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J C Cooke

Publications and source records attributed to J C Cooke.

29 records · Page 2Linked to original sources

A comparison between pancreas and heart allotransplantation after administration of donor-specific antigen and cyclosporine.

These experiments compared the effect of a five-day course (days - 1 to +3) of cyclosporine therapy coupled with pretransplant (day - 1) administration of donor-specific antigen (whole blood or splenocytes) on either pancreatic or heart allograft survival in the Buffalo to Lewis rat donor-recipient combination. CsA therapy alone significantly (P less than 0.001) prolonged both heart (16.2 +/- 1.6 days) and pancreas (12.5 +/- 1.5 days) graft survival when compared with nonimmunosuppressed control heart and pancreas grafts (7.7 +/- 1.8 and 7.9 +/- 1.0 days, respectively). Pretransplant transfusion with either 2 ml of BUF whole blood or 2 x 10(8) red cell-free splenocytes on day -1 also resulted in a significant (P less than 0.001) prolongation of heart survival (14.0 +/- 1.2 and 14.0 +/- 1.6 days, respectively) but did not improve pancreas allograft survival (9.4 +/- 1.5 and 8.5 +/- 1.0 days, respectively). Combination CsA and antigen therapy further improved heart graft survival to 26.5 +/- 6.1 days (whole blood) and 28.8 +/- 5.8 days (splenocytes) but did not improve pancreas graft survival over that of CsA therapy alone. Extension of CsA therapy by adding two additional 3-day cycles on days 10-12 and 17-19 further improved heart graft survival both after CsA alone (35.2 +/- 3.2 days) and after CsA coupled with whole-blood transfusion (45.3 +/- 8.6 days), but did not have a salutary effect on pancreas allograft survival. Portal vein administration of donor antigen was equally effective as systemic inoculation in prolonging heart graft survival when the splenocytes were given alone (11.6 +/- 1.7 days). Conversely, pancreas allograft survival was not beneficially effected by portal antigen administration whether or not CsA was given. These data demonstrate the ability of pretransplant donor-specific antigen administration and short-term CsA therapy to significantly prolong rat heart allograft survival across a strong MHC histocompatibility barrier-but, surprisingly, they also demonstrate the failure of this regimen to have a salutary effect on pancreas allograft survival.

Animals↗

The accuracy of mammography alone and in combination with clinical examination and cytology in the detection of breast cancer.

The accuracy of mammography alone and in combination with clinical examination and aspiration cytology was assessed in 402 patients who attended the Early Diagnostic Unit of the Royal Marsden Hospital, London. The sensitivities of mammography, clinical examination and cytology in identifying breast cancer were 76.9%, 81.7% and 63.5% respectively; the specificities of each test were 90.0%, 87.6% and 99.3%. The calculated sensitivity was increased to 96.2% if one positive test out of the three was regarded as an indication to undertake breast biopsy. If this approach was adopted the number of breast cancers missed would be two out of 104 and the yield of positive biopsies would be approximately one in four (27.6%). The implications of proceeding to breast biopsy on the basis of a single positive test are discussed.

Aged↗

A quantitative analysis of the spatial relationships of grouped microcalcifications demonstrated on xeromammography in benign and malignant breast disease.

The mammograms of 444 patients who had a breast biopsy leading to a definitive histological diagnosis were reviewed. In 21 cases (4.7%) grouped microcalcifications were identified as the only mammographic abnormality. These groups of microcalcifications were analysed to determine whether there was any quantitative difference between benign and malignant lesions with respect to a shape parameter of the group, the spatial frequency of the particles and neighbour-to-neighbour relationships of the particles. This analysis did not reveal any significant difference between the spatial relationships of the grouped microcalcifications found in benign and malignant breast disease.

Biopsy↗

The appearances of multiple biliary hamartomas of the liver (von Meyenberg complexes) on computed tomography.

Computed tomography is well established in the management of patients with malignant disease, both as a staging procedure before initiation of treatment and in follow up. The presence of unsuspected metastases may affect the decision to perform surgery on the primary tumour and may alter the management of suspected recurrent tumour. Two cases are presented of patients with primary carcinoma whose computed tomography images showed multiple focal hepatic lesions suggestive of metastases. However multiple biliary hamartomas were found on histology, in one case by biopsy and in the other at post mortem. The differential diagnosis and significance of multiple liver defects on computed tomography is considered.

Aged↗

Role of computed tomography in diagnosis of bronchiectasis.

Bronchograms and computed tomograms were performed in 27 patients who presented consecutively for bronchography with chronic sputum production. The films were reported separately by three consultant radiologists, who had been asked to give a diagnostic interpretation of the films for each bronchopulmonary segment. The reporting of bronchiectasis on computed tomograms was compared with that on bronchograms. The sensitivity and specificity of computed tomography at segmental level compared with bronchography was 66% and 92%, respectively. We conclude that computed tomography alone is not yet suitable for accurate characterisation and localisation of disease in patients in whom surgery is contemplated. Computed tomography may be useful in patients in whom bronchography is contraindicated and for monitoring progression of disease after initial combined computed tomography and bronchography.

Bronchiectasis↗

Interpretation of bronchograms and chest radiographs in patients with chronic sputum production.

Bronchograms and plain chest radiographs of 27 patients with chronic sputum production were reported separately in random order and independently by two pulmonary radiologists to establish the diagnostic rate of each investigation and to assess interobserver variation. Both radiologists agreed on the presence of bronchiectasis on bronchography in 19 of 27 (70%) patients and in 94 of 448 (21%) bronchopulmonary segments. One radiologist only interpreted the films as showing bronchiectasis in a further two (7%) patients and 26 (6%) segments. There was more disagreement about the presence or absence of individual bronchographic abnormalities. Two main groups of patients with bronchiectasis were identified by bronchography: 11 with bronchiectasis alone and eight with bronchiectasis and bronchographic features suggestive of "chronic bronchitis". There was no clinical difference between these two groups. Plain chest radiographs were insensitive, being diagnostic (both radiologists agreeing) of bronchiectasis in only nine of 19 (47%) patients with definite bronchiectasis on bronchography.

Adolescent↗

The supine pneumothorax.

The consequences of an undiagnosed pneumothorax can be life-threatening, particularly in patients with trauma to the head or multiple injury and in those requiring mechanical ventilation. Yet it is these patients, whose films will be assessed initially by the surgeon, who are more likely to have a chest X-ray taken in the supine position. The features of supine pneumothoraces are described and discussed together with radiological techniques used to confirm the diagnosis, including computed tomography (CT) which may be of particular importance in patients with associated cranial trauma.

Diaphragm↗

Isolation of a porcine liver plasma membrane fraction that binds low density lipoproteins.

Large amounts of injected radiolabeled low density lipoproteins have been found by others to accumulate primarily in the liver and studies in various types of isolated cells, including hepatocytes, have indicated the presence of specific cell membrane recognition sites for lipoproteins. In the present studies, the high affinity binding of radiolabeled low density lipoproteins ([125I]LDL, d 1.020--1.063 g/mL) was measured in the major subcellular fractions of porcine liver homogenates. The nuclear and mitochondrial fractions were 1.9- and 1.4-fold enriched in binding activity with respect to unfractionated homogenates and contained 15% and 12% of the total binding activity, respectively. The microsomes, which contained most of the plasma membranes and endoplasmic reticulum, were approximately 4-fold enriched in binding and contained 73% of the binding activity. Microsomal subfractions obtained by differential homogenization and centrifugation procedures were 5.6--7.0-fold enriched in LDL binding and contained 54--58% of the homogenate binding activity. They were separated by discontinuous sucrose density gradient centrifugation into fractions which contained "light" and "heavy" plasma membranes and endoplasmic reticulum. The heavy membrane fraction was 2--4 fold in binding with respect to the parent microsomes (16--22 fold with respect to the homogenate). There was no enrichment of binding activity in the other two fractions. Two plasma membrane "marker" enzymes, nucleotide pyrophosphatase and 5'-nucleotidase, were also followed. Of the two, binding in the sucrose density gradient subfractions most closely followed nucleotide pyrophosphatase, which was also most highly enriched (3.2--3.3-fold) in the heavy membrane fraction, but did not follow it exactly. The enzyme was 2-fold richer in the light membranes than in the parent microsomes, though the light membrane binding activity was only 0.4--1.4 times that of the parent microsomes. High affinity binding was time and temperature dependent, saturable, and inhibited by unlabeled low density lipoproteins but not by unrelated proteins. Binding was stimulated 2--3 fold Ca2+, was not affected by treatment with Pronase or trypsin and was inhibited by low concentrations of phospholipids and high density lipoproteins (HDL). Heparin-Mn2+ treatment of HDL did not affect its ability to inhibit [125I] LDL binding. The LDL recognition site was distinct from the liver membrane asialoglycoprotein receptor; LDL binding was not inhibited by desialidated fetuin. We conclude that porcine liver contains a high affinity binding site that recognizes features common to both pig low density and high density lipoproteins. Further studies may elucidate the significance of this binding site in lipoprotein metabolism.

Animals↗