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Biomedical subjects

B M Miller

Publications and source records attributed to B M Miller.

At least 55 records · Page 3Linked to original sources
PubMed1983

Interorgan relationships of alanine and glutamine during fasting in the conscious dog.

This study was designed to assess the interorgan relationships of glutamine and alanine in the conscious, overnight fasted dog, and to determine changes which occur with progressive fasting. Dogs were fasted for 18 hr (n = 6), 48 hr (n = 6), and 96 hr (n = 6) prior to the study. Catheters had been previously implanted in the femoral artery, renal vein, portal vein, and hepatic vein, and were used for blood sampling at 30-min intervals during the 3-hr experimental period. Hepatic and renal blood flows were determined by indocyanine green and para-aminohippuric acid (PAH) extraction methods, respectively. Balance data (micromoles/kilogram/minute) were estimated by multiplying the appropriate arteriovenous concentration differences by blood flows. Hepatic uptake of glutamine decreased 50% after a 48-hr fast, and by 96 hr, the liver became a net producer of glutamine. Gut utilization remained constant throughout fasting. The kidney's utilization gradually increased with fasting. The hepatic extraction of alanine fell with fasting, declining to 40% of its original uptake at 96 hr. The gut's production of alanine fell during the first 48 hr of fasting, but remained stable thereafter. The kidney's production of alanine increased throughout the period of starvation. The arterial concentration of glutamine rose with fasting, while that of alanine fell even with a 48 hr fast. The liver, by becoming a net producer of glutamine, and the kidney, by increasing its production of alanine, decrease demands for peripheral release of these two amino acids, and thus may have protein-sparing actions during fasting.

Alanine↗
PubMed1983

The effect of acute and chronic glucocorticoid excess on leucine kinetics and protein turnover in vivo.

The present studies were undertaken to assess the effects of excess cortisol on amino acid exchange in the conscious dog. Three groups of 18-hr fasted dogs with catheters chronically implanted in the femoral artery were studied: Group I (n = 6) received saline; Groups II and III (n = 5, each) received ACTH intravenously (1 U/min) for 7 hr; in addition, Group III received ACTH, 500 U/day intramuscularly for 4 days. Leucine rates of appearance (Ra) and clearance were measured using a constant infusion of L-4,5-[3H]leucine. ACTH treatment resulted in a 9-fold increase in plasma cortisol in Groups II and III (from 2 +/- 1 to 18 +/- 1 and 17 +/- 2 micrograms/dl, in II and III, respectively P less than 0.001), with no effect on either plasma insulin or glucagon. Plasma leucine (mmole/liter) increased from 118 +/- 6 (I) to 153 +/- 6 (II, P less than 0.005) to 275 +/- 35 (III, P less than 0.001). Leucine Ra (micromoles/kilogram/minute) did not change in II, but rose by 39% (P less than 0.005) in III. Clearance (milliliters/kilogram/minute) dropped from 25 +/- 2 (I) to 18 +/- 2 (II, P less than 0.005), to 15 +/- 2 (III, P less than 0.001). It is concluded that acute elevations of cortisol increased plasma leucine only by inhibiting its rate of disposal, whereas chronic elevations had a dual effect; they inhibited leucine disposal and increased its entry into the plasma compartment, suggesting an inhibition of protein synthesis and stimulation of protein breakdown.

Adrenocortical Hyperfunction↗
PubMed1983

Treatment with suramin and 2-substituted 5-nitroimidazoles of chronic murine Trypanosoma brucei infections with central nervous system involvement.

Mice infected with either of two isolates of Trypanosoma brucei, GVR 23/1 or GVR 35/1, develop a chronic infection in which trypanosomes are localized in the central nervous system. These infected mice were used to evaluate the efficacy of a combination drug treatment comprising suramin and one of three 2-substituted 5-nitroimidazoles. None of the three 5-nitroimidazoles tested alone, cured mice when administered 21 days after infection. However, it was found that T. brucei GVR 23/1 infections could be cured by a single dose of 20 mg/kg suramin followed by a single dose of 80 mg/kg L611,744 [3a,4,5,6,7,8,9,9a-octahydro-3-(1-methyl-5-nitroimidazol-2yl)cycloocta(D) isoxazole]. The single dose of 20 mg/kg suramin had to be followed by four doses of 80 mg/kg L611,744 to cure mice infected with another stabilate, T. brucei GVR 35/1. A single dose of 20 mg/kg suramin followed either by four doses of 250 mg/kg MK 436 [3a,4,5,6,7,7a-hexahydro-3-(1-methyl-5nitro-1H-imidazol-2-yl)-1, 2-benzisoxazole] or four doses of 70 mg/kg of a dihydroxy analogue of MK 436 [cis-3a,4,5,6,7,7a-hexahydro-3-(1-methyl-5-nitro-1H-imidazol-2-yl)-1, 2-benzisoxazole-6,7-diol] also permanently cured all T. brucei GVR 35/1.

Animals↗
PubMed1983

Effects of calcium channel blockers on isolated carotid baroreceptors and baroreflex.

Our study determined the effects of the calcium antagonists, nifedipine and verapamil, on the carotid sinus baroreceptors and baroreflex. The left carotid sinus region in dogs was vascularly isolated and filled with oxygenated physiological salt solution. Steady-state multiunit activity was recorded from the carotid sinus nerve for sinus pressures of 50-200 mmHg after bathing the carotid sinus region in a solution containing no drug, 10 micrograms/ml nifedipine (n = 6), or 5 micrograms/ml verapamil (n = 5). The slopes of the curves relating carotid sinus nerve activity (% of maximum control) to carotid sinus pressure were control, 0.81 +/- 0.06; nifedipine, 1.29 +/- 0.14; and verapamil, 0.48 +/- 0.06%/mmHg, indicating that nifedipine increased and verapamil decreased the sensitivity of the carotid sinus baroreceptors. Additional studies with bilateral carotid sinus isolation (carotid sinus nerves intact) indicated that nifedipine enhanced and verapamil attenuated carotid baroreflex control of renal sympathetic nerve activity. Pressure-volume curves generated in the isolated carotid sinus showed that effects on smooth muscle do not account for the opposing effects of the two Ca2+ antagonists. Omitting Ca2+ from the physiological solution resulted in increased carotid sinus nerve activity, an effect blocked by verapamil but not nifedipine. Verapamil, but not nifedipine, inhibited veratrine-induced (Na+-dependent) excitation of carotid baroreceptors. Thus the excitatory effects of nifedipine on the carotid sinus baroreceptors are dependent on Ca2+ mechanisms, whereas the inhibitory effects of verapamil may be due mainly to interference with the inward Na+ current.

Animals↗
PubMed1983

In vitro and in vivo evaluations of the antibiotic efrotomycin.

Experiments were conducted to determine the potential of the antibiotic efrotomycin as a growth permittant for poultry and to further elucidate the mode of action of antimicrobial agents for that purpose. Efrotomycin as the semipurified antibiotic and as fermentation solids demonstrated excellent activity against Clostridium perfringens at .1 to .2 ppm based on suppression of gas production in an anaerobic tube test. Supplementing a soybean protein and sucrose-based diet with levels of 2.2, 11, and 55 ppm of the antibiotic, from the two sources each with two different purities, improved weight gain of chicks an average of 23% and improved feed efficiency an average of 13% at the higher levels (all P less than .01). Computed indexes for each antibiotic treatment, which represent the combined effects of both weight gain and feed efficiency, showed that a maximum response was generally obtained at the 11 ppm level and that the antibiotic as fermentation solids was slightly more active than the semipurified material. Supplementing the soybean protein and sucrose-based diet with levels of 1.1, 5.5, 16.5, and 55 ppm of efrotomycin reduced the numbers of C. perfringens organisms in ileal contents of chicks (all P less than .01). The effects were dose-related. Control chicks in this experiment averaged greater than 7.7 log10 of C. perfringens counts per gram of contents. The results of these experiments show that efrotomycin has excellent growth-permittant activity and the activity correlates with the antibacterial activity against C. perfringens.

Animals↗
PubMed1983

Quaternary heterocyclylamino beta-lactams. V. L-640,876 treatment of induced enterotoxigenic colibacillosis (scours) in calves and piglets.

A new semisynthetic cephalosporin antibiotic designated L-640,876, 7-beta-(1-benzylpyridinium-4-yl)amino-3-[( (1-methyl-1H-tetrazol-5-yl)thio] methyl)ceph-3-em-4-carboxylate, was highly active in vitro against 110 enteropathogenic strains of Escherichia coli and Salmonella species of animal origin. The MIC90 was 0.125 microgram/ml for the E. coli strains, 2 micrograms/ml for the S. choleraesuis strains and 4 micrograms/ml for the S. typhimurium strains. In colostrum-fed calves infected with E. coli strain B44, L-640,876 administered by gavage at 30 mg/calf (0.67 mg/kg) twice a day for 3 days, starting at 20-hour post-inoculation, eliminated the diarrhea and reduced the mortality from 82% in the infected, nonmedicated calves to 11% in the infected, medicated calves (P less than 0.05). In colostrum-fed piglets infected with E. coli strain P155, L-640,876 administered by gavage at 12.5 or 20 mg/piglet (10 or 16 mg/kg) twice a day for 3 days, starting at 6-hour post-inoculation, eliminated the diarrhea and reduced the mortality from 79% in the infected, nonmedicated to 25% in the infected, medicated piglets (P less than 0.05). Thus, L-640,876 was highly effective in restoring the calves and piglets to good health by eliminating diarrhea and reducing mortality.

Animals↗
PubMed1983

Histoplasma infection of abdominal aortic aneurysms.

Fungal endarteritis resulting from progressive disseminated histoplasmosis may cause arterial aneurysms, or lead to infection of pre-existing aneurysms. Three patients with Histoplasma capsulatum infections of abdominal aortic aneurysms are reported. All had previous disseminated histoplasmosis and atherosclerotic peripheral vascular disease. All were considered cured of systemic infection when their aneurysms were discovered. Atherosclerotic vascular lesions may become infected during the course of systemic fungal disease and may serve as a haven for viable organisms in patients whose dissemination recurs despite seemingly adequate antifungal therapy. In treating these patients, resection of all infected arterial tissue, revascularization through uninfected tissues, and long-term antimicrobial therapy are recommended.

Adult↗
PubMed1983

Nutritional influences on plutonium absorption from the gastrointestinal tract of the rat.

Rats that were fasted and/or fed diets consisting of whole milk, dry milk, milk supplement, orange juice, low calcium, or low vitamin D were gavaged with 238Pu nitrate to measure plutonium absorption. All dietary variations resulted in increases in both absorption and retention. The increases ranged between 2 and 20 times the absorption values obtained for rats fed commercial chow. Sucklings of dams fed a calcium-deficient diet also exhibited increased 238Pu absorption. The results indicate that nutrition is an important factor influencing gastrointestinal absorption of plutonium.

Animal Nutritional Physiological Phenomena↗
PubMed1983

The effect of mass on the gastrointestinal absorption of plutonium and neptunium.

Absorption and retention of plutonium were determined in mice after intragastric administration of either 6 X 10(-4) or 1.5 mg/kg in bicarbonate, citrate, or nitrate media. At the higher concentration, absorption of the citrate was greater than that of the nitrate; at the lower concentration, chemical form was not an important factor in absorption. Concentration and chemical form had much less influence on absorption by the neonatal (versus the adult) rat. The transfer factor (f1) for neonates was between one and two orders of magnitude higher than for adults. Absorption and retention of neptunium were determined in rats and/or mice after intragastric administration at doses ranging from 2.2 X 10(-7) to 43 mg/kg in nitrate solutions of pH 1.5. At the higher concentrations, absorption was 1.5 to 2.7%. For lower concentrations, absorption was 25 to 65 times less. In contrast to results obtained in adult animals, absorption of neptunium by neonates decreased with increasing dose. The data obtained in adult animals suggest that the f1 factor recommended by the ICRP for plutonium should be increased by a factor of 10, but the neptunium f1 factor, in contrast, should be decreased by a factor of 10.

Animals↗
PubMed1983

The effect of X rays, DTPA, and aspirin on the absorption of plutonium from the gastrointestinal tract of rats.

To measure the effect of radiation on plutonium transport, rats that were exposed to 250-kVp X rays were given 238Pu 3 days afterwards by either gavage or injection into a ligated segment of the duodenum. In a second group of experiments, rats were either injected intraduodenally with 238Pu-DTPA or administered the chelate intravenously and the 238Pu by gavage. In a third experiment, rats that had been gavaged with 200 or 400 mg/kg/day of aspirin for 2 days were injected intragastrically with 238Pu nitrate. Results of the first experiment showed a dose-dependent increase in 238Pu absorption between 800 and 1500 rad of lower-body X irradiation. Intravenous or intraduodenal injections of DTPA caused a marked increase in 238Pu absorption but resulted in decreased plutonium deposition in the skeleton and liver. Retention of 238Pu in the skeleton of rats given aspirin was double that of controls, but the effect on plutonium absorption was less marked than that of DTPA.

Animals↗
PubMed1981

Patenting of hybridomas and genetically engineered microorganisms.

Many new technologies arrived at through basic research have practical applications. Two recent breakthroughs in microbiology, recombinant DNA techniques and hybridoma techniques, will permit designing cells for specific practical purposes resulting in new products or functions of commercial significance. The unique cell or its usefulness, or both, may satisfy the requirements of a patentable invention, i.e. an inventive act having utility and novelty. Ownership of such patents permits recovery of expenses incurred in the invention process and investment for all concerned in additional research. An integral part of the patenting process is submission of the new cell to an official repository, an outstanding example of which is The American Type Culture Collection.

DNA, Recombinant↗
PubMed1981

Etomidate and fentanyl for maintenance of anaesthesia.

An infusion of etomidate and fentanyl was compared with halothane or morphine plus nitrous oxide in oxygen for the maintenance of anaesthesia in 200 patients. Cardiovascular and respiratory changes were found to be similar in the two groups. There was a prolongation of recovery time in the etomidate-fentanyl group: this was possibly a result of lack of flexibility in the infusion technique.

Anesthesia, Inhalation↗
PubMed1981

Cephamycin C treatment of induced swine salmonellosis.

Weanling pigs in groups of 12 were infected orally with Salmonella choleraesuis and were treated intramuscularly with doses of cephamycin C ranging from 12.5 to 337.5 mg twice daily for 10 days beginning 1 day postinoculation. Pigs in two other infected groups either received 300 mg of tetracycline orally on a similar schedule or served as nonmedicated controls. Optimal responses to cephamycin C were achieved at a twice daily dose of 112.5 mg. With this regimen, the febrile response was significantly reduced on day 2 and eliminated by day 5 postinfection, and the shedding of Salmonella spp. in feces was eliminated by day 5 postinfection; essentially, no lesions were found in the gastrointestinal tract at necropsy (day 26 postinfection). There was no mortality among recipients of the 112.5-mg dose; diarrhea was present on only 2% of the observation days. In contrast, 83% of the infected, nonmedicated pigs and 25% of the tetracycline-medicated pigs died, and diarrhea was present in these groups on 63 and 54% of the observation days, respectively. The striking benefits of cephamycin C treatment was achieved without adverse reactions. The weight gain and feed efficiency of the infected pigs treated with the 112.5-mg dose of cephamycin C and the noninfected, nonmedicated control pigs were equivalent.

Animals↗
PubMed1980

Cephamycin C treatment of induced enterotoxigenic colibacillosis (scours) in calves and piglets.

Cephamycin C is a beta-lactam antibiotic that has broad gram-negative activity and is resistant to degradation by beta-lactamases and safe for use in animals. In colostrum-fed calves infected with Escherichia coli strain B44, cephamycin C administered by gavage at 31.3 to 1,000 mg per calf (0.75 to 24 mg/kg) twice a day for 6 days starting at 20 h post-inoculation eliminated the diarrhea and reduced the mortality from 90% in infected, nonmedicated calves to 14% in infected, medicated calves (P < 0.01). Comparable results were obtained with a shorter treatment regimen (30 mg of cephamycin C per calf [0.71 mg/kg] twice a day for 3 days). In colostrum-fed piglets infected with E. coli strain P155 and housed in cages, cephamycin C administered prophylactically by gavage at 12.5 mg per piglet (10.4 mg/kg) twice a day for 4 days completely prevented both diarrhea and mortality, whereas nonmedicated piglets had 100% diarrhea and all died. When eight doses of cephamycin C were given therapeutically starting at 6 h post-inoculation, mortality was reduced from 79 to 23% (P < 0.02), and diarrhea was eliminated in the surviving medicated piglets by 4 days post-inoculation. In infected suckling piglets, cephamycin C administered therapeutically by gavage at 12.5 mg per piglet twice a day for 3 days starting at 6 h post-inoculation, diarrhea and mortality were reduced (P < 0.05): infected, nonmedicated piglets had 87% diarrhea and 75% mortality, whereas infected, medicated piglets had 25% diarrhea and 31% mortality. All surviving medicated piglets had solid feces by 2 days post-inoculation. Thus, cephamycin C was highly effective in restoring the calves and piglets to good health by eliminating diarrhea and reducing mortality.

Animals↗
PubMed1979

Urinary metabolites of 3a,4,5,6,7,7a-hexahydro-3-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,2-benzisoxazole in the dog.

The antiprotozoal drug 3a,4,5,6,7,7a-hexahydro-3-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,2-benzisoxazole (I), which exhibits activity against trypanosomiasis, is also antibacterial in vivo. Since the urine from a dog dosed with I showed a broader spectrum of antibacterial activity than I itself, metabolites from this urine were isolated and partially characterized. The metabolites were mono- and dihydroxy-substituted species with the hydroxyl groups on carbons 4--7 of the hexahydrobenzisoxazole ring. These observations led to the synthesis of several such hydroxy derivatives of I, and their properties fully supported the proposed positions of metabolic hydroxylation. One synthetic compound, the 6,7-cis-dihydroxy compound, exhibited higher antibacterial activity against Salmonella schottmuelleri in mice and greater trypanocidal activity in vivo against Trypanosoma cruzi (Brazil strain) than I.

Animals↗