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Biomedical subjects

C Saunders

Publications and source records attributed to C Saunders.

At least 55 records · Page 3Linked to original sources

Receptors coupled to pertussis toxin-sensitive G-proteins traffic to opposite surfaces in Madin-Darby canine kidney cells. A1 adenosine receptors achieve apical and alpha 2A adrenergic receptors achieve basolateral localization.

The alpha 2A adrenergic receptor (alpha 2AAR) previously was shown to be directly delivered to and retained on the lateral subdomain of renal epithelial cells. The present studies demonstrate that, in contrast, wild-type and epitope-tagged canine A1 adenosine receptors (A1AdoR) are apically enriched (65-83%) in Madin-Darby canine kidney (MDCKII) and porcine renal epithelial (LLC-PKI) cells, based on surface biotinylation strategies detecting photoaffinity-labeled A1AdoR. Confocal microscopy corroborated the apical enrichment of the epitopetagged A1AdoR. Metabolic labeling studies revealed that this steady-state polarization is achieved by direct delivery to both the apical (60-75%) and basolateral surface. Growth of A1AdoR-expressing cells as monolayers presence of A1AdoR antagonists, which decreased cell growth, suggesting that A1AdoR elicit MDCKII cell proliferation. The preferential apical but detectable basolateral localization of A1AdoR provides a molecular understanding of published reports that functional responses can be elicited following apical as well as basolateral delivery of adenosine agonists in varying renal preparations. These findings also suggest that receptor chimeras derived from the Gi/Go-protein-coupled alpha 2AAR and A1AdoR will be informative in revealing structural features critical for basolateral versus apical targeting.

Amino Acid Sequence↗

Nursing home residents' perceptions of the quality of their care.

This pilot study employed qualitative interviews to assess nursing home residents' perceptions of their "best" and "worst" experiences in the nursing home. Findings suggest residents are least satisfied with the care provided by nurse aides, and most satisfied with that provided by professional staff members. The quality of interpersonal relationships with staff was the basis for the majority of both residents' best and worst experiences. Qualitative analyses identified specific "adaptive responses" that were associated with how residents interpreted and responded to negative experiences with care.

Aged↗

Investigation of a new pure antiestrogen (ICI 182780) in women with primary breast cancer.

We have conducted a clinical trial of a novel pure antiestrogen, 7 alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl]estra-1,3,5,(1 0)-triene-3,17 beta-diol (ICI 182780), to assess its tolerance, pharmacokinetics, and short term biological effects in women with primary breast cancer. Fifty-six patients were randomized to either a control group (n = 19), in which they received no preoperative treatment, or a treatment group (n = 37), in which they received daily i.m. injections of ICI 182780 at doses of 6 mg (n = 21) or 18 mg (n = 16) for 7 days prior to primary breast surgery. Serum drug concentrations, gonadotropin levels, and sex hormone-binding globulin levels were measured during the study period by radioimmunoassay. Expression of estrogen receptors (ER), progesterone receptors, the estrogen-induced protein pS2, and the cell proliferation-related antigen Ki67 was determined immunocytochemically in pre- and poststudy tumor samples. Treatment with ICI 182780 caused no serious drug-related adverse events and had no effect on serum gonadotropin or sex hormone-binding globulin levels. Minor adverse events occurred in 5 patients receiving the 6-mg dose and 3 patients receiving the 18-mg dose. The serum concentration of ICI 182780 was dose dependent but showed variation between individuals. There was evidence of an approximately 3-fold drug accumulation over the short treatment period but steady state levels were not reached by the end of the 7 days. In patients with ER-positive tumors, treatment with ICI 182780 was associated with significant reductions in the tumor expression of ER (median ER index, 0.72 before versus 0.02 after treatment; P < 0.001), progesterone receptor (median progesterone receptor index, 0.50 before versus 0.01 after treatment; P < 0.05), and Ki67 (median Ki67 labeling index, 3.2 before versus 1.1 after treatment; P < 0.05). Treatment with ICI 182780 also resulted in a significant reduction in pS2 expression (P < 0.05) but this appeared unrelated to tumor ER status. In conclusion, ICI 182780 was well tolerated after short term administration and produced demonstrable antiestrogenic effects in human breast tumors in vivo, without showing evidence of agonist activity. These properties identify ICI 182780 as a candidate agent with which to evaluate whether a pure estrogen antagonist offers any additional benefit in the treatment of human breast cancer over conventional nonsteroidal antiestrogens, typified by tamoxifen, which exhibit variable degrees of agonist activity.

Aged↗

Euthanasia--definition, dangers and alternatives.

There is as yet (1992) no law specifically allowing euthanasia, the active intervention to end a patient's life. The discussion has so far been restricted to such action as taking place at a patient's request, but evidence from the Netherlands appears to show that the move to involuntary euthanasia is a real danger. Palliative medicine offers appropriate treatment for relief and support where limits are set on interventions that would no longer be in a patient's best interests. It is possible to relieve distress by using the increasing knowledge in this field. It is important to distinguish this from euthanasia and the term "passive euthanasia" is confusing and unfortunate. Those with extensive experience in the treatment of advanced cancer have much to share with practitioners in other specialties, not least in the possible achievements of both patient and family at the end of life. Society has the responsibility for including them in its concern to the end of life and for supporting those who find it difficult to believe in any meaning in their existence.

Euthanasia↗

Postprandial glycemic response in three male endurance athletes.

The determination of blood glucose response to various carbohydrate foods may help athletes in their choice of preexercise feedings. This case study documented the postprandial glycemic responses of three male endurance athletes at rest after ingestion of 50-gram portions of three carbohydrate foods: graham crackers, orange juice, and oatmeal. Plasma glucose response differed in each subject for each test food. Two of the three subjects exhibited similar glycemic responses, but not to the same test food. Future studies will clarify the relationship between carbohydrate ingestion and postprandial glucose response.

Adult↗

Surgical nutrition: a review.

The metabolic response to critical illness is an integrated process producing profound changes to multiple systems. The altered metabolism of carbohydrates, lipids, and proteins in critically injured patients, and the crucial role of cytokine mediators such as tumour necrosis factor, interleukins, and interferons are described in detail. A general approach with guidelines for nutritional support is taken. A detailed description of enteral versus parenteral therapy is given, including advantages, disadvantages, contraindications, and complications. The research on specifically enriched amino acid formulations with glutamine, branched-chain amino acids, and arginine solutions is reviewed with emphasis on both theoretical and clinical issues. The role of dietary lipids in the production of specific modulators of immunoresponsiveness and investigations focusing on metabolic modulation relating to nutritional support are summarized.

Critical Illness↗

Magnesium and arachidonic acid metabolism.

The arachidonic acid content of plasma lipoproteins is altered during dietary magnesium deficiency, although the tissue arachidonic acid content seems to be unchanged. The primary event triggering these changes is probably the loss of extracellular Mg2+, as it is not clear whether dietary magnesium deficiency produces loss of intracellular Mg2+. In the isolated rabbit heart, in vitro perfusion conditions which produce loss of intracellular Mg2+ also result in disturbances of arachidonic acid metabolism. The metabolism of exogenous arachidonic acid to prostaglandins is increased without changing the Km or Vmax of cyclo-oxygenase. The incorporation of arachidonic acid into tissue phospholipids is significantly reduced, although the incorporation of oleate, stearate, and linolenate is either increased or unchanged. These data indicate that the activity of the enzymes (CoA synthetases and acyl transferases) which mediate arachidonate incorporation is reduced during Mg2+ depletion. Since protein-kinase-C-mediated phosphorylation of both CoA synthetase and acyl transferase reduces their activity, and since protein kinase C has an Mg2+ binding site, it is possible to speculate that loss of intracellular Mg2+ may lead to the activation of protein kinase C, with the consequent reduction of arachidonic acid reacylation enzyme activity.

Animals↗

Motor neurone disease: a hospice perspective.

OBJECTIVE: To describe and evaluate the management of patients with motor neurone disease from the perspective of a hospice. DESIGN: Retrospective analysis of hospice medical and nursing notes. SETTING: Established 62 bed teaching and research hospice. SUBJECTS: 124 patients with motor neurone disease cared for by the hospice between January 1980 and November 1990. MAIN OUTCOME MEASURES: Patient profile; functional status; symptom control and use of opioids; insight; mode and management of death. RESULTS: 124 patients (67 women, 57 men) had a mean age 63.9 years. The median length of admission was 61.5 days (range 1 to 2147). 84 patients (68%) were aware of their diagnosis and its implications when first seen by a hospice doctor. Functionally, the patients were very dependent. Symptoms such as pain, dyspnoea, and insomnia were major problems that responded well to opioids. Many patients were noted to deteriorate "suddenly," and in 58% of cases death occurred within 24 hours of this deterioration. When dying, 106 patients (94%) were peaceful and settled. 101 patients (89%) received opioids during this dying period. No patient chocked to death. CONCLUSIONS: Although motor neurone disease is an uncommon disorder, many of its symptoms occur commonly in medical practice and must be actively treated. Opioids are both safe and effective for such treatment. The term chocking is both inaccurate and inappropriate in describing the cause of death in motor neurone disease and its use should be abandoned.

Adult↗

The 1989 Loma Prieta earthquake: impact on hospital patient care.

STUDY OBJECTIVE: To provide an overview of the Loma Prieta earthquake regarding patient care in affected hospitals. DESIGN: A retrospective review of medical records using International Classification of Disease, ninth revision (ICD-9) codes and a personal interview questionnaire. SETTING: Fifty-one hospitals in the six-county area most affected by the earthquake. TYPE OF PARTICIPANTS: Patients seeking care in emergency departments of study hospitals and supervising emergency physicians and ED nurses at the time of the earthquake. MEASUREMENTS: ED census data, complaint and diagnosis, disposition, and operative procedures for patients seen during the study period. MAIN RESULTS: Affected hospitals experienced a 15% increase in ED census during the study period. Minor trauma was the most common patient complaint. Open wound (870-897), contusion (920-924), and fracture (800-829) were the most common ICD-9 diagnostic categories. The percentage of patients presenting to EDs during the study period who were hospitalized increased slightly compared with baseline. Seventy-five percent of operative procedures were earthquake related; 63.7% of these were for fracture reduction. Physicians and nurses had somewhat conflicting opinions on adequacy of ED staffing. A small number of emergency physicians had difficulty in obtaining diagnostic tests on the night of the earthquake. Physicians noted no differences in diagnosis or treatment resulting from the earthquake. CONCLUSION: The Loma Prieta earthquake resulted in minimal negative impact on patient care in hospitals in the study area. The use of the ICD-9 classification deserves further consideration and study to improve the predictive value of disaster illness and injury reporting. The event has provided the stimulus for Bay Area hospitals to further improve plans for patient care during a disaster.

California↗

"Catch-up" growth in steroid dependent dermatomyositis treated with cyclosporin-A.

OBJECTIVE: To improve the short-term growth, and hopefully final height attainment, of children with dermatomyositis treated with chronic daily corticosteroid regimens. METHODS: We have examined the growth of nine pre-pubertal children (7F, 2M), mean age 8.9 (range, 5.7-12.3) years, who had severe juvenile dermatomyositis and required persistent corticosteroid therapy. All were treated with cyclosporin-A. RESULTS: During a mean period of 1.3 years (range 1.0-1.7) cyclosporin-A treatment was associated with a marked decrease in the dosage of prednisolone, from a mean of 12.4 to 6.6 mg/day (p < 0.02), and an increase in height velocity standard deviation score from a mean of -1.37 to +1.39 at 6 months (p < 0.02) and -0.33 at one year. During the first year of treatment with cyclosporin-A, seven patients were able to either withdraw or reduce their prednisolone dose. No side effects of treatment were observed. CONCLUSIONS: Cyclosporin-A was a useful treatment modality in juvenile dermatomyositis and allowed a decreased dose of corticosteroids and associated "catch-up" growth.

Body Height↗

An evaluation of communication skills training for physiotherapy students.

This evaluation study concerned the modules of communication skills training in the second, third and fourth years of an undergraduate programme of study in an honours degree course in physiotherapy. Questionnaires were administered to the students to ascertain their attitudes to the training programme. Lecturers in physiotherapy who were not involved in the training programme were interviewed regarding their perceptions of the importance of this communication skills training. The results show a positive attitude towards the skills training, and the important relationship with good clinical practice was emphasized.

Attitude↗

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

In vitro studies have suggested a potential role for calcium channel blockers in manipulating the basic ionic defect of cystic fibrosis. In 17 adult patients with cystic fibrosis nicardipine was administered either intravenously or topically using iontophoresis or occlusive dressings. Sweat tests were performed before and after drug administration and examined using two way analysis of variance. No statistically significant difference was observed. We conclude that nicardipine used in vivo does not exert the easily demonstrable effect on the chloride ion defect that has been observed with other agents in vitro.

Adult↗

Beneficial effects of long-term treatment with SK&F 105685 in murine lupus nephritis.

MRL/Mp-lpr/lpr (MRL/lpr) mice were studied from 6 to 19 weeks of age. Proteinuria began to increase at 15 weeks, and continued to increase until the animals were sacrificed at 19 weeks. This proteinuria was associated with lymphadenopathy and splenomegaly, as well as changes in lymph node cell phenotype and histologic changes in the glomeruli. Oral administration of SK&F 105685 starting at 12 weeks of age prevented the increased urinary protein loss, inhibited the histologic changes in the glomeruli, reduced the increase in spleen and lymph node weight and modified the phenotypic profile of the lymphoid cells. SK&F 105685 appears to act by increasing the number/activity of nonspecific suppressor cells in MRL/lpr mice. On the basis of this evidence, we conclude that SK&F 105685 can attenuate the progression of renal damage in MRL/lpr mice by exerting a unique effect on cells which may be involved in the autoimmune process.

Animals↗