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Biomedical subjects

T G Cleary

Publications and source records attributed to T G Cleary.

At least 73 records · Page 4Linked to original sources

Protection of suckling mice from heat-stable enterotoxin of Escherichia coli by infant formulas.

Human milk contains factors that protect suckling infants against enteropathogen-induced diarrhea. One nonspecific protective factor found in human milk is a small molecular weight material that protects suckling mice from death due to the heat-stable enterotoxin of Escherichia coli. This study demonstrated that cow's milk and most formulas derived from cow's milk also contain a factor(s) that can protect against heat-stable enterotoxin of E. coli in suckling mice.

Animals↗

Shiga-like cytotoxin production by enteropathogenic Escherichia coli serogroups.

The mechanism by which enteropathogenic Escherichia coli (EPEC) cause disease remains to be defined. We studied EPEC and non-EPEC strains of E. coli from stool specimens obtained from infants and adults for production of Shiga-like cytotoxin. Although it was common for healthy infants and adults to have cytotoxin-producing E. coli as part of the fecal flora, Shiga-like cytotoxin was detected more commonly and in greater amounts among EPEC than among other fecal E. coli. These results suggest a role for Shiga-like cytotoxin in the pathogenesis of EPEC-related gastroenteritis.

Adult↗

Comparative pharmacokinetics of cefoxitin in postpartum normotensive and pregnancy-induced hypertensive patients.

Limited pharmacokinetic data exist on cefoxitin, a semisynthetic cephamycin antibiotic, in the obstetric patient. Thirteen normotensive and five subjects with severe pregnancy-induced hypertension were identified within the first two postpartum days after cesarean section. After a 2 gm intravenous infusion, serial samples of blood were obtained and analyzed for cefoxitin by high-pressure liquid chromatography. Peak cefoxitin concentrations after infusion were 53.3 +/- 18.6 and 50.8 +/- 25.2 micrograms/ml for the normotensive and pregnancy-induced hypertensive groups, respectively. The only significant difference in pharmacokinetic parameters between these groups was a higher serum trough concentration of cefoxitin in the patients with pregnancy-induced hypertension as compared to the normotensive group. Because of diminished trough levels in our study patients, attention may need to be given to the adjustment of dosages in postpartum women with serious infections.

Adult↗

Anti-infective therapy of infectious endocarditis.

Because of its high morbidity and mortality, endocarditis will remain an important pediatric problem. Obtaining adequate culture information prior to starting antibiotics to ensure an accurate early diagnosis coupled with aggressive medical and surgical management is likely to give the best outcome. These patients are generally best handled by a team approach with the child's primary physician, cardiologist, infectious disease consultant, and cardiovascular surgeon working in close harmony.

Anti-Bacterial Agents↗

Protection of suckling mice from the heat-stable enterotoxin of Escherichia coli by human milk.

Human milk contained a factor or factors that protected suckling mice from lethal fluid loss due to Escherichia coli heat-stable toxin. This protective effect was present throughout lactation. The factor was heat stable, acid and alkali stable (pH 2 and 12), and of low molecular weight. Ion-exchange chromatography indicated that it was uncharged at neutral pH. The factor was insensitive to proteinase K digestion and partitioned in the aqueous phase in 2:1 (vol/vol) chloroform-methanol. Acid hydrolysis (2 N HCl at 100 C for 3 hr) destroyed the protective effect. Neither an amino acid mix simulating human milk nor lactose in phosphate-buffered saline was protective. These data indicate that the protective factor in human milk is neither a lipid nor a protein but appears to be a carbohydrate.

Amino Acids↗

Inhibition of human polymorphonuclear leukocyte function by components of human colostrum and mature milk.

To compare the effect of human colostrum (days 1 to 3 postpartum) and mature milk (days 170 +/- 24 postpartum) on the function of polymorphonuclear leukocytes (PMNL), Ficoll-Hypaque-separated PMNL from the blood of 60 healthy volunteers were incubated with whole colostrum, colostral lipid, and colostral aqueous phase from 30 mothers, or with mature whole milk and its separated components from 30 mothers, and tested for resting and zymosan-stimulated oxidative metabolism, functional activity, and the presence of Fc receptors. Stimulated oxygen consumption, quantitative nitroblue tetrazolium dye reduction, [1-(14)C]glucose utilization, and Fc receptors were significantly (P < 0.05 to P < 0.001) less in PMNL exposed to whole human colostrum or colostral lipid than in non-lipid-exposed cells or cells exposed to the aqueous phase of colostrum. In contrast, PMNL exposed to whole mature milk or to its lipid or aqueous phase caused no significant decrease in any of these parameters when compared to nonexposed cells. In assays of phagocytosis, colostral PMNL or blood PMNL exposed to colostral lipid had a significant (P < 0.001) decrease in their ability to ingest [methyl-(3)H]thymidine-labeled Staphylococcus aureus when compared to non-lipid-exposed PMNL. Blood PMNL exposed to lipid from mature milk had no decrease in ability to ingest S. aureus. Analysis of total lipid and total and individual fatty acid content revealed a uniform increase in all components in mature milk when compared to colostrum. Lipid or lipid-soluble material present in human colostrum but not mature milk causes inhibition of phagocytosis and respiratory burst-related activities of PMNL.

Blood Bactericidal Activity↗

Mechanisms of intralipid effect on polymorphonuclear leukocytes.

The effect of Intralipid, a lipid emulsion used in total parenteral nutrition, on polymorphonuclear leukocytes (PMNL) was studied in vitro. Preincubation of PMNL with Intralipid was found to depress oxidative metabolic and phagocytic functions. Preincubation of PMNL with intralipid also caused a decrease in Fc receptors. However, when Intralipid was added at the start of metabolic assays, it stimulated the respiratory burst. We interpret these findings as suggesting that Intralipid, acting as a particulate stimulus, activated and exhausted metabolic pathways involved in the respiratory burst and phagocytosis and that it also decreased numbers or availability of Fc receptors on PMNL. Individual components of Intralipid did not induce these changes. This dysfunction may contribute to the infections seen in patients receiving parenteral hyperalimentation with Intralipid supplementation.

Adult↗

Modulation of polymorphonuclear leukocyte function by doxorubicin (Adriamycin) and alpha tocopherol (vitamin E).

The effect of various concentrations of Adriamycin alone and Adriamycin plus vitamin E on human polymorphonuclear leukocyte (PMNL) function was determined. Aliquots of PMNLs were incubated at 37 degrees C with saline or vitamin E and then exposed to Adriamycin. A significant decrease in 1-14C glucose utilization and oxygen consumption by zymosan stimulated PMNLs occurred when PMNLs were incubated with 1, 10, 20, 1000 and 200 micrograms/ml concentrations of Adriamycin. Preincubation of the PMNLs with vitamin E afforded partial protection at lower concentrations. The total uptake at 3, 10 and 20 min of methyl 3H thymidine labeled S. aureus by control PMNL was significantly greater than by PMNLs exposed for 60 min to 100 micrograms/ml of Adriamycin. Intracellular Adriamycin concentrations increased in a dose dependent fashion. Viability of cells before and after incubation was 95%. Adriamycin inhibited oxidative metabolic and functional activity of PMNLs in a dose related manner. Preincubation of PMNLs with vitamin E partially protected them from the effects of Adriamycin.

Chromatography, High Pressure Liquid↗

Influence of subsalicylate bismuth on absorption of doxycycline.

The influence of a typical 60-mL dose of subsalicylate bismuth (Pepto-Bismol) on the absorption of 200 mg of orally administered doxycycline hyclate was studied. Bioavailability of doxycycline was significantly reduced by 37% and 51%, respectively, when subsalicylate bismuth was given simultaneously and as a multiple-dose regimen before doxycycline. Peak serum concentrations of doxycycline were significantly decreased when subsalicylate bismuth was given two hours before doxycycline but not when given two hours after doxycycline. Subsalicylate bismuth should not be taken when doxycycline is used for therapeutic purposes, and we suggest travelers should not take the agents together in an effort to prevent diarrhea.

Adult↗

Leukocyte function in healthy neonates following vaginal and cesarean section deliveries.

Oxidative metabolic activities of polymorphonuclear leukocytes from cord blood of 15 full-term infants delivered by cesarean section without labor, five infants delivered by cesarean section with labor, and 15 infants delivered vaginally, as well as 35 healthy adult control subjects, were evaluated. The absolute polymorphonuclear leukocyte counts of cord blood from infants delivered vaginally and by cesarean section with labor were significantly higher when compared to cord blood APCs from infants delivered by cesarean section without labor and healthy adult control APCs. Zymosan-stimulated oxygen consumption, hexose monophosphate shunt activity, and quantitative nitroblue tetrazolium dye reduction were significantly lower in cord blood PMNLs from infants delivered vaginally and by cesarean section with labor than in cord blood PMNLs from infants delivered by cesarean section without labor or control PMNLs. Metabolic activity of PMNLs from healthy adults and infants born by cesarean section without labor did not differ significantly. This study indicates that the function of PMNLs isolated from cord blood varies with the method of delivery. These observations may explain previous discrepancies in the literature as well as the propensity of certain neonates to infection.

Cesarean Section↗

Effect of glucose concentration and time on polymorphonuclear leukocyte function.

Polymorphonuclear leukocyte (PMNL) to oxidative metabolism and functional activities were assayed after varying periods of exposure to glucose concentrations ranging from 100-600 mg/dl. Oxygen consumption, superoxide generation and phagocytosis and killing of radiolabeled S. aureus by PMNL were not affected by hyperglycemic conditions for incubation periods up to 18 hours. Elevated glucose levels per se do not appear to be responsible for PMNL abnormalities reported in patients with diabetes mellitus.

Diabetes Mellitus↗

Salicylate absorption from a bismuth subsalicylate preparation.

The active ingredient in Pepto-Bismol (PB) (Norwich-Eaton), a common antidiarrheal, is bismuth subsalicylate. The absorption of salicylate after oral PB was studied in six fasted men. Plasma concentrations of total salicylate and the urinary excretion profile of salicylate were determined as a function of time and dose. After 60 ml PB, 500.1 +/- 33.6 mg (mean +/- SD) salicylate were recovered in urine, representing 95.0 +/- 6.4% of salicylic acid equivalents in 60 ml of the formulation. Peak plasma salicylate levels were reached 0.5 to 3 hr after ingestion and averaged 40.1 +/- 17.3 micrograms/ml. Absorption of salicylate was also essentially complete after 15- and 30-ml doses of the antidiarrheal preparation, and a linear relationship between dose and recovery of salicylate in the urine was found. Salicylate kinetics was nonlinear after a multiple-dose regimen of 60 ml every 6 hr for five doses.

Adult↗

Clinical pharmacology of two chloramphenicol preparations in children: sodium succinate (iv) and palmitate (oral) esters.

The clinical pharmacology of chloramphenicol was evaluated in 14 children with serious bacterial infections. The children received chloramphenicol sodium succinate intravenously for five to six days at which time orally administered chloramphenicol palmitate was substituted for an additional five to six days of therapy. The mean peak serum chloramphenicol concentration when given iv (28.2 +/- 5.1 micrograms/ml) occurred within one hour after the termination of the 60-minute iv infusion and when given orally (19.3 +/- 2.6 micrograms/ml) occurred two to three hours after ingestion. Differences in serum levels of chloramphenicol after iv compared to oral administration of the same dose could be demonstrated at various time points studied during the dose-response curves; however, the areas under the chloramphenicol curve were not significantly different after iv (140 +/- 116 micrograms/ml/hour) versus oral (95 +/- 26 micrograms/ml/hour) administration. In seven patients who had concomitant serum and CSF chloramphenicol levels determined, a CSF to serum ratio of 23 to 85% occurred. The CSF levels (5.5 to 13 micrograms/ml) were not directly proportional to serum levels. All patients recovered from their infection and no side effects from chloramphenicol were encountered. Administration of chloramphenicol orally in the palmitate form produces serum concentrations and areas under the disappearance curve similar to those achieved after iv administration of the same dose, indicating that the oral route is an effective method of achieving therapeutic concentrations of chloramphenicol in serum.

Administration, Oral↗