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Biomedical subjects

C L Elliott

Publications and source records attributed to C L Elliott.

At least 19 recordsLinked to original sources

Fatal transfer of malignant melanoma from multiorgan donor to four allograft recipients.

BACKGROUND: In this report we describe the transfer of malignant melanoma from a single donor to four solid organ transplant recipients, all of whom died from metastatic melanoma. METHODS AND CASE HISTORIES: The donor of a heart, liver, and two kidneys to four separate recipients died of intracerebral hemorrhage. The donor had no history or clinical evidence of melanoma. All four recipients, treated with standard immunosuppression protocols, developed metastatic malignant melanoma within 1 year after transplantation Three patients died within 14 months after transplantation, although the fourth, whose immunosuppressive therapy was discontinued, died of metastatic melanoma 30 months after renal transplantation. FINDINGS: Tumors from all recipients were histologically identical. Donor origin of tumor cells was confirmed by polymerase chain reaction (PCR)-based DNA analysis for polymorphic short tandem tetrameric repeats (Geneprint STR, Promega Corp., Madison, WI). DNAs from nontumorous donor tissue and tumor tissue available from three recipients tested positive for CSF1P0 alleles 10 and 12 and for TH01 alleles 6 and 7, although DNAs from nonneoplastic recipient tissues all exhibited different allelotypes. INTERPRETATION: Transmission of fatal or potentially fatal malignant tumors, notably malignant melanoma, from donor to recipient is an uncommon complication of solid organ transplantation. PCR-based genetic analysis permits definitive assignment of the source of posttransplant tumors.

Adult↗

The effect of mifepristone administration on leukocyte populations, matrix metalloproteinases and inflammatory mediators in the first trimester cervix.

Cervical ripening is analogous to an inflammatory reaction characterized by an influx of inflammatory cells and an increase in inflammatory mediators. The anti-gestogen mifepristone is highly effective in inducing cervical ripening in women throughout gestation. However, its mechanism of action is largely unknown. The aim of the study was to investigate the effect of in-vivo administration of mifepristone on inflammatory cells and mediators in the cervix. Cervical biopsies were taken from women undergoing a first trimester termination of pregnancy at 0, 6, 12, 24 and 36 h (n = 6 per group) after mifepristone administration. Biopsies were fixed for immunohistochemistry and also cultured for subsequent analysis of culture media by radioimmunoassay or enzyme-linked immunosorbent assay. After administration of mifepristone (6-24 h), there was an increase in immunostaining for leukocyte common antigen (CD45), neutrophil elastase, monocytes (CD68), and matrix metalloproteinases (MMP)-1, -8 and -9. Immunostaining for MMP-2 and tissue inhibitor of metalloproteinases (TIMP)-1, -2 and -4 were unaffected by mifepristone treatment. Secretion of monocyte chemotactic protein (MCP-1) was significantly (P < 0.05) increased from biopsies taken 6-24 h after mifepristone administration. Cervical biopsies also released interleukin-8 (IL-8), prostaglandin (PG) E(2), PGF(2alpha) and prostaglandin metabolites (PGEM and PGFM) although their secretion was unaffected by mifepristone treatment. This study suggests that mifepristone may, in part, effect cervical ripening by modulating the influx of inflammatory cells into the cervix, up-regulating MMP expression and inducing chemokine secretion by cervical tissue.

Abortifacient Agents, Steroidal↗

Interleukin 8 expression in human myometrium: changes in relation to labor onset and with gestational age.

PROBLEM: Preterm labor remains the major cause of perinatal mortality and morbidity in normally formed babies. The mechanisms involved in the onset of preterm labor are poorly understood, mainly because the mechanisms initiating term labor remain ill-defined. METHOD OF STUDY: Human myometrial samples were collected at cesarean delivery from preterm (26-36 weeks gestation) and term (37-41 weeks) women. Women at term were either non-laboring or laboring. The expressions of interleukin-8 (IL-8) mRNA and protein were measured by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: The expression of both IL-8 mRNA and protein significantly increased in the term laboring group, compared with either the term non-laboring or preterm groups. Levels of IL-8 expression did not alter with advancing gestational age. CONCLUSIONS: The increased expression of IL-8 in laboring myometria at term supports the hypothesis that up-regulation of IL-8 has a role in the initiation of labor in association with an influx of neutrophils and the release of their collagenolytic enzymes into uterine tissues.

Enzyme-Linked Immunosorbent Assay↗

Regulation of interleukin 8 production in the term human placenta during labor and by antigestagens.

OBJECTIVE: Our purpose was to assess the effects of labor and antigestagens on production of interleukin 8 by the term human placenta and to localize interleukin 8 in first- and third- trimester placentas. STUDY DESIGN: The study was conducted by the Department of Obstetrics and Gynaecology of the University of Edinburgh. Five placentas were collected after spontaneous and cesarean deliveries. Explants were cultured in the presence of mifepristone, lilopristone, or onapristone. The production of interleukin 8 was determined by specific radioimmunoassay, and the immunolocalization of interleukin 8 was determined in sections of first- and third-trimester placentas. RESULTS: All explants produced interleukin 8. Production was significantly increased (P < .05) after spontaneous delivery. In placentas delivered spontaneously, onapristone significantly increased production of interleukin 8 (P < .05), whereas in those from cesarean deliveries lilopristone caused a significant increase in production (P < .05). In the third-trimester placenta interleukin 8 was localized in the perivascular area of fetal vessels. In first-trimester villi it was peripherally located in syncytiotrophoblast. CONCLUSION: The human placenta at term is capable of producing interleukin 8, which is localized around the perivascular area of the villi. Production is increased after spontaneous labor and to varying degrees by the antigestagens studied. Interleukin 8 may have a role in the onset of parturition by recruiting and activating neutrophils at the placental site.

Culture Techniques↗

The effects of mifepristone on cervical ripening and labor induction in primigravidae.

OBJECTIVE: To compare the effects of 50 mg or 200 mg of oral mifepristone with placebo on cervical ripening and induction of labor in primigravid women at term with unfavorable cervices. METHODS: This was a double-blind study in which 80 primigravidae at term with a modified Bishop score of 4 or less were randomly assigned to one of three treatment groups. They were assessed at 24-hour intervals for 72 hours, after which labor was induced if it had not occurred spontaneously. RESULTS: Two hundred milligrams of mifepristone resulted in a favorable cervix (with a Bishop score greater than 6 or in spontaneous labor) in significantly more women than placebo (P = .01). An improvement in cervical ripening was seen in the group given 50 mg of mifepristone, but this was not statistically significant. There were more cesarean deliveries performed for fetal distress in the group treated with 200 mg of mifepristone than placebo, but this was not statistically significant and was not associated with any differences between groups in terms of neonatal outcome. CONCLUSION: Mifepristone, a progesterone antagonist, is known to cause softening and dilation of the human early pregnant cervix and an increase in uterine activity. It is theoretically attractive for use as an adjunct in cervical priming and labor induction. In this study, 200 mg of mifepristone was significantly more likely to result in a favorable cervix than placebo.

Adolescent↗

Dexamethasone-induced leucocytosis in pregnancy.

The effect of intramuscular dexamethasone administration in late pregnancy on the maternal peripheral white cell count was examined in 20 women. The mean total white cell count increased from a baseline of 11.3 x 10(9)/L (SD 2.3) to 16.2 x 10(9)/L (SD 4.6) on day 1, normalising thereafter. This 43% increase represented composite changes in the neutrophil and lymphocyte counts which, on average, increased by 62% and decreased by 22%, respectively. It is concluded that prenatal dexamethasone induces a significant neutrophilia on the first day following administration. This information may be helpful when monitoring for infection.

Adolescent↗

The pharmacokinetics of oral and intramuscular administration of dexamethasone in late pregnancy.

BACKGROUND: To compare the pharmacokinetics of orally administered dexamethasone with intramuscular administration in antenatal patients at risk of preterm delivery. METHOD: Ten antenatal patients at risk for preterm delivery were given two intramuscular and then one oral dose of dexamethasone. Plasma which was collected at set intervals following the first intramuscular dose and the oral dose was assayed for dexamenthasone. The results were analyzed using pharmacokinetic data-fitting software and pharMacokinetic parameters calculated. RESULTS: After oral adminIstration of dexamethasone the mean maximum plasma concentration obtained was 65% that of the intramuscular dose and the bioavailability of the oral route was calculated as 72% of the intramuscular route. The terminal half-lives of dexamethasone were similar for both routes. CONCLUSIONS: These limited data would suggest that if dexamethasone is to be administered orally, which would be both preferable to patients and more economic, then a proportionately increased dose of oral dexamethasone would be required to provide similar maternal plasma pharmacokinetics to the intramuscular dose in current use. Further, larger studies are now required to confirm this.

Administration, Oral↗

Prostaglandin and cytokine release by trophoblastic villi.

Trophoblastic villi may have several protective mechanisms against the maternal immune system. They do not display major human leukocyte antigen antigens, and therefore a T cell-mediated response is unlikely. The syncytiotrophoblast provides a seamless coating, and the microvilli on its surface represent a very large surface area which has a high capacity for absorbing antibody. The syncytiotrophoblast also contains inhibitors of complement. Although these mechanisms are essential, they may not be sufficient protection. An additional mechanism by which the trophoblast could control its immediate environment in the decidua or maternal blood may be through the release of prostaglandins (PG) and cytokines. This possibility has been investigated here by measuring PG and several cytokines released from first trimester trophoblastic villi cultured for 24 h. PGE is the main primary prostaglandin with a release of 240 +/- 95 pg/mg/24 h. There was an extensive accompanying production of metabolites (13,14-dihydro-15-keto PGF, 2.4 +/- 0.4 ng/mg/24 h, and 13,14-dihydro-15-keto PGE, 0.61 +/- 0.11 ng/mg/24 h). Cytokines were measured in culture fluid by specific enzyme-linked immunosorbent assays. Interleukin (IL)-2 and IL-10 release were not detectable, but IL-1 beta (5.2 +/- 1.1 pg/mg/24 h) and tumour necrosis factor (TNF) alpha (2.3 +/- 0.5 pg/mg/24 h) were found to be accompanied by much higher concentrations of inhibitors, IL-1 receptor antagonist (200 +/- 44 pg/mg/24 h) and soluble receptors for TNF types I (19.5 +/- 1.6 pg/mg/24 h) and II (19.3 +/- 2.8 pg/mg/24 h). Because PGE can influence the function of many leukocytes by raising intracellular cAMP concentrations, the release of humoral factors from the villous trophoblast might be important in pregnancy maintenance.

Chorionic Villi↗

Another look at chemical immobilization of raccoons (Procyon lotor) with ketamine hydrochloride.

Forty-one wild raccoons (Procyon lotor) were captured in Kentucky (USA) and immobilized with 7 to 16 mg/kg of ketamine hydrochloride, January to May 1987. Eight raccoons had muscle tremors in response to ketamine, but recovered with no other observable adverse effects. Mean (+/- SD) induction and duration of immobilization times were 3.2 +/- 1.8 and 42.3 +/- 14.5 minutes, respectively. Based on multiple regression analysis, the interaction of sex (P = 0.0030), body mass (P = 0.0036), dose (P = 0.0159), and the interaction of sex x dose (P = 0.0030) and body mass x dose (P = 0.0021) had a significant effect on the duration of raccoon immobilization.

Animals↗

Clinical depression and implicit memory.

We investigated performance on implicit and explicit memory tasks in subjects diagnosed with major depression and matched controls. Depressed subjects showed impaired performance on both the explicit and implicit tasks in comparison with controls. These findings are in contrast to groups such as amnesic patients and older adults, who show preserved abilities on implicit tasks and deficits on explicit tasks.

Adult↗

Firing without fear. Heading off litigation in employee terminations.

Under most state laws, employee handbooks carry the status of employment contracts, or such contracts are implied through various employment conversations. Unlike in the past, when a management decision to discharge an employee could be challenged only for statutory or public policy reasons, today's employer may have to prove that he or she did not violate an employee's contractual right to employment. Employers can reduce the risk of employment liability through practical steps such as careful monitoring and documenting of the hiring, performance appraisal, and disciplinary processes, and a credible grievance procedure. Many employers have found, however, that taking these steps does not always prevent litigation. Certain legal precautions, such as written disclaimers and other handbook revisions, can result in the dismissal of such actions before trial and will deter many plaintiffs' attorneys from taking the case. The strongest legal protection in termination situations is a release of all claims executed by the employee and supported by severance pay or other valuable consideration to which the employee would not be otherwise entitled.

Employee Discipline↗

Cerebral specialization in individuals with Down syndrome.

Recent research in which investigators examined cerebral specialization in individuals with Down syndrome was reviewed. Although dichotic listening studies seem to indicate that individuals with Down syndrome are more likely than those without Down syndrome to display a left ear/right hemisphere advantage for speech sounds, evidence from other experimental paradigms makes a simple model of reversed cerebral specialization for individuals with Down syndrome untenable. We proposed a model of cerebral specialization that has as its main feature the biological dissociation between speech perception and the production of speech and other complex movements. In light of this feature, possible directions for future research were discussed.

Dominance, Cerebral↗

What trustees can do to maintain nonunion status.

Key issues causing hospital employees to seek unionization include wages and benefits, job security, supervision, staffing, and interprofessional relationships. The board should address these issues through board policy, and it should monitor the implementation of that policy in several key areas.

Governing Board↗