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Biomedical subjects

J Steel

Publications and source records attributed to J Steel.

At least 19 recordsLinked to original sources

Detection of interleukin-1 signal transduction inhibitors: action of protein kinase inhibitors.

The dysregulated production of IL-1 has been shown to play an important role in many pathological processes. Despite the apparent value of compounds able to inhibit either the secretion of IL-1 or its signal transduction pathway in a specific manner, there are no such compounds suitable for clinical use. A major problem in identifying novel and specific inhibitors of signal transduction is the lack of knowledge of the intracellular events which mediate the cellular actions of IL-1. In this study a simple cellular assay has been established to screen natural product and synthetic compound libraries for low molecular weight inhibitors of the cytokine signalling pathways of potential therapeutic value. In addition, we have studied the action of several known modulators of signal transduction on the actions of IL-1.

Cell Division

Inappropriate--the patient or the service?

The inappropriate use of Accident and Emergency (A & E) departments by the public has been the subject of debate for many years. Patients often attend departments with problems which could equally have been treated by the primary care services in the community. However, despite much research into why patients choose to visit A & E departments rather than their general practitioners, efforts to reverse this trend have generally failed. If the professional view of what is appropriate cannot be enforced, perhaps the label 'inappropriate' belongs to the A & E services rather than the patient.

Emergency Service, Hospital

Lack of association between maternal phosphoglucomutase-1 phenotype and fetal macrosomia in diabetic pregnancy.

OBJECTIVE: To assess the reports that maternal phosphoglucomutase-1 (PGM1) phenotype is highly related to macrosomia in diabetic pregnancy. This could be either a direct metabolic phenomenon, or the PGM1 locus could be a marker for a tightly linked gene involved in the maternal control of fetal growth. DESIGN: A comparative biochemical genetic study. SETTING: A large diabetic pregnancy clinic. SUBJECTS: One hundred and fifty-two women who had diabetes during pregnancy, 136 being insulin dependent before pregnancy. Two hundred and thirty-six women without pre-existing medical or pregnancy complications who functioned as a control group. MEASURES: PGM1 phenotype was assessed by conventional electrophoresis and subgroups were examined using iso-electric focusing. OUTCOME: Standardised birthweight was corrected for sex, maternal parity and gestation confirmed in every case by early pregnancy ultrasound. Maternal diabetes control was assessed by glycosylated haemoglobin. RESULTS: No differences were found in the observed phenotype frequencies for diabetics and control pregnant women. No association between PGM1 phenotype and macrosomia in diabetic pregnancy was found. PGM1 did not make a significant contribution to birthweight, standardised birthweight, length or ponderal index of the baby as assessed by multiple regression. CONCLUSIONS: Our study of a larger number of insulin dependent diabetics in Scotland makes the claim that macrosomia in diabetic pregnancy is associated with PGM1 phenotype unlikely to be of general significance.

Analysis of Variance

Preparing advanced practice nurses for acute care.

BACKGROUND: As a result of changes occurring in healthcare, providers have become increasingly specialized, resulting in fragmented care of patients and their families. With these changes, the need has developed for professionals who possess both advanced clinical decision-making ability and expanded psychomotor skills to serve as case managers in collaboration with physicians. As a result, evolving and innovative roles for advanced practice nurses have developed in American hospitals. The development of such roles, within the acute care hospital environment, has led directly to the creation of graduate programs to prepare acute care nurse practitioners. OBJECTIVE: This article describes the efforts to develop a specific graduate program to prepare nurses as acute care nurse practitioners. These efforts include the needs assessment, curriculum and role development, implementation, and evaluation of the program. RESULTS: Phase 1 evaluation showed significant support for acute care nurse practitioners. External support for the training and use of nurse practitioners in acute care was evidenced by significant financial support for this program provided by an acute care hospital and a private foundation. The first graduates are now practicing as acute care nurse practitioners; Phase 2 evaluation of patient outcomes is under way. CONCLUSION: The emergence of acute care nurse practitioners has been stimulated by changes in American healthcare. Support for the use of acute care nurse practitioners is significant, but barriers to implementing the role and patient and fiscal outcomes must be studied.

Acute Disease

Evidence against a major role for integrins in calcium-dependent intercellular adhesion of epidermal keratinocytes.

It is well established that integrins mediate keratinocyte adhesion to extracellular matrix proteins, but, in addition, there is some evidence that they mediate intercellular adhesion. We have investigated the role of integrins in keratinocyte-keratinocyte adhesion by adding anti-integrin antibodies to cells in three assays that differ according to the calcium ion concentration of the medium, the presence or absence of an adhesive substrate (glass or tissue culture plastic) and the timing of antibody addition. As previously reported by Larjava et al., (J. Cell Biol. 110:803-815), a monoclonal antibody to the beta 1 subunit perturbed cell-cell adhesion when added to adherent monolayers in low calcium medium (0.1 mM calcium ions), but did not prevent cell-cell adhesion or stratification induced by raising the level of calcium ions to 1.8mM (the concentration in standard medium). Monoclonal antibodies to both the alpha 3 and beta 1 subunits inhibited the attachment, spreading and motility of keratinocytes in low or standard calcium medium when added at the time of plating; however, they had only a modest effect on the accumulation of cells in adherent clusters. Aggregation of keratinocytes in suspension required a calcium ion concentration of greater than 0.1mM and was not inhibited by any of a large panel of anti-integrin antibodies, including three new antibodies that recognise alpha 2 beta 1. We conclude that any inhibitory effects of individual anti-integrin antibodies on cell-cell adhesion are abrogated by a calcium ion concentration above 0.1mM and that in low calcium medium at least some of the inhibition of cell-cell adhesion is a consequence of the inhibition of cell-substrate adhesion and motility.

Antibodies, Monoclonal

Treatment of uterine sarcomas.

During a 21-year period, 66 patients with uterine sarcomas were treated at California Medical Center. Histological diagnoses were mixed mesodermal sarcoma in 32 patients (48%), leiomyosarcoma in 24 (36%), and endometrial stromal sarcoma in 10 (15%) patients. The majority of patients (73%) had Stage I tumors. The treatment consisted of surgery alone in 27 (41%), surgery in combination with radiation therapy in 36 (55%), and radiation therapy alone in three (4%) patients. The overall 1-, 2-, and 5-year actuarial survival was 74%, 57%, and 38%, respectively. The 1-, 2-, and 5-year actuarial survival for the 27 surgery alone patients was 73%, 50%, and 25%, which compared with 75%, 61%, and 44% for the 36 surgery plus radiation therapy patients (P = 0.12). The disease-free survival was better for the surgery plus radiation therapy patients, as compared with the surgery alone group (38% vs. 18% at 5 years, P = 0.081). The 5-year survival by histology was 70% for the 10 endometrial stromal sarcoma patients, 40% for the 24 leiomyosarcoma patients, and 23% for the 32 mesodermal sarcoma patients (P = 0.064). As expected, survival depended on the stage of disease (P less than 0.0001). Treatment failure was observed in 35 (53%) patients, which included 9 (14%) with failure in the pelvis. There was no difference in the incidence of failure among patients in the three treatment groups and also in the three histologic groups. There was, however, a significant difference in the incidence of pelvic failure between surgery alone and surgery plus radiation therapy patients. In the 27 surgery alone patients, nine (33%) relapsed in the pelvis, whereas none of the 36 surgery plus radiation therapy patients had locoregional failure, P less than 0.0001. Adjuvant radiation therapy is an important treatment in the management of patients with sarcoma of the uterus.

Adult

Occupational hazard in hospital staff exposed to 2 per cent glutaraldehyde in an endoscopy unit.

The occupational hazards associated with exposure to 2 per cent glutaraldehyde have been assessed in medical and nursing staff working in an endoscopy unit. Eight of the nine staff were affected and the clinical manifestations included watering of eyes, rhinitis, dermatitis, respiratory difficulties, nausea and headache. The atmospheric concentrations of glutaraldehyde were assessed and the effect on clinical manifestations is discussed. Glutaraldehyde is an irritant and sensitiser. Guidelines for those exposed to the compound are discussed to prevent, monitor and manage any health hazard.

Aldehydes

Evidence for neuropeptide Y synthesis in the rat anterior pituitary and the influence of thyroid hormone status: comparison with vasoactive intestinal peptide, substance P, and neurotensin.

Neuropeptide Y (NPY), a 36-amino acid member of the pancreatic polypeptide family, was found to be present by RIA and immunocytochemistry in the rat anterior pituitary gland. NPY prohormone messenger RNA (mRNA) was identified in the pituitary by Northern blot analysis. The possible regulation of NPY was examined by determining the effects of thyroid hormone manipulation on peptide synthesis. Three other anterior pituitary neuropeptides, neurotensin (NT), substance P (SP), and vasoactive intestinal peptide (VIP), were studied for comparison. Hypothyroidism was found to significantly increase the pituitary content of NPY, SP, and VIP and their respective mRNAs but to decrease the quantity of NT. Immunocytochemistry revealed very weak NPY immunoreactivity in scattered cells in control rat anterior pituitaries, but in hypothyroid rats a greater number of positive cells were seen, and the staining was relatively intense. These positive cells were identified as a subset of thyrotropes. In T4-induced hyperthyroidism NPY, NT, and VIP levels were unaffected whereas SP concentrations fell considerably. TRH treatment produced a decrease in NT and had no effect on NPY, SP, or VIP. These changes were found only in the pituitary; no net change occurred in hypothalamic peptide and mRNA levels. Since the changes in pituitary peptide and mRNA levels occurred coordinately it appears that regulation by thyroid hormone status occurs, at least in part, directly at the level of gene transcription. The changes in these 4 regulatory peptides in hypothyroidism and their known powerful effects on pituitary function suggest that they may have a significant paracrine or autocrine influence in controlling the alterations in pituitary secretion.

Animals

Intrauterine contraceptive devices in diabetic women.

11 of 30 (36.6%) insulin-dependent diabetic women fitted with intrauterine contraceptive devices (IUCDs) became pregnant within 1 year, whereas the pregnancy rate for non-diabetic women fitted with the same types of IUCD by the same consultant gynaecologists over a similar time period was 4 per 100 women years (4%). As soon as the high risk was recognised, devices were removed (2 from diabetic women who were pregnant and 19 from non-pregnant diabetic women), and patients were advised about other methods of contraception. The IUCDs were examined in a scanning electron microscope with X-ray microprobe analysis to measure the amount of copper eroded from the wire, the extent of the encrustation (if any) deposited on the wire, and the composition of the deposit, and the data were compared with those for 111 devices removed from non-diabetic women, 40% of the IUCDs from diabetic women had sulphur and chloride in the deposit, compared with 15.3% of IUCDs from normal women, and fewer IUCDs from diabetic women had calcareous deposits. In devices from normal women, erosion and deposition seemed to occur independently, but in IUCDs from diabetic women, there was high erosion, there were also large deposits, and where there was little deposit, the erosion was slight. 7 of 14 IUCDs taken from normal women who had become pregnant with an IUCD in situ had a high sulphur plus chloride deposit; none of these IUCDs had a predominantly calcareous deposit compared with 19.8% of the IUCDs from non-pregnant normal women. The evidence militates against the insertion of IUCDs in diabetic patients and indicated that, even in non-diabetic women, there may be small groups for whom the risk of becoming pregnant is very high.

Adult