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Biomedical subjects

C Saunders

Publications and source records attributed to C Saunders.

At least 73 records · Page 4Linked to original sources

Cyclosporin in juvenile dermatomyositis.

Juvenile dermatomyositis in fourteen children who had not responded fully to steroids and other immunosuppressants and who had had chronic active disease for an average of 3 years was successfully treated with cyclosporin. Twelve patients had serious complications of the disease or of previous treatment. The response to cyclosporin included recovery of muscle strength and function and resolution of complications. It was possible to stop steroids or to reduce the steroid dose, which had previously been difficult, in all fourteen patients. In general, a low dose of cyclosporin (2.5-7.5 mg/kg daily) was sufficient and no serious side-effects were seen.

Child↗

The effect of nicardipine, a calcium channel blocker, on the sweat test in adult patients with cystic fibrosis.

Impaired cell membrane chloride ion movement in cystic fibrosis results in reduced resorption of sodium and chloride from sweat gland ductules producing the high concentrations measured in the sweat as a diagnostic test. Normal chloride ion movement can be restored in vitro by blocking transepithelial calcium flux with lanthanum, suggesting a potential role for calcium channel blocking drugs in the management of cystic fibrosis. We studied the effect of nicardipine, a calcium channel blocker, on the sweat sodium in 17 adult patients with cystic fibrosis. Nicardipine was administered intravenously or topically using iontophoresis or occlusive dressing. No significant change in sweat sodium concentration was observed between pre- and post-drug administration. We conclude that nicardipine used in vivo does not exert the same effect as lanthanum demonstrates in vitro on transepithelial cell membrane chloride ion movement in cystic fibrosis.

Administration, Topical↗

Regulation of mesangial cell growth by polypeptide mitogens. Inhibitory role of transforming growth factor beta.

Proliferation of mesangial cells is a common histologic abnormality in glomerular diseases. In vivo studies suggest a role for platelets and monocytes-macrophages in mediating glomerular hypercellularity. The authors recently reported that several peptide growth factors stimulate DNA synthesis and growth of human mesangial cells. This article reports that transforming growth factor beta (TGF-beta), a peptide released by inflammatory cells and platelets, inhibits DNA synthesis and growth of human mesangial cells. The stimulatory and inhibitory effects of these mitogens on DNA synthesis and growth was confirmed by autoradiography and cell counting. The inhibitory effect of TGF-beta is not mediated at the receptor level because TGF-beta did not inhibit the binding of epidermal growth factor (EGF) or platelet-derived growth factor (PDGF) to mesangial cells. Because peptide growth factors that stimulate DNA synthesis in mesangial cells induce expression of PDGF mRNAs, the effect of TGF-beta on PDGF mRNAs expression induced by peptide growth factors was studied. TGF-beta did not lower the increased levels of PDGF mRNAs caused by EGF or PDGF. These data show that TGF-beta is a potent inhibitor of DNA synthesis and growth of mesangial cells. The mechanism of the inhibitory effect of TGF-beta remains to be determined.

Cell Division↗

Oral fluconazole as suppressive therapy of disseminated cryptococcosis in patients with acquired immunodeficiency syndrome.

PURPOSE: Because of the increasing numbers of patients with acquired immunodeficiency syndrome (AIDS) who will require treatment for cryptococcosis and because of the problems associated with long-term administration of intravenous amphotericin B, an alternative therapeutic approach in the form of an efficacious and easily administered oral antifungal drug would be of great benefit. Fluconazole, a new triazole antifungal agent, represents such an alternative. We therefore conducted an open, non-randomized trial of oral fluconazole as maintenance suppressive therapy of disseminated cryptococcosis in patients with AIDS. PATIENTS AND METHODS: Twenty patients with AIDS, 19 of whom had cryptococcal meningitis, were studied. Patients were followed for up to 21 months. All patients received amphotericin B as primary therapy, from 20 to 257 days prior to entry (500 to 5,080 mg total dose). Eight also received flucytosine. After administration of amphotericin B for acute disseminated cryptococcosis, and prior to initiation of fluconazole therapy, Cryptococcus neoformans was isolated from the cerebrospinal fluid (CSF) in two patients and from the blood in one patient. Fluconazole was given once daily, in doses of 50 to 200 mg/day. RESULTS: Following initiation of fluconazole, results of CSF and blood cultures continued to be negative, except for the CSF culture in one patient who had a relapse in the 32nd week of therapy. Fluconazole therapy has been successfully continued in nine patients, for a median of 11 months (nine to 21 months). Seven patients died; five had no evidence of active cryptococcosis at the time of death. Two patients had a relapse, although the CSF culture showed growth of the fungus in only one patient. One patient was lost to follow-up after five months of therapy and one was unevaluable. Fluconazole had to be discontinued in only one patient in whom thrombocytopenia developed, and then resolved when the drug was stopped. CONCLUSION: We conclude that oral fluconazole represents a significant advance in the management of cryptococcal meningitis and should be useful in the long-term suppressive therapy of this opportunistic infection in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Spiritual pain.

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Attention↗

Age differences in the rating of life-stress events: does contextual detail make a difference?

Twenty-four young (20 to 25 years) and 24 elderly (61 to 81 years) subjects rated the short-term (ST) and long-term (LT) threat of 36 life-events drawn from a community study of elderly people. Subjects were presented either with full contextual detail about the respondent and the event or with an edited version in which only a basic outline of the event was presented. Assignment of subjects to conditions was random. Agreement of subjects within and between groups as to what events were threatening was high and the untrained groups were also in close agreement with the consensus ratings of a trained panel. There were no significant main effects of age or contextual condition. It is concluded that the concept of the 'threat' of an event is generalizable over samples. Analysis of a significant age x context interaction showed that only young subjects rating LT threat were affected by contextual condition. Events supplied with context were rated by them as less threatening than those presented in outline. Some evidence was found to support the view that there may be age differences in the perceived impact of an event over time.

Adult↗

The philosophy of terminal cancer care.

Relief for the often complex suffering of far advanced disease is part of the therapeutic challenge of oncology. Effective practice has been shown to be possible in a variety of settings, including the patient's own home, but a limited number of special centres have been essential resources for research and teaching. Basic principles have been defined and are being interpreted in many situations and cultures. With the fundamental aim of enabling patients to live to the maximum potential in physical ability, relationships and personal choice, they include family support both before and after a patient's death. Symptom control must be the first essential, carried out by an experienced clinical team working together with its nursing and other professional members. Continuity of care will be made possible by co-operation with a Home Care Programme. Research and analysis will give an objective basis enabling such a team to meet the demands of the multi-disciplinary teaching that has been a major aim of the hospice movement. A search for meaning should be recognised in both patients and staff.

Home Nursing↗

Antihemophilic factor [factor VIII] preparations inhibit lymphocyte proliferation and production of interleukin-2.

To examine the role of antihemophilic factor (factor VIII) preparations in the pathogenesis of subclinical immunodeficiency in hemophilia, we tested the in vitro effects of these products on immune function. Both lyophilized antihemophilic factor (LAHF) and cryoprecipitates inhibited lymphocyte proliferation in a dose-dependent fashion. Further studies indicated that LAHF interfered with an early event in proliferation and also that prolonged incubation of human lymphocytes with LAHF resulted in an irreversible inhibition of lymphocyte proliferation without detectable cytotoxic effects. LAHF also inhibited the production of interleukin-2 (IL-2) by human lymphocytes and by Jurkat tumor cells, suggesting that inhibition of IL-2 production was not mediated through effects on interleukin-1. Gel filtration of LAHF revealed two peaks of inhibitory activity; one with mol wt greater than 2 X 10(6) comigrated with factor VIII coagulant activity and antigen, whereas another with mol wt approximately 6 X 10(5) was devoid of factor VIII activity and antigen. Further study will ascertain whether administration of factor VIII-containing preparations contributes to the subclinical immunodeficiency seen in patients with hemophilia or serves as a cofactor in the development of clinical immunodeficiency after exposure to the retrovirus human T-lymphotropic virus type III.

Acquired Immunodeficiency Syndrome↗

Mapping of the glucose dehydrogenase gene in Bacillus subtilis.

A 4.0-kilobase DNA fragment containing the developmentally regulated gene for glucose dehydrogenase (gdh) from Bacillus subtilis was incorporated into the plasmid pGX345, which contains a marker conferring chloramphenicol resistance (cat). The resistance marker of the resulting integration vector was used to map the gdh gene on the B. subtilis chromosome. Using PBS1 transduction, the gene order was determined to be aroI cat (gdh) mtlB dal. The cat (gdh) marker was also cotransformable with mtlB. The genetic location of the gdh gene established by this indirect method was confirmed by the fact that the original phage lambda EF2, containing a 10-kilobase B. subtilis DNA fragment from which the 4-kilobase gdh region had been subcloned, also contained the mtlB gene.

Bacillus subtilis↗

Living with dying.

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Attitude to Death↗

Ultrastructural organization of yeast chromatin.

The ultrastructural organization of yeast chromatin was examined in Miller spread preparations of samples prepared from spheroplasts or isolated nuclei of Saccharomyces cerevisiae. Micrographs from preparations dispersed in 1 mM Tris (pH 7.2) illustrate that the basic chromatin fiber in yeast exists in two ultrastructurally distinct conformations. The majority (up to 95%) of the chromatin displays a beaded nucleosomal organization, although adjacent nucleosomes are separated by internucleosomal linkers of variable lengths. Ribonucleoprotein (RNP) fibrils are only occasionally associated with chromatin displaying the conformation. The remaining 5-10% of the chromatin appears to be devoid of discrete nucleosomes and has a smooth contour with a fiber diameter of 30-40 A. Transcriptional units, including putative ribosomal precursor RNA genes, defined by the presence of nascent RNP fibrils are restricted to chromatin displaying this smooth morphology. Chromatin released from nuclei in the presence of 5 mM Mg++ displays higher-order chromatin fibers, 200-300 A in diameter, these fibers appear to be arranged in a manner than reflects the two forms of the basic chromatin fiber.

Cell Nucleus↗

The hospice: its meaning to patients and their physicians.

Terminal care, whether provided in the hospice, hospital, or home, must be integrated with the best of medicine. The role of the physician is not diminished when the focus shifts from curing to caring and when the goal is enhancement of the quality of the patient's remaining life, rather than its prolongation. The embodiment of this concept in London's St. Christopher's Hospice is described.

Hospices↗