Biomedical subjects
P Davis
Publications and source records attributed to P Davis.
A fortunate inquest: the report of the cervical cancer inquiry.
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Alpha-melanocyte stimulating hormone inhibits the contractile action of a mu opioid agonist in the isolated colon of the rat.
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Sarcoidosis of the small intestine.
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Immunoresponsiveness in ulcerative colitis and Crohn's disease--effect of colectomy and suppression of disease activity.
We evaluated the effect of medically induced symptomatic disease improvement on in vitro tests of cell-mediated immune responses in 33 patients with Crohn's disease. When results obtained in 17 patients with ulcerative colitis were compared with those of 10 patients with ulcerative colitis who had undergone a colectomy, no significant correlation was detected between individual clinical and laboratory variables or the Crohn's disease activity index and in vitro tests of cell-mediated immunity. A different pattern emerged from the longitudinal tests of cell-mediated immunity: when these test results were initially abnormal in patients with Crohn's disease, clinical improvement as assessed by the Crohn's disease activity index was associated with normalizing cell-mediated immunity. In contrast, when the test results were initially normal, clinical improvement was not associated with any change in the immune response. Following colectomy in patients with ulcerative colitis, some abnormalities of suppressed immune responses remained, although patients were cured of their disease. Factors other than clinical disease activity may be responsible for the suppressed immunoresponsiveness in some patients with inflammatory bowel disease, and variable changes in cell-mediated immunity occur after both surgical and medical treatment.
Properties of coronavirus IBV after removal of the S1 subunit of the spike glycoprotein.
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Gold compounds alter distribution of protein kinase C activity in human neutrophils.
Slow translocation of protein kinase C was observed by both auranofin and gold sodium thiomalate pretreatment of neutrophils. Both gold compounds failed to influence the activity of this enzyme directly when cell-free studies were performed. In intact neutrophils incubated with 5.1-20.3 microM auranofin, protein kinase C activity decreased in the cytosol in a time- and dose-dependent manner. Concomitantly, the levels of the membrane-associated protein kinase C were significantly elevated, although the amount of activity recovered could not account for that lost from the cytosol. Gold sodium thiomalate (5.0 microM-0.505 mM) demonstrated similar effects but with lesser potency than auranofin. In confirmation of previous results, phorbol myristate acetate (PMA), a cellular stimulus, also induced the translocation of protein kinase C. Key differences were that the reaction was rapid (occurring within minutes after PMA addition) and that relative recovery of kinase activity from the particulate fraction was fourfold greater. The relationship between gold compound-mediated kinase C redistribution and inhibition of neutrophil responses remains to be elucidated.
Depressed superoxide radical generation by neutrophils from patients with rheumatoid arthritis and neutropenia: correlation with neutrophil reactive IgG.
Neutrophils of 31 patients with neutropenia and rheumatoid arthritis (RA) have been studied to assess their ability to generate superoxide radicals (O-2) on activation. Seventeen patients had classical Felty's syndrome and 14 presumed chrysotherapy related neutropenia. Results were compared with those from age and sex matched controls with uncomplicated RA and from normal subjects. Neutrophils from patients with Felty's syndrome had a significantly reduced ability to generate superoxide radicals when compared with the other three groups. In addition, serum levels of IgG polymorphonuclear leucocyte binding activity (IgG PBA) were also raised in the group with Felty's syndrome. A statistically significant inverse correlation existed between O-2 generation and IgG PBA. It is concluded that neutrophil reactive IgG may have an important role in both quantitative and qualitative defects in neutrophil function in Felty's syndrome.
Suppression of superoxide generation by normal polymorphonuclear leukocytes preincubated in plasma from patients with Felty's syndrome.
Polymorphonuclear leukocytes (PMN) isolated from patients with Felty's syndrome (FS) generate fewer superoxide anions (O-2) upon stimulation with fmet-leu-phe than PMN from normal controls or patients with rheumatoid arthritis (RA). In this study, plasma samples were obtained from 12 patients with RA and 12 patients with FS. Incubation of normal PMN in plasma from Felty patients resulted in a significant reduction in both the rate and total quantity of O-2 generation when activated with fmet-leu-phe. This was not observed with plasma from RA patients. The capacity of a plasma sample to suppress O-2 generation correlated with plasma IgG-PMN-binding activity (IgG-PBA) and, to a lesser extent, with the content of circulating immune complexes (CIC). These data suggest that IgG-PBA and possibly CIC have a pathogenetic role in both qualitative and quantitative defects in PMN in Felty patients.
Comparison between sodium aurothiomalate and auranofin in rheumatoid arthritis. Results of a two-year open randomized study.
We compared the effectiveness of Auranofin, and sodium aurothiomalate (SATM) given for 2 years to patients with rheumatoid arthritis. This was an open trial with randomized entry to 2 treatment groups of 60 patients each. Only 40% of patients completed 2 years of treatment but these showed significant improvement in their indices of disease activity. Adverse reactions were a more common reason for withdrawal from SATM than from Auranofin, while insufficient therapeutic response was more common with Auranofin. This study also shows that inefficacy, toxicity, complicating illnesses, and lack of compliance limit the beneficial outcome of long-term chrysotherapy.
Reversal of depressed neutrophil superoxide production in Felty's syndrome after gold therapy.
Six patients with Felty's syndrome were reevaluated after a course of chrysotherapy. In 5 patients, white cells and absolute neutrophil counts had returned to normal. In 4 of these, there was significant concomitant improvement in neutrophil function as assessed by the ability of cells to generate superoxide radicals.
Immunosuppression as initial treatment for gold induced aplastic anemia.
Three patients who received antithymocyte globulin therapy for severe aplastic anemia due to gold therapy are described. In 2 patients the hemoglobin, white blood cell count and neutrophils were normal and platelet counts exceeded 100 X 10(9)/1 more than 2 years after treatment. The 3rd patient did not respond to antithymocyte globulin or to cyclosporine therapy; subsequent allogeneic bone marrow transplantation resulted in satisfactory engraftment at 12 months. In all 3 patients the arthritis was improved after the episode of marrow aplasia and its treatment. Including these 3 patients, 12 reported patients with severe aplastic anemia due to gold have now been treated with antithymocyte globulin; 8 have shown significant improvement. These results are better than those reported for any other treatment. Antithymocyte globulin may be optimal initial treatment for this serious disorder.
Content of a preceptorship experience: effects of location, gender, and specialty choice.
Ambulatory care experiences for 37 medical students during six consecutive three-week preceptorships in family practice were assessed using student logbooks and end-of-preceptorship feedback forms. Comparisons were made by site of preceptorship (university or nonuniversity), by gender of medical student, and by the students' subsequent specialty choices. Rank orders of diagnoses using a Spearman's rho comparison of ranks were significantly correlated with national data as were most student-to-group comparisons. Students tended to see more patients of their own age group, and female students tended to see more female patients of child bearing age. Students with preceptors in the university setting saw patients who were older than those patients seen by students in nonuniversity preceptorship settings. Students in the university setting also saw fewer patients and performed fewer procedures during the three week preceptorship but had a higher level of participation in patient care. Females reported a lower level of participation in patient care than male students, and students who subsequently went into family practice residencies reported a higher level of participation than those students who entered other specialties.
A case of drug induced lupus due to carbamazepine.
We report a case of drug induced lupus related to carbamazepine. Both clinical and serological data are described. This represents the first documented case of carbamazepine induced lupus erythematosus in the literature with serological confirmation.
Therapeutic options in the selection of nonsteroidal, antiinflammatory drugs in the treatment of osteoarthritis: a review.
The size of the consumer market has resulted in an increasing number of antiinflammatory drugs available on prescription for osteoarthritis. Despite the development of newer chemical compounds, similarities in pharmacologic properties, efficacy in clinical trials, and toxicity profiles do not support a claim that any one drug is consistently better than another. Differences in pharmacokinetic profiles and formulations do allow for considerable flexibility in clinical therapeutics. Variabilities in drug action, effects on other organ systems, and drug interactions, particularly in the elderly, must always be considered when prescribing an individual medication. However, variability in patient response to individual drugs (both clinical benefit and toxicity) and the size of the clinical problem largely justify the number of nonsteroidal antiinflammatory drugs available.
HLA-DR antigens in gold-induced neutropenia.
We studied the clinical courses of 9 patients who developed acute gold-induced neutropenia with marrow aplasia. Eight of these carried HLA-DR4, compared with only 2 of 9 who had mild, chronic, isolated neutropenia (P less than 0.05). Only 1 of 9 patients with myelotoxicity carried HLA-DR3. We conclude that these groups are immunogenetically distinct, and that HLA-DR3 is not a significant risk factor for severe gold-induced neutropenia.
Effect of gold compounds on NADPH oxidase system of human neutrophils.
The inhibitory effects of gold compounds on the NADPH oxidase system of human polymorphonuclear leukocytes (PMNs) has been investigated. Auranofin (0.5-4.0 micrograms Au/ml) suppressed the rate of superoxide anion generation as well as the total yield in cells stimulated with phorbol myristate acetate and f-Met-Leu-Phe. This implies that drug action may be occurring at the level of protein kinase C or steps subsequent to this in the signal transduction sequence. Sodium aurothiomalate (1-100 micrograms Au/ml) lacked such activity. Neither gold compound altered the ability of the granule-rich fraction of PMNs to produce oxy radicals whether this fraction was obtained from drug-treated cells or was treated after its isolation. Therefore, in order for auranofin to exhibit its inhibitory effects on the NADPH oxidase system, an intact cell membrane is necessary.
Effects of gold compounds on function of phagocytic cells. Comparative inhibition of activated polymorphonuclear leukocytes and monocytes from rheumatoid arthritis and control subjects.
The effect of sodium aurothiomalate and auranofin on the generation of superoxide anions (O2-) by polymorphonuclear leukocytes (PMNLs) and adherent mononuclear phagocytic cells (AMNCs) has been investigated. Sodium aurothiomalate at final concentrations of 1, 10, and 100 micrograms Au/ml and auranofin ranging from 0.1 to 2.0 micrograms Au/ml were used in the reactions involving all cell types. Results have been compared between cells drawn from normal controls and patients with active rheumatoid disease. The effect of gold compounds on both cell types was assessed following activation by phorbol myristate acetate (1 X 10(-8) M) and N-formyl-methionyl-leucyl-phenylalanine (1 X 10(-4) M) using a cytochrome c reduction method. Sodium aurothiomalate at the maximum concentration modestly inhibited O2- generation by PMNLs but not AMNCs. Auranofin inhibits O2- generation by both cell types. Inhibition of cells from patients with rheumatoid arthritis was greater than that seen with cells from normal controls.