Conchotome and needle percutaneous biopsy of skeletal muscle.

Percutaneous muscle biopsy is an important and acceptable technique in the study of conditions involving human skeletal muscle. A review of 436 conchotome and needle muscle biopsies obtained over 18 months in this centre is presented.     

Resistance to recombinant human erythropoietin due to aluminium overload and its reversal by low dose desferrioxamine therapy.

Seventeen severely anaemic and transfusion-dependent haemodialysis patients with a haemoglobin less than 7 g/dl were treated with recombinant human erythropoietin (r-Hu-EPO). Aluminium toxicity was diagnosed by a positive desferrioxamine (DFO) test and bone biopsy. Seven out of eight patients without aluminium toxicity responded to r-Hu-EPO therapy. Similarly all patients with aluminium toxicity (n = 4) but pre-treated with standard dose of DFO prior to r-Hu-EPO therapy responded but none of the patients with untreated aluminium toxicity (n = 5) responded to r-Hu-EPO therapy. In order to achieve adequate response in these patients, r-Hu-EPO and DFO had to be given in combination. The dose of desferrioxamine used to reverse r-Hu-EPO resistance was less and also used for a short time. We therefore confirm r-Hu-EPO resistance owing to aluminium overload and report its successful and safe reversal with low dose DFO therapy.     

Morphometric analysis, ploidy and response to chemotherapy in squamous carcinomas of the head and neck

The histopathology of 54 squamous carcinomas of the head and neck was evaluated by qualitative grading and morphometry in order to identify those features which predicted a good response to cisplatinum chemotherapy. The histopathology of 66 cases was correlated with tumour ploidy, determined by flow cytometry of paraffin-embedded material, since a separate study has shown that aneuploid carcinomas respond better to chemotherapy. The degree of differentiation was a poor predictor of ploidy, although diploid carcinomas did show more keratin and less nuclear pleomorphism than aneuploid carcinomas. The prominence of nucleoli in tumour cells and the surface area to volume (s/v) ratio of the tumour islands were the variables most strongly correlated with ploidy, with diploid carcinomas having prominent nucleoli and a low s/v ratio. A good response to chemotherapy was related partly to the architecture of the carcinoma (pushing border and low s/v ratio), and partly to the tumour cells (well differentiated) and the percentage of necrotic tumour. A lack of inflammatory reaction or desmoplasia was associated with a poor response. The results indicate that both subjective and objective histopathological criteria may be used to predict ploidy and the response to cisplatinum chemotherapy of squamous carcinoma of the head and neck. A combination of s/v ratio and the percentage of necrotic tumour can be used to identify a group of patients with a relatively good survival.     

Use of lectin histochemistry in pancreatic cancer.

Lectin peroxidase histochemical analysis was carried out on pancreatic tissue from patients with pancreatic carcinoma and chronic pancreatitis and from subjects with normal pancreas to find a tumour specific pattern of lectin binding that would aid histological and cytological diagnosis. There were striking differences between the lectin binding characteristics of the different cell types in the normal pancreas. Acinar cells were uniformly positive for binding with wheat germ agglutinin and soy bean agglutinin while islet cells were usually negative for these lectins. Ulex europaeus I lectin however, was found not to be specific for endothelium, showing positivity also for acinar and ductal tissue. Griffonia simplicifolia II lectin was found to be highly specific for ductal epithelium, and because of this was tested in a hamster pancreatic cancer model where it was not specific for ductal epithelium, reflecting differing carbohydrate expression in the hamster pancreas. Pancreatic carcinomas and chronic pancreatitis bound all five lectins without any qualitative distinction from each other or from normal pancreatic tissue, but there was increased intensity of peanut agglutinin binding to secreted mucins in pancreatic carcinoma, which may be of potential use in radiolabelled lectin scanning.     

Stress and glucocorticoid inhibit apical GLUT2-trafficking and intestinal glucose absorption in rat small intestine

We have proposed a new model of rat intestinal sugar absorption in which high glucose concentrations promote rapid insertion of GLUT2 into the apical membrane, so that absorptive capacity is precisely regulated to match dietary intake. Construction and building work during expansion and refurbishment of our department permitted opportunistic experiments on the effects of building-induced stress on the GLUT2 component of absorption. In fed rats perfused with 75 m m glucose in vivo , stress rapidly inhibited glucose absorption 36.4 ± 3.0% compared with control rats. Selective inhibition of the GLUT2 component with phloretin demonstrated that stress inhibited the GLUT2 component by 42.8 ± 3.8%, which correlated with a corresponding diminution in apical GLUT2 levels: the SGLT1 component and its level were unaltered by stress. Effects of stress were reversed by the administration in drinking water of metyrapone, which inhibits 11-β-hydroxylase. Injection of dexamethasone into control rats 60 min before perfusion resulted in absorption and transporter properties indistinguishable from stressed rats. Our data are consistent with the view that stress activates the hypothalamus–pituitary–adrenal (HPA) axis, causing release of glucocorticoid. The ensuing inhibition of GLUT2 trafficking and absorption seems necessary to prevent enhanced intestinal delivery of glucose to the circulation from antagonizing the essential stress response of glucorticoid in mobilizing peripheral energy stores for emergency purposes.     

The occupation of fishing as a risk factor in cancer of the lip.

To study the role of commercial fishing and related factors in the development of lip cancer, a project that included a case-control study and a cohort analysis was undertaken in Newfoundland. Household survey data were linked with cancer-registry and census data. In comparison with other males, fishermen had a probability of development of lip cancer that was 1.5 times higher (by the case-control method, P less than 0.05) or 4.4 times higher (by cohort analysis, P less than 0.001). Despite the effect of pipe smoking, "outdoorness" and age on the development of lip cancer in general, the occupation of fishing was an additional, independent contribution to the risk. Unexpectedly, using the mouth as a third hand to handle tar-coated nets seemed to protect fishermen from the disease. It was not possible to attribute the higher risk to a particular work activity, nor was a specific responsible carcinogen identified.     

Lectin binding and desmin expression during necrosis, regeneration, and neurogenic atrophy of human skeletal muscle

Changes in the cytoplasm of skeletal muscle fibres during necrosis, regeneration, and neurogenic atrophy have been studied in a wide range of human neuromuscular diseases with a panel of eleven biotinylated lectins and by immunohistochemical staining for the cytoskeletal protein desmin. Increased binding of several lectins was observed in both necrotic and regenerating fibres, with Concanavalin A the most consistently positive lectin. Staining for desmin was strong in the cytoplasm of regenerating and partially damaged fibres and was lost in necrotic fibres, although there were differences in the staining reactions of the two antidesmin antibodies used. In fibres which had undergone neurogenic atrophy, cytoplasmic lectin binding was seen only with Griffonia simplicifolia 1 lectin, and desmin was expressed more strongly than in normal fibres. Lectin binding and immunohistochemical staining from desmin can supplement the information obtained from muscle biopsies by conventional histochemical methods and lead to a better understanding of the mechanisms of muscle damage.     

p53 Protein expression in tumours from head and neck subsites,larynx and hypopharynx,and differences in relationship to survival

The present study involves an immunohistochemical analysis of p53 protein expression in head and neck tumours located at two separate subsites, the larynx and hypopharynx. It attempts to relate differences in expression to differences in the behaviour of these tumours. Detection of the p53 protein was performed using immunohistochemistry on 32 specimens of hypopharyngeal squamous cell carcinoma and 35 specimens of laryngeal squamous cell carcinoma. p53 overexpression was found in 66% of the hypopharyngeal tumours and in 51% of the laryngeal specimens analysed. Some differences between the two tumour types were noted in the pattern staining. p53 staining in those with hypopharyngeal tumours was associated with a statistically significant increased survival. For laryngeal carcinoma the converse was true but did not reach statistical significance. Differences in the behaviour of different head and neck tumour types may be reflected in differences in expression of the p53 protein. While p53 protein expression does not appear to be a useful prognostic indicator in laryngeal carcinoma it might be a useful prognostic indicator in tumours of the hypopharynx. Moreover, it may help predict those tumours which are radioresistant, thus suggesting other modes of treatment for these tumours. Of particular importance is the molecular basis for the observed differences in survival associated with p53 expression in the two tumour sites. This is under further investigation.