricular filling. These wall vibrations, assessed by the filtered diameter, correlated well with the third heart sound (S3) on the phonocardiogram. The peak frequency of the wall vibrations increased with increased diastolic pressure (p = 0.004), probably reflecting an increase in myocardial wall stiffness. In contrast, the amplitude of the vibrations varied directly with left ventricular filling rate (p = 0.0001). Thus, S3 seemed to be related specifically to ventricular wall vibrations during rapid filling, and the spectra of the amplitude-frequency relation shifted toward the audible range with increases in diastolic pressure, wall stiffness or filling rate. Spectral analysis of S3 may be useful in assessing pathologic changes in myocardial wall properties.

Animals

Comparison of preload recruitable stroke work, end-systolic pressure-volume and dP/dtmax-end-diastolic volume relations as indexes of left ventricular contractile performance in patients undergoing routine cardiac catheterization.

The end-systolic pressure-volume relation, the relation between stroke work and end-diastolic volume, termed the preload recruitable stroke work relation, and the relation between the peak of the first derivative of left ventricular pressure (dP/dtmax) and end-diastolic volume have been employed as linear indexes of left ventricular contractile performance in laboratory animals. The purpose of this study was to examine the relative utility of these indexes during routine cardiac catheterization in seven human subjects (mean age 48 +/- 18 [SD] years) with a normal left ventriculogram and coronary angiogram. Left ventricular pressure was recorded continuously with a micromanometer catheter, and left ventricular volume was derived from digital subtraction contrast ventriculograms obtained at 30-ms intervals. Transient occlusion of the inferior vena cava with a balloon-tipped catheter was employed to obtain beat to beat reductions in left ventricular pressure and volume over 8.7 +/- 1.7 cardiac cycles. Stroke work declined by 49 +/- 13% during vena caval occlusion, but end-systolic pressure fell by only 26 +/- 11%, and changes in dP/dtmax were small and inconsistent (12 +/- 22%). Consequently, the range of data available for determination of the preload recruitable stroke work relation greatly exceeded that for the end-systolic pressure-volume relation and the dP/dtmax-end-diastolic volume relation, and much less linear extrapolation from the measured data was required to determine the volume-axis intercept. Preload recruitable stroke work relations were highly linear (r = 0.95 +/- 0.07), and much more so than end-systolic pressure-volume relations (r = 0.79 +/- 0.23).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography, Digital Subtraction

A method for estimating the uncertainty of future bone mass.

The development of statistical models for estimating fracture probability is a promising method for quantitating and optimizing the clinical utility of bone mass measurements. Earlier models have assumed that future bone mass could be predicted exactly and were, therefore, limited to analyses that assume the loss rate is known in advance. Since bone loss rates may vary over time and cannot be predicted accurately, we have developed a new model, based on empirical data, that estimates the degree of uncertainty associated with predicted bone mass. Without a bone mass measurement, the population mean must be assumed for an individual. For the calcaneus, the standard deviation of the population distribution is about 60 mg/cm2. By measuring bone mass, one can determine how close or far from the mean an individual's true bone mass is, with a standard deviation (SD) of about 3 mg/cm2. Without a subsequent bone mass measurement, our model predicts that the uncertainty (standard deviation) in calcaneal bone mass will increase approximately sixfold (relative to the reproducibility at the initial measurement) over a period of five years for women under age 60, from 3 mg/cm2 to 19 mg/cm2. The five-year increase in uncertainty is approximately fourfold for women over age 60, from 3 to 13 mg/cm2. However, the uncertainty in bone mass for an individual five years after the initial measurement is still only one third to one fifth that of the entire population, and can be reduced to the initial level by obtaining another measurement. Furthermore, the predicted (or measured) values are usually much better estimates of an individual's true bone mass than simply assuming the population average.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

An analysis of errors causing morbidity and mortality in a trauma system: a guide for quality improvement.

The purpose of auditing trauma care is to maintain quality assurance and to guide quality improvement. This study was conducted to identify the incidence, type, and setting of errors leading to morbidity and mortality in trauma patients. Determinations of the Medical Audit Committee of San Diego County were reviewed and classified by the authors for identification of preventable errors leading to morbidity or mortality. Errors were classified by type and categorized by phase of care. Errors were identified in the cases of 4% of all patients admitted for trauma care over a 4-year period. Of all trauma patient deaths, 5.9% were considered preventable or potentially preventable. The most common single error across all phases of care was failure to appropriately evaluate the abdomen. Although errors in the resuscitative and operative phases were more common, critical care errors had the greatest impact on preventable death. The detected error rate of 4% may represent the baseline error rate in a trauma system. While regionalized trauma care has dramatically reduced the incidence of preventable death after injury, efforts to further reduce preventable morbidity and mortality may be guided by an identification of common errors in a trauma system and their relationship to outcome.

California

An evaluation of provider-related and disease-related morbidity in a level I university trauma service: directions for quality improvement.

As the number of preventable trauma-related deaths plateaus as a result of trauma system development, new directions for quality improvement in trauma care must come from analyzing morbidity with standardized methods to establish thresholds for provider-related and disease-specific complications. To establish such thresholds and determine priorities for improvements in quality all trauma patients who died, who were admitted to the ICU or OR, who were hospitalized for more than 3 days, or who were interfacility transfers to an academic trauma service, were concurrently evaluated for 1 year. All complication events were defined, reviewed, tabulated, and classified using 135 categories of complications. These categories were subdivided into provider-specific and disease-specific complications. Provider-related complications were classified as justified or unjustified to allow identification of events with a potential for improvement. A total of 1108 patients were admitted (mean ISS, 17); there were 97 deaths. Three potentially preventable deaths were identified, 857 complication events were identified, and 285 provider-related complications were responsible for errors with potential for improvement in 59 events (21%). Disease-specific morbidity was primarily related to infection; pneumonia accounted for 36% of all infectious complications and systemic infection for only 8.6% of infectious complications. Organ failure and other major systemic complications occurred in 2%-8% of patients. This type of analysis forms the basis on which to determine thresholds of provider-specific and disease-specific morbidity in a trauma hospital and serves as a guide to direct efforts toward continuous quality improvement.

Adult

Time course of some effects of cigarette smoking on platelets.

Eight male habitual smokers smoked two cigarettes over a 20-min period following a 12-h period of abstinence. Antecubital venipuncture was performed immediately before, immediately after, and 55 min and 2 h after smoking had ceased. At these times, the mean values (+/- SD) of collagen-induced platelet aggregation were 45 +/- 5, 68 +/- 5, 59 +/- 6 and 52 +/- 5 chart units, respectively, while the corresponding values for the mean platelet aggregate ratio were 0.91 +/- 0.01, 0.82 +/- 0.03, 0.87 +/- 0.02 and 0.90 +/- 0.02, respectively. Mean collagen-induced platelet aggregation was significantly (P less than 0.005) higher immediately after, and 55 min and 2 h after smoking. The mean platelet aggregate ratio was significantly (P less than 0.001) lower immediately after and 55 min after smoking. Correlation coefficients between the concentration of nicotine in each of the 24 plasma samples obtained after smoking and the corresponding values of collagen-induced platelet aggregation and the platelet aggregate ratio were 0.41 (P less than 0.05) and -0.50 (P less than 0.02), respectively. It is concluded that when habitual smokers abstain from smoking overnight, a 20-min period of cigarette smoking may enhance platelet aggregability for as long as 2 h.

Adult

Cervical enamel projection with gingival fenestration in a maxillary central incisor: report of a case.

Bacterial plaque has been implicated as the primary etiologic factor in the initiation and progression of periodontal disease. Anatomic factors, such as cervical enamel projections, enamel pearls, and radicular grooves, are often associated with advanced localized periodontal destruction. Enamel projections and pearls are most often associated with molars, while radicular grooves are usually located on the palatal aspect of maxillary incisors. Gingival fenestrations are of uncertain etiology and have rarely been reported in the dental literature. An unusual case is presented of a cervical enamel projection located on the facial aspect of a maxillary central incisor in association with gingival fenestration. Rationale for therapy and likely healing results are discussed.

Adolescent

Quantitative analysis of regional wall thickening by transesophageal echocardiography.

To develop a method for quantitative analysis of regional left ventricular function from transesophageal two-dimensional echocardiograms, we conducted studies 10 and 20 minutes after induction of anesthesia in 16 patients with normal hearts who were undergoing minor orthopedic operations. Wall thickening was measured with the centerwall method along 100 chords drawn perpendicular to a line constructed around the center of the ventricular wall, midway between the endocardial and epicardial contours. Thickening, either normalized by the length of the end-diastolic perimeter or expressed as a percentage of the end-diastolic wall thickness at each chord, was compared with measurements of endocardial motion. Wall motion was relatively diminished in the anteroseptal region and enhanced on the contralateral wall, but wall thickening was homogeneous throughout the contour. Normalized wall thickening was significantly less variable (standard deviation/mean, 0.47 +/- 0.13) in the normal population than were either percent wall thickening (0.53 +/- 0.012) or wall motion (0.51 +/- 0.09) (p less than 0.005 for both comparisons). There was no significant change in regional or global function between 10 minutes and 20 minutes after the induction of anesthesia. In summary, normalized wall thickening as a parameter of regional left ventricular function is more homogeneous and less variable in subjects with normal hearts than is endocardial motion because wall thickening measurements are not subject to cardiac translocation artifacts. This low variability suggests that normalized wall thickening measured by the centerwall method may prove particularly useful for intraoperative and postoperative monitoring of regional left ventricular function by transesophageal echocardiography in patients undergoing both cardiac and noncardiac surgical procedures.

Adult

Pre-existing fractures and bone mass predict vertebral fracture incidence in women.

OBJECTIVE: To determine the independent contributions of bone mass and existing fractures as predictors of the risk for new vertebral fractures. SUBJECTS: Postmenopausal Japanese-American women. MEASUREMENTS: Baseline measurements of the distal radius, the proximal radius, and the calcaneus were obtained in 1981 using single-photon absorptiometry. Measurements of the lumbar spine were obtained in 1984 using dual-photon absorptiometry. Prevalent vertebral fractures were identified using dimensions measured on lateral radiographs; vertebral height values more than 3 SD below vertebra-specific means were considered to indicate fracture. Statistical models were used to evaluate the utility of bone mass and existing (prevalent) fractures to predict the risk for new fractures during an average follow-up of 4.7 years. MAIN RESULTS: Differences of 2 SD in bone mass were associated with fourfold to sixfold increases in the risk for new vertebral fractures. A single fracture at the baseline examination increased the risk for new vertebral fractures fivefold. Presence of two or more fractures at baseline increased the risk 12-fold. A combination of low bone mass (below the 33d percentile) and the presence of two or more prevalent fractures increased the risk 75-fold, relative to women with the highest bone mass (above the 67th percentile) and no prevalent fractures. Stature, body mass index, arm span, and spinal conditions such as scoliosis, osteoarthritis, and sacroiliitis did not predict fracture incidence (P greater than 0.05). Weight was marginally predictive (P = 0.04) of fracture incidence but became nonpredictive after adjusting for bone mass (P greater than or equal to 0.05). CONCLUSIONS: Both bone mass and prevalent vertebral fractures are powerful predictors of the risk for new vertebral fractures. Combining information about bone mass and prevalent fracture appears to be better for predicting new fractures than either variable alone. Physicians can use these risk factors to identify patients at greatest risk for new fractures.

Absorptiometry, Photon

A comparison of hip fracture incidence among native Japanese, Japanese Americans, and American Caucasians.

Hip fracture incidence rates among men and women of Japanese ancestry living on Oahu, Hawaii, from 1979 to 1981 were compared with rates for Japanese living on Okinawa, Japan, from 1984 to 1985. Both rates were further compared with those for various American Caucasian populations, including that of Rochester, Minnesota, from 1978 to 1982. Age-specific and cumulative (age 50-84 years) hip fracture rates among persons of Japanese ancestry were approximately half that of Caucasians for both sexes. Although diet and other cultural attributes of the Oahu group have become more westernized than the Okinawan population, there were no detectable differences in hip fracture rates between Oahu and Okinawa Japanese. Additional studies are needed to determine whether the observed differences in fracture rates between Caucasians and Japanese might be related to differences in bone mass, body size, frequency of falls, or other factors.

Adult

Evaluation of adverse health outcomes associated with vertebral fractures.

Little is known about the frequency or degree to which vertebral fractures cause pain and physical disability. The purpose of this investigation was to examine the advantages of risk analysis over other statistical techniques (e.g., correlation analysis) for quantifying relationships between vertebral fractures and outcomes such as pain and disability. Subjects who volunteered to participate in studies of osteoporosis were asked about pain and disability. The number and degree of vertebral deformities were assessed from radiographs. Strong associations were observed between the most severe vertebral deformities and the risk of high pain or disability scores, while weaker associations were observed for moderate deformities. There did not appear to be any association between vertebral deformity and risk of moderate levels of pain or disability. Because of the potential for bias in cross-sectional studies such as this, the magnitude of these findings must be considered tentative. We conclude that risk analysis is an appropriate method for quantifying the relationship of vertebral fractures with pain and disability, but that prospective studies are now needed.

Back Pain

Effects of perfluorodecanoic acid on de novo fatty acid and cholesterol synthesis in the rat.

Perfluorodecanoic acid (PFDA) is a peroxisome proliferator that causes a dose-dependent (20-80 mg/kg) increase in hepatic triacylglycerol and cholesteryl ester levels in the rat. We hypothesized that PFDA may cause an increase in the de novo synthesis of fatty acids and cholesterol in this species, which would explain observed effects. The incorporation of 3H2O into tissue lipids was examined 7 days after rats received vehicle or 20 or 80 mg/kg of PFDA. PFDA treatment decreased the rate of synthesis of cholesterol and fatty acids in the live and in epididymal fat pad. At a PFDA dose (20 mg/kg) that decreased de novo synthesis of fatty acids and cholesterol, there was no effect on the concentration of fatty acids and cholesterol in the liver, epididymal fat pads, and plasma. We conclude that PFDA induced fatty liver is due to either a decrease in the oxidation of fatty acids in the liver, or an impairment of triacylglycerol catabolism and/or export from the liver, and is not the result of an increase in de novo synthesis of fatty acids and cholesterol.

Adipose Tissue

Long-term precision of bone loss rate measurements among postmenopausal women.

Repeated measurements of bone mineral content can indicate the rate of bone loss among postmenopausal women. The clinical utility of such loss rate measurements will depend upon the long-term precision of the measurements. We have analyzed the precision of appendicular bone measurements among 495 Japanese-Americans followed for an average of 5.3 years and of both appendicular and axial measurements among 70 clinical trial participants followed for 2 years. Tables were derived from these analyses to quantitate the precision of individual loss rates under varying measurement conditions that might be encountered in clinical practice. The results demonstrate that only unusually rapid loss rates could be identified with confidence within short intervals, such as 1 year or 2. Extending the length of follow-up, however, appreciably improved the measured loss rate precision. In comparisons between bone sites, appendicular sites were determined to achieve a specified precision within the shortest intervals, followed by spine dual photon absorptiometry measurements. Spine quantitative computerized tomography measurements and measurements of hip sites required considerably longer follow-up intervals to achieve comparable precision.

Aged

Degradation of organic cyanides by Pseudomonas aeruginosa.

A bacterium capable of utilizing acetonitrile (methyl cyanide) as the sole source of carbon and nitrogen was isolated from soil and identified as Pseudomonas aeruginosa. This bacterium could also utilize and oxidize numerous lower-mol-wt nitrile compounds and their corresponding amides as growth substrates. A metabolite of acetonitrile in the culture medium was determined to be ammonia. The accumulation of ammonia in the culture medium was proportional to the concentration of the substrate and the inoculum. Cell extracts of the bacterium contained activities corresponding to nitrile aminohydrolase (E C 3.5.5.1) and amidase (E C 3.5.1.4), which regulate the degradation of acetonitrile. Both enzymes were inducible and hydrolyzed a wide range of substrates, and it was determined that the specific activity of amidase was far greater than the activity of nitrile aminohydrolase.

Acetonitriles