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Biomedical subjects

D Gilmore

Publications and source records attributed to D Gilmore.

At least 19 recordsLinked to original sources
PubMed2000

A randomised comparison and economic evaluation of laparoscopic-assisted hysterectomy and abdominal hysterectomy.

OBJECTIVES: To determine the safety, cost effectiveness and effect on quality of life of laparoscopic-assisted vaginal hysterectomy (LAVH) compared with total abdominal hysterectomy (TAH) in the management of benign gynaecological disease. DESIGN: Randomised controlled trial and economic evaluation. SETTING: Three hospitals in the West of Scotland. PARTICIPANTS: Two hundred women scheduled for an abdominal hysterectomy for benign gynaecological disease. MAIN OUTCOME MEASURES: Conversion rate of LAVH to TAH, complication rates, NHS resource use and costs, quality of life using EuroQol 5 D visual analogue scale, and achievement of milestones. RESULTS: The overall incidence of operative complications was 14% in the TAH group and 8% in the LAVH group, with an 8% conversion rate. Length of operation was significantly greater in the women having LAVH at 81 +/- 30 min vs 47 +/- 16 min (P < 0.001). There was no difference in analgesic requirements between the groups although there was a significantly shorter hospital stay for those having LAVH. The rate of post-surgery recovery, satisfaction with operation and quality of life at four weeks post-operative were similar in the two groups of women. LAVH was significantly more expensive than TAH and remained more expensive for all but the most extreme scenario. CONCLUSIONS: This study demonstrates that despite the decreased length of hospital stay, LAVH is more expensive than TAH. In addition, recovery following operation and patient satisfaction were not affected by the route chosen. It is unlikely that LAVH represents an efficient use of NHS resources.

Adult↗
PubMed1998

Epidemiology of immediate and early trauma deaths at an urban Level I trauma center.

The objective of this study is to identify and differentiate the injury patterns and causes of death among patients who died within the 1st hour and those in the period between 1 and 48 hours after hospital admission. Information was collected from the 1994 to 1996 trauma data base at an urban Level I trauma center. The records of 155 trauma patients who died within the 1st hour (immediate trauma death, ITD) and between 1 and 48 hours (early trauma death, ETD) were examined retrospectively. Total and constituent Injury Severity Score (ISS), Trauma Score (TS), and Glasgow Coma Score were analyzed. ITDs constituted 49 per cent of all deaths within 48 hours. Blunt mechanisms accounted for 37 per cent of ITDs and 40 per cent of ETDs (not significant), whereas penetrating trauma accounted for 59 per cent of ITDs and 56 per cent of ETDs (not significant). Exsanguination most commonly caused death among ITDs (54%) and head injury (51%) among ETDs (P < 0.01). Patients who died within the 1st hour had higher ISS (42.6 +/- 23.2, P < 0.03), lower TS (1.7 +/- 1.9, P < 0.0001), and lower Glasgow Coma Score (3.1 +/- 1.1, P < 0.0001) than those who died after the 1st hour. Patients with ITD had a significantly worse chest ISS than those with ETD (47.4 +/- 28.6 vs 19.0 +/- 19.1, P < 0.0001). We conclude that 1) ITD is caused primarily by exsanguination, whereas ETD is largely due to the sequelae of severe neurologic injury; 2) ITD has a significantly lower TS and higher ISS than ETD; and 3) thoracic injuries are more severe among patients with ITDs than among those with ETDs. The severity of thoracic injury among ITDs suggests that rapid surgical intervention is critical during the resuscitation of these severely injured patients.

Adolescent↗
PubMed1994

Age-related decrease in the proportion of germinal center B cells from mouse Peyer's patches is accompanied by an accumulation of somatic mutations in their immunoglobulin genes.

Somatic hypermutation of immunoglobulin genes and the generation of memory B cells seems to take place in germinal centers, which are chronically present in Peyer's patches. Age-associated changes in the germinal center B cell compartment of Peyer's patches and in the mutations of a kappa light chain transgene were analyzed in unimmunized mice. Somatic mutations accumulate in germinal center B cells slowly and continuously to reach an apparent plateau when the animals are around 5 months old. In contrast, the proportion of germinal center B cells reaches a maximum in very young mice (about 2 months old) and decreases progressively thereafter. These results suggest that the highly mutated B cells in older mice arise by the successive accumulation of mutations in memory cells. The data also show that the optimum time for the analysis of hypermutation of transgenes in Peyer's patches is when the mice are about 5 months old.

Aging↗
PubMed1993

Randomized phase I chemoprevention dose-seeking study of alpha-difluoromethylornithine.

BACKGROUND: alpha-Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase (ODC), the key enzyme in mammalian polyamine biosynthesis. Levels of ODC are closely related to tumor promotion, and inhibition of ODC is associated with suppression of tumor development in laboratory animals. DFMO has shown a dose-response effect in tumor inhibition in mice. PURPOSE: A randomized phase I study of DFMO was conducted to determine the lowest daily oral dose that can achieve at least 50% inhibition of ODC activity induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in human skin, with minimal clinical toxicity (grade 1 or lower; Eastern Cooperative Oncology Group [ECOG]). METHODS: Cancer patients entered in steps 1 and 2 of the study had been treated and had no clinical evidence of cancer. In step 1, 13 patients received 0.125, 0.25, 0.5, or 0.75 g/m2 DFMO four times a day. In step 2, 13 patients received 0.125 or 0.25 g/m2 four times a day or 0.5 or 1.0 g/m2 every day. The 26 patients treated in steps 1 and 2 (range, < 1-6 months) had colon, prostate, or bladder cancer. In step 3, six cancer-free subjects at risk for colorectal cancer received 0.5 g/m2 every day for 5-12 months. To evaluate the effectiveness of DFMO in reducing TPA-induced ODC activity, we calculated the percent change from pretreatment ODC levels in skin biopsy specimens and the percentage of subjects with at least a 50% reduction in ODC levels. RESULTS: In step 1 of the study, treatment-limiting audiotoxicity was observed at the three highest doses. Because the only dose with no major toxic effects in step 2 was 0.5 g/m2 every day, that dose was administered in step 3, with no major toxic effects. Seven subjects treated with 0.5 g/m2 every day had pretreatment ODC levels in the normal range; five averaged a reduction in ODC activity of at least 50%. DFMO had linear pharmacokinetics over the entire dose range. When 0.5 g/m2 was given every day, the peak plasma concentration was 47.1 +/- 5.1 microM at 3-4 hours (monthly mean +/- SE, 14.5 +/- 5.2 microM); half-life was 3.5 hours; and area under the curve for plasma concentration x time for a single dose of DFMO was 311 +/- 39 microM x hour. CONCLUSIONS: These data support phase II chemoprevention studies with DFMO given at a dose of 0.5 g/m2 every day. IMPLICATIONS: Studies investigating prevention of cancers with DFMO are under consideration.

Adult↗
PubMed1993

Clinical predictors of post-traumatic seizures in children with head trauma.

STUDY OBJECTIVES: To determine the clinical characteristics associated with early post-traumatic seizures in children with head trauma. DESIGN, SETTING, AND TYPE OF PARTICIPANTS: Retrospective chart review; urban trauma center/pediatric emergency department. Trauma patients aged 3 months to 15 years given discharge diagnosis ICD-9-CM codes indicating head trauma and seen from 1988 to 1990 were eligible for the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 194 patients, 96% suffered blunt trauma and 53% had a loss of consciousness. Fifty-one percent of 141 computed tomography (CT) scans of the head were abnormal, most frequently demonstrating skull fractures (34%), subdural hematomas (15%), and cerebral contusions (14%). Eighteen patients (9.3%) suffered post-traumatic seizures. A loss of consciousness, a low Glasgow Coma Scale (GCS) score (3 to 8), and an abnormal CT scan were associated with post-traumatic seizures (P < .02, .001, and .02, respectively). However, only a low GCS score was predictive of post-traumatic seizures when these factors were considered simultaneously (P < .001), with 38.7% of patients with low GCS scores suffering post-traumatic seizures and 3.8% of patients with high GCS scores suffering post-traumatic seizures. In children with low GCS scores, treatment with phenytoin was associated with a decrease in post-traumatic seizures. CONCLUSION: In the pediatric head trauma patient, a GCS score of 3 to 8 appears to be predictive of post-traumatic seizures. The data from this retrospective study are consistent with the hypothesis that prophylactic phenytoin reduces post-traumatic seizures in the pediatric head trauma patient with a low GCS score.

Adolescent↗
PubMed1987

The induction of class I HLA by interferon-alpha is independent of the cell cycle, but the expression is enhanced by a G1/S block.

The induction of class I HLA expression by interferon-alpha (IFN-alpha) was studied in lymphoid cells arrested or traversing different stages of the cell cycle. Exponential cultures of MOLT-4 cells and the MOLT-4 cell variant YHHH were treated with the cell cycle inhibitors aphidicolin and colcemid to obtain cell populations arrested in G1/S and G2/M, respectively, and also cells traversing from S to M and vice versa. Cytofluorimetry with the monoclonal antibody YTH/76.3 (which specifically detects those class I molecules which are most susceptible to IFN-alpha induction) was used to quantitate the class I HLA response to IFN-alpha. The results showed that the response to IFN-alpha is not restricted to a given stage of the cell cycle. These studies also revealed that when the cells were arrested at G1/S, the absolute level of class I HLA expression was enhanced 2-3-fold, both in the presence or absence of either IFN-alpha or IFN-gamma. Therefore, even when absolute levels changed, the ratio of IFN-induced expression to basal expression remained constant at all cell cycle stages. The level of expression of another surface antigen (the CD1 antigen HTA-1) was not affected by the G1/S block. The results were confirmed by dot blot hybridization of poly(A)+ RNA using cDNA-specific probes. These findings suggest that the effect of IFN-alpha is continuous throughout the cell cycle but that a G1-dependent event determines the extent of class I HLA expression, and leads to a synergistic superinduction by IFN in G1/S-arrested cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1985

Stimulation of HLA-A,B,C by IFN-alpha. The derivation of Molt 4 variants and the differential expression of HLA-A,B,C subsets.

Spontaneous mutants with altered HLA-A,B,C response to interferon-alpha (IFN-alpha) were isolated from the human thymus leukemia cell line Molt 4. Using fluorescein isothiocyanate (FITC)-conjugated W6/32 (a monoclonal antibody to HLA-A,B,C) and the fluorescence-activated cell sorter, the cells with highest and lowest fluorescence after 24-48 h of IFN-alpha treatment were selected and expanded. After several cycles of selection, mutant clones with low (greater than 10% of wild-type) and high (three times better) response were obtained. A similar protocol was employed to derive high responder mutants with the monoclonal antibody YT76, which recognises a subset of HLA strongly induced by IFN-alpha. Stable clones were derived for which YT-HLA induction was 7-fold that of Molt 4 cells and for which HLA induction occurred at 100-fold lower concentrations of IFN-alpha. The high response phenotype of the mutants was not accompanied by a significant increase in the constitutive level of expression of HLA-A,B,C (in the absence of IFN). The increase in the level of HLA-A,B,C expression after IFN-alpha treatment is mostly accounted for by the increase in the expression of a subset of HLA molecules, detected by the monoclonal antibody YT76 including HLA-B molecules.

Cell Line↗
PubMed1983

Separation of hemopoietic cells from adult mouse marrow by use of monoclonal antibodies.

Primitive hemopoietic progenitor cells from adult mouse marrow have been substantially enriched by virtue of a negative selection procedure with monoclonal antibodies. It has been possible to segregate erythroid progenitor cells at distinct stages of differentiation on the basis of their cell surface antigens. This has been achieved with two monoclonal antibodies reactive with the mature elements of bone marrow. YBM 34.3 binds to a heat-stable antigen expressed on B lymphocytes, neutrophils, and cells of the erythroid lineage. YBM 6.1 reacts with cells of the neutrophil, eosinophil, and monocyte series but does not bind to colony-forming cells. Separation is achieved by indirect immunoadsorption (panning) with YBM 34.3 on Protein-A-coated plastic plates followed by FACS II cell sorting with YBM 6.1. The combined procedures yield a marrow population containing 58% immature cells (blasts, promyelocytes, and myelocytes) and 9.5% clonogenic cells. In addition, differential binding of YBM 34.3 can be used to segregate erythroid progenitor cells at distinct stages of differentiation (day 7 BFU-E, day 5 BFU-E and CFU-E) either by cell sorting or panning. It is shown that both techniques give a comparable degree of resolution of the different cell types with, however, an appreciable advantage of panning over cell sorting in allowing the rapid handling of large numbers of cells.

Animals↗
PubMed1982

Effect of rubella vaccination programme in schools on rubella immunity in a general practice population.

Between November 1979 and January 1980 all patients aged 13-21 years who attended a general practice in Glasgow were tested for their immunity against rubella (single radial haemolysis test). All of the women in the sample should have been vaccinated at 13 as part of the rubella vaccination programme, which began in Glasgow in 1971. The programme excludes boys. Of the 77 females and 64 male patients studied, nine (11.7%) and 10 (15.6%), respectively, were susceptible to the infection. For only 34 women was evidence of vaccination documented in the practice records, and three of those either had failed to seroconvert or had antibody below detectable values. Overall there was no significant differences between the proportion of men and women who were susceptible to the disease. The rubella vaccination programme had clearly failed to reduce the number of susceptible women in this practice. Hence the immune state of all girls should be checked at about 15 years of age, so that as many as possible may be rendered immune before they leave school.

Adolescent↗