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Biomedical subjects

J Steel

Publications and source records attributed to J Steel.

At least 19 recordsLinked to original sources

Type 1 diabetes and pregnancy: trends in birth weight over 40 years at a single clinic.

OBJECTIVE: To examine changes in perinatal mortality and birth weight of babies born to mothers with pregestational type 1 diabetes over 40 years in a single teaching hospital clinic. METHODS: This was a retrospective survey of cases from the combined diabetes and obstetrics antenatal clinic at the Royal Infirmary of Edinburgh and Simpson Memorial Maternity Pavilion, Edinburgh, Scotland. Birth weight, standardized birth weight, and perinatal mortality were obtained from 643 singleton babies born after 28 weeks of gestation to mothers with pregestational type 1 diabetes between 1960 and 1999. RESULTS: There was a dramatic improvement in perinatal mortality rate, falling from 225 (per 1,000 total births after 28 weeks of gestation) in the 1960s to 102 in the 1970s, 21 in the 1980s, and 10 in the 1990s (P < .001 for effect of birth year). In contrast, standardized birth weight (adjusted for sex, gestational age, and parity), which was significantly higher than the background population (+1.41 standard deviations above the population norm, P < .001) showed no significant change over time. CONCLUSION: Changes in diabetic management and obstetric practice over the 40 years of our survey have resulted in enormous improvements in the outlook for offspring of mothers with diabetes. Somewhat surprisingly this has not been associated with a reduction in overgrowth of the fetus. LEVEL OF EVIDENCE: II-2.

Adult↗

The role of psychosocial factors in the progression of hepatocellular carcinoma.

The number of deaths per year from hepatocellular carcinoma (HCC) exceeds 250000, placing it sixth as the cause of death from cancer worldwide. The primary etiology of most cases of HCC in the US is hepatitis B and/or C. Extensive research has demonstrated that the relationship between hepatitis B infection and the progression to HCC is mediated by the immune system. A substantial, but unrelated literature, describes the relationship between psychosocial factors (e.g., stress, psychiatric morbidity), immune system reactivity, and disease progression in patients with cancer. However, the role of these factors in the progression of HBV-HCC has not been explored. An understanding of the relationship among virology, immunology, and behavior in the development and recurrence of HCC may provide alternative methods for secondary prevention of HCC (e.g., behavioral) until a vaccine and/or pharmacological treatments are developed, feasible, and affordable.

Carcinoma, Hepatocellular↗

The role of intrauterine bacteria in brain injury.

Organisms appear to be present in human fetal membranes without any apparent impact on pregnancy maintenance or the fetal brain. A clear link between chorioamnionitis and fetal brain damage suggests that tissue responses at the feto-maternal interface may be the key determinant of whether preterm labour and brain damage occur.

Bacterial Infections↗

Alternative methods of interpreting quality of life data in advanced gastrointestinal cancer patients.

Understanding of how to analyse and interpret quality of life (QoL) data from clinical trials in patients with advanced cancer is limited. In order to increase the knowledge about the possibilities of drawing conclusions from QoL data of these patients, data from 2 trials were reanalysed. A total of 113 patients with pancreatic, biliary or gastric cancer were included in 2 randomised trials comparing chemotherapy and best supportive care (BSC) with BSC alone. Patient benefit was evaluated by the treating physician (subjective response) and by using selected scales and different summary measures of the EORTC QLQ-C30 questionnaire. An increasing number of drop-outs (mainly due to death) with time did not occur in a random fashion. Therefore, the mean scores in the different subscales of the QLQ-C30 obtained during the follow-up of interviewed patients did not reflect the outcome of the randomised population. The scores of the patient-provided summary measure, 'Global health status/QoL', were stable in a rather high proportion of the patients and could not discriminate between the 2 groups. 3 other summary measures revealed greater variability, and they all discriminated between the 2 groups. A high agreement was also seen between the changes in the summary measures and the subjective response. A categorisation of whether an individual patient had benefited or not from the intervention could overcome the problem with the selective attrition.

Adult↗

Characterization of human sialoadhesin, a sialic acid binding receptor expressed by resident and inflammatory macrophage populations.

Sialoadhesin is a macrophage-restricted cellular interaction molecule and a prototypic member of the Siglec family of sialic acid binding immunoglobulin (Ig)-like lectins. So far, it has only been characterized in rodents. Here, we report the molecular cloning, binding properties, and expression pattern of human sialoadhesin. The predicted protein sequences of human and mouse sialoadhesin are about 72% identical, with the greatest similarity in the extracellular region, which comprises 17 Ig domains in both species. A recombinant protein consisting of the first 4 N-terminal domains of human sialoadhesin fused to the Fc region of human IgG1 mediated sialic acid-dependent binding with a specificity similar to its mouse counterpart, preferring sialic acid in the alpha2,3 glycosidic linkage over the alpha2,6 linkage. By flow cytometry with peripheral blood leukocytes, recombinant sialoadhesin bound strongly to granulocytes with intermediate binding to monocytes, natural killer cells, B cells, and a subset of CD8 T cells. Using antibodies raised to the recombinant protein, sialoadhesin was immunoprecipitated from the THP-1 human monocytic cell line as an approximate 200-kd glycoprotein. The expression pattern of human sialoadhesin was found to be similar to that of the mouse receptor, being absent from monocytes and other peripheral blood leukocytes, but expressed strongly by tissue macrophages in the spleen, lymph node, bone marrow, liver, colon, and lungs. High expression was also found on inflammatory macrophages present in affected tissues from patients with rheumatoid arthritis.

Amino Acid Sequence↗

Cell contact dependent extended release of adenovirus by microparticles in vitro.

Adenoviral vectors remain one of the most promising methods of gene delivery but are plagued by several inherent problems including immune inactivation and transient expression. This paper reports a novel microparticle-based delivery system for adenovirus that allows high uptake of virus, stable complex formation and extended release. In addition, this microparticle/adenovirus complex has been demonstrated to only release virus upon cell contact. The significant clinical implications of this delivery system are discussed.

Adenoviruses, Human↗

Incidence of blindness due to diabetic eye disease in Fife 1990-9.

AIMS: In the light of goals for reducing blindness due to diabetes, published in the St Vincent Declaration, 1989, the aim of this study was to find the incidence and prevalence of blindness in the diabetic population of Fife. METHODS: All blind registrations for the period 1990-9 were studied. Those with diabetes as the first or main diagnosis were included as new diabetic blind. The prevalence of diabetes was studied in a large sample population and extrapolated to the estimated population of Fife. RESULTS: The incidence of blindness due to diabetes was 64 (SD 24, 95% CI 49-79) per 100 000 diabetic population/year. The point prevalence of blindness due to diabetes on 31 December 1999 was 210 per 100 000 diabetic population. CONCLUSION: The incidence of blindness due to diabetes, in a diabetic population, is now known. Without this benchmark it is impossible to assess the implementation of the St Vincent Declaration.

Blindness↗

Siglec-8. A novel eosinophil-specific member of the immunoglobulin superfamily.

We describe the characterization of siglec-8, a novel sialic acid-binding immunoglobulin-like lectin that is expressed specifically by eosinophils. A full-length cDNA encoding siglec-8 was isolated from a human eosinophil cDNA library. Siglec-8 is predicted to contain three extracellular immunoglobulin-like domains, a transmembrane region, and a cytoplasmic tail of 47 amino acids. The siglec-8 gene mapped on chromosome 19q13.33-41, closely linked to genes encoding CD33 (siglec-3), siglec-5, siglec-6, and siglec-7. When siglec-8 was expressed on COS cells or as a recombinant protein fused to the Fc region of human IgG(1), it was able to mediate sialic acid-dependent binding to human erythrocytes and to soluble sialoglycoconjugates. Using specific monoclonal antibodies, siglec-8 could be detected only on eosinophils and hence appears to be the first example of an eosinophil-specific transmembrane receptor.

Amino Acid Sequence↗

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↗