Quality in the NHS: real or illusionary change.
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Biomedical subjects
Publications and source records attributed to N Harris.
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Alcohol (ethanol) and cocaine preference in a free-choice, two-bottle situation was measured in two groups of male and female "low" and "high" plasma catecholamine stress responding rats. Alcohol intake of a 5% solution (percent or mg/kg) showed markedly different but individually consistent intake among animals. "High" plasma catecholamine stress responders consumed more ethanol than did "low" responders. A similar finding was made when animals consumed a 10% solution; fluid intake fell but total ethanol intake remained the same. "High" responders drank more than did "low" responders. After a period of 4 weeks of water only, animals were reexposed to 5% ethanol and a significant positive correlation was seen in the drinking habits of the animals. Afterwards, exposure to a 0.02% cocaine solution resulted in cocaine intake which varied among animals, but was consistent for an individual rat and did not correlate with alcohol consumption. In general, ethanol and cocaine consumption correlated positively with the plasma catecholamine stress response. No significant differences in drinking habits were observed between the sexes. Thus, alcohol preference is a relatively stable characteristic of an animal, is higher in "high" as compared to "low" plasma catecholamine stress responders and does not correlate with voluntary cocaine consumption.
Crohn's disease is a chronic inflammatory disorder for which an immunologic etiology has been proposed. Food hypersensitivity may contribute to part of the pathogenesis of this disorder. In preliminary studies, we evaluated 11 Crohn's patients by history, skin testing (ST), total and specific(s) IgE and sIgE/sIgG4 levels to five food proteins [egg (E), milk (M), wheat (W), soy (S), and corn (C)] using a sensitive enzyme monoclonal antibody assay. Skin testing was also performed using grass and mold allergens. Lymphocyte concanavalin (Con A) mitogenic and antigenic responses to food proteins were also determined by tritiated thymidine incorporation. Mean sIgG4 values for four food proteins are listed below: (Table: see text). No patient reacted with elevated sIgE or sIgG4 to corn. All patients had low to negative sIgE levels to all foods and only three had increased total IgE. Three of eight were history and ST positive to M, E, and W. Six of eight had at least one positive ST to M, E, W, and S. All patients had negative sIgG4 to tested inhalants and two had elevated sIgE to grass pollen. Although mean lymphocyte Con A mitogenesis was significantly decreased in eight patients compared with controls (P less than .05), an increased food stimulatory response to milk protein was observed (P less than .05). Perhaps, decreased sIgE and cell-mediated mitogenic responsiveness may lead to an enhanced humoral IgG response. The increased sIgG4 humoral response to egg protein and cellular sensitivity to milk protein may indicate mucosal antigenic stimulation or leakage in patients with Crohn's disease in spite of negative sIgE levels.
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Thrombotic microangiopathy (TM) occurred 14 to 27 months after last chemotherapy in two patients with diffuse large cell lymphoma and in one patient with Hodgkin's disease. Death from TM occurred in two patients who had no evidence of lymphoma at postmortem examination, and the lone survivor's disease is in complete clinical remission. All three patients had prominent arthritis. Occurrence of TM in non-Hodgkin's lymphoma has not previously been reported: its cause is uncertain; it may be to a late sequela of successful lymphoma chemotherapy.
Long-term hemopoiesis in culture depends upon the presence of an adherent layer composed of a variety of stromal cells. A subtype of endothelial-adipocytes from the bone marrow stroma (clone 14F1.1) was previously shown to induce long-term myelopoiesis and renewal of pluripotent stem cells. One of a series of stromal cell lines and clones from mouse thymus stroma (STAC-1.2) has now been found to support long-term hemopoiesis. These marrow- and thymus-derived stromal cell clones also have lymphopoietic activities: precursor T cells, or pre-B cells accumulated in co-cultures of thymus cells and the stromal clones, as indicated by cell surface markers, T cell receptor and immunoglobulin gene rearrangements. The predominance of a cell type in these cultures depended upon the serum used to supplement the medium. Recombinant interleukin 2 (IL-2) and the 14F1.1 clone synergistically promoted the proliferation of thymocytes, while a thymus hormone, THF-gamma 2, shifted the population to a relatively mature phenotype. It is proposed that one major function of stromal cells, whether from the bone marrow or thymus, is to restrain the maturation flow and preferentially support the accumulation of cells at early differentiation stages.
The cell surface antigenic phenotype of 18 cases of central nervous system (CNS) large-cell lymphoma (14 primary, four secondary) was examined by an immunoperoxidase technique using antibodies that identify B cell restricted and associated antigens. All cases were shown to be of B cell origin by virtue of the expression of monotypic immunoglobulin (Ig) (16 IgM, two IgG) and the pan B cell antigen B1 (CD20). A panel of monoclonal antibodies directed against B cell restricted and associated activation antigens including B5, Blast-1, Blast-2 (CD23), BB1, interleukin 2 receptor (IL2R, CD25), T9 (transferrin receptor) and TNK-TAR (4F2) was used on 12 of the cases. The majority expressed T9 and TNK-TAR. Blast-1 was expressed by less than half the cases and Blast-2 and B5 by one of 12 cases each. This is in contrast to 10 non-CNS diffuse large cell lymphomas where B5 and Blast-1 were present on all cases. This study confirms previous observations that primary CNS large cell lymphomas are of B cell derivation. Moreover, the differences in expression of B cell activation antigens on CNS large cell lymphomas as compared to non-CNS lymphomas raise the possibility that a subset of neoplastic B cells may have unique tropism for the CNS.
The same male and female rats with indwelling jugular catheters were stressed (immobilization) on two occasions at the ages of 3 to 4 and 15 to 16 months. Plasma levels of the catecholamines (CA) norepinephrine (NE) and epinephrine (E) were determined before and during stress at each session. During stress, plasma NE and E levels increased markedly. At the younger age, female animals showed markedly higher CA levels than male animals. After one year, stress CA levels were higher for both sexes, but had increased markedly in male and little in female animals. A positive correlation was found between the plasma CA stress response of individual animals at both sessions; this correlation was stronger for males and NE. This indicates that "high" responders usually remain high responders, "low" responders remain low and intermediate responders intermediate. In conclusion, the plasma CA stress response increases markedly in male, but little in female rats over the period of 1 year and the relative magnitude of the individual stress response remains a characteristic of each given animal.
The influence of buspirone upon plasma catecholamine levels, heart rate, and mean arterial blood pressure was studied in stressed and nonstressed rats. Measures were obtained directly via indwelling aortic catheters. Drug or vehicle were given acutely (10 mg/kg, IP) or twice a day for 10 days (10 mg and 20 mg/kg, SC). In nonstressed rats, a single dose of buspirone increased markedly plasma norepinephrine and epinephrine levels and decreased significantly heart rate with no effect on blood pressure. During stress, stress-induced increases in catecholamine levels were further elevated by the drug, whereas stress-induced increases of heart rate and mean arterial blood pressure were reduced. In chronically-pretreated rats, the effects of buspirone were similar to those observed after an acute injection. These effects of buspirone on plasma catecholamines are very different from those seen with other anxiolytics, whereas effects on heart rate and blood pressure are more similar.
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"The paper presents a discussion of the economic justification for taking cities seriously, a section outlining the scale of urbanisation and some of the issues raised, a section that discusses the policy approaches, one that looks at the local agencies for the formulation and execution of policy, and a short final part on some of the implications for aid policy." The focus is on the importance of the urban sector for economic development in developing countries.
This case represents the first known instance of reversal of Addison's disease after antineoplastic therapy. Malignant infiltration of the adrenal glands was demonstrated by cytologic findings of needle biopsy in a 57-year-old man suffering from disseminated large cell lymphoma and Addison's disease. He was treated with combination chemotherapy and adrenal hormone replacement. Improvement shown in his computed tomography (CT) scan and clinical status led to the successful discontinuance of cortisone and 9-alpha fluorohydrocortisone. Basal adrenal function and response to ACTH stimulation recovered.
A factor analysis of the Adolescent Reinforcement Survey Schedule (ARSS) with a male and female college freshman (N = 231) population yielded 10 interpretable factors: Heterosexual Dating, Peer Interaction, Sibling/Family Interaction, Sexual Pleasure, Anti-School/Work, Leisure/Work Activity, Drugs/Acting Out, Entertainment/Social Activity, Home Avoidance, and Romantic Fantasy Activity. The first three factors are similar to a Positive Social interaction factor identified in a study that used the adult form of the Reinforcement Survey Schedule with a male and female college population. Suggestions are made from the ARSS responses of the college freshmen re interventions to facilitate social skill competency and the relationship aspects of sexual activity. A recommendation is made to replicate the current study with groups of early and mid-adolescents in order to study reinforces during different periods of adolescent development.
Anticardiolipin antibodies (aCL) were measured in the serum of 22 patients with systemic lupus erythematosus (SLE) and 101 of their first degree relatives. Four patients' sera (18%) were positive. Eight sera from relatives were strongly positive (7.9%). All 8 relatives came from different families, and only 3 of them were related to a positive positive proband. All 8 had clinical and/or other serological abnormalities, compared with only 30% of the aCL negative relatives (p less than 0.05). There were no reports or evidence of thrombosis, thrombocytopenia or spontaneous abortion among the aCL positive relatives. Our data indicate a strikingly higher incidence of aCL among relatives of lupus patients compared with controls. This may be associated with an increased incidence of abnormal clinical or serological findings in these individuals, and constitute a feature of a genetic predisposition to SLE.
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The human p53 tumor antigen comprises several physically distinct proteins. Two p53 proteins, separable by polyacrylamide gel electrophoresis, are expressed by the human transformed cell line SV-80. The individual cDNAs which code for these proteins were isolated and constructed into the SP6 transcription vector. The proteins encoded by these clones were identified by in vitro transcription with the SP6 vector and translation in a cell-free system. p53-H-1 and p53-H-19 cDNA clones code for the faster- and slower-migrating p53 protein species, respectively, of SV-80. The in vitro-expressed proteins of p53-H-1 and p53-H-19 had the same antigenic determinants and were structurally indistinguishable from their in vivo counterparts. By expressing defined restricted cDNA fragments in vitro, the region of heterogeneity between the respective cDNAs was located at the 5' end of the cDNAs. Exchanging the 5' fragments of interest and expressing the chimeric clones in vitro confirmed that the DNA heterogeneity was responsible for the difference in the electrophoretic mobility of these proteins. The sequences of the two cDNAs revealed a single base pair difference (G versus C) in the coding region of the clones. This sequence difference resulted in an arginine being coded for in clone p53-H-1 and a proline being coded for at the equivalent position in clone p53-H-19. This variation accounted for the change in the electrophoretic mobility of the individual p53 protein species.