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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 397 records · Page 22Linked to original sources

Trial of repeated low-dose aspirin in diabetic angiopathy.

We compared the ability of aspirin to suppress platelet aggregation and thromboxane synthesis in ten normal subjects and ten patients with diabetic angiopathy and high rate of entry of new platelets into the circulation. When single doses of 100 to 1,000 mg aspirin were ingested daily for 1 month, there were time gaps between doses in which platelets from diabetics and normals aggregated and formed thromboxane ex vivo in response to the combination of arachidonic acid plus collagen. Similar gaps were also found for diabetics, but not for normals, following four daily doses (every six hours) of 25 or 100 mg. Our data show that dose schedules of aspirin which may suffice in normals are not effective in patients with diabetic angiopathy, presumably because these patients have a high rate of entry of new platelets into the circulation. We suggest that continual suppression of platelet thromboxane synthesis and aggregation by low-dose, "slow-release" preparations of aspirin would be an ideal long-term approach for the prevention of thrombosis in patients with a high rate of entry of new platelets into the circulation.

Adenosine Triphosphate↗

Platelet storage for transfusion.

An overview is given about the different variables which are of influence during platelet storage. After reinfusion of 51Cr-labeled platelets of PRP stored in first generation containers and evaluation of in vivo recovery and half life optimum, range of storage temperature was found to be 20-24 degrees C. Storage of PC in first generation containers showed a significant fall of pH which was in a clear relationship to platelet concentration, lactate production, and glucose consumption. If pH fell below 6.0 irreversible morphological changes and decrease of in vivo recovery/survival was observed. The second generation containers (PL-732, CLX, PL-1240) resulted in superior pH maintenance which was due to superior O2 and CO2 transport through the walls of the bags and a lower rate of glycolysis. In vivo recovery showed a gradual decline from 57% for fresh platelets to 42% after 7-day-storage. Platelet survival curves after 7-day-storage lay just at the lower limit of the range for fresh platelets. The success of prolonged storage depends critically on the mode of agitation used which was demonstrated by comparing three different agitators. A lot of questions remain still to be answered concerning the substrates of the oxidative metabolism, the morphological changes, and especially the in vitro function of platelets after prolonged storage.

Adenosine Triphosphate↗

Eicosanoid synthesis and release from primary cultures of rat central nervous system astrocytes and meningeal cells.

Primary cultures of astrocytes and meningeal cells derived from neonatal rat brain synthesize and release thromboxane A2 and prostacyclin, respectively. Exogenously supplied arachidonic acid and the calcium ionophore, A23187, promote the release of eicosanoids; these effects are blocked by indomethacin and the calcium chelator, ethyleneglycoltetraacetic acid. The finding that astrocytes synthesize and release thromboxane A2 is discussed in the light of our recent findings of receptor-linked membrane phospholipid turnover in these cells.

Animals↗

Astrocyte opioid receptors: activation modifies the noradrenaline-evoked increase in 2-[14C]deoxyglucose incorporation into glycogen.

Astrocyte-enriched cultures of the newborn rat cortex accumulated 2-[14C]deoxyglucose (2-DG), a proportion portion of which was incorporated into glycogen. Exposure to exogenous noradrenaline resulted in an increase (30%) in the incorporation of 2-[14C]DG into glycogen in these cultures. The extent to which noradrenaline evoked an increase in 2-[14C]DG labelling of glycogen was modified by both morphine and methionine-enkephalin. Whereas morphine augmented the noradrenaline-induced increase in 2-[14C]DG incorporation into glycogen in these cultures, methionine-enkephalin attenuated this response.

Animals↗

Platelet dysfunction in uremia. Multifaceted defect partially corrected by dialysis.

In an attempt to elucidate the nature of the bleeding tendency in uremia, some in vitro functions of platelets from eight patients undergoing long-term hemodialysis were studied. None of the patients had diabetes. All had bleeding times longer than eight minutes. Threshold aggregating concentrations for collagen, adenosine diphosphate, and epinephrine, when used singly or in pairs, were two to three times higher than normal in platelet-rich plasmas from these patients. In contrast, those for arachidonic acid and U-46619, a cyclic endoperoxide/thromboxane A2 analogue, were within the normal ranges. Thromboxane B2 formation was normal in response to arachidonic acid (0.2 to 1 mM), whereas it was decreased by 30 to 50 percent in response to thrombin (0.5 to 10 units/ml), collagen (0.5 to 10 micrograms/ml), and the combination of collagen with adenosine diphosphate or epinephrine. There was a partial (about 35 percent) reduction of the platelet granular content of adenosine diphosphate. Secretion of adenosine triphosphate by 5 units/ml of thrombin was 25 to 50 percent less than in normal subjects. Thus, there was a storage pool defect as well. Similar but less severe defects were found in platelets from uremic patients who had never undergone hemodialysis. Partial correction of aggregation and thromboxane B2 formation was seen after dialysis, although platelet adenosine diphosphate content did not increase. It is concluded that the platelet dysfunction in uremia is multifaceted. There appears to be an aggregation and secretion defect related to impaired arachidonic acid release from platelet phospholipids as well as a storage pool defect. The first is improved with dialysis; the second is not.

Adenosine Diphosphate↗

Prenatal prediction of child abuse and neglect: a prospective study.

Five hundred eighty-seven women in a combined Maternity-Infant, Children and Youth project were interviewed at between 3 and 6 months of gestation by a skilled masters degree social worker (M.S.W.) using a Family Stress Checklist developed at the University of Colorado Health Sciences Center. Only 7% of the women were scored as "high risk" for serious parenting problems. Neither single status nor teenage status increased the risk significantly. A review of charts of 100 of the children whose mothers had been considered "at risk" was conducted 2 to 2.5 years later, and compared with 100 charts on children whose mothers had been considered at "no risk," giving the following results: Twenty-five children had experienced failure to thrive, neglect or abuse. Twenty of these were from the original high risk mothers, giving an incidence of neglect/abuse in that group of 52%. The no risk control group of 100 mothers showed a 2% incidence of abuse/neglect; a low risk group showed a 4% incidence of abuse/neglect; and a mid-score group had an abuse/neglect rate of 5%. The scale proved a remarkably accurate predictor, with a sensitivity (percent correct negatives) of 89%. The authors suggest use of such scales prenatally or even before conception as a step toward the development of true preventive measures.

Adolescent↗

Glycoprotein composition and turnover in subcellular fractions from the cerebral cortex of normal and reeler mutant mice.

Twenty-day-old reeler and normal mice were either injected intraventricularly with radiolabelled fucose before subcellular fractionation of the cerebral cortex followed by SDS-PAGE, or gels of such fractions were overlaid with [125I]concanavalin A (ConA). While there were no differences in polypeptide profiles of normal and reeler subcellular fractions there were marked differences in the abundance of particular ConA-binding glycoproteins and in fucose incorporation into particular glycoproteins, especially in the synaptic plasma membrane (SPM) and 100,000 g soluble fractions. In addition there was a significantly lower binding (greater than 50%) of quinuclidinyl benzilate to reeler microsomal and SPM fractions as compared with normal. The differences in glycoprotein expression may be pertinent to anatomical observations of abnormal interactions between neurons and glial fibres during development of the reeler cerebrum.

Animals↗

Microbiology of chronic otitis media with effusion among Australian Aboriginal children: role of Chlamydia trachomatis.

Serum, eye secretions, post-nasal swabs, external ear swabs and middle ear effusions (MEE) were collected from 131 Australian Aboriginal children with chronic otitis media with effusion (COME). The children were all resident in a trachoma endemic region. Chlamydia trachomatis was recovered from the MEE of 2 children. Probable bacterial pathogens were isolated from 34 (12.7%) ears. The remainder were sterile (52.4%) or contained normal skin flora (34.9%). Serum and secretions were examined by the microimmunofluorescent technique for the presence, titre and serotype of anti-chlamydial antibody. Antibody, predominantly of the C serotype, was found in a high percentage of sera (80%) and secretions (approximately 50%). This serotype is associated with ocular trachoma. It is concluded that C. trachomatis is associated with COME among some Aboriginal children in this trachoma endemic area.

Adolescent↗

Activation of muscarinic and of alpha 1-adrenergic receptors on astrocytes results in the accumulation of inositol phosphates.

Astrocyte-enriched cultures prepared from the newborn rat cortex incorporated [3H]myo-inositol into intracellular free inositol and inositol lipid pools. Noradrenaline and carbachol stimulated the turnover of these pools resulting in an increased accumulation of intracellular [3H]inositol phosphates. The effects of noradrenaline and carbachol were dose-dependent and blocked by specific alpha 1-adrenergic and muscarinic cholinergic receptor antagonists, respectively. The increase in [3H]inositol phosphate accumulation caused by these receptor antagonists was virtually unchanged when cultures were incubated in Ca2+-free medium, but was abolished when EGTA was also present in the Ca2+-free medium. Cultures of meningeal fibroblasts, the major cell type contaminating the astrocyte cultures, also accumulated [3H]myo-inositol, but no increased accumulation of [3H]inositol phosphates was found in response to either noradrenaline or carbachol.

Animals↗

Evidence for the involvement of B lymphoid cells in polycythemia vera and essential thrombocythemia.

Previous studies with the X-chromosome-linked glucose-6-phosphate dehydrogenase (G6PD) as a marker of cellular mosaicism demonstrated that polycythemia vera (PV) and essential thrombocythemia (ET) are clonal disorders of hematopoietic stem cells that can differentiate to erythrocytes, granulocytes, and platelets. To determine if the involved stem cells could also differentiate along the B-lymphoid pathway, we studied one woman with PV and one woman with ET. Of 117 Epstein-Barr virus-transformed B-lymphoblastoid lines expressing a single G6PD derived from the patient with PV, 108 expressed G6PD type A, the type characteristic of the abnormal clone. The ratio of 108:9 was significantly different from the one to one ratio predicted for this patient, which suggested that at least some circulating progenitors for B-lymphoid cell lines differentiate from the stem cell involved by the disease. Results obtained from the patient with ET were similar--104 of the 109 lymphoblastoid lines monotypic for G6PD expression displayed the enzyme type found in the abnormal clone of marrow cells. Therefore, in these patients, PV and ET, like chronic myelogenous leukemia, involve a stem cell pluripotent for the lymphoid as well as the myeloid series.

Adult↗

Cystic fibrosis in Pueblo Indian children.

Three Pueblo American Indian children with cystic fibrosis are described. The three cases constitute a higher incidence of cystic fibrosis in Pueblo Indians than would be expected from the known rarity of this disease in American Indian populations. This report discusses the possible genetic implications and emphasizes the need to consider the diagnosis of cystic fibrosis in American Indians with appropriate symptoms.

Child↗

Coagulopathy induced by continuous infusion of high doses of human lymphoblastoid interferon.

Seven patients with myeloblastic leukemia were treated for 10 days with high-dose (15 or 30 million units/m2/day), human lymphoblastoid interferon (Wellferon) by continuous iv infusion. All patients developed prolonged activated partial thromboplastin time, and four developed prolonged prothrombin time. Factor assays demonstrated low levels of II, VII, IX, X, and XII. Coagulation abnormalities improved after discontinuation of interferon therapy.

Adolescent↗

Platelet kinetics in patients with idiopathic thrombocytopenic purpura and moderate thrombocytopenia.

We studied ten normal subjects and 20 patients with stable, untreated idiopathic thrombocytopenic purpura (ITP) and platelet counts in the range of 35,000 to 110,000/microL. The diagnosis was made by clinical criteria. Platelet-associated IgG was increased in all nine of the nine patients studied. Autologous platelets were labeled with chromium 51 and reinfused for measurement of mean cell life and platelet production rate. Mean cell life was calculated by two methods, weighted mean and multiple hit, with excellent agreement between the two. As expected, mean cell life was significantly reduced in ITP patients as compared to the normal subjects (2.9 days v. 8.0 days, P less than .001). However, mean platelet production rates in ITP patients and normal subjects, 3.5 and 3.8 X 10(9) platelets/k/d respectively, were not significantly different. Platelet production rate was above and below the normal range (2 to 5.6 X 10(9) platelets/k/d) in two and four patients, respectively. We conclude that the rate of platelet production is not increased in most patients with ITP who have platelet counts greater than 35,000/microL. We did find that platelet size was increased in eight of the 12 patients in whom it was measured, including two of the patients with low platelet production.

Adolescent↗