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Biomedical subjects

L Murray

Publications and source records attributed to L Murray.

At least 91 records · Page 5Linked to original sources
PubMed1996

Push enteroscopy in the investigation of small-intestinal disease.

We report our experience with small-bowel push enteroscopy in 50 patients. The indications for push enteroscopy were: anaemia/occult gastrointestinal bleeding (22 patients); overt gastrointestinal bleeding (17 patients); abnormal small-bowel radiology (8 patients) and miscellaneous (3 patients). In those with undiagnosed gastrointestinal bleeding/anaemia, abnormalities were detected in 24/39 patients (62%): small bowel arteriovenous malformations (AVMs) were detected in 19 (49%), and five (13%) had lesions in the upper gastrointestinal tract. Seventeen patients had heater-probe ablation therapy of vascular lesions: nine patients had small-intestinal lesions, four patients gastric lesions, and four patients combined gastric and small-intestinal lesions. In those with abnormal small-bowel radiology, abnormalities were detected in 6/8 patients. We conclude that (i) push enteroscopy can establish a diagnosis in a high proportion of patients with gastrointestinal bleeding; (ii) heater-probe ablation therapy of vascular lesions can be performed routinely at the time of enteroscopy; (iii) a significant proportion of patients (9/50) referred for enteroscopy with undiagnosed gastrointestinal bleeding have lesions in the stomach/proximal duodenum missed at diagnostic endoscopy. Push enteroscopy is a valuable diagnostic and therapeutic endoscopic procedure.

Adult↗
PubMed1996

The cognitive development of 5-year-old children of postnatally depressed mothers.

As part of a longitudinal study of the influence of postnatal depression on child development, the cognitive functioning of index and control children was assessed at age 5 years. There was no evidence of an adverse effect of postnatal depression, even amongst sub-groups of children suggested to be vulnerable (boys and children from low SES families). However, early experience of insensitive maternal interactions predicted the persistence of poorer cognitive functioning. A number of factors in the child's current environment, including stimulation at home, social class and, for boys, the experience of schooling, contributed to cognitive performance. The findings are considered in relation to the ongoing debate on sensitive periods.

Child of Impaired Parents↗
PubMed1996

The role of infant factors in postnatal depression and mother-infant interactions.

A large group of infants of primiparous women who were at high risk fo r postnatal depression (N=188) and a smaller group of those at low risk (N=43) were assessed in the neonatal period using the Neonatal Behavioural Assessment Scale. Poor motor scores and high irritability were strongly predictive of the onset of maternal depression by eight weeks postpartum. These effects obtained after taking account of both maternal mood in the neonatal period and maternal perceptions of infant temperament. Poor motor scores and high levels of infant irritability in the neonatal period also predicted less optimal infant behaviour in face-to-face interactions with the mother at two months postpartum. Neonatal behaviour did not predict the persistence of depression, nor did it predict the quality of maternal behaviour in interaction with the infant.

Adult↗
PubMed1996

Organochlorine compounds in human brain.

Having observed polychlorinated biphenyls (PCBs) in brain tissue obtained post mortem from two men we have carried out a study of organochlorine compounds in frontal cortex from patients with Parkinson's disease (PD) and from controls. No PCBs were found in any of those samples. There was no difference in the concentration of the DDT metabolite pp'-DDE in the PD brain samples. Dieldrin (HEOD) was significantly decreased in PD brain when analysed by lipid weight. While these findings would not support the hypothesis that PCBs may contribute to the development of Parkinson's disease in humans it remains possible that they may cause damage to the basal ganglia before being displaced from brain tissue.

Aged↗
PubMed1996

The impact of postnatal depression and associated adversity on early mother-infant interactions and later infant outcome.

The impact of maternal depression and adversity on mother-infant face-to-face interactions at 2 months, and on subsequent infant cognitive development and attachment, was examined in a low-risk sample of primiparous women and their infants. The severe disturbances in mother-infant engagement characteristic of depressed groups in disadvantaged populations were not evident in the context of postpartum mood disorder in the present study. However, compared to well women, depressed mothers were less sensitively attuned to their infants, and were less affirming and more negating of infant experience. Similar difficulties in maternal interactions were also evident in the context of social and personal adversity. Disturbances in early mother-infant interactions were found to be predictive of poorer infant cognitive outcome at 18 months. Infant attachment, by contrast, was not related to the quality of 2-month interactions, but was significantly associated with the occurrence of adversity, as well as postpartum depression.

Adult↗
PubMed1995

Signal transduction by the receptors for thrombopoietin (c-mpL) and interleukin-3 in hematopoietic and nonhematopoietic cells.

Antisense oligonucleotide to the translation initiation sequence of human c-mpI reduced the proliferation of human CD34+ bone marrow cells in response to interleukin-3 (IL-3) alone or to the combination of IL-3 and thrombopoietin (TPO). To investigate the molecular basis for these cytokine interactions, we analyzed the relationship between the receptor subunits for IL-3 and TPO and determined whether both receptors activate identical signal transduction pathways. The function of the receptor subunits was characterized in transiently transfected hepatoma cells and fibroblasts by the activation of gene expression via specific regulatory elements and by the stimulation of DNA-binding activity of STAT proteins. Although c-mpl and IL-3 receptor (IL-3R) reconstituted a qualitatively comparable gene regulatory response, there was no detectable functional interaction between their respective receptor subunits. By comparing the receptor action in different cell lines, we observed that in human hepatoma cells the signaling of c-mpI was 100-fold less sensitive to TPO than in rat hepatoma cells. However, IL-3R signaling was comparable between the two cell types, suggesting that c-mpI and IL-3R do not use identical signal transducing mechanisms. The cytoplasmic domains necessary for c-mpI signaling were determined by testing deletion mutants. The membrane-proximal box 1 sequence motif was critical for gene regulation and for STAT protein activation that seemed to involve the Janus kinase 2 (JAK2). Because IL-3R was less dependent on JAK2 than c-mpI, different levels of JAK2 expression may account, in part, for the quantitative difference in IL-3 and TPO response among various cell lines.

Animals↗
PubMed1995

Enrichment of human hematopoietic stem cell activity in the CD34+Thy-1+Lin- subpopulation from mobilized peripheral blood.

The number of CD34+ cells in the peripheral blood of cancer patients is known to be increased following the administration of high dose chemotherapy and hematopoietic growth factors. These so-called peripheral blood stem cell grafts are now frequently used for autologous transplantation of patients with malignancies. In this report, we address the question of whether true long-term repopulating pluripotent hematopoietic stem cells (PHSC) are mobilized into peripheral blood following chemotherapy plus granulocyte/macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) mobilization. We have examined the presence of stem cells in mobilized peripheral blood (MPB) by using an antibody to the human Thy-1 molecule to stain the CD34+Lineage- (Lin-) population. The kinetics of mobilization of CD34+Thy-1+ Lin- cells into peripheral blood were studied, and the percentage of cells with this phenotype was found to vary widely depending on the day of leukapheresis. A CD34+Thy-1+Lin- cell population, potentially containing PHSCs, was isolated by fluorescence activated cell sorting (FACS) and analyzed for activity. The multilineage differentiative capacity of this candidate stem cell-containing population in MPB was determined using an in vitro long-term culture system, in which cobblestone area formation was used as a means of detecting PHSCs. We also measured repopulating capacity by using two in vivo models in which severe combined immunodeficiency (SCID)-hu mice were implanted with human fetal bone or thymus grafts. Using these assays, we show that the highest frequency of cobblestone area-forming cells (CAFC) after 7 weeks of culture was observed in a subpopulation of CD34+Lin- cells, which expressed low levels of Thy-1. This cell population was capable of producing both B and myeloid cells, and maintaining CD34+Lin- cells in these long term cultures. Moreover, the CD34+Thy-1+Lin- cell subset possessed a higher ability to engraft and to demonstrate multilineage differentiative potential at 8 weeks in the SCID-hu bone assay. However, in the SCID-hu thymus model, both Thy-1+ and Thy-1- subpopulations were capable of donor T-cell engraftment at 6 weeks, suggesting the presence of cells capable of initiating T lymphopoiesis in both populations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Course and recurrence of postnatal depression. Evidence for the specificity of the diagnostic concept.

BACKGROUND: It is unclear whether the causative factors of non-psychotic postnatal depression are the same as those of depression at other times. METHOD: The course and recurrence of postnatal depression was studied in two groups of primiparous women experiencing an index episode of postnatal depression: those for whom the mood disorder had arisen de novo (n = 34), and those for whom it was a recurrence of previous affective disturbance (n = 21). The mental state of these two groups, together with a psychiatrically well control group (n = 40), was studied for five years. RESULTS: It was found that those for whom the index episode was a recurrence of depression were at raised risk of further non-postpartum episodes but not postpartum episodes, and that those for whom the index episode had arisen de novo were at raised risk for further episodes of postnatal depression but not for non-postpartum episodes. CONCLUSION: These findings suggest a specific nosologic reference for the concept of postnatal depression.

Adult↗
PubMed1995

Cytokine-mobilized peripheral blood CD34+Thy-1+Lin- human hematopoietic stem cells as target cells for transplantation-based gene therapy.

Gene-therapy of blood-borne disorders may be best achieved using hematopoietic stem cells (HSC) which have extensive self renewal potential as well as multilineage repopulating potential as a cellular target. The human HSC, which is CD34+Thy-1+Lin- has been isolated from fetal, adult bone marrow and cytokine-mobilized peripheral blood (MPB) (1-3). Results presented in this study show that the degree of mobilization of HSC into peripheral blood of cancer patients is highly variable and that the combined use of high dose chemotherapy and GM-CSF as a mobilization strategy is superior to the use of G-CSF with regard to the mobilization of true HSC. A multistep cell isolation procedure has been developed which utilizes high speed flow-cytometric cell sorting and allows the isolation of sufficient numbers of HSC from MPB to permit their use as an hematopoietic graft for clinical transplantation. Hematopoietic stem cells isolated from MPB are capable of self-renewal and differentiation into multiple hematopoietic lineages as shown by their behavior in both in vitro and in vivo assays. Mobilized PB mononuclear cells isolated from cancer patients are frequently contaminated with tumor cells. Using this cell isolation procedure, HSC preparations from patients with multiple myeloma have been created with greatly reduced tumor cell burdens. These CD34+Thy-1+Lin- cells are capable of being stably transduced at high efficiency (32-75%) by co-culture on a cell line producing recombinant retroviruses containing the neomycin-resistant gene. These HSC cell populations are likely ideal targets for hematopoietic cell-based gene therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Cytokine-specific central monoamine alterations induced by interleukin-1, -2 and -6.

Cytokine-specific alterations of monoamine activity were evident in the hypothalamus, hippocampus and prefrontal cortex 2 h following peripheral administration of recombinant interleukin (IL)-1 beta, IL-2 and IL-6 (200 ng, i.p.) in male, BALB/c mice. IL-1 induced the broadest range of neurochemical changes, affecting central norepinephrine (NE), serotonin (5-HT) and dopamine (DA) activity. In particular, IL-1 enhanced NE turnover in the hypothalamus and hippocampus, 5-HT turnover in the hippocampus and prefrontal cortex (owing to increased utilization and reduced content of the transmitters in these brain regions), and enhanced DA utilization in the prefrontal cortex. IL-6 increased 5-HT and DA activity in the hippocampus and prefrontal cortex in a manner similar to IL-1, but failed to affect central NE activity. Moreover, IL-2 increased hypothalamic NE turnover (reflecting a profound increase in NE utilization) and enhanced DA turnover in the prefrontal cortex, but did not influence central 5-HT activity. Hence, these cytokines differentially altered neurochemical activity in brain regions that mediate neuroimmune interactions and that are influenced by physical and psychological stressors. In addition to the neurochemical changes, plasma corticosterone concentrations were profoundly enhanced in IL-1-treated animals, but not significantly altered by IL-2 or IL-6 treatment. The IL-1-induced corticosterone elevations did not significantly correlate with alterations of hypothalamic NE activity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Short report: the effect of misoprostol on the anaemia of NSAID enteropathy.

BACKGROUND: Small bowel ulceration is an increasingly recognised complication of therapy with non-steroidal anti-inflammatory drugs (NSAID). The ulceration is a potent site of blood loss contributing to unexplained iron deficiency anaemia in patients with arthritis. No drug is currently available to treat NSAID small bowel ulcers. METHODS: We have retrospectively examined the effect of therapy with the prostaglandin E1 analogue misoprostol on the anaemia of patients with enteroscopically proven NSAID small bowel enteropathy. RESULTS: All of the patients had proven iron deficiency anaemia. Eleven patients received misoprostol and ten received no treatment. Haemoglobin in the misoprostol-treated group rose significantly from median (range) 9.1 (6.2-10.6) g/dL (95% confidence intervals 8.76, 10.13) to 10.6 (6.5-16.8) g/dL (95% confidence intervals 10.06, 11.82); P = 0.004). Those patients who did not receive misoprostol had no significant change in their haemoglobin: 9.1 (7.5-10.6) g/dL to 8.1 (5.6-14.7) g/dL (P = N.S.). CONCLUSION: Misoprostol therapy was associated with an improvement in the anaemia in patients with proven NSAID enteropathy.

Adult↗
PubMed1994

Beta amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer's disease.

In a recent preliminary study it was reported that a severe head injury resulted in the deposition of beta amyloid protein (beta AP) in the cortical ribbon of 30% of patients who survived for less than two weeks. Multiple cortical areas have now been examined from 152 patients (age range 8 weeks-81 years) after a severe head injury with a survival time of between four hours and 2.5 years. This series was compared with a group of 44 neurologically normal controls (age range 51 to 80 years). Immunostaining with an antibody to beta AP confirmed the original findings that 30% of cases of head injury have beta AP deposits in one or more cortical areas. Increasing age seemed to accentuate the extent of beta AP deposition and potential correlations with other pathological changes associated with head injury were also investigated. In addition, beta amyloid precursor protein (beta APP) immunoreactivity was increased in the perikarya of neurons in the vicinity of beta AP deposits. The data from this study support proposals that increased expression of beta APP is part of an acute phase response to neuronal injury in the human brain, that extensive overexpression of beta APP can lead to deposition of beta AP and the initiation of an Alzheimer disease-type process within days, and that head injury may be an important aetiological factor in Alzheimer's disease.

Adolescent↗
PubMed1994

Analysis of human hematopoietic stem cell populations.

Purification of human hematopoietic stem cells (HSC) may be useful clinically for preparation of tumor-free grafts to be used for autologous transplantation and as targets for gene therapy. To analyze the phenotype of the human HSC, assays were used that measure the unique properties of stem cells, i.e., their long-term repopulating ability and their multilineage potential. These assays include: (1) an in vitro long-term hematopoietic culture system, using the murine bone marrow stromal cell line SyS1, which supports both B lymphopoiesis and myelopoiesis; (2) fetal human bone grafts implanted in SCID-hu mice, in which maintenance of CD34+ cells and B and myeloid differentiative capacity of candidate stem cell populations may be measured; (3) fetal human thymus grafts in SCID-hu mice, which allow the analysis of in vivo T-cell potential of a candidate stem cell population. Stem cells in adult bone marrow (ABM) or cytokine-mobilized peripheral blood (MPB) are thought to express CD34 but lack expression of markers indicating lineage commitment. This CD34+ Lineage- (Lin-) subpopulation has been isolated by fluorescence-activated cell sorting and tested for activity in the assays described here. CD34+ Lin- cells from both ABM and MPB demonstrated long-term engraftment in the SCID-hu bone model. This CD34+ Lin- population can be subfractionated further using an antibody to Thy-1. The Thy-1+ subset of CD34+Lin- cells is enriched for both long-term culture-initiating cells (LTC-1C) and has the ability to engraft in vivo.

Animals↗
PubMed1994

Interleukin-2-induced enhancement of an antigen-specific IgM plaque-forming cell response is mediated by the sympathetic nervous system.

Interleukin (IL)-2, a lymphokine produced by activated T-cells, stimulates T-cell proliferation and differentiation and potentiates B-cell production of antigen-specific immunoglobulins. IL-2 also increases hypothalamic norepinephrine turnover without affecting plasma corticosterone levels, which suggests that it selectively impacts on central sites that mediate sympathetic outflow to lymphoid organs. Because sympathetic stimulation during the early phases of an immunoglobulin (Ig)M plaque-forming cell (PFC) response to sheep red blood cells results in an increase in the subsequent number of antibody-forming cells, we assessed whether the enhancing effects of IL-2 on the PFC response are mediated by the sympathetic nervous system. The peak splenic IgM PFC response was increased in male Sprague-Dawley rats and BALB/c mice administered recombinant human IL-2 (50, 100 or 200 ng i.p.) in close temporal congruity with sheep red blood cell administration (i.e., 1 day before or immediately before immunization), compared with vehicle-treated controls. IL-2 administered at a later interval after immunization (i.e., 2 days) did not increase the number of antibody-forming cells. Intact sympathetic innervation of the spleen was required for the IL-2-induced immunoenhancement to occur because cutting the splenic nerve 10 days prior to IL-2 administration blocked the lymphokine's potentiation of the IgM PFC response. The immunostimulatory effects of IL-2 were also blocked in mice administered the beta adrenergic antagonist propranolol (5 mg/kg) immediately and 1 day after IL-2 administration. The alpha adrenergic antagonist phentolamine (5 mg/kg) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Drug therapy during pregnancy and lactation.

This article reviews the altered physiology of pregnancy and its impact on drug pharmacokinetics together with the pharmacokinetics of drug transport across the placenta and into the breast milk. Also reviewed are the potential adverse effects of maternal drug therapy on the fetus and neonate and the difficulties in assessing the potential risks of therapy. Finally, these principles are applied in the discussion of a number of specific drugs frequently prescribed in the emergency department setting.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1993

Psychosocial factors associated with the early termination of breast-feeding.

The relation between a number of psychosocial factors and the early termination of breast-feeding was examined in two large independent samples of puerperal women. The findings were remarkably similar. In both cohorts there was a significant association with depressive disorder which in the great majority preceded the cessation of breast-feeding. Other factors of importance were low social class, being young and lower educational attainment.

Adult↗
PubMed1993

Specificity variants in monoclonal antibodies reactive with peptide epitopes of the ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum.

It has been suggested that repeat sequence antigens of Plasmodium falciparum may serve the parasite in immune evasion by modifying the host antibody response and impairing the development of protective immunity. According to this proposal networks of cross-reactive, repeat sequence malarial antigens have the ability to stimulate a high proportion of all somatically mutated B cells with altered antibody specificity, and thus to hinder the normal process of antibody affinity maturation. To determine the rate at which immunoglobulin mutations produce new reactivities with repeat sequence antigens, hybridoma cell lines specific for the ring-infected erythrocyte surface antigen (RESA) were examined for the incidence of specificity variants that arose naturally or as a result of treatment with the chemical mutagen ethylmethane sulphonate (EMS). From one of the cell lines variants were readily isolated having reactivity towards a very closely related repeat sequence epitope within the same RESA antigen. However, the other hybridoma/antigen combinations revealed no variants. In general, mutations giving rise to antibodies with altered specificity for related repetitive antigens were not readily induced and only limited support of the hypothesis was obtained.

Amino Acid Sequence↗