A 25-year computerised survey of deaths in the United Kingdom among diabetic patients of 19 years of age and under was performed. Suitable pancreatic material was available in 119 out of the 498 identified patients. The duration of diabetes was known in 95 of the 119 patients. In 60 patients it had been present for less than 1 year. Insulitis was present in 47 of the 60 patients (78%) with recent onset disease, and was also found in 3 patients who had been treated for diabetes for between 1 and 6 years. In cases in which it was identified, insulitis affected 23% of islets containing insulin, but affected only 1% of islets which were insulin deficient, thus supporting the concept that insulitis represents an immunologically mediated destruction of insulin secreting B cells. Four patients appeared to have a different disease from classical Type 1 (insulin-dependent) diabetes in that there was no evidence of insulitis and all islets contained insulin. The age of onset of diabetes was eighteen months or less in these patients.

No abstract

Twenty-three patients with recent onset Type 1 (insulin-dependent) diabetes in whom residual insulin secreting B cells were present and 12 patients with disease of more prolonged duration (maximum 9 years), 8 of whom had residual B cells, were studied. Aberrant expression of Class II major histocompatibility complex molecules was demonstrated immunohistochemically on insulin secreting B cells in 21 out of 23 patients with recent onset disease and 6 of the patients with more prolonged disease. No such expression was seen on glucagon secreting A cells or somatostatin secreting D cells. Islets where there was marked hyperexpression of Class I major histocompatibility complex molecules on islet endocrine cells were seen in all cases in which residual B cells were present. Ninety-two per cent of insulin containing islets but only 1% of insulin deficient islets exhibited this phenomenon (p less than 0.001, Chi-squared test). There was evidence to suggest that both these abnormalities of major histocompatibility complex expression preceded insulitis within a given islet. They also appeared to be unique to Type 1 diabetes, being absent in pancreases of patients with Type 2 (non-insulin-dependent) diabetes, chronic pancreatitis, cystic fibrosis, graft-versus-host disease and Coxsackie B viral pancreatitis. The development of autoimmunity to B cells in Type 1 diabetes may be a "multistep" process in which abnormalities of major histocompatibility complex expression on islet endocrine cells are crucial events.

This study sought to determine, firstly, the relative frequency of lymphocytes and macrophages and, secondly, the percentage of lymphocytes containing interferon-gamma in inflamed islets (insulitis) of patients with type 1 (insulin-dependent) diabetes. Autopsy pancreases of 12 patients who had died of recent-onset type 1 diabetes and one pre-diabetic patient who had died of cardiomyopathy were examined immunohistochemically. In the 87 islets that were studied, the lymphocyte macrophage ratio was 9.7:1 and approximately 40 per cent of the lymphocytes contained interferon-gamma. Interferon-gamma release in the insulitis process may be involved in the pathogenesis of type 1 diabetes.

Changes in cross-sectional area are currently used to assess tumour response to treatment. The aims of this study were to validate a helical CT technique for volume determination using a series of phantoms and to compare tumour responses indicated by one-, two- and three-dimensional measures of tumour size change in patients treated for germ cell cancer or lymphoma. All studies were performed on an IGE HiSpeed Advantage helical CT scanner with an Advantage Windows workstation. Phantom volumes were calculated using volume reconstruction software and compared with reference volumes determined by water displacement. 20 lymph node masses were studied on serial CT scans in 16 patients treated with chemotherapy for germ cell cancer or lymphoma. For each lesion the maximum diameter, maximum cross-sectional area and volume were determined before and after treatment. Tumour response was assessed using the standard World Health Organisation criteria (i.e. changes in cross-sectional area) and the newly proposed unidimensional response evaluation criteria in solid tumour (RECIST). The CT volume measurement error was 1.0-5.1% for regularly shaped phantoms larger than 35 cm3. In the assessment of treatment response there was 90% agreement between one-dimensional (1D) and two-dimensional (2D) measurements and 100% agreement between 2D and three-dimensional (3D) measurements. CT volume measurements are accurate and reproducible, particularly for larger structures. Assessment of tumour response using 1D, 2D and 3D measures had limited influence on the classification of treatment response. However, the impact of CT assessment of tumour response using 1D, 2D and 3D measurements on clinical decisions and patient outcome remains to be determined.

Using an antiserum raised to a recombinant coxsackie virus B 3 capsid protein, VP1, an immunocytochemical technique was developed which was capable of detecting the presence of all coxsackie B viruses in formalin fixed paraffin embedded infected tissue culture cells. This technique was tested on autopsy heart and pancreas from 21 patients who were thought to have died of acute coxsackievirus B myocarditis. Cardiac myocytes were positive for the VP1 protein in 12 of 20 cases where the heart was available for study. Insulitis was present in the pancreas in seven of these cases and in all seven islet endocrine cells containing VP1 were found. VP1 was only rarely found in exocrine pancreas. In heart and pancreas, cells shown to contain VP1 usually showed signs of necrosis. Autopsy pancreases from 88 patients who had died at clinical presentation of Type 1 (insulin-dependent) diabetes mellitus showed no evidence of the presence of VP1. The continuing destruction of insulin-secreting B cells seen at the time of death in the diabetic pancreas is unlikely to be due to a direct cytopathic effect of a coxsackie B virus. However, this study does not exclude the possibility that a persistent infection of B cells by a defective enterovirus may result in their destruction by an autoimmune mechanism.

No abstract

Aims-To assess the diagnostic accuracy of lymph node fine needle aspiration (FNA) cytology to distinguish reactive lymphoid hyperplasia from malignant lymphoma, and to evaluate the contribution of ancillary techniques applied to cytological material. Methods-Two hundred and seventy seven consecutive lymph node FNA specimens reported to be consistent with reactive lymphoid hyperplasia (n = 213) or suggestive/diagnostic of malignant lymphoma (n = 64) were reviewed. Follow up data were obtained by case record review or by histological correlation. The value of immunocytochemistry, in situ hybridisation for immunoglobulin light chain mRNA, and polymerase chain reaction (PCR) towards the final clinicopathological diagnosis was assessed in 92, 61, and 45 cases, respectively. Results-Sixty one of 67 lymphomas and 207 of 209 reactive lymph nodes were accurately diagnosed by FNA cytology. There were six false negative aspirates including three cases of follicular lymphoma, two cases of Hodgkin's disease, and one chronic lymphocytic leukaemia. Two FNA specimens considered suspicious of lymphoma proved reactive on histology or clinical follow up. One metastatic small cell carcinoma was wrongly diagnosed as lymphoma. Ancillary studies contributed to the correct diagnosis in most cases although occasional misleading results were obtained, particularly with PCR. Conclusions-FNA cytology accurately distinguished reactive lymphoid hyperplasia from malignant lymphoma in 97% of cases. However, occasional wrong diagnoses occurred owing to sampling error or misinterpretation. Ancillary studies can be applied to cytological samples and contribute to the diagnosis in most cases. (J Clin Pathol 1998;51:197-203)