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J Gibson

Publications and source records attributed to J Gibson.

At least 181 records · Page 10Linked to original sources
PubMed1994

Assessment of proliferative responses to granulocyte-macrophage colony-stimulating factor (GM-CSF) in acute myeloid leukaemia using a fluorescent ligand for the nucleoside transporter.

Nucleoside transporter expression has been linked to proliferation in a variety of haemopoietic cell types. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was given for 72 h before commencing chemotherapy in 15 patients with relapsed or refractory acute myeloid leukaemia (AML) and in 11 patients serial bone marrows were taken for measurement of [3H]thymidine labelling index, Ki-67 positivity and maximal binding of 5-(SAENTA-x8)-fluorescein, a flow cytometry ligand which enumerates nucleoside transporter sites. GM-CSF caused proliferation of marrow myeloblasts in eight of 11 patients, while in three patients there was no change in proliferative indices. The expression of nucleoside transporters increased up to 4-fold in the myeloblasts from the patients showing a proliferative response to GM-CSF but there was no increase in transporters on the myeloblasts from the three non-responding patients. A close correlation was found between the fold increase in nucleoside transporter expression and the fold increase in labelling index of marrow myeloblasts (r = 0.86, n = 9, p < 0.01). In one patient with acute megakaryoblastic leukemia, GM-CSF caused parallel increases in labelling index, Ki-67 positivity and numbers of nucleoside transporters on peripheral blood blast cells. Thus induction of proliferation by cytokine increases the expression of nucleoside transporters on leukaemic myeloblasts studied in serial samples from the same source (bone marrow or blood). The suitability of 5-(SAENTA-x8)-fluorescein for two colour flow cytometric analysis allows the rapid enumeration of nucleoside transporters in the myeloblast compartment of heterogeneous marrow samples.

Acute Disease↗
PubMed1993

A measurement process for evaluating clinical teachers in internal medicine.

With input from faculty members and residents in the internal medicine residency training program at McMaster University, Hamilton, Ont., the authors developed a form to evaluate attending physicians in clinical teaching units according to 14 domains of performance. Although brief, the form included all main areas of teacher performance, allowed specification of attending physician behaviour and differentiated areas of strengths and weaknesses between and within attending physicians. The authors describe the new evaluation process and the results for 41 attending physicians.

Canada↗
PubMed1993

Advancement of multiple myeloma from diagnosis through plateau phase to progression does not involve a new B-cell clone: evidence from the Ig heavy chain gene.

The Ig heavy chain (IgH) gene was used as a marker to investigate clonal succession and the origin of the neoplastic cell in multiple myeloma. The polymerase chain reaction (PCR) was used to amplify a section of the rearranged IgH gene at diagnosis and at progression in 21 patients who had exhibited a plateau phase. A monoclonal PCR product was seen for 16 of the patients and the product present at progression was of the same molecular weight as that at diagnosis. This finding suggests that the IgH rearrangement present at diagnosis and progression was the same. This was confirmed by sequencing the IgH gene in 10 patients. The IgH genes were found to be hypermutated at diagnosis, but no further hypermutation occurred during the course of the disease. The results provide evidence that the neoplastic cell in myeloma may originate as a memory B cell, plasmablast, or plasma cell, and suggest that progression beyond the plateau phase is not caused by clonal succession.

B-Lymphocytes↗
PubMed1993

Serum thymidine kinase as a prognostic indicator for patients with multiple myeloma: results from the MRC (UK) V trial.

The significance of serum thymidine kinase (STK) as a prognostic indicator for patients with myeloma has been evaluated by determining the pre-treatment level of STK in a retrospective study of 547 patients from the Medical Research Council (MRC) V Myeloma Trial. Overall, STK was a highly significant prognostic factor (Chi 2 = 7.91; P = 0.005). At the time of censor, 23.4% of patients with a presentation STK of < 6 U/l but only 7.9% of the patients with an STK of > 11 U/l were still alive. STK proved to be a highly significant prognostic indicator for the 270 melphalan-treated patients (Chi 2 = 12.37; P = 0.0004) but had no prognostic significance for the 277 ABCM (adriamycin, BCNU, cyclophosphamide and melphalan) treated patients (Chi 2 = 0.29; P = 0.59). When the STK data was stratified for serum B-2-microglobulin (SB2M) it was demonstrated that STK was independent of SB2M and provided additional prognostic information for patients who were treated with melphalan. Thus patients with both a low STK and SB2M had the best prognosis (median survival 1677 d) and those patients with a high STK and SB2M had the worst prognosis (median survival 519 d). STK is a good prognostic marker for patients treated with melphalan but the prognostic significance of STK may disappear with the introduction of new chemotherapy regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

A computerized expert system for handling the output of the Technicon H1 haematology analyser.

A computer-based expert system is described which handles the output of the Technicon H1 in the haematology laboratory of a large teaching hospital. Using patient request data, analyser results, error and morphology flags, the expert system decides; whether to validate the main indices plus differential; whether a blood film is required for manual review; and which abnormal results require phoning to the requesting doctor. The results of this computer-assisted analysis are sent to a printer adjacent to the analyser. The print-out details any further action required of the operator before release of results to the main hospital computer, and serves as a log of all samples run on that analyser. Benefits of the expert system include greatly simplified interpretation of the large array of analyser flags, and consistency in sample handling for all operators over all shifts.

Algorithms↗
PubMed1993

Cell-free plasma human immunodeficiency virus type 1 titer assessed by culture and immunocapture-reverse transcription-polymerase chain reaction.

The relationship between plasma human immunodeficiency virus type 1 (HIV-1) infectious titer, determined by quantitative fivefold end-point dilution culture, and the detection of genomic HIV-1 RNA by immunocapture-cDNA-polymerase chain reaction was determined. The optimal plasma specimen collection and storage conditions for the use of such virologic markers for clinical trials were also determined. The variabilities in the measurement of infectious HIVLAI titer associated with intra- and interdonor peripheral blood mononuclear cells were 1.2 and 0.86 log10 50% tissue culture infective doses (TCID50)/ml (95% confidence interval range), respectively. Plasma HIV-1 titers did not change significantly after storing whole blood for 6 h either at 4 degrees C or ambient temperature or plasma for a median of 267 days (range, 259 to 482) at -70 degrees C. The detection of genomic HIV-1 RNA encapsulated in viral particles was very consistent, reproducible, and unaffected by either heparin or acid citrate or by multiple freeze-thawing. The HIV-1 RNA titers also appeared to generally correlate with the biologic titer obtained by the microculture assay. The consistency in infectious HIV-1 titer was evaluated by using 27 unfrozen plasma specimens collected from five subjects over 1 to 9 days. The median change in HIV-1 titer relative to baseline was -0.5 log10 TCID50/ml (interquartile range, -1.03 to 0.175 log10). In contrast, no significant change in HIV-1 RNA for the same frozen plasma specimens was noted. As such, immunocapture-cDNA-polymerase chain reaction may be a useful measure of plasma viremia for studying the natural history of HIV disease and assessing response to therapy.

Blood Specimen Collection↗
PubMed1993

C-reactive protein (CRP) levels do not reflect disease status in patients with multiple myeloma.

It has recently been suggested that a combination of C-Reactive Protein (CRP) and beta-2-microglobulin (beta 2M) can be used to devise a simple prognostic model for patients with multiple myeloma. In this study we have measured serum beta 2M, CRP and thymidine kinase (STK) in a series of 215 samples to determine their value as a monitor of disease status. A longitudinal study was also performed with 6 individual patients. CRP levels did not correlate with disease status. The mean of the stable (23.62 mg/L) and the progressive disease 23.64 mg/L) groups were almost identical (t = 0.003; p = NS) with ranges of < 5-150 mg/L and < 5-100 mg/L respectively. There was no correlation between CRP and STK (r = 0.11) or CRP and beta 2M (r = 0.05). In longitudinal studies, CRP did not necessarily reflect changes in disease activity. We conclude that CRP measurements are not valuable as a monitor of disease activity in patients with myeloma.

C-Reactive Protein↗
PubMed1993

Single daily ceftriaxone and tobramycin in the empirical management of febrile neutropenic patients: a randomised trial.

A single-institution, randomised pilot trial was conducted to compare the clinical efficacy, microbiological efficacy and possible toxicity of empirical single daily antibiotic administration in febrile neutropenic patients with haematologic disorders (absolute neutrophil count < 1 x 10(9)/l). Upon the development of signs of sepsis, patients received either single daily dose tobramycin (5 mg/kg per day) plus ceftriaxone (2 g/day) (C + T, n = 47) or tobramycin (1.5 mg/kg, every 8 h) plus azlocillin (4 g, every 6 h) (A + T, n = 45). In addition, flucloxacillin (1-2 g, every 4 h) could be added if there was clinical suspicion of staphylococcal infection (17 in each arm). Analysis was performed for the whole group and for the subset which did not receive flucloxacillin. When evaluated at 96 h, 62% of patients randomised to C + T and 67% randomised to A + T had responded (95% confidence interval (CI) for the difference in rates, -25% to +15%). Ninety-six hour response rates for those who did not receive flucloxacillin were 73% and 78%, respectively (95% CI, -17% to +27%). Overall, 42 (89%) and 41 (91%) patients, respectively, eventually became afebrile (95% CI, -14 to 10%) and there was no evidence of altered renal function or electrolyte imbalance in patients randomised to single daily antibiotic therapy compared with the conventional (multi-daily dose) arm. Within 10 days of antibiotic commencement there was 1 death in the C + T arm and 4 deaths in the A + T arm, although overall there were 4 deaths in each arm. Our results suggest that single daily empirical antibiotic therapy with tobramycin and ceftriaxone is efficacious and is not associated with an increased incidence of renal dysfunction or electrolyte imbalance compared with conventional administration schedules of azlocillin plus tobramycin. Single daily therapy has the potential to lead to savings in nursing-staff time and materials and may well contribute to an improved quality of life for febrile neutropenic patients.

Adolescent↗
PubMed1993

Interleukin-6 receptor expression and saturation on the bone marrow cells of patients with multiple myeloma.

Expression of the interleukin-6 (IL-6) receptor on B cells and plasma cells in the bone marrow (n = 18) and peripheral blood (n = 32) of patients with multiple myeloma and the relative saturation of these receptors with endogenous IL-6 has been determined by dual-labelled flow cytometric analyses. B cells were identified using an anti-CD19 monoclonal antibody and plasma cells were identified by gating on cells with high fluorescent staining with anti-CD38. With the exception of one patient, very few bone marrow plasma cells expressed the IL-6 receptor (IL-6R) (mean = 2%). This was in contrast to cells from the U-266 plasma cell line, 90% of which had IL-6R. IL-6R expression was lower on bone marrow B cells (mean = 11%) than on peripheral blood B cells (mean = 69%). Studies using either monoclonal or polyclonal anti-human IL-6 to detect endogenous receptor-bound IL-6 found that the IL-6R on bone marrow B cells and plasma cells from patients with multiple myeloma were not saturated with endogenous IL-6 and the presence of receptor-bound IL-6 tended to be associated with stable disease. Thus dysregulated IL-6R expression was not evident on the B cells and plasma cells of patients with multiple myeloma and the increased IL-6R expression on the U-266 plasma cell line was not found on patients' cells.

B-Lymphocytes↗
PubMed1992

Autoantibodies to thrombomodulin: development of an enzyme immunoassay and a survey of their frequency in patients with the lupus anticoagulant.

In order to investigate the possibility that autoantibodies to thrombomodulin (TM) may exist in patients with the lupus anticoagulant (LA) and perhaps be implicated in the pathogenesis of recurrent thrombosis seen in such patients, we developed an enzyme-immunoassay to screen serum samples for anti-human TM activity. The major technical problem encountered in developing this assay was to reduce the non-specific binding of serum components from both the LA positive and the negative population. Considerable reduction of non-specific binding was achieved by use of a phosphate/citrate buffer at pH 8.0 and the use of an optimal sample dilution of 1/40. In addition, samples were always tested in parallel in blank wells and results are expressed as an OD ratio. Samples from 113 patients with the LA were assayed and compared to 78 patients referred for LA testing but found to be negative. The mean OD values for the LA positive patients (+/- SD) was 1.36 (0.44) with a range of 0.78-2.57. This was virtually identical to the values for the LA negative population (1.38 +/- 0.40, range 0.76-2.77). The results of this study indicate that there is no evidence for the presence of a significant autoantibody activity to TM in patients with the LA when compared to LA negative patients. If such autoantibodies do exist their frequency must be quite low.

Autoantibodies↗
PubMed1992

Predictive diagnosis of familial adenomatous polyposis with linked DNA markers: population based study.

OBJECTIVES: To evaluate the use of polymorphic DNA probes linked to the APC gene in the presymptomatic diagnosis of familial adenomatous polyposis. DESIGN: Four DNA probes were tested on an unselected population of patients at risk of familial adenomatous polyposis. SUBJECTS: The first 47 families notified to the West Midlands familial adenomatous polyposis register. Plus five families sent to our hospital as part of the West of Britain DNA consortium. MAIN OUTCOME MEASURES: The proportion of families and family members in whom DNA testing could be used to adjust the estimate of risk. RESULTS: Only 17 families on the register (containing 46% (74/162) of the population at risk) had a suitable pedigree structure for DNA analysis. DNA was analysed in 12 of these families plus the five families from the West of Britain consortium. At least one probe was informative in 27 of the 33 subjects born with 50% risk, but the most informative probe (pi 227) was the one with the highest recombination rate (10%). Flanking markers were informative in only four of the 33 subjects. CONCLUSIONS: These findings confirm the potential for accurate predictive diagnosis of familial adenomatous polyposis with polymorphic DNA probes, but such an approach is currently limited to about one third of affected families. A combined approach to presymptomatic diagnosis, which includes DNA testing and indirect ophthalmoscopy, is advocated.

Adenomatous Polyposis Coli↗
PubMed1992

Role of congenital hypertrophy of the retinal pigment epithelium in the predictive diagnosis of familial adenomatous polyposis.

A study was carried out to evaluate congenital hypertrophy of the retinal pigment epithelium (CHRPE) as a disease marker in a defined population with familial adenomatous polyposis (FAP). Indirect ophthalmoscopy was performed on 75 individuals from 25 known families with FAP, of whom 32 were known to be affected and 43 were at a 50 per cent prior risk of developing the disease. A further ten individuals from five families with hereditary non-polyposis colorectal cancer (HNPCC) were also tested. CHRPE was seen in 28 of the 32 affected individuals, 27 of whom met the criteria for a positive examination. Three individuals at risk of FAP also had positive examinations. Five individuals from the families with HNPCC also had CHRPE, although none met the criteria for a positive examination. Of four types of CHRPE analysed, one (small pigmented dots) was found to be more frequent in older family members (P = 0.012), suggesting that this type of lesion may proliferate with age. Compliance with ophthalmic screening was 97 per cent in families with FAP. Using a combined set of diagnostic criteria, CHRPE identified affected individuals with a specificity of at least 94 per cent and a sensitivity of 84 per cent. Results argue for a combined screening programme for FAP of DNA analysis, indirect ophthalmoscopy and bowel examination.

Adenomatous Polyposis Coli↗
PubMed1992

Laparoscopic cholecystectomy as a routine procedure for gallstones: results of an 'all-comers' policy.

A total of 165 consecutive patients with gallstones were considered for laparoscopic cholecystectomy. Three were excluded. The median age was 52 years and 76 per cent were women. Eighteen patients underwent urgent operation. Laparoscopic cholecystectomy was successful in 160 of the 162 patients (99 per cent). The two failures were the result of dense adhesions and stones in the bile duct. There were no deaths but major complications occurred in three patients: fenestration of the colon sutured laparoscopically; bleeding from a cannulation site and subsequent laparotomy for a strangulated hernia; and subphrenic abscess. There were 13 minor complications, but no bile duct injuries or peritonitis. The median postoperative hospital stay was 1 day. Bile duct stones were present in 14 patients (9 per cent) and were removed by endoscopic sphincterotomy (11 patients), by laparoscopic exploration of the common duct (two) and by conversion to laparotomy (one). These results suggest that laparoscopic cholecystectomy is applicable to the large majority of patients who require elective or urgent cholecystectomy, if appropriate radiological and endoscopic support is available.

Adolescent↗