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Biomedical subjects

L K Pickering

Publications and source records attributed to L K Pickering.

At least 181 records · Page 10Linked to original sources
PubMed1981

Interferon induction of natural killer cytotoxicity in human neonates.

Low natural killer cytotoxicity has been associated with serious herpes simplex virus infections. Neonates' mononuclear cells had significantly lower NKC to HSV infected (P less than 0.001) and uninfected (P less than 0.005) target cells than did adults' MC. Under appropriate conditions, both neonates' MC to NKC was increased by exogenous human leukocyte interferon. Although neonates' and adults' MC had a similar sensitivity to interferon, there was a significant (P = 0.05) lack of consistency in neonates' MC response. Twenty-three percent (4/17) of neonates' MC samples did not respond with increased NKC in the presence of interferon, unlike adults' MC, all of which demonstrated increased NKC. Neonates' MC did not suppress adults' MC-NKC. These data demonstrate the efficacy of interferon as an NKC stimulator in the neonate, but indicate a heterogeneous response of neonatal cells. We are encouraged with the prospect of clinical trials of interferon to treat severe viral infections in neonates. We urge the inclusion of immune surveillance in these trials.

Adult↗
PubMed1981

Diarrhea caused by Shigella, rotavirus, and Giardia in day-care centers: prospective study.

We conducted a 19-month prospective study of children attending 20-day-care centers to determine the occurrence, causes, and transmission of gastroenteritis among children, staff, and family members. Nine centers had 15 outbreaks of diarrhea involving 195 patients. An enteropathogen was identified in all outbreaks. Shigella was detected in five outbreaks, rotavirus in two, giardia in one, and in the remaining seven multiple enteropathogens were identified. Rotavirus and Giardia occurred only in children less than 3 years of age; shigellosis occurred at all ages. In six DCC 68 single cases of diarrhea were not associated with an outbreak; an enteropathogen was identified in only three (4%) persons. Thirty-four family members (11%) developed diarrhea associated with the occurrence of gastroenteritis in children in six DCC evaluated for this problem. Secondary attack rates of diarrhea in families according to organisms identified in the DCC outbreaks were: Shigella 26%, rotavirus 15%, and G. lamblia 17%. DCC may play an important role in the epidemiology and transmission of gastroenteritis in the United States.

Child↗
PubMed1981

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↗
PubMed1981

Effect of concentration and time upon inactivation of tobramycin, gentamicin, netilmicin and amikacin by azlocillin, carbenicillin, mecillinam, mezlocillin and piperacillin.

Carbenicillin and ticarcillin have been shown to inactivate aminoglycoside antibiotics. This study evaluated the effect of time upon in vitro interaction between mixtures of four aminoglycoside antibiotics at two concentrations with azlocillin, mecillinam, mezlocillin, piperacillin and carbenicillin at three concentrations. By linear regression analysis, the inactivation of each aminoglycoside antibiotic was shown to be directly proportional to the concentration of the semisynthetic penicillin. Aminoglycoside inactivation was greater after 72 hr of incubation with the penicillins than after 24 hr of incubation. Inactivation by each semisynthetic penicillin was greater for tobramycin and gentamicin than for netilmicin and amikacin, especially at higher concentrations of the penicillins. At concentrations of 500 microgram/ml, significantly less inactivation of amikacin occurred when compared to netilmicin. There was little difference in inactivation of a specific aminoglycoside by any of the semisynthetic penicillin antibiotics. No significant change in aminoglycoside activity occurred when the aminoglycosides were stored with the semisynthetic penicillin derivatives at -70 degrees C for 30 days. Conclusions from this study are: 1) serum specimens containing aminoglycoside-penicillin combinations should be tested immediately or frozen before antibiotic assay and 2) aminoglycoside inactivation by the newer semisynthetic penicillins may be important in patients with renal failure who are receiving these antimicrobial agents.

Amdinocillin↗
PubMed1981

Protection of neonatal mice against herpes simplex viral infection by human antibody and leukocytes from adult, but not neonatal humans.

Neither human immune globulin nor human mononuclear leukocytes (containing lymphocytes and monocytes) from herpes simplex virus (HSV) seronegative adult donors could protect infant C57BL/6 mice from a lethal HSV infection. In contrast, a combination of 5 X 10(6) leukocytes and a subneutralizing dose of antibody protected the mice. Leukocytes (5 X 10(6) or 1 X 10(7)) from neonatal humans and antibody could not mediate this protection. This is the first correlation between defective human neonatal leukocyte antibody-dependent cellular cytotoxicity (ADCC) in vitro and defective human neonate leukocyte-antibody protection against HSV infection in vivo in mice.

Animals↗
PubMed1980

Effect of antineoplastic drugs on human leukocyte-mediated cytotoxicity against herpes simplex virus infected cells.

We evaluated the effect of five antineoplastic drugs on the ability of human leukocytes to destroy herpes simplex virus (HSV) infected target cells in the presence of antibody (antibody-dependent cellular cytotoxicity) and in its absence (natural killer cytotoxicity). Leukocytes from healthy volunteers were separated into macrophages, polymorphonuclear leukocytes, and lymphocytes. Adriamycin, cyclophosphamide, prednisone, procarbazine, and vincristine, at various concentrations and incubation periods, were tested for their effects on the natural killer and antibody dependent cellular cytotoxicity of macrophages, lymphocytes, and polymorphonuclear lymphocytes in a 51Cr release microcytotoxicity assay against HSV-infected cells. All drugs at therapeutic concentrations inhibited natural killer and antibody dependent cellular cytotoxicity; an exception was cyclophosphamide, which did not inhibit the natural killer cytoxicity of lymphocytes. The antibody dependent cellular cytotoxicity of macrophages and polymorphonuclear leukocytes appeared to be more than that of lymphocytes. The results of short incubation (2 hours) of the drug with either effector cells or target cells, followed by drug removal, suggests that the drug effect occurred early and predominantly at the effector cell level. Antineoplastic drugs had an inhibitory effect on natural killer and antibody dependent cellular cytotoxicity against HSV-infected cells. This inhibitory action may partially explain the increased susceptibility of patients receiving chemotherapy to developing viral infections.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1980

Prevention of traveler's diarrhea (emporiatric enteritis). Prophylactic administration of subsalicylate bismuth).

The efficacy of a daily dosage regimen of subsalicylate bismuth in preventing or reducing the severity of diarrhea among young healthy adults was evaluated in a double-blind, randomized, placebo-controlled trial. Diarrhea developed in 14 (23%) of 62 students receiving subsalicylate bismuth compared with 40 (61%) of 66 students taking a placebo. The protective effect of subsalicylate bismuth was apparent within a day or two of the study onset and became more obvious as the number of days at risk increased. The students treated with subsalicylate bismuth experienced fewer intestinal complaints and were less likely to pass soft or watery stools of any number. Once diarrhea occurred, enteropathogens were less commonly identified in stools of students receiving subsalicylate bismuth (33%) compared with placebo (71%). Subsalicylate bismuth was well tolerated by students during the 21-day trial.

Adult↗
PubMed1980

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↗
PubMed1980

Polymorphonuclear leukocytes of human colostrum. I. Oxidative metabolism and kinetics of killing of radiolabeled Staphylococcus aureus.

Polymorphonuclear leukocytes (PMNLs) were isolated from the colostrum of 57 women. Colostral cells were identified by fluorescent microscopy after supravital staining with acridine orange. Numerous intracellular fat globules within colostral PMNLs were shown by Oil Red O stain and electron microscopy. Oxidative metabolic activity during phagocytosis of opsonized zymosan particles was significantly greater in blood PMNLs compared with colostral PMNLs. The total uptake and killing of [methyl-3H]thymidine-labeled Staphylococcus aureus by blood PMNLs were significantly greater than by colostral PMNLs. Similar defects were produced in blood PMNLs incubated with the lipid fraction of colostrum, but not in those incubated with the aqueous fraction. Surface Fc receptors of colostral PMNLs and blood PMNLs incubated with colostral lipid were significantly reduced in number compared with those of control PMNLs or PMNLs preincubated with the aqueous fraction of colostrum. The metabolic and phagocytic defects of PMNLs from human colostrum appear to be related to colostral substances that alter PMNL surface structure and subsequent function.

Cell Count↗
PubMed1980

Human colostral cytotoxicity. II. Relative defects in colostral leukocyte cytotoxicity and inhibition of peripheral blood leukocyte cytotoxicity by colostrum.

Colostral cells have been previously shown to mediate antibody-dependent cellular cytotoxicity (ADCC) to herpes to simplex virus-infected cells. A comparison of colostral cells to matched peripheral blood mononuclear cells has revealed significantly lower ADCC activity, higher antibody requirements, and slower kinetics of colostral cell ADCC against infected cells. Colostral cells failed to mediate natural killer cytotoxicity. Lymphocytes, monocyte macrophages, and polymorphonuclear leukocytes isolated from peripheral blood and incubated with colostrum from virus-immune or nonimmune women markedly inhibited ADCC. Inhibitory activity was found in lipid and aqueous fractions and was due to an effect on leukocytes, not target cells. A partial explanation was inhibition of expression of leukocyte Fc receptors, a prerequisite for ADCC, by acellular colostrum. These results raise questions concerning the potential antiviral activity of colostral cells in vitro.

Antibody-Dependent Cell Cytotoxicity↗