Comparison of cytotoxicity mediated by human monocyte-macrophages and lymphocytes after prolonged in vitro incubation.
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Biomedical subjects
Publications and source records attributed to L K Pickering.
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During a 22-month period, 595 children with diarrhea and 210 age-matched controls attending clinics in Houston (367 children) and Mexico (438) were prospectively evaluated for enteric pathogens. Enteropathogens associated with disease were Shigella (18%), rotavirus (14%), Salmonella (9%), toxigenic Escherichia coli (6%), and others (12%), including 14 Proteus isolates that caused rounding of adrenal cells. Enteropathogens were isolated from a greater (P less than 0.001) number of children with diarrhea (59%) than from asymptomatic controls (6%). Paired sera tested for antibody to heat-labile toxin of E. coli rarely demonstrated a fourfold rise during episodes of diarrhea. This study demonstrates: (1) more striking illness in children from Mexico; (2) more common occurrence of Shigella in Houston, and of rotavirus and Salmonella in Mexico; (3) lack of seasonal occurrence of rotavirus isolation in either population and a summertime occurrence of Shigella in Houston; (4) lack of toxigenic E. coli isolation in endemic diarrhea of either population; and (5) a significant (P less than 0.001) age-related acquisition of E. coli LT antibodies.
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The role of rotavirus in adult diarrhea was evaluated in 165 students attending a Mexican university. Students were divided into three groups: newly arrived summer students from the United Sttes, regular students from the United States, and Mexican and Venezuelan students. Ninety-one students with diarrhea and 74 corresponding, matched, asymptomatic control students were included in the study. The frequency of rotavirus in stools was determined by electron microscopy with use of the pseudoreplica technique. Twenty-five percent of those who were ill and 12% of the controls had rotavirus in their stools. A significantly (P less than 0.05) greater number of newly arrived United States summer students with diarrhea had rotavirus in their stool than did matched controls (26% vs. 3%). There was no significant difference in rate of recovery of bacterial pathogens from rotavirus-positive and rotavirus-negative stools (52% vs. 53%) from students with diarrhea. Although significantly more rotavirus was identified from ill American summer students than from controls, the role of rotavirus as a cause of diarrhea in these students could not be established in all cases since bacterial pathogens were also commonly found in stool.
The pharmacokinetics of tobramycin were evaluated in 50 pediatric patients (two to 18 years of age) with malignancies and normal renal function. Patients receiving either 240 or 300 mg/m2 per 24 hr (8 or 10 mg/kg per 24 hr) divided into doses given every 4 hr had peak serum concentrations (mean +/- standard error) of 3.10 +/- 0.23 microgram/ml and 4.23 +/- 0.25 microgram/ml, respectively, at the end of a 1-hr infusion. Serum concentrations at 4 hr were 0.82 +/- 0.15 and 1.05 +/- 0.15 microgram/ml, respectively. The half-life of the drug was 96.6 min and was inversely correlated with age of the patients. The total clearance rate of tobramycin was 164 +/- 15 mg/min per 1.73 m2 and was directly correlated with age. The mean volume of distribution was 0.42 +/- 0.038 liter/kg and was inversely correlated with age. No accumulation of tobramycin was noted, and no side effects occurred. If therapeutic serum concentrations of tobramycin are to be achieved and maintained in children, the currently recommended dose and frequency of administration should be changed to 300 mg/m2 per 24 hr given in divided doses every 4 hr.
Seventeen patients had intraoperative peritoneal lavage with a solution containing one gram of kanamycin in 200 ml of 0.9% NaCl. The solution was removed by suction at two or five minutes. Venous blood samples were obtained at 15 minute intervals for two hours following lavage. Despite diligent attempts, an average of only 60% of the solution was recovered by suction. The peak concentration of kanamycin in serum correlated directly with the kanamycin dose (p less than 0.025). In six patients lavaged for five minutes, peak absorption occurred at 15 minutes with serum concentrations of 20.3 +/- 2.0 microgram/ml. In five patients lavaged for two minutes insignificantly (p greater than 0.1) lower peak serum concentrations (15.3 +/- 1.8 microgram/ml) occurred at 15 minutes. Six additional patients had peak kanamycin serum concentrations which occurred at 75 minutes and reached 23.2 and 24.0 microgram/ml in two patients. In three patients who received intravenous gentamicin prior to surgery, nine paired serum and peritoneal fluid samples obtained during three hours preceding lavage showed no significant differences in gentamicin concentrations (p less than 0.5). These pharmacokinetic data demonstrate the penetration of parenterally administered aminoglycosides into intraoperative peritoneal fluid. Kanamycin lavage for wound prophylaxis should be used cautiously and should be abandoned in patients who have renal impairment where prolonged toxic serum concentrations could develop.
During a two-month period, 6% of Gram stains of predominantly CSF specimens revealed gram-negative bacilli with no growth. The source of the false-positive Gram stain results was an alcohol storage bath from which slides were taken and flamed to remove residual alcohol. All 11 patients in the outbreak had further diagnostic tests or changes in therapy. In the laboratory, false-positive slides could be created by contaminating a slide bath with 10(5) bacilli/ml, flame drying, and staining. In addition, contaminated crystal violet caused a false-positive result when applied to a warm but not to a cool slide. To prevent false-positive Gram stain results, the storage of slides in alcohol baths should be abandoned, slides should not be flamed to remove alcohol, and specimens should be Gram-stained only when the heat-fixed slide has thoroughly cooled.
A radioimmunoassay and a radioenzymatic assay for netilmicin, a new aminoglycoside, were developed in our laboratories to assist in the study of the pharmacology of the drug and to establish values for use in its monitoring. The assays are sensitive, precise, and rapid, giving results that correlate (r = 0.90) with each other and with those of a microbiological assay in which Klebsiella pneumoniae is used as the test organism. Preliminary pharmacological studies show the drug to have a biological half-life of 135 min. which is comparable to that for other aminoglycosides.
Four children had vertebral osteomyelitis due to Staphylococcus aureus. Abdominal signs and fever were frequent clinical manifestations. Back pain was an uncommon symptom except as a late manifestation in one patient. The portal of entry of the organism generally was not apparent. Location of infection was in the lower thoracic and lumbar spine. Diagnosis was based on roentgenographic changes, radionuclide imaging, and bacteriologic corroboration. We conclude that symptoms and signs of vertebral osteomyelitis in children can be atypical and that a diligent attempt to rapidly diagnose and promptly treat this condition will prevent orthopedic and neurologic sequelae.
Human colostral cells in combination with antibody were able to destroy Herpes simplex virus-infected cells (Antibody-dependent cellular cytotoxicity--ADCC) while demonstrating very low spontaneous (non-antibody mediated) cytotoxicity (SCT). The colostral cells involved in ADCC required a high effector to target ratio, were mononuclear, adherent and totally inhibited by latex particles. These results demonstrate that a subpopulation of human colostral macrophages can mediate ADCC against virus-infected target cells. The biologic implications of intact colostral cell ADCC and low SCT in regard to protecting the neonate from infection and maternal cell mediated gastrointestinal damage are discussed.
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The inhibition of the activity of enterotoxins by bismuth salts was assessed in laboratory models. In the Y-1 adrenal cell tissue culture system, a commercial preparation containing bismuth subsalicylate reduced the activity of crude toxin from Vibrio cholerae by 10(4)-fold as compared with the activity of controls. Similar results were obtained with use of the adult rabbit ligated intestinal loop model. The preparation failed to affect crude Escherichia coli or cholera toxin activity once these toxins had become bound to intestinal mucosa. Pretreatment of ligated loops with the preparation reduced the fluid accumulation mediated by crude E. coli and cholera toxins by 78% and 91%, respectively. Bismuth subsalicylate and the complex vehicle of the preparation also inactivated toxin; however, bismuth subsalicylate was more effective when combined with the vehicle. Bismuth subcarbonate failed to inhibit fluid accumulation in ligated loops. Preparations containing bismuth subsalicylate may be effective in the prevention of diarrhea mediated by toxigenic E. coli.
A clinic was established at Universidad de las Americas, Cholula, Puebla, Mexico for the study of acute diarrhea rates in newly-arrived students and full-time students. Diarrhea occurred in 22 of 55 newlly-arrived U.S. summer students (40%), compared to 28 of 142 U.S. full-time students (20%), 4 of 29 Venezuelan summer and full-time students (14%) and 7 of 66 Mexican full-time students (11%) (the differences were significant, p less than 0.005). Recurrent episodes of diarrhea during the month of study occurred in 15% of U.S. summer students, 4% of U.S. full-time students, and were non-existent in students from Latin America. As well as the 61 students with diarrhea enrolled in the incidence study, all students who developed diarrhea at the univeristy were encouraged to visit the clinic. This gave a total population of 130 cases of diarrhea. The illness that developed in students form the U.S. varied widely, but it typically consisted of seven to 13 unformed stools during the first 48 hours of illness, with illness persiting three to five days. Illness tended to be more severe in the U.S. students. Fifty per cent of the U.S. students with diarrhea had "severe" illness (greater than or equal to 10 unformed stools in first 48 hours) compared to 23% of the Latin Americans. This study indicates that the agents responsible for diarrhea in Latin America are widespread and that resistance to infection develops after prolonged or repeated exposure.