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Biomedical subjects

L A Wheeler

Publications and source records attributed to L A Wheeler.

At least 55 records · Page 3Linked to original sources

Stimulation of endogenous cyclic AMP levels in ciliary body by SK&F 82526, a novel dopamine receptor agonist.

The effect of dopamine and SK&F 82526 on cyclic AMP metabolism in ocular tissues has been examined. The in vitro incubation of human and bovine ciliary body with these agonists produced a dose-dependent increase in endogenous levels of cyclic AMP. This stimulation was blocked by the selective DA1 receptor antagonist SK&F 83566, but not by the beta-receptor antagonist propranolol. The response to SK&F 82526 was stereoselective, with SK&F R-82526 being approximately 100 times more potent than SK&F S-82526 in this preparation. This stimulation of ciliary body cyclic AMP content was not observed in the rabbit or cat, nor was it seen in human, bovine or rabbit iris tissue. These data suggest that adenylate cyclase linked dopamine receptors are present in both human and bovine ciliary body.

Animals↗

A data base approach to laboratory computerization.

The Regenstrief Clinical Laboratory System (RCLS) has been operational since 1975 at Wishard Memorial Hospital in Indianapolis, Indiana. The clinician support, use of a true data base management system, and the user interfaces distinguish this system from many commercially available laboratory systems. Physician reports include laboratory, clinical (e.g., physical examination), pharmacy, and radiology data in a single, compact flow sheet. The system can search patient medical records for conditions that may require corrective action and inform physicians of the reasons these actions should be considered. The RCLS data base and its flexible data retrieval capabilities provide a variety of effective technics for monitoring laboratory utilization. The site-specific modifications required to transport this system do not require reprogramming. Important laboratory support features include highly "user friendly" design, multiple specimen numbering sequences, large amounts of free text, reports that can be tailored by non-programmer personnel, CAP accounting statistics, online instrument interfaces, and extensive online instructional facilities.

Clinical Laboratory Techniques↗

Hematologic malignancies associated with primary mediastinal germ-cell tumors.

Three men with primary mediastinal germ-cell tumors subsequently developed a malignant hematologic disorder characterized by pancytopenia and marrow infiltration with hematopoietic blast cells. Two of these patients were classified as having acute megakaryocytic leukemia and the third was believed to have a myelodysplastic syndrome with a prominent megakaryocytic component. Analysis of clinical characteristics of these patients and review of the literature suggest that the proximate association of mediastinal germ-cell tumors with malignant hematologic disorders is neither a coincidence nor a consequence of chemotherapy given for the germ-cell tumor. We believe this association represents the evolution of a neoplastic disorder that initially involves a totipotent germ cell. These germ cells, when located in the mediastinum, apparently acquire hematologic phenotypes and are manifested clinically as a hematologic malignancy.

Acute Disease↗

Computer-selected exchange lists approximations for recipes.

A computer program has been developed to aid dietitians and patients in determining the best Exchange Lists for Meal Planning representation for a serving of a recipe. Applying an optimization program to information obtained from a nutrient data base and a recipe file results in a printout of the five best Exchange Lists representations and the macronutrient and caloric content of the recipe serving compared with the Exchange Lists approximate nutrient values for each of the "best fit" solutions. The nutritional analysis of one serving of the recipe (including 26 nutrients), as well as a breakdown by recipe ingredients, is also provided. Analysis of a 10-item recipe takes about 17 minutes of coding, entry, and evaluation time and 6 seconds of mainframe computer time. This program has been used to compute Exchange Lists representations for the recipes in Vol. II of The American Diabetes Association/The American Dietetic Association Family Cookbook.

Computers↗

The induction of prophage expression in different Salmonella typhimurium strains by DNA cross-linking and monoadduct forming psoralens and longwave ultraviolet radiation.

The cytotoxicity, and ability to induce the expression of prophage in Salmonella typhimurium LT2 strains has been examined for 4 furocoumarins, 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 3-carbethoxypsoralen (3-CP), and 5-methylisopsoralen (5-MI) given with ultraviolet-A radiation (u.v.A). 8-MOP and 5-MOP have a linear tricyclic structure and possess two photoreactive sites, the 3,4 and 4',5' double bonds, enabling them to form both monoadducts and interstrand cross-links with DNA. The angular structure of 5-MI imposes steric constraints preventing it from forming interstrand cross-links with DNA although it possesses both of the photoreactive double bonds. The substituent group at position C-3 in 3-CP blocks the 3,4 reactive site and 3-CP is thus incapable of forming interstrand cross-links; 3-CP is reportedly, unlike the other three furocoumarins, non-carcinogenic in mice. 8-MOP, 5-MOP, and 5-MI were very cytotoxic to both the base-pair (TA1535) and frame-shift (TA1538) tester strains when given with u.v.A. Comparable amounts of 3-CP given with u.v.A were much less toxic. 8-MOP, 5-MOP, and 5-MI were potent inducers of prophage expression in both TA1535 and TA1538. 3-CP was a very poor inducer of prophage. The cytotoxicity and prophage inducing ability of 5-MI + u.v.A indicate that these actions are not necessarily restricted to the DNA crosslinking psoralens. The lower toxicity of 3-CP + u.v.A is not a simple function of the ability of 3-CP to form only monoadducts with DNA. The ability or inability to induce the expression of prophage in S. typhimurium may be a rapid and useful screen for the potential phototoxicity and carcinogenicity of novel psoralens.

DNA, Bacterial↗

Intravenous metronidazole for treatment of infections involving anaerobic bacteria.

Intravenous metronidazole was administered, either by continuous or intermittent infusion, to 20 patients with infections involving anaerobic bacteria; 14 of the 20 patients were changed to oral administration of metronidazole for completion of therapy. Six of eight patients with infections derived from oropharyngeal bacterial flora were cured; the addition of ampicillin was required in one patient, however, because of an incomplete response to metronidazole. Eight of eleven evaluable patients with infections derived from bowel flora were also cured by metronidazole or metronidazole plus an aminoglycoside. Of 93 anaerobic bacteria isolated before therapy, 89 were susceptible to 16 micrograms or less of metronidazole per ml. Mean plasma levels of metronidazole were 27.6 +/- 11.4 micrograms/ml in patients receiving continuous infusions of drug and 19.9 +/- 10.7 micrograms/ml (trough) in patients receiving intermittent infusions. Two patients developed peripheral neuropathy during therapy. Metronidazole is an effective agent for the treatment of anaerobic infections. Because metronidazole is not active against facultative and aerobic bacteria, the addition of a second antimicrobial agent may be required for the treatment of mixed anaerobic-aerobic infections.

Adult↗

Mutagenicity of urine from psoriatic patients undergoing treatment with coal tar and ultraviolet light.

The possible percutaneous absorption of the mutagens from patients receiving crude coal tar (CCT) and ultraviolet light was investigated. Urine samples were collected from nonsmoking volunteers, smoking, and nonsmoking psoriatic patients. Patients were treated with 1% CCT U.S.P. or 1 to 10% CCT in petrolatum in the evening. The following morning, patients received coal tar baths and then ultraviolet light (mainly 290-320 nm, UVB). Nonpolar organics in urine samples were extracted by adsorption onto XAD-2 resin and the extracted organics assayed in the Ames Salmonella/Microsome test. TA98 was the most sensitive bacterial strain to detect mutagenicity. Except for smoking psoriatic patients, the addition of liver homogenate was necessary to see mutagenicity. No increase in the number of revertants was observed when B-glucuronidase was added to the assay. Of 14 patients studied 12 had at least one mutagenic urine sample. Typical values for nonsmoking psoriatics treated with CCT ranged from 42 to 496 his +/20 ml of urine after the subtraction of spontaneous his + counts (26 +/- 6). Two nonsmoking normal volunteers were found to excrete mutagenic urines. Smoking psoriatic patients ranged from 213 to 1,100 his +/20 ml urine. This study demonstrates the percutaneous absorption of mutagens from CCT and indicates that its effects may not be limited to the skin.

Absorption↗

A clinical evaluation of various delta check methods.

To evaluate the performance of delta check techniques, we analyzed 707 unselected pairs of continuous-flow test results, using three different delta check methods. If any of the test results (plus the urea nitrogen/creatinine ratio and the anion gap) failed one of the checks, the reason for the failure was sought by examining subsequent test results, retesting specimens, and (or) reviewing te patient's chart. Each delta check failure was accordingly classified as a true or false positive. The percentage of positives we judged to be true positives ranged from 5 to 29%. Each of the three methods had test types with low and high percentages of true positives. We conclude that with the delta check methods one can detect errors otherwise overlooked, but at the cost of investigating many false positives, because, in the population we studied, disease processes or therapy often caused large changes in a series of test results for a patient.

Chemistry, Clinical↗

Mutagenesis within the gastrointestinal tract determined by histidine auxotrophs of Salmonella typhimurium.

The Ames Salmonella mutants can be maintained for months within the gastrointestinal tract of otherwise germfree rats. The ingestion of various carcinogens, but not structurally related non-carcinogens, results in an increased concentration of his+ revertants in the feces. Rats, associated with strain TA1538, were also associated with either L. plantarum of B. vulgatus and with both of these strains. After 2-nitrofluorene ingestion (3.4 mg) the concentration of fecal revertants increased except in rats associated only with strains TA1538 and B. vulgatus. The concentration of B. vulgatus. The concentration of B. vulgatus in the stomach of individual rats correlated negatively with their response to 2-nitrofluorene. Since only B. vulgatus reduces nitrofluorene to the less mutagenic 2-aminofluorene, it appears that B. vulgatus diminishes the revertant response by metabolic removal of the more potent direct acting mutagen from the gut. The ingestion of 1,2-dimethylhydrazine (21 mg/kg) and azoxymethane (19 mg/kg) provokes increased fecal revertants only in some animals associated with strain TA1535 or TA100.

Animals↗