Biomedical subjects
Publications and source records attributed to A Busuttil.
Rhabdomyosarcoma is a rare primary bladder tumor, with the majority occurring in children. A case arising in a 75-year-old woman is reported. Complete tumor regression occurred after radiation therapy.
The presence of specific and high affinity epidermal growth factor receptors (EGF-R) has been demonstrated in human prostate cancer (CaP). Scatchard analysis of the binding data revealed a linear plot consistent with a single class of binding sites with a mean dissociation constant (Kd) +/- s.d. = 1.6 +/- 0.4 nmol 1-1. Additionally the binding was specific for EGF since no other competitor than EGF was able to displace the binding of the labelled ligand from its receptor. Comparison of the concentrations of EGF-R in tissues from 19 patients with CaP with those measured in a group of 18 patients with benign prostatic hyperplasia (BPH) reveal that the expression of EGF-R was significantly higher in BPH (mean +/- s.d. = 125 +/- 7 fmol mg protein-1) than in CaP (52 +/- 11 fmol mg protein-1; P less than 0.01). Furthermore, in CaP the expression of EGF-R varied according to the histological grade of the cancer: well differentiated tumours demonstrated more receptors (84 +/- 13 fmol mg protein-1) than poorly differentiated tumours (22 +/- 5 fmol mg protein-1; P less than 0.01). Clearly the depletion in the expression of EGF receptors in CaP is a function of the histological grade of the cancer and as such EGF receptors could be used as a biochemical marker for tumour differentiation.
The local immune response to intravesical BCG therapy for widespread carcinoma in situ and superficial bladder tumour was assessed using immunohistochemical methods on serial biopsies obtained during treatment. The main findings were the induction of a strong level of HLA-DR expression by urothelial cells which persisted for several months after completion of therapy. This coincided with a mononuclear cell infiltrate in the bladder wall consisting predominantly of activated helper T lymphocytes. Smaller numbers of macrophages, suppressor cytotoxic T lymphocytes and B lymphocytes were also found. These new findings confirm that the inflammatory response to BCG involves the urothelium in an immunological reaction and suggest that the success of immunotherapy with intravesical BCG may be due to enhanced tumour antigen recognition.
A retrospective study of all patients who died following trauma in the Accident and Emergency Department of the royal Infirmary of Edinburgh over a 4-year period revealed 50 patients (0.0002% of total attendances). Injury severity scores (ISS) and probabilities of survival (Ps) were calculated for all patients. Two-thirds had a Ps of zero while 7 (14%) had a Ps of 0.5 or more. From the information in the case records and at autopsy four deaths (8%) were considered to have been potentially avoidable on the basis of inadequate or inappropriate management. There were a further eight cases (16%) whose management appeared to have been unsatisfactory but who would have been expected to die even if given optimal treatment. These cases are discussed in detail. Difficulty in diagnosing thoracic injuries and delay in giving appropriate treatment were by far the commonest errors encountered. A protocol for the treatment of patients in cardiorespiratory arrest with thoracic injuries is presented. The importance of regular audit of trauma cases and deaths is emphasized.
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We report a case of malignant mesothelioma of the testicular tunica vaginalis. A preceding hydrocele showed mesothelial hyperplasia of its lining. The tumor was treated surgically as well as with a combination of radiotherapy and chemotherapy but it progressed, resulting in death within 21 months from the diagnosis. The relationship of the tumor to mesothelial hyperplasia and to previous exposure to asbestos is discussed.
A modified method has been devised which enables the pathologist to evaluate more efficiently the seminiferous tubules and to present a more detailed histological report on testicular biopsies in patients investigated for infertility. This basically involves the production of a diagrammatic representation of the actual biopsy onto a specifically designed reporting form: a detachable prismatic arm attached to an ordinary light microscope enables the pathologist to transfer an actual outline of each of the seminiferous tubules contained in the biopsy onto this form. The seminiferous epithelium and Leydig cells are scored using the method of Johnsen. This method was evaluated using 20 consecutive biopsies. Skill in its usage was quickly acquired and it has been found to be a more clinically acceptable way of histopathological reporting, further facilitating standardization and inter-laboratory comparison.
Of 403 consecutive cases of prostatic carcinoma 69 were diagnosed incidentally and were managed with a deferred treatment policy. The mean age at diagnosis was 74 years and mean follow-up was 42 months. Retrospective analysis confirmed that many such patients die of intercurrent disease before symptomatic tumour progression. However, patients aged 70 years or less at diagnosis with diffuse, high grade disease were shown to be at greater risk of symptomatic tumour progression. In this study 60% progressed to skeletal metastases within 3 years. Deferral of treatment in such patients appears inappropriate.
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This paper reports further study of the identity and function of a protein shown to be elevated in serum from cystic fibrosis (CF) patients and clinically normal heterozygotes. Monoclonal antibodies, specifically recognizing the tentatively named cystic fibrosis antigen (CFAg), were produced. Immunoaffinity purification of CFAg from several sources revealed two components: 11 x 10(3) and 14 x 10(3) Mr protein. cDNA clones corresponding to each protein have been isolated. Data-base comparisons of the deduced amino acid sequences suggest that both genes encode related but distinct calcium-binding proteins. We propose the name calgranulin A and B, for the 11 x 10(3) and 14 x 10(3) Mr components, respectively. It is clear from the assignment of the calgranulin genes to chromosome 1 that neither is the product of the mutant CF gene, which maps to chromosome 7. We have used the monoclonal antibodies to study the tissue distribution of the two proteins in a wide-ranging immunohistological survey. Where possible the pattern of expression was confirmed by RNA blot analysis. Strong calgranulin expression in granulocytes was confirmed. In addition to myeloid cells, a restricted subset of normal stratified squamous epithelia were found to be calgranulin-positive. These included tongue, oesophagus and buccal cells, the last of which has been shown to have altered calmodulin activity in CF patients. Using indirect alkaline phosphatase staining, tissue sections of lung, pancreas and skin (normally considered sites where the CF defect is expressed) were not calgranulin-positive. However, by indirect immunofluorescence, nasal polyp sections showed weak patchy calgranulin expression in some epithelial cells, and stronger, higher frequency expression when such cells were briefly cultured.(ABSTRACT TRUNCATED AT 250 WORDS)
Full thickness specimens of normal colon (n = 15), and colon from patients with diverticular disease (n = 5) were obtained at operation or autopsy. In the isolated submucosa the ultrastructure of the constituent collagen fibres was examined by transmission electron microscopy. Collagen fibrils in the left colon become smaller (p less than 0.001) and more tightly packed (p less than 0.001) than those in the right colon with increasing age. This difference is accentuated in diverticular disease (p less than 0.01). Factors which contribute to the development of colonic diverticulosis, such as raised intraluminal pressure, may be responsible for premature change in submucosal structure.
The authors have investigated lymphocyte subpopulations and macrophages in normal human testes and the testes of patients under investigation and treatment for subfertility. Specific monoclonal antibodies were used in an indirect immunoperoxidase technique. In normal tissues, T lymphocytes (Leu 4-positive cells) were present in the rete testis with a preponderance of cells of the suppressor/cytotoxic phenotype. In contrast, no lymphocytes were detected within the peripheral portions of the testis. Cells reacting with the anti-Leu M3 monoclonal antibody, which defines monocytes/macrophages, were detected in appreciable numbers in peripheral testis with a specific location around the seminiferous tubules. HLA-DR-positive cells (human leukocyte antigens--class II [DR] determinants of the major histocompatibility complex) also were identified and showed a similar pattern of distribution to that of the Leu-M3 positive cells. While no lymphocytes were seen in the normal peripheral testis, T lymphocytes were detected in testicular biopsies from subfertile patients. Suppressor/cytotoxic T cells (Leu 2a-positive) predominated in patients with oligozoospermia and obstructive azoospermia while T cells of the helper/inducer phenotype predominated in patients with unilateral testicular obstruction and in postvasectomy patients. Sperm antibody measurements correlated with these findings.
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In animal models of intestinal hypersensitivity, lymphocyte-mediated damage to the small-bowel mucosa produces a characteristic pattern of morphologic abnormalities. Similar findings in human jejunal biopsy specimens may also indicate that T cells are involved in a disease process. To test the hypothesis that there is a generalized activation of mucosal T cells throughout the small-intestinal mucosa in Crohn's disease, measurements of the lengths of crypts and villi and intraepithelial lymphocyte (IEL) counts were made on jejunal specimens from 33 patients with this condition, and the results compared with the established reference values and with results of specimen measurements in a group of normal subjects. Taken as a group, the specimens from Crohn's patients had abnormal villus length, crypt length, and IEL counts. Focal histologic abnormalities such as ulcers, fissures, or granulomas were present in 10 of the specimens. When specimens with and without a focal abnormality were compared, the former showed shorter villi (median, 249.6 versus 331 microns, p less than 0.01), longer crypts (median, 330.4 versus 108.2 microns, p less than 0.01) and higher IEL counts (60.5 versus 32 IEL/100 enterocytes, p less than 0.01). These findings suggest that there is a mucosal cell-mediated immune response in the jejunum in Crohn's disease and that this is pronounced in the vicinity of microscopic, focal lesions.