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Biomedical subjects

L E Davis

Publications and source records attributed to L E Davis.

At least 91 records · Page 5Linked to original sources

Advances in the treatment of unstable angina pectoris.

The pathogenesis, clinical manifestations and diagnosis, and drug and nondrug therapies of unstable angina pectoris are reviewed. Coronary-artery plaque fissure and rupture, with subsequent platelet aggregation and thrombosis, are the primary underlying stimuli for unstable angina. Unstable angina has been defined as consisting of new-onset angina; angina that is increasing in frequency, intensity, or duration (crescendo angina); or angina at rest. The diagnosis of unstable angina is based on the clinical presentation, electrocardiographic findings, the lack of evidence of myocardial infarction (MI), exercise testing, and coronary angiography. I.V. nitroglycerin is the cornerstone of medical therapy for unstable angina, it relieves chest pain and has a short onset of action. I.V. nitroglycerin, however, has not been shown to reduce the occurrence of MI or death, and its beneficial effects may decrease over time. Aspirin reduces the occurrence of MI and death in patients with unstable angina, but the ideal dosage has not been established. Heparin may reduce the frequency of angina and MI, but its effect on mortality is unknown. Nifedipine has produced beneficial effects in small trials, whereas larger trials have suggested that the drug has deleterious effects when used in the treatment of unstable angina. Verapamil and diltiazem may be effective in relieving chest pain. Calcium-channel blockers have generally not been proved to reduce the risk of MI and death. Data evaluating the efficacy of beta-adrenergic blockers as monotherapy for unstable angina are lacking; these drugs should not be used in patients with vasospastic or Prinzmetal's angina. Thrombolytic therapy has produced mixed results when used in the treatment of unstable angina. Nondrug therapies for unstable angina include intra-aortic balloon counterpulsation, percutaneous transluminal coronary angioplasty, and coronary-artery bypass surgery. Numerous drug and nondrug therapies may be employed in the treatment of unstable angina pectoris.

Angina, Unstable↗

Metabolic emergencies in obstetrics.

This article reviews maternal and fetal aspects of diabetic ketoacidosis, thyroid storm, Cushing's syndrome, addisonian crisis, pheochromocytoma, and hyper- and hypothyroidism.

Addison Disease↗

A possible receptor-binding function for the N-terminus of connective tissue activating peptide III.

Connective tissue activating peptide III (CTAP-III) is an 85-residue peptide which has been purified from platelets and shown to possess mitogenic activity toward a variety of fibroblastic cell lines. beta-Thromboglobulin (beta TG) is an 81-residue peptide which is derived from CTAP-III by cleavage of the N-terminal tetrapeptide Asn-Leu-Ala-Lys which results in the loss of mitogenic activity. The near-UV CD spectra for the two proteins indicated that the conformations as well as the electronic environments of the two disulfide bonds, and also of the single aromatic tyrosine residue, were similar in CTAP-III and beta TG. However, differences in the far-UV CD spectra of these proteins indicated a substantial decrease in alpha-helical content for beta TG (29%) as compared to CTAP-III (38%). Structure prediction analysis also suggested that the longer N-terminal segment of CTAP-III may form an alpha-helix. The N-terminal region of beta TG, which lacks this tetrapeptide, was predicted to be in an unordered, or possibly a turn, conformation. This predicted structural difference appears to be due to the high helix-forming potential of the N-terminal tetrapeptide Asn-Leu-Ala-Lys in CTAP-III. These results suggest a possible structural role for the N-terminal region of CTAP-III in the expression of the biologic activities of this protein. On the basis of these studies, a reasonable hypothesis to account for the difference in mitogenic activity between beta TG and CTAP-III is that the N-terminal region must be helical for receptor binding to occur.

Amino Acid Sequence↗

Pharmacokinetics and metabolism of fenbendazole in channel catfish.

Fenbendazole (FBZ) was administered intravenously (1 mg/kg) and orally (5 mg/kg) to catheterized, confined channel catfish. Blood samples were collected for 72 h, and resulting FBZ plasma concentrations were pharmacokinetically modelled. Following intravenous administration t 1/2 alpha was 0.51 h, t 1/2 beta was 16.8 h, body clearance (C1B) was 0.0598 L/kg/h, and Vd (area) was 1.45 L/kg. After oral administration the t 1/2 (abs) was 1.47 h, the t 1/2 beta was 20.1 h, and the tlag was 0.1 h. Following oral administration of 5 mg FBZ/kg body weight, the following tissues and body fluids were sampled for concentrations of FBZ, oxfendazole (FBZ-SO), sulphone metabolite (FBZ-SO2) and hydroxy metabolite (FBZ-OH): liver, posterior kidney, fat, muscle, bowel contents and urine. Fenbendazole was detected in the highest concentrations in abdominal fat, whereas oxfendazole was found primarily in the kidney, liver and abdominal fat. The sulphone metabolite was detected only in urine and bowel contents, while the hydroxy metabolite was found most often in the liver and abdominal fat samples.

Absorption↗

Pre-mortem diagnosis of Creutzfeldt-Jakob disease by detection of abnormal cerebrospinal fluid proteins.

Creutzfeldt-Jakob disease (CJD) may be difficult to diagnose early or when it has an atypical presentation. We describe two patients with progressive dementia in whom the results of diagnostic brain biopsies were unhelpful. Spinal fluid from these patients, analyzed by two-dimensional electrophoresis, contained two abnormal proteins (Nos. 130 and 131, with relative molecular masses of 26,000 and 29,000 daltons and isoelectric points of 5.2 and 5.1). These findings suggested a provisional diagnosis of Creutzfeldt-Jakob disease, which was confirmed in both patients at autopsy. Detection of these abnormal cerebrospinal fluid proteins appears to be a valuable laboratory adjunct in evaluating patients with an unexplained progressive dementia.

Aged↗

The influenza B virus mouse model of Reye's syndrome: clinical, virologic and morphologic studies of the encephalopathy.

The influenza B virus mouse model of Reye's syndrome was studied to learn more about the encephalopathy in Reye's syndrome. One to 3 days after intravenous influenza B/Lee virus, Balb/c mice became lethargic, seized and lapsed into a fatal coma. Wide-spread cerebral edema without inflammation developed 1-3 days after virus inoculation. Swollen astrocytic foot processes containing increased glial fibrillary acidic protein were located around capillaries. Viral particles were not seen by electron microscopy and complete viral replication did not occur. Immunohistochemical studies demonstrated influenza B viral antigen within many endothelial cells but not within other brain cells. Qualitative (Evans blue dye) and quantitative (percent brain water and technetium -99 pertechnetate) studies of the blood-brain barrier demonstrated abnormalities. This model reproduced many clinical, virologic and pathologic features of the Reye's syndrome encephalopathy. In addition, a non-permissive viral infection of brain endothelial cells occurred which may be important in the pathogenesis of the mouse encephalopathy and may participate in the encephalopathy of Reye's syndrome.

Animals↗

The sequence of changes in liver and brain in the influenza B virus mouse model of Reye's syndrome.

The time course of morphologic changes in the influenza B mouse model of Reye's syndrome is described and compared to the clinical, virologic, and biochemical changes. Following an intravenous inoculation of a lethal dose of an egg adapted strain of influenza B/Lee/40 virus, mice first showed clinical signs of lethargy and ruffled fur at 12 hours (h) post inoculation (pi). The earliest morphologic changes in the liver occurred at 12 h pi, and consisted of a slight increase in fat and loss of glycogen in hepatocytes. Over the next 36 h, the accumulation of microvesicular fat increased, and mitochondrial abnormalities such as pleomorphism and loss of dense bodies developed. There was no increase in peroxisomes. In the brain, focal cerebral edema was detected as early at 6-12 h pi. The edema, manifested as swelling of astrocytic foot processes, increased in severity with time. Endothelial cells were not abnormal. Myelin sheath splitting rarely was observed. Since changes occurred simultaneously in the liver and in the brain, we suggest that influenza B virus caused a simultaneous primary insult to both organs.

Animals↗

Antifungal activity in human cerebrospinal fluid and plasma after intravenous administration of Allium sativum.

Commercial Allium sativum (garlic) extract was given intravenously to two patients with cryptococcal meningitis and three patients with other types of meningitis. Plasma titers of anti-Cryptococcus neoformans activity rose twofold over preinfusion titers. Anti-C. neoformans activity was detected in four of five cerebrospinal fluid samples but not in pooled normal cerebrospinal fluid.

Antifungal Agents↗

Deep cerebral infarcts in the People's Republic of China.

We reviewed computed tomograms and clinical characteristics for 1,124 consecutive stroke patients from Shanghai, People's Republic of China. While there were many similarities between lacunar syndromes in these patients and patients from Europe and the United States, several differences were noted. Deep cerebral infarcts identified by computed tomography were more common in patients from Shanghai and accounted for 27% of all ischemic infarcts. Small deep infarcts occurred more commonly in women from Shanghai (44%) than in women from the West. Deep cerebral infarcts in patients from Shanghai were larger than those usually seen in patients from the West. The mean infarct volume in patients from Shanghai was 2.4 ml, and 49% were giant lacunes (greater than 15 mm in maximal diameter).

Aged↗

Effect of an aqueous extract of black walnut (Juglans nigra) on isolated equine digital vessels.

An aqueous extract was made from black walnut (Juglans nigra) heartwood obtained in the fall of the year. Ten hours after nasogastric administration of 5 L of the extract, a 550-kg, 13-yr-old Quarter Horse gelding experienced Obel grade-3 laminitis. The effect of aqueous extract of black walnut on vascular contractility was then tested, using isolated equine digital arteries and veins. The vessels were maintained in Krebs bicarbonate buffer with 95% oxygen at 37 C. The extract did not induce a direct contractile effect. It did, however, reversibly enhance the vasoconstriction induced in the isolated vessels by administration of epinephrine potentiated with hydrocortisone. In contrast, aqueous extracts made, using the same techniques, from the shavings of eastern white pine (Pinus strobus), eastern red cedar (Juniperus virginiana), and pin oak (Quercus palustrus) had no effect on epinephrine-induced digital vessel contractions.

Animals↗

Pharmacokinetics of etomidate in cats.

Pharmacokinetic variables of etomidate were determined after IV administration of etomidate (3.0 mg/kg of body weight). Blood samples were collected for 6 hours. Disposition of this carboxylated imidazole best conformed to a 2- (n = 2) and a 3- compartment (n = 4) open pharmacokinetic model. The pharmacokinetic values were calculated for the overall best-fitted model, characterized as a mixed 2- and 3-compartmental model. The first and most rapid distribution half-life was 0.05 hour and a second distribution half-life was 0.35 hour. Elimination half-life was 2.89 hours, apparent volume of distribution was 11.87 +/- 4.64 L/kg, apparent volume of distribution at steady state was 4.88 +/- 2.25 L/kg, apparent volume of the central compartment was 1.17 +/- 0.70 L/kg, and total clearance was 2.47 +/- 0.78 L/kg/h.

Animals↗

A nursing home rotation in a family practice residency.

A nursing home rotation can be a complementary component of geriatrics education in a family practice residency curriculum. Using nursing homes in teaching geriatrics has been done for some time but has of late received more emphasis. This increasing emphasis has been brought about by the growing health care needs of an aging population and a concomitant focus on education in geriatrics. If implementation of a nursing home rotation is contemplated, both the positive and negative aspects of such action as it relates to the residents, the nursing home, and the nursing home patients should be explored. The rotation as incorporated into the geriatrics curriculum of the Family Practice Residency, Knoxville Unit, University of Tennessee College of Medicine, involves all second-year and third-year residents in the medical care for patients of a 222-bed long-term care facility. From an educational standpoint, overall evaluation of the rotation reflects satisfaction. The experience exemplifies personal and comprehensive continuity of patient care. Other educational benefits include desensitization to the nursing home environment, understanding the kinds of medical care that can be delivered in this setting, and appreciation for the cost not only to the patient and the family but also to the medical care system as well.

Family Practice↗

Influence of Rhodococcus equi on the respiratory burst of resident alveolar macrophages from adult horses.

Opsonized Rhodococcus equi activated the respiratory burst of resident alveolar macrophages (AM) from adult horses in a logarithmic-linear, mass-related manner. The effect of R equi was not significantly different from that of equal masses of opsonized zymosan A. Therefore, R equi does not appear to attenuate the respiratory burst of equine AM. The stimulatory effect of R equi was not reflected by increased production of superoxide anion (O2-), but increased activity of the hexose monophosphate shunt was observed. These results suggest a similarity between the respiratory burst of AM from horses and that of AM from rabbits. We concluded that resident AM from adult horses do not produce O2- concurrently with an increase in activity of the hexose monophosphate shunt when stimulated with either opsonized zymosan A or opsonized R equi. This suggests that O2- is not an important component of the antibacterial defenses of equine AM. Whether equine AM are incapable of producing O2- or require different stimuli to produce it was not determined.

Animals↗

Elimination of salicylic acid in goats and cattle.

Sodium salicylate was administered to cattle and goats IV and PO according to a crossover design. Total urinary excretion of SA and its metabolites was measured for 3 days after dosing. Salicyluric acid (SUA) was the only metabolite detected in urine of either species. Recovery of sodium salicylate and SUA in goats amounted to 67.9 and 34.6% of the dose, respectively, after IV administration. After oral dosing, total recoveries were 30.2% (sodium salicylate) and 71.7% (SUA) of dose. By comparison, cattle excreted significantly (P less than 0.05) less sodium salicylate (54.0%) and more SUA (49.9%) after IV dosing. The same pattern was observed after oral administration, wherein cattle excreted less than 12% as sodium salicylate and more than 99% as SUA. In both species, almost 90% of the drug excreted as sodium salicylate was found in urine within the first 12 hours after an IV dose and within 24 hours after oral dosing. The excretion of SUA was somewhat slower in both species, especially after oral administration. The data suggested that there were only quantitative differences in the metabolism and elimination of sodium salicylate between the 2 species, with cattle excreting a higher proportion of the drug as the glycine conjugate SUA.

Administration, Oral↗

Pharmacokinetics of flunixin meglumine in lactating cattle after single and multiple intramuscular and intravenous administrations.

The pharmacokinetics of flunixin were studied in 6 adult lactating cattle after administration of single IV and IM doses at 1.1 mg/kg of body weight. A crossover design was used, with route of first administration in each cow determined randomly. Plasma and milk concentrations of total flunixin were determined by use of high-pressure liquid chromatography, using an assay with a lower limit of detection of 50 ng of flunixin/ml. The pharmacokinetics of flunixin were best described by a 2-compartment, open model. After IV administration, mean plasma flunixin concentrations rapidly decreased from initial concentrations of greater than 10 micrograms/ml to nondetectable concentrations at 12 hours after administration. The distribution phase was short (t1/2 alpha, harmonic mean = 0.16 hours) and the elimination phase was more prolonged (t1/2 beta, harmonic mean = 3.14 hours). Mean +/- SD clearance after IV administration was 2.51 +/- 0.96 ml/kg/min. After IM administration, the harmonic mean for the elimination phase (t1/2 beta) was prolonged at 5.20 hours. Bioavailability after IM dosing gave a mean +/- SD (n = 5) of 76.0 +/- 28.0%. Adult, lactating cows (n = 6) were challenge inoculated with endotoxin as a model of acute coliform mastitis. After multiple administration (total of 7 doses; first IV, remainder IM) of 1.1 mg/kg doses of flunixin at 8-hour intervals, plasma flunixin concentrations were approximately 1 microgram/ml at 2 hours after each dosing and 0.5 micrograms/ml just prior to each dosing. Flunixin was not detected in milk at any sampling during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Clinical significance of cerebrospinal fluid tests for neurosyphilis.

From 1978 to 1987, 1,665 cerebrospinal fluid (CSF) fluorescent treponemal antibody absorption (CSF-FTA-ABS) tests were performed as the screening procedure for neurosyphilis. The CSF samples from 48 patients were reactive, and the medical history and results of the CSF-Venereal Disease Research Laboratory test (CSF-VDRL) for syphilis for 38 of these patients were reviewed. Likely active neurosyphilis was diagnosed if the patient had a reactive CSF-FTA-ABS test, recent onset of neurological signs consistent with neurosyphilis, abnormal CSF, and no other recognized cause for the neurological illness. Fifteen patients were so classified. Four had a reactive CSF-VDRL test. The specificity of the CSF-VDRL in diagnosing likely active neurosyphilis was 100%, but the sensitivity was only 27%. The insensitivity of the CSF-VDRL test limits its usefulness as a screening test for neurosyphilis. The CSF-FTA-ABS test appears more sensitive for screening but is less specific than the CSF-VDRL test in distinguishing currently active neurosyphilis from past syphilis. These findings imply that clinical judgment is still essential in establishing the diagnosis of active neurosyphilis.

Adolescent↗

Purification and immunochemical characterization of ascitic fluid glycoproteins containing certain tumor-associated and blood group antigen markers.

Ascitic fluids from patients with various types of cancer were screened for the CA 19-9 and CA 125 tumor-associated antigenic activities. Two fluids exhibiting the highest activities were tested for their binding to various lectin-Sepharose columns resulting in both being bound best to wheat germ agglutinin (WGA) Sepharose. The WGA column eluate of one fluid was further chromatographed by HPLC and three peaks were obtained with approximate molecular weights of 3.65 MDa, 664 kDa and 330 kDa, of which only the largest fraction contained the CA 19-9 activity. The fluids were also fractionated on a Sephacryl S-400 column with most of the activity being present in or near the void volume. Monoclonal antibodies were used to demonstrate that the purified glycoproteins also contained the blood group A determinant, the four Lewis determinants Le(a), Le(b), Le(x) and Le(y), and the sialylated-Le(x) determinant, while other antibody analyses failed to detect other blood group and/or carbohydrate sequence determinants. Some of the blood group expressions could be separated from the CA 19-9 and CA 125 active glycoproteins by adsorption with various lectins other than the WGA.

Antibodies, Monoclonal↗