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Biomedical subjects

L E Davis

Publications and source records attributed to L E Davis.

At least 109 records · Page 6Linked to original sources

Magnetoencephalographic comparison of cortical sensorimotor extrema evoked by flexion of index finger and thumb.

A seven sensor array (6 sensors equally spaced on a 4 cm dia. with 1 sensor at the center) was used to differentiate two close sensorimotor sources (voluntary movements of right index finger and right thumb). Magnetic field amplitude data was analyzed from a single-session recording (single sensor-array location). The sensor array was positioned to record the peak magnetic field amplitude (an extremum) of one or both digits (analyzed at 145 ms after the electromyogram). An extremum was obtained by plotting a topographic field map and also by mathematical interpolation (both) from the seven-sensor amplitudes while at a fixed location. This method of analysis graphically showed digit extrema separation in all subjects over the negative extrema and thus separation of the neural generator populations at this specific time. Statistical significance of the seven sensor amplitudes was examined by null hypotheses testing. The digit extrema separation (over the negative extrema) was influenced by errors primarily due to noise, signal-to-noise ratio = 6 +/- 2.4, and the subjects' variability in digit flexion. This analysis eliminated sensor array position error and minimized the analysis time to a single session. From the plotted distribution of extrema pertaining to a particular flexion (same subject), obtained from repeated sessions, a mean extrema location for each digit was determined. In this manner, a separation between the digit extrema was demonstrated. The mapped distribution also provided a clear display of the error in plotting extrema locations. For both digits the error in mapping extrema locations (negative only) was 0.9 cm.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Mapping↗

Thyrotoxicosis complicating pregnancy.

During the 12-year period from 1974 through 1985, nearly 120,000 women were delivered of infants at Parkland Hospital, and pregnancy was complicated by overt thyrotoxicosis in 60 of them (1:2000). Initial treatment was based on clinical assessment, and propylthiouracil was usually given in doses of 300 to 800 mg daily. In compliant women seen by midpregnancy, euthyroidism was achieved by a mean of 8 weeks; however, the daily dose was decreased to less than or equal to 150 mg by delivery in only 10%. Metabolic status at delivery correlated directly with pregnancy outcome, and women treated earlier in pregnancy were more likely to be euthyroid at delivery and to have good outcomes. Diagnosis of thyrotoxicosis antecedent to pregnancy was associated with earlier treatment, and 80% of 28 such women were euthyroid by delivery. Conversely, 32 women with a first diagnosis during pregnancy had the preponderance of morbidity, including five of six stillbirths and six of seven cases of heart failure. This group was characterized by a relative delay in gestational age at diagnosis. Preterm delivery, perinatal mortality, and maternal heart failure were more common in women who remained thyrotoxic despite treatment and in those who were never treated. Although we infrequently achieved maintenance doses recommended by most, because there were minimal adverse effects from therapy described here and because uncontrolled thyrotoxicosis caused significant maternal and perinatal morbidity, aggressive medical therapy seems appropriate, especially when pregnancy is advanced.

Adult↗

Antagonism in isolated equine digital vessels of contraction induced by epinephrine in the presence of hydrocortisone and an aqueous extract of black walnut (Juglans nigra).

Prazosin, isoxsuprine, and nifedipine were screened for ability to reverse contraction of isolated equine digital vascular strips produced by epinephrine (Epi) in the presence of hydrocortisone (Hc) and an aqueous extract of black walnut (Juglans nigra) (BW). Two arteries and two veins from each of three horses for each drug (n = 9) were maintained in isolated tissue baths in Krebs' bicarbonate buffer with 95% oxygen at 37 degrees C. Six-point Epi concentration-response (C-R) curves were obtained for each vessel in the presence of Hc, BW, and the appropriate vehicle. This was repeated for each vessel using one of two concentrations of one of the three test drugs. Each drug and concentration combination was tested on a total of three arteries and three veins. Prazosin produced a concentration-dependent shift of the Epi C-R curve to the right but the curve maintained the same maximum height and slope, which is consistent with competitive alpha 1 adrenergic blockade. Isoxsuprine exhibited similar behavior, although the precise mechanism of action for isoxsuprine is unknown. Conversely, nifedipine did not shift the curve but did depress maximum contraction, suggesting a non-competitive interaction consistent with its mechanism of calcium-channel blockade.

Animals↗

Vascular pressure-volume relationships in pregnant and estrogen-treated guinea pigs.

We investigated the relationship between mean circulatory filling pressure (MCFP) and blood volume in nonpregnant (NP), estrogen-treated (E), and pregnant (P) guinea pigs. Reversible circulatory arrest was produced by rapid ventricular pacing or acetylcholine in unanesthetized animals remote from surgery. MCFP (mmHg) was higher for E (7.1 +/- 0.3) than for NP (5.8 +/- 0.5) or P (5.3 +/- 0.4). The gradient for venous return, the difference between MCFP and right atrial pressure (mmHg), did not differ in NP- (6.0 +/- 0.5), P- (5.8 +/- 0.5), or E- (5.8 +/- 0.4) treated animals. Capacitance, the blood volume (ml/kg) at an MCFP of 6 mmHg, was increased in P (84 +/- 6) and E (89 +/- 7), compared with NP (64 +/- 5) animals. Compliance, the ratio of the change in volume to change in pressure in the range of 6-12 mmHg (ml.kg-1.mmHg-1), was greater in P (4.4 +/- 0.3) than NP (3.5 +/- 0.3) animals. Hexamethonium blockade did not affect MCFP, capacitance, or compliance. We conclude that the effect of blood volume expansion on the circulation in pregnancy cannot be predicted from knowledge of MCFP-blood volume relationships in the nonpregnant animal, because capacitance and compliance are altered. Estrogen administration to nonpregnant animals reproduces some of these effects.

Animals↗

Rabbit plasma fibronectin levels associated with Staphylococcus aureus enterotoxin B: an acute-phase reaction.

Variation in fibronectin (Fn) levels and white blood cell counts (WBC) following staphylococcal enterotoxin B (SEB) or SEB + cryoprecipitate containing Fn challenge was studied in New Zealand white rabbits. Increased plasma Fn levels were observed 2 h after the intravenous injection of SEB and peaked at 48-72 h (from a mean level 194.6 +/- 4.5 micrograms/ml prechallenge Fn level to a 72-hour postchallenge mean level of 407.9 +/- 25.4 micrograms/ml). Fn levels then decreased over the succeeding 5 days to approximately prechallenge levels. The total WBC count decreased by 88% within 2 h after the SEB injection. A slow increase in circulatory WBC was observed over the next 24 h. SEB caused an increase in plasma Fn levels and decreased WBC counts with lymphopenia that was followed by a normal lymphocyte count within 5 days. These data suggest that an acute-phase reaction was induced by interleukin-1. Fn prophylaxis provided no change in clinical signs when given at the time of SEB injection.

Acute-Phase Reaction↗

Pharmacokinetic properties of theophylline given intravenously and orally to ruminating calves.

The disposition of theophylline in healthy ruminating calves was best described by a first-order 2-compartment open pharmacokinetic model. The drug had a mean elimination half-life of 6.4 hours and a mean distribution half-life of 22 minutes. Total body clearance averaged 91 ml/kg/h. The mean values for the pharmacokinetic volume of the central compartment, pharmacokinetic volume of distribution during the terminal phase, and volume of distribution at steady state were 0.502, 0.870, and 0.815 L/kg, respectively. Theophylline was readily absorbed after oral administration to the ruminating calf, with a mean fraction of 0.93 absorbed. The plasma concentrations after oral dosing peaked in approximately 5 to 6 hours, with a mean absorption half-life of 3.7 hours. A flip-flop model (rate constant of input is much smaller than the rate constant of output) of drug absorption was not found because the elimination process roughly paralleled that of the study concerning IV administration. In a multiple-dose trial that used a dosage regimen based on single-dose pharmacokinetic values, clinically normal calves responded as predicted. However, diseased calves had higher than expected plasma concentrations after being given multiple oral doses of theophylline at 28 mg/kg once daily. Overt signs of toxicosis were not seen, but this aspect of the drug was not formally investigated. Theophylline can be used as an ancillary therapeutic agent to treat bovine respiratory disease, but not without risk. The suggested oral dose of theophylline at 28 mg/kg of body weight once daily should be tailored to each case.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Predictive model for plasma concentration-versus-time profiles of investigational anticancer drugs in patients.

We report a model that provides a strong correlation between mouse toxicity data [mouse lethal dose 10% (LD10)] and human plasma concentration-versus-time (CXT) data for 22 commonly used anticancer agents. Mouse toxicity data (LD10) from two dosing schedules, daily times one and daily times seven, were evaluated for the two mouse strains BDF/1 and Swiss. Data from BDF/1 mice were selected for analysis because they were more abundant. Strong correlations were found between LD10 and human plasma CXT data for both daily times one and daily times seven dosing schedules--ln (CXT) = -1.6504 + [0.8408 X ln (LD10)], r = .84, P less than .0001, and ln (CXT) = -0.0754 + [0.8954 X ln (LD10)], r = .90, P less than .0001, respectively. These correlations may serve as useful models to predict the maximally tolerated dose of an investigational anticancer agent prior to entry into clinical trials and to assist in the selection of clinically relevant in vitro CXTs for new-agent screening against human tumors.

Animals↗

Tumor-associated blood group antigen expressions and immunoglobulins associated with tumors.

As outlined in Figures 1 and 2, the biosynthetic pathways for the expression of the A, B and H, and the Lewis determinant carbohydrate sequence structures, as well as sialylated structures, involves both type 1 and type 2 precursor chains (which may be present as glycolipids and N- or O-linked glycoproteins), and many glycosyltransferases. For tumor cells, there appears to be increased expressions of fucosyl- and sialyltransferases yielding such structures as the Le(x), sialyl-Le(a), and many other similar determinants, which are not found on the normal cell progenitor of the tumor. The types of structures expressed on tumor cells is dependent on the particular fucosyl-, sialyl- and other glycosyltransferase genes activated in the transformation and tumor progression events, the availability of the substrates for the glycosyltransferases (both the precursor sequences and the nucleotide-sugar substrates) which is partly dependent on metabolites available to the tumor mass, and on the genotype of the individual regarding particular glycosyltransferases. Both the loss of A, B and/or H blood group antigen expressions of tumor cells and the relative expressions of the Lewis and sialylated-oligosaccharide determinants may be a consequence of the competing biosynthetic pathways and the glycosyltransferases for common substrate sequences, as well as due to the loss of particular glycosyltransferases concomitant with transformation. All of these factors probably account for the variable expressions of the complex of carbohydrate sequence determinants when comparing tumor sections of different individuals as well as the heterogeneity of expression of particular determinants within a single tumor tissue section. As described above, the A, B and/or H determinants, and the precursor sequences, are also expressed to differing extents on epithelial cells depending on the tissue type and cellular location in the tissue. Thus, the differentiation state of the particular epithelial cell also determines the quantity and types of carbohydrate sequences expressed. However, because of the complex nature of the competing biosynthetic pathways for the carbohydrate sequences of glycolipids and glycoproteins, and the relative activations of fucosyl- and sialyltransferases of tumor cells, it would seem that simple deductions as to the state of differentiation of particular tumors with A, B, H and precursor sequence expressions is not warranted.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Neoplasm↗

Natural history of frequent recurrences of herpes simplex labialis.

We prospectively studied all herpes simplex labialis (HSL) episodes in a group of 84 (age, 6 to 71 years) persons who previously had frequent recurrences of HSL to determine whether their recurrences of HSL were different from those of the general population. The mean +/- standard error for number of HSL outbreaks for 6 months was 2.7 +/- 0.3. Age, gender, or season did not influence the recurrence rate. The mean time to vesicle healing of 214 outbreaks was 6.4 +/- 0.2 days. Again, age or gender did not influence healing time. An episode of HSL did not elicit a refractory period to the next attack of HSL. Furthermore, the severity of the previous HSL lesion did not influence the interval to next recurrence or the location of the next lesion. In 47%, the next recurrence of HSL crossed the midline of the face, and in 45%, it moved from one lip to the other. The high recurrence frequency and multiple facial locations of HSL lesions seen in these persons differed from the general population, who report infrequent lesions of HSL at the same facial location.

Adolescent↗

Inhibition of fatty acid beta oxidation by influenza B virus and salicylic acid in mice: implications for Reye's syndrome.

Injection of concentrated influenza B/Lee/40 virus into 4-week-old Balb C mice resulted in 60% inhibition of 14C-palmitate oxidation in isolated hepatic mitochondria. Oral feeding of carnitine to infected mice prevented the inhibition of fatty acid oxidation. High concentrations of salicylic acid given orally also inhibited 14C-palmitate oxidation. Serum free fatty acid concentrations of infected mice and of those fed salicylic acid were significantly higher than in control mice. A combination of low-dose virus and low-dose salicylic acid inhibited palmitate oxidation, suggesting an additive effect on the metabolic derangement when the two agents were present simultaneously.

Animals↗

Causes of death of patients in an institution for the developmentally disabled.

The causes of death of 53 severely to profoundly developmentally disabled patients who died in an intermediate care facility were reviewed. Respiratory disease, predominantly pneumonia and aspiration, accounted for 72% of deaths. Seven patients died of nonrespiratory causes, and in 8 patients, no cause of death could be determined, even after a complete autopsy or investigation. The median age at death was 20 years. The weights of these patients' organs at autopsy were lower than those for normal individuals of the same age. The lifespan of these severely impaired individuals continues to be significantly shortened, even with improved methods of care.

Adolescent↗

Hypothyroidism complicating pregnancy.

Hypothyroidism rarely complicates pregnancy because most affected women are anovulatory. In this report, we describe 28 complicated pregnancies cared for over a ten-year period at Parkland Memorial Hospital. In the group of 16 pregnancies in 14 overtly hypothyroid women, maternal complications were common and included anemia (31%), preeclampsia (44%), placental abruption (19%), postpartum hemorrhage (19%), and cardiac dysfunction. Perinatal morbidity and mortality were also high mainly because of placental abruption, and reflected frequent low birth weight (31%) and fetal death (12%). In a group of 12 women with subclinical hypothyroidism, these complications were less impressive. We speculate that overt thyroid deficiency is associated with adverse pregnancy outcome related to preeclampsia and placental abruption. Thyroxine replacement probably improves these outcomes even if subclinical hypothyroidism persists.

Female↗

Distribution of chloramphenicol in the genital tract of postpartum cows.

Chloramphenicol was administered by constant IV infusion to 7 healthy postpartum cows at rates predicted to approach a steady-state plasma concentration of 5 micrograms/ml. After 8 hours of constant IV infusion, uterine tissues were removed surgically and were assayed for chloramphenicol concentrations. Mean plasma-to-tissue ratios of chloramphenicol concentrations were 3.05, 3.63 (6 cows only), and 3.22 for caruncles, endometrium, and uterine wall, respectively. Plasma-to-tissue ratios of the 3 tissues were not significantly different (P greater than 0.10). Intrauterine (IU) injections of chloramphenicol (20 mg/kg of body weight) were administered to 3 healthy post-partum cows. The mean value of the fraction of the drug absorbed from the uteri of these cows was 0.40. Mean concentrations of chloramphenicol were 43.8 micrograms/g in caruncles, 34.6 micrograms/g in endometrium, 2.8 micrograms/g in uterine wall, and 2.9 micrograms/ml in plasma 8 hours after IU injections. Chloramphenicol has now been banned for use in food-producing animals in the United States because of its potential for causing toxicosis in human beings. It is illegal to use chloramphenicol in food-producing animals in the United States and in some other countries as well. This includes use by the IU route of administration because chloramphenicol and most drugs are absorbed from the uterus into the bloodstream and are distributed to milk and tissues.

Animals↗

Pharmacokinetics of thiamylal in cats.

Pharmacokinetics of thiamylal were determined after 13.2 mg of thiamylal/kg of body weight was administered IV to 6 healthy cats. Blood samples were obtained for 12 hours. Disposition of thiamylal best conformed to 2 multicompartmental models, a 2-compartment (n = 1) and a 3-compartment (n = 5) open pharmacokinetic model. The pharmacokinetic values were calculated for the overall best-fitted model, a mixed 2- and 3-compartmental model. The first or rapid distribution half-life was 1.91 minutes and a second, or slower, distribution half-life was 26.51 minutes. The elimination half-life was 14.34 hours. The apparent volume of distribution was 3.61 +/- 1.8463 L/kg, whereas the apparent volume of the central compartment was 0.46 +/- 0.2034 L/kg, and the total clearance was 0.135 +/- 0.0616 L/kg/h.

Animals↗