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Biomedical subjects

P G Toner

Publications and source records attributed to P G Toner.

At least 19 recordsLinked to original sources

Parathyroid cyst of the thymus.

A case is described of primary hyperparathyroidism in a patient with both a parathyroid cyst within the thymus gland and a concomitant parathyroid adenoma. The parathyroid adenoma contained microcystic areas of degeneration, and it is thought that the parathyroid cyst reflected degenerative change in a pre-existing adenoma. Parathyroid cyst should be considered in the differential diagnosis of cystic lesions within the thymus. Fine needle aspiration and parathyroid hormone assay on cyst fluid may provide a preoperative diagnosis.

Adult

Use of the autopsy in Northern Ireland and its value in perioperative deaths.

A report on the pilot study of the Confidential Enquiry into Perioperative Deaths was published recently in the United Kingdom. The scheme was designed as a specialized form of clinical audit relating to perioperative patient care. Because the report placed little emphasis on autopsy, we have looked at all autopsied perioperative deaths, as defined by the enquiry, over a three-year period (1986-88) in a defined catchment area of Northern Ireland. Class I major discrepancies of diagnosis between clinical and postmortem records were found in 21% of 213 autopsied perioperative deaths. By definition, these represented instances in which an adverse impact on patient survival had resulted from the discrepancy. In an additional 29% of cases, there were Class II major discrepancies, which were discrepancies in the primary diagnosis not relevant to life-saving treatment. In 30% of cases there was a discrepancy in a secondary diagnosis, which might have affected the eventual prognosis, had the patient survived, but which was not related directly to the cause of death; these were termed Class III discrepancies. In 47% of cases, there were Class IV discrepant secondary diagnoses, which were 'incidental' findings and had no bearing on prognosis. To put these findings in context, the autopsy rate in Northern Ireland was 12% in 1987, with a higher rate (23%) in the two main teaching hospitals and a lower rate (8%) in all other hospitals. The rate of coroner's autopsies, 6%, is uniform throughout Northern Ireland. Coroner's autopsies are carried out mostly by the salaried staff of the State Pathologist's department. The observed differences in the rates of hospital autopsies reflect local deficiencies of pathologists in relation to the work load. In a series of consecutive autopsies carried out at one of the main teaching hospitals, the highest autopsy rate (68%) was found for paediatric patients, with rates of 29% for surgical and 23% for medical cases. The proportion of hospital autopsies carried out in perioperative surgical patients was the same as that for medical patients, reflecting the fact that no particular emphasis is placed on use of the autopsy as a form of clinical audit for the perioperative group.

Adolescent

The blood-testis barrier in experimental unilateral cryptorchidism.

Unilateral cryptorchidism was induced in Wistar rat pups within 48 h of birth. After a period of 150 days, the blood-testis barrier was evaluated in the cryptorchid and contralateral scrotal testis, using a lanthanum immersion technique. The barrier was demonstrated to be competent, with tracer confined to the basal and intermediate compartments.

Animals

Value of the necropsy in perioperative deaths.

A series of 213 perioperative deaths was studied out of a total of 1451 consecutive necropsies carried out over three years. Discrepancies between the clinical and the necropsy diagnosis were assessed under four classes of discrepant diagnosis: class I, patient survival affected, treatable; class II, patient survival affected but not treatable; class III, correlated to cause of death but treatable; and class IV, incidental diagnosis which could not have been made before death. Major discrepancies of classes I and II were found in 44 (21%) and 62 (29%) cases, respectively. Minor discrepancies of classes III and IV were found in 63 (30%) and 101 (47%) cases, respectively. No discrepancies were found in 50 (23.5%) cases. These results confirm the continuing value of the necropsy in the assessment of perioperative deaths.

Adolescent

Tartrate resistant acid phosphatase positive splenic lymphoma: a relatively benign condition occurring in a time-space cluster?

Conventional light and electron microscopic studies, together with cytochemical and immunocytochemical staining procedures, were carried out to ascertain whether the lymphomata of four elderly female patients living within 10 kilometers of each other, who presented within a short space of time with massive splenomegaly and varying cytopenia, belonged to any particular subgroup of lymphoma. In each case the lymphoma had a diffuse pattern and mature B cell phenotype. The malignant cells were of uniform cell type, slightly larger than admixed polymorphonuclear leucocytes, and showed minimal nuclear irregularity and positivity for tartrate resistant acid phosphatase (TRAP) staining. Their clinical and morphological features were compared with those of other lymphoproliferative disorders, but while sharing some features in common with each condition, this small group of patients seemed to have a unique combination of findings. The cytopenias of all four responded well after removal of the spleen and their disease has not been aggressive. It is concluded that these patients have a distinct subgroup of lymphoma, which it is important to recognise so that inappropriate use of aggressive cytotoxic drugs can be avoided.

Acid Phosphatase

Gastric paraganglioma: an immunohistological and ultrastructural case study.

This is a report of the immunohistochemical and ultrastructural features of a case of paraganglioma of the stomach in a 61-year-old woman who presented with melaena. The typical 'Zellballen' arrangement of epithelial cells with granular cytoplasm was present and the tumour was highly vascular. The polygonal epithelial cells stained strongly for neuron specific enolase and the intervening elongated sustentacular or support cells were positive for S100 protein and vimentin. Many dense core granules were present within the epithelial cells while the elongated support cells contained plentiful diffuse intermediate filaments. No hybrid cells or ganglion cells were present in the tumour. This is the sixth recorded case of gastric paraganglioma and the first to be studied in detail by immunostaining and electron microscopy.

Female

The use of electron microscopy and immunocytochemistry to characterise spontaneously-arising, transplantable rat tumors.

When examined by light microscopy, transplanted animal tumors frequently bear little resemblance to the original neoplasm. If such tumors are to be used as models of human cancer they should be characterised as regards extant rather than historical features. Consequently, we have examined, by electron microscopy and immunocytochemistry, five spontaneously arising tumors transplantable in the WAB/Not rat that are currently diagnosed on the basis of historical features only. A typical sarcoma was used for comparison. Of four spontaneously arising tumors previously classified as carcinoma, Sp4 possessed epithelial features on both ultrastructural and immunocytochemical analysis, Sp107 on ultrastructural analysis only and Sp15 and Sp22 by neither technique. Expression of vimentin was most marked with Sp15 and Sp107. The putative sarcoma, Sp24, showed clear evidence of epithelial differentiation but no evidence of vimentin expression. This study (a) records the phenotypic drift of experimental tumors on transplantation (most clearly with Sp107) and the co-expression of cytokeratins and vimentin in putative carcinomas, (b) confirms the inadequacy of routine histology for accurate characterisation of such tumors and (c) details techniques for a more thorough assessment of state of differentiation that should guide the choice of experimental model.

Animals

Necropsies in clinical audit.

The need for specialised forms of clinical audit was highlighted by the report of the Confidential Enquiry into Perioperative Deaths (CEPOD). Necropsy rates in a Northern Ireland teaching hospital were studied with particular reference to perioperative deaths. To provide an overall context for these observations, the pattern of the necropsy services in Northern Ireland as a whole was also determined. For 600 consecutive deaths in a major teaching hospital, the overall necropsy rate was 180 (30%). In the 74 perioperative deaths in this group (as defined by the CEPOD) the necropsy rate was 26 (35%), compared with 16 out of 72 (22%) for other surgical deaths and 89 out of 386 (23%) for medical cases. More coroners' necropsies were carried out in the perioperative group. These figures are within the range of the CEPOD experience. In 1987, in the whole of Northern Ireland, there were 8859 hospital deaths, 520 (5.9%) hospital necropsies, and 516 (5.8%) coroners' necropsies, giving an overall necropsy rate of 11.7%. Outside the two major Belfast teaching hospitals, however, there were 6799 hospital deaths, 76.6% of all hospital deaths for Northern Ireland. In this group there were 180 (2.6%) hospital necropsies and 383 (5.6%) coroners' cases, the overall necropsy rate being only 8.2%. These wide variations reflect the fact that the number of pathologists in post in the peripheral areas of the province falls substantially short of levels recommended by the Royal College of Pathologists. If clinical audit along CEPOD lines is to be effective nationally, more emphasis should be placed on the value of necropsy and local deficiencies in provision will have to be identified and remedied. It is suggested that this could be achieved by combining audit provisions with budgetary incentives.

Autopsy

Familial expansile osteolysis. A new dysplasia.

We report 40 cases in one family of an autosomal dominant bone dysplasia, which, though similar in some aspects to Paget's disease, seems unique in some features and in its natural history. The disease shows both general and focal skeletal changes, the latter being mainly in the limbs with an onset from the second decade. Progressive osteoclastic resorption is accompanied by medullary expansion which leads to pain, severe deformity and a tendency to pathological fracture. The serum alkaline phosphatase and urinary hydroxyproline are variably elevated, while other biochemical indices are normal. Most patients had an associated deafness of early onset and loss of dentition. No previous description of this disease has been found in the literature.

Deafness

Mechanism of actinomycin D-induced resistance in Ridgway osteogenic sarcoma: an ultrastructural study.

The ultrastructural appearances of actinomycin D treated sensitive and resistant sublines of Ridgway osteogenic sarcoma (ROS) have been correlated with the suggested mechanism of drug-induced resistance. The resistant subline (designated ROS/ADX/G2) was developed by repeated suboptimal treatment of tumor bearing animals and passage of the fastest growing tumors. In the present experiments, animals bearing sensitive and resistant tumors were given a single intraperitoneal injection of actinomycin D (0.3 microgram/g) and examined at 1, 6 and 24 h after injection. The principal effect of actinomycin D treatment in both cell lines was the development of nucleolar segregation. This change, however, followed a different time-scale in each case, appearing more prominently at an early stage and returning more quickly to normal in the actinomycin D resistant cell line. These findings can be interpreted as being in agreement with the suggestion that reduced drug retention or an increased rate of detoxification provides the mechanism of acquired resistance.

Animals

Functional and structural changes of the human proximal small intestine after cytotoxic therapy.

The effects of cytotoxic therapy on the structure and function of the proximal jejunum were studied in six patients receiving intravenous cyclophosphamide (300 mg/m2), methotrexate (40 mg/m2), and 5-fluorouracil (600 mg/m2) as adjuvant therapy for breast cancer. Using a steady state, triple lumen tube perfusion system the absorption of water and electrolytes was measured before and 48 h after administration of the cytotoxic agents. Jejunal biopsies were obtained at each perfusion. Median (range) water absorption fell from 126 (40-142) to 84 (46-142) ml/h/30 cm, with parallel changes for electrolytes; none of the changes was significant. Brush border disaccharidases did not change at 48 h after chemotherapy, while mature enterocytes appeared normal by both light and electron microscopy. Crypt cells and immature enterocytes, however, showed focal vacuolation by light microscopy, corresponding to the occurrence of large residual bodies (secondary lysosomes) containing partially degraded fragments of damaged crypt cells. The confinement of ultrastructural changes to the immature cell population may explain the failure of this study to show a consistent change in the absorptive function of the jejunum 48 h after chemotherapy.

Adult

Correlative scanning electron microscopy in gastrointestinal pathology.

Some applications of SEM to the study of gastrointestinal pathology are illustrated and discussed, along with a review of recent literature in this field. Particular emphasis is placed on correlative microscopy, involving, for example, the reprocessing of SEM specimens for LM and TEM, and of LM paraffin blocks for SEM. In terms of diagnosis and prognosis, the relevance of SEM data at present remains quite limited, calling for the further exploration of clinical and diagnostic problems through correlative techniques.

Digestive System

Effect of bile salt perfusion and intraduct pressure on ionic flux and mucosal ultrastructure in the pancreatic duct of the cat.

Net ionic flux and mucosal ultrastructure were examined following perfusion of the cat pancreatic duct with bicarbonate or sodium taurocholate solutions (5-40 mM). Taurocholate perfusion increased net Cl- gain, net HCO3- loss and net K+ gain and was associated with significant widening of lateral intercellular spaces and increased complexity of intercellular labyrinths. Increased perfusion pressure (30 mm Hg) did not affect flux or ultrastructure during perfusion with bicarbonate but increased net ion flux significantly during perfusion with 40 mM sodium taurocholate. Ultrastructural changes during perfusion of 40 mM taurocholate at increased pressure were not consistent but focal epithelial disruption and cell shedding were seen occasionally. The hypothesis is advanced that taurocholate perfusion triggers physiological transport mechanisms and may make the duct mucosa more vulnerable to other potentially harmful agents. The significance of these changes in the pathogenesis of acute pancreatitis in man remains uncertain and care must be exercised before extrapolating from observed net ion flux data in this animal model.

Animals