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D Bell

Publications and source records attributed to D Bell.

At least 145 records · Page 8Linked to original sources
PubMed1990

Comparison of DNA antibody idiotypes in human sera: an international collaborative study of 19 idiotypes from 11 different laboratories.

The distribution of and relationships between 18 anti-DNA antibody idiotypes and one anti-acetylcholine receptor antibody idiotype have been tested in an international collaborative study of human sera from 180 individuals. The main finding is that the serum levels of many of these idiotypes, whether of murine or human origin, show a high degree of statistical correlation. The studies in a wide range of autoimmune rheumatic diseases confirm that none of the idiotypes tested is disease specific, but 13 of 15 (87%) whose levels were recorded as OD units or cpm correlated strongly with anti-ssDNA antibody levels and 11 of 15 (73%) with total serum IgM. Expression of several idiotypes was found to fluctuate in parallel with disease activity in SLE; levels of others were also elevated in the healthy relatives of lupus patients whilst a few were also raised in the spouses of these patients. The data support the notion that there may be only a few groups of related DNA antibody idiotypes. The correlations between the idiotypes with regard to their quantities, association with disease activity, and wide distribution in different diseases and healthy individuals suggest at least two explanations. First, all of these idiotypes may be present in normal immunoglobulin repertoires and simply increase in response to poly- or oligoclonal B-cell activation in autoimmune diseases. Secondly, these idiotypes may be structurally linked to each other, so that their behaviour under conditions of specific antigenic stimulation is similar. Genetic and structural studies will be required to distinguish between these possibilities.

Autoantibodies↗
PubMed1990

A randomised trial of cisplatin and vindesine versus supportive care only in advanced non-small cell lung cancer.

The value of chemotherapy in advanced non-small cell lung cancer (NSCLC) remains contentious. Because of this two separate but very similar trials were set up in Australia and Southampton (UK). Two hundred and one patients with stage IIIb or IV NSCLC were randomly assigned to cisplatin 120 mg m-2 on days 1 and 29 and vindesine 3 mg m-2 weekly x 6 or to no chemotherapy. Both groups were eligible to receive radiotherapy or other palliative treatment as required. Of 188 evaluable patients, 97 received chemotherapy and 91 were in the control arm. Response was assessed between days 42 and 49. Responders continued chemotherapy at the same doses though cisplatin being given 6 weekly x 4 and the vindesine 2 weekly x 12. The overall response rate to chemotherapy was 28%; there were no significant differences according to major prognostic criteria. Although the overall survival of the chemotherapy group (median 27 weeks) was longer than that of the no chemotherapy group (median 17 weeks) this was not statistically significant (log rank P = 0.33). For patients without dissemination (IIIb), median survival was 45 weeks in the chemotherapy arm and 26 weeks in the non-chemotherapy (log rank P = 0.075). Toxicity was universal and frequently severe: of 17 patients discontinuing chemotherapy after one cycle, 13 did so because of unacceptable toxicity. This chemotherapy cannot be recommended as routine treatment. Further phase III studies of chemotherapy in advanced NSCLC should continue to use a no chemotherapy control and should also attempt to measure quality of life, an issue not addressed effectively in this or other recent trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Glutathione S-transferase isoenzymes in human bronchoalveolar lavage: a possible early marker for the detection of lung cancer.

The levels of glutathione S-transferase (GST) isoenzymes, GST pi, B1, B2 and mu were measured, by radioimmunoassay, in human bronchoalveolar lavage fluid from a series of patients presenting with neoplastic (n = 12) and non-neoplastic lung diseases (n = 10). Lavage fluid was obtained from the suspected abnormal area of lung and a presumed normal area of lung at the time of bronchoscopy. Concentrations of GST B1 and GST B2 were found to be significantly raised (P less than 0.02) in the lavage fluid obtained from the suspected abnormal areas of lung compared with the presumed normal area of lung, in patients later diagnosed as having cancer of the bronchus. The findings of the radioimmunoassay, of greater levels of GST B1 and B2 than GST pi in lavage fluid, were confirmed by a one-step purification of GST from lung lavage, using affinity chromatography, followed by their identification using SDS-polyacrylamide gel. We conclude that measurement of GST B1 or GST B2 in lung lavage fluid could be a useful aid in the diagnosis of lung malignancy.

Adult↗
PubMed1990

Leucocyte mobilization and release of neutrophil elastase following acute insulin-induced hypoglycaemia in normal humans.

Insulin-induced hypoglycaemia in humans is associated with the rapid mobilization of leucocytes in peripheral blood. The aim of the present study was to determine whether neutrophil activation, manifested in plasma by neutrophil elastase concentration, occurs in response to insulin-induced hypoglycaemia. Acute hypoglycaemia (mean blood glucose 1.3 +/- 0.2 mmol l-1; mean +/- SD) was induced with intravenous insulin in 15 normal human subjects, and provoked an increase in the neutrophil count from 3.4 (range 1.9-6.5) to 10.7 (9.4-16.3) X 10(9) l-1 (p less than 0.001), and in the total leucocyte counts from 5.7 (4.1-8.1) to 12.8 (11.3-18.6) X 10(9) l-1 (p less than 0.001), with associated elevations in plasma neutrophil elastase concentration from 21 (12-34) to 29 (14-70) micrograms l-1 (p less than 0.05), and in total neutrophil elastase concentration from 5.90 (3.13-8.20) to 25.20 (23.00-52.00) mg l-1 (p less than 0.001). As neutrophil elastase is implicated in the development of vascular disease, this rise in response to hypoglycaemia may be of pathological importance in insulin-treated diabetic patients.

Adult↗
PubMed1990

Inflammatory response, neutrophil activation, and free radical production after acute myocardial infarction: effect of thrombolytic treatment.

Activated neutrophils releasing proteolytic enzymes and oxygen free radicals have been implicated in extending myocardial injury after myocardial infarction. Neutrophil elastase was used as a marker of neutrophil activation and the non-peroxide diene conjugate of linoleic acid was used as an indicator of free radical activity in 32 patients after acute myocardial infarction; 17 were treated by intravenous thrombolysis. Patients with acute myocardial infarction had higher plasma concentrations of neutrophil elastase and the non-peroxide diene conjugated isomer of linoleic acid than normal volunteers or patients with stable ischaemic heart disease. Patients treated by thrombolysis had an early peak of neutrophil elastase at eight hours while those who had not been treated by thrombolysis showed a later peak 40 hours after infarction. The plasma concentration of non-peroxide conjugated diene of linoleic acid was highest 16 hours after the infarction irrespective of treatment by thrombolysis. Quantitative imaging with single photon emission tomography showed decreased uptake of indium-111 labelled neutrophils in the infarcted myocardium (as judged from technetium-99m pyrophosphate) in those who had received thrombolysis, suggesting a decreased inflammatory response. The results indicate increased neutrophil activation and free radical production after myocardial infarction; they also suggest that thrombolysis does not amplify the inflammatory response and may indeed suppress it.

Adult↗
PubMed1990

A human anti-cardiolipin autoantibody is encoded by developementally restricted heavy and light chain variable region genes.

Based on recent structural analyses of monoclonal autoantibodies, it appears that a number of these antibodies express germ-line immunoglobulin variable region (V) genes with little or no somatic mutation. In addition, our group and others have noted the identity or near identity of some autoantibody-associated V genes to V genes apparently expressed preferentially in the fetal pre-B cell repertoire. To extend these data, we now report that the heavy and light chain V genes of an anti-cardiolipin antibody derived from a healthy individual display 99% nucleotide sequence homology with V genes expressed in early B cell ontogeny. Sequence comparisons indicate the likely use of fetal-restricted V genes by this autoantibody. Taken together with other data on autoantibody V gene usage, these findings provide further evidence for overlap between the autoantibody-associated and early ontogeny expressed V gene repertoires and suggest that natural autoreactivity may be instrumental in the development and maintenance of the normal immune repertoire.

Amino Acid Sequence↗
PubMed1990

Lengthening of the humerus using the Ilizarov technique. Description of the method and report of 43 cases.

From 1982 to 1986, 43 humeral lengthenings were performed on 29 patients using the Ilizarov technique. Diagnoses included achondroplasia, old septic arthritis, birth palsy, fracture, congenital shortening, and benign neoplasm. The achondroplastic patients (14) had bilateral lengthenings. There were 16 male and 13 female patients aged ten to 36 years (mean, 18 years). The total lengthening in each segment ranged from 5 to 16 cm (mean, 9 cm) and mean treatment time from four to 14 months (mean, eight months). The average follow-up time was 2.7 years (range, 0.5-5.5 years). Functional and aesthetic results were all graded as excellent or good. There were no cases of osteomyelitis or deep infection. Three patients sustained neuropraxias that subsequently resolved completely. There were seven fractures in six patients following removal of the apparatus. Five were treated with casts and two with replication of the apparatus. All healed uneventfully. Humeral lengthening can be safely performed with excellent clinical results using the Ilizarov technique.

Adolescent↗
PubMed1990

Lengthening of the forearm by the Ilizarov technique.

The Ilizarov technique was used for lengthening 13 forearms in 12 patients. The different types of treatment were: lengthening of the radius alone, lengthening of the ulna alone with or without radial head relocation, lengthening of one-bone forearms, lengthening of the radius and ulna to the same extent, and differential lengthening of the radius and ulna. The lengthenings ranged from 2 cm to 13 cm (10%-143%). Bone consolidation was achieved in three to 19 months without the need for bone grafting. Eleven of 12 patients were functionally and cosmetically improved. In nine patients, the cosmetic improvement made a significant psychologic difference to the patient. There were 11 complications, including three temporary deep radial nerve palsies, one sympathetic dystrophy, one malunion, one delayed malunion, two refractures, and three mild loss of motion. All of these dysfunctions were temporary, but mild stiffness persisted in three patients. The goals of treatment were achieved in all patients.

Activities of Daily Living↗
PubMed1989

A comparison of coronary risk factors in groups of trained and untrained adolescents.

Fifty-five experimental (29 male, 25 female) and 38 control (20 male, 18 female) adolescent subjects participated in this study to investigate the differences in coronary heart disease (CHD) risk factors in groups of trained and untrained adolescents. As expected the trained group (both sexes) had higher maximal aerobic power (VO2max) and lower systolic blood pressure at rest. The level of total cholesterol was the same in both groups, but the levels of high-density lipoprotein and its lipoprotein subfractions apolipoprotein (Apo-A) and Apo-A1 were higher, and low-density lipoprotein, Apo-B and triglycerides were significantly lower in the experimental group. The value of risk factors from the family history was the same in both groups, but the behavioural and physical risk factors such as smoking and percentage of body fat were lower in the trained group. It would appear that the group of adolescents, trained for several years in athletics and swimming, had a more beneficial lipoprotein profile and a lower level of behavioural and physical risk factors than the control group. For methodological reasons it remains an open question whether these profile differences are the consequences of self-selection procedures or the effects of training.

Adolescent↗
PubMed1989

Neutrophil activation during cell separation procedures.

Leucocytes labelled with 111In or 99Tcm are used as diagnostic agents for detecting sites of infection by scintigraphy. Before radiolabelling is performed, leucocytes are isolated from whole blood. The effect of isolation procedures on neutrophil activation has been studied by measuring the neutrophil elastase produced during incubation of whole blood with three erythrocyte sedimentation agents (dextran 70, hydroxyethyl starch and methylcellulose) and two density gradient media (Percoll and Mono-Poly Resolving Medium). Neutrophil elastase was measured using a standard radioimmunoassay. At 21 degrees C, dextran caused no elastase release while hydroxyethyl starch and methylcellulose induced significant release (p = 0.01 and p less than 0.01 resp.). All three agents caused significant elastase release at 37 degrees C. When whole blood was incubated with Percoll and Mono-Poly Resolving Medium, no release of neutrophil elastase was observed. These results show that neither density gradient medium induces neutrophil activation but that certain erythrocyte sedimentation agents do. Of the three sedimentation agents investigated, dextran is the agent of choice if neutrophil activation is to be minimized.

Cell Separation↗
PubMed1989

Relationship of skin thickness to duration of diabetes, glycemic control, and diabetic complications in male IDDM patients.

Skin thickness is primarily determined by collagen content and is increased in insulin-dependent diabetes mellitus (IDDM). We measured skin thickness in 66 IDDM patients aged 24-38 yr and investigated whether it correlated with long-term glycemic control and the presence of certain diabetic complications. With univariate analysis, skin thickness was increased and significantly related to duration of diabetes (P less than .001), previous glycemic control (P less than .001), retinopathy (P less than .001), cheiroarthropathy (P less than .001), and vibration-perception threshold (P less than .05). There was a negative correlation between forced expiratory volume at 1 s (P less than .05) and vital capacity (P less than .05) with duration of diabetes. Neither skin thickness nor ankle arteriomedial wall calcification correlated with abnormal autonomic function tests. When corrected for duration of diabetes, there was a weak correlation between skin thickness and glycemic control (P less than .05) but no correlation with retinopathy, cheiroarthropathy, and vibration-perception threshold. This study confirms that there are widespread connective tissue changes in diabetes mellitus, although the biochemistry needs further elucidation.

Adult↗
PubMed1989

Empiric single agent or combination antibiotic therapy for febrile episodes in neutropenic patients: an overview.

Febrile episodes during chemotherapy-induced neutropenia are a frequent cause of morbidity and mortality in cancer patients. Empiric antibiotic therapy commencing at the onset of fever is selected according to three principles: intravenous therapy is used to rapidly achieve bactericidal serum levels, antibiotics with appropriate antibacterial spectra are required, and combinations of antibiotics have been preferred for their synergistic activity. Initial empiric monotherapy with single antibiotics such as imipenem which have a sufficiently broad antibacterial spectrum in their own right are potentially as efficacious as conventional combination therapies. Granulocytopenic periods complicated by fever are significantly longer in patients receiving chemotherapy for leukaemia than in patients undergoing treatment for lymphoma and solid tumours. However, defervescence of fever following commencement of antibiotic therapy occurs equally rapidly in these three groups. The persistent granulocytopenia leaves leukaemic patients at greatest risk of breakthrough or second infections. These patients therefore appear to be the most likely to benefit from the clinical use of haemopoietic growth factors such as granulocyte and granulocyte-macrophage colony-stimulating factor.

Agranulocytosis↗
PubMed1989

Neutrophil activation detected by increased neutrophil elastase activity in type 1 (insulin-dependent) diabetes mellitus.

Neutrophils have been implicated in the development of vascular disease, and increased plasma neutrophil elastase indicates increased neutrophil activation. The aim of this study was to determine whether neutrophil elastase levels, measured by radioimmunoassay, are altered in diabetes. One hundred Type 1 (insulin-dependent) diabetic patients and 35 comparably-aged control subjects were studied. There was no difference in the total white cell count, but the diabetic group had a higher neutrophil count (p less than 0.05). Plasma neutrophil elastase (p less than 0.001) and total neutrophil elastase (p less than 0.02) were increased in the diabetic group. The total neutrophil elastase levels reflected the neutrophil count, but plasma neutrophil elastase was independent of the number of neutrophils. The increased plasma neutrophil elastase level was not related to age, duration of diabetes, plasma glucose or HbA1. The results suggest an association between diabetes and neutrophil activation which may play a role in the development of vascular disease.

Adult↗
PubMed1988

A phase II trial of oral 4'demethoxydaunorubicin (DMDR) in inoperable non small cell lung cancer.

4'Demethoxydaunorubicin, an orally active daunorubicin analogue, was administered to 22 patients with inoperable non small cell lung cancer (NSCLC). Patients were stratified into good and poor risk categories and received doses of 45 mg/m2 and 40 mg/m2 respectively at 28 day intervals. All 22 patients were evaluable for response: No tumour responses occurred. Therapy was well tolerated. Mild gastrointestinal toxicity occurred in 41% of patients. Leucopenia with a wcc less than 3 x 10(9)/L occurred in 33% of patients and thrombocytopenia less than 100 x 10(9)/L in 9%. Severe marrow toxicity was rare and there appeared to be no difference in terms of toxicity between the different dose levels. DMDR appears to have no useful clinical activity in NSCLC.

Administration, Oral↗
PubMed1988

Altered lung vascular permeability during intermittent haemodialysis.

Hypoxia is known to develop during intermittent haemodialysis. To investigate if increased pulmonary capillary permeability to protein contributes to this phenomenon, a dual-isotope technique using Indium-labelled transferrin and Technetium-labelled red blood cells was used. Lung vascular permeability was measured in eight patients with dialysis-dependent chronic renal failure immediately before and during intermittent haemodialysis with cuprophane membranes. As a group there was a significant increase in lung vascular permeability during the early stages of haemodialysis, compared to predialysis values (P less than 0.05) and this increase occurred during the period when the patients were leucopenic and maximally hypoxic. During the haemodialysis period, but not the predialysis period, the permeability index was also significantly increased compared to a group of eight controls (P less than 0.05). These results suggest that increased vascular permeability may contribute to dialysis-induced hypoxia and that this may relate to neutrophil activation within the pulmonary vascular bed.

Adolescent↗