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No satisfactory medical therapy exists for the treatment of primary hyperparathyroidism. Calcitonin and diphosphonates do not give good long-term control. This work examines the efficacy of the somatostatin analogue octreotide in the management of hyperparathyroidism. Twenty-one patients were admitted before parathyroid surgery and were treated for 6 days with subcutaneous octreotide 100 μg twice daily. Fasting blood samples were taken for determination of serum levels of calcium and parathyroid hormone, and 24-h urinary calcium excretion was measured before and after treatment. A significant decrease in urinary calcium was demonstrated, but the reduction in serum calcium level was not statistically significant and there was no change in serum parathyroid hormone concentration. Octreotide may provide therapy for patients with hyperparathyroidism and for those who have undergone unsuccessful neck exploration or who are unfit for operation. It may ameliorate hypercalciuria and reduce stone formation. The octapeptide may also have a potential role as a diagnostic test in primary hyperparathyroidism by determining the symptomatic effect of reducing raised levels of serum and urinary calcium.

Research is currently a requirement to allow progress in surgical training. For most trainees this is a period of two years and success is judged by the acquisition of a thesis, production of papers for peer review journals and making presentations at meetings. Funding is required for this activity which is obtained from many sources, ranging from soft money to grants from research councils or Government departments. With the development of a more cost-conscious environment there is a need to establish the degree of funding required to support surgical research. With the potential changes inherent in the Calman Report the role of research may be examined critically. A study sponsored by the SRS was conducted to try and obtain information regarding costs and opinions of surgical research.

In the first year of screening in Avon, 93 malignant lesions were detected of which one-half were impalpable. Of the impalpable lesions, one-half were in situ or showed areas of microinvasion only. One-fifth of the malignant lesions were invasive tumours of special histological type which are known to carry a good prognosis even when not detected by screening. One-quarter of the lesions had clinical or pathological features which would be expected to confer a poor prognosis. Only 16 invasive ductal carcinomas measuring 1 cm or less in diameter were detected--a small proportion of the total number of malignant lesions. Although these early figures suggest that the effect of screening on mortality from breast cancer may be small, continued high-quality screening and careful detailed analysis are essential to determine the effect of screening on the mortality from breast cancer and the effect on the population as a whole.

Medullary thyroid carcinoma accounts for 5–10 per cent of thyroid malignancies and occurs sporadically, and in three familial settings with autosomal dominant inheritance. Calcitonin, a 32 amino acid 3.5-kDa protein, is a biochemical marker of the tumour. Serum levels correlate with disease burden. Treatment initiated by screening allows disease removal at a premalignant phase: C cell hyperplasia. Genetic linkage studies locate the multiple endocrine neoplasia type 2A gene near the centromere of chromosome 10. Flanking genetic markers may allow polymorphic probes to examine DNA from a once-only blood sample to identify affected individuals. At what age thyroidectomy should be carried out in these patients is unclear.

Background The precise cause of hyperparathyroidism (HPT) is uncertain. Alteration of growth factors (epidermal growth factor, fibroblast growth factor) and genetic mutations (parathyroid hormone (PTH) gene (11p15), PRAD1 oncogene (11q13) and multiple endocrine neoplasia type 1 (MEN1) gene (11q13)) are implicated in the pathogenesis. The escape of secretory function from physiological control and excess growth is still incompletely understood. The insulin-like growth factor (IGF) axis is a ubiquitous growth and regulatory system (IGF-1 and -II, IGF receptors (IGFRs) and binding proteins (IGFBPs)). Hormonal/endocrine signals (e.g. androgens, thyroid-stimulating hormone) and tumour supressor genes (e.g. Wilms' tumour suppressor gene (WT-1) (11p13) and p53) modulate the IGF axis. Expression of the WT-1 gene is tissue specific (kidney, mesothelium, prostate). Wild-type WT-1 governs normal kidney development and mutation results in Wilm's tumour. Loss of transcriptional repression of WT-1 and IGF control can lead to mitogenesis. A mutation (chromosome 11) appears to be the key event in the evolution of primary HPT. This mutation may increase IGFR expression, IGF production giving rise to unregulated autocrine growth. In polyclonal hyperplasia (secondary HPT and MEN1) a serum factor initiates polyclonal growth, thereby increasing the susceptibility to mutation and resulting in nodular hyperplasia. Methods Immunohistochemical examination of paraffin-embedded parathyroid glands was done using polyclonal anti-WT-1 (C19, Santa Cruz) and anti-IGFR-I (C20, Santa Cruz) antibodies and a horseradish peroxidase-labelled secondary antibody for detection. The strength of immunoreactivity was graded using a standardized colour chart and assessed independently by three observers. Results Two hundred and fifty-four parathyroid glands from 112 patients were examined. There were 81 women and 31 men (2·6: 1). Of these, 94 had primary HPT (70 women) and 18 secondary HPT (11 women). Immunoreactivity to WT-1 was found in normal parathyroid glands. In contrast, reduced WT-1 immunostaining was observed in abnormal parathyroid glands. Positive immunostaining for IGFR-I was found in all parathyroid glands. Increased immunoreactivity was found in pathological compared with normal glands. Conclusion WT-1 and IGFR are expressed in parathyroid cells. Abnormal expression of WT-1 and the IGF axis may play a role in the pathogenesis of HPT.

Seventy-three patients with chronic renal failure who underwent parathyroidectomy between March 1978 and April 1987 were reviewed. Thirty-four patients had undergone sub-total parathyroidectomy, and 39 patients had undergone total parathyroidectomy with parathyroid autograft into the forearm. Eight patients showed persistent hyperparathyroidism requiring a second surgical procedure. In all other patients there was highly statistical improvement in parathyroid hormone, total calcium, ionized calcium, alkaline phosphatase and a significant reduction in calcium x phosphate product. Histological evidence of osteitis fibrosa was present in 21 of 22 patients before surgery. Postoperatively, four showed complete resolution and improvement. Three patients developed histological evidence of osteomalacia during the study period. Only four of the 39 patients who underwent total parathyroidectomy with autograft had true recurrent hyperparathyroidism and only two of the 34 patients who underwent sub-total parathyroidectomy had recurrent disease, indicating that there is little to choose between the two techniques in the control of secondary hyperparathyroidism and its subsequent recurrence. In one patient with recurrence of hyperparathyroidism from a forearm parathyroid graft the histological picture was different from that of normal hyperplastic parathyroid tissue. Although it is probable that abnormal parathyroid tissue had been implanted there was no evidence of invasive growth into the forearm muscle. The most striking feature of long term follow-up was the difference in calcium x phosphate product in patients in whom vascular calcification increased compared to those patients with no change or regression of calcification. Mean calcium phosphate product in those patients with progressive vascular calcification was 4.93 for small and medium size vessels and 5.38 for large vessels compared to 4.10 for small and medium vessels and 4.09 for large vessels. In the former case the serum phosphate was 2.00 and 2.17 as compared to 1.75 or 1.73, suggesting that the aim in patients with end stage renal failure maintained by dialysis should be to control the serum phosphate concentration to 1.8 mmol or less and the calcium x phosphate product to less than 4.2.

Abnormalities of the p53 gene and protein were examined in 81 primary breast carcinoma samples. Using a polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis, mutations in p53 exons 5-8 were identified in 13 of 81 tumours (16 per cent) and confirmed by DNA seguencing. Positive staining for p53 protein was detected in ten of 77 (13 per cent) of these tumours using polyclonal CM1 antibody on formalin-fixed tissue. Mutations detected by PCR-SSCP analysis were more common in grade III tumours (P=0.015), but no correlation was found with tumour size, node status or level of epidermal growth factor receptor expression. A p53 mutation was associated with positive antibody staining in only two patients

Background: Primary HPT predominately affects females and has a peak incidence at the perimenopausal period. This has led to speculations that an estrogen imbalance may have a role in this condition. We have previously demonstrated the importance of the insulin-like growth factor (IGF) axis in HPT. The SERM, tamoxifen (tam) has been shown to modulate the IGF axis. We propose to examine the interactions of SERMs and IGF in a primary parathyroid cell culture model. Methods: Estrogen (E2) receptors were evaluated by Western immuno-ligand blotting. Sixteen parathyroid glands from 14 patients were included. Following adhesion, the cells were transferred to serum free media and dosed once with IGF (I or II) ± estrogen ± SERMs (Tam), faslodex (fas, ICI 182780)) for 96 h. Proliferation was assessed by measuring tritiated thymidine incorporation. Results: Both primary (1) and secondary (2) HPT express α and β ERs. 1HPT and 2HPT had comparable responses and were analysed together. Compared with control (100%), IGFs (I & II) induced a significant increase in DNA synthesis. E2 at 10−8 and 10−7m (physiological range) inhibited DNA synthesis but had no significant effects on IGF (I & II) (P > 0.05). Tam inhibited basal DNA synthesis (P < 0.05) and abolished the effects of both IGF I and II (P < 0.05). To clarify whether these effects can be ascribed to Tam's ER antagonist property, Fas (a pure ER antagonist) was examined. Fas at 10−7m inhibited both IGF I and II (P < 0.05). Conclusions: Tam and Fas are capable of reducing basal and IGF stimulated DNA synthesis. There are obvious implications for cancer biology as well as therapeutic potential for SERMs in HPT.

Background Quality of life (QL) measurement is important for patients with oesophageal cancer but longitudinal studies may contain a bias because assessments only include healthy survivors who are able to complete questionnaires. This study examined QL in patients undergoing oesophagectomy by comparing results from those surviving 2 years after operation with results from patients dying within 2 years. Methods Between November 1993 and May 1995, 52 patients (36 men; mean age 67 years) underwent oesophagectomy. Prospective QL assessments were performed with the European Organisation for Research on Treatment of Cancer QLQ-C30 and the dysphagia scale from the oesophageal cancer module before treatment, 6 weeks, 3, 6, 9 and 12 months after operation, and at 6-month intervals thereafter, for a minimum of 3 years after operation. Mortality and morbidity rates and survival data were recorded. Results Two years after operation, 17 patients (33 per cent) were alive (group 1) and 35 had died (group 2). Groups were comparable for age, sex, tumour histology and length, dysphagia grade and performance scores. Six weeks after surgery patients in group 1 had worse functional, symptom and global health QL scores than before treatment. These subsequently improved such that by 9 months after operation most QL scores had returned to preoperative levels, except for persisting problems with dyspnoea and diarrhoea. Six weeks after operation patients in group 2 also reported worse QL in all domains, but this never recovered. Six months after treatment patients in group 2 had significantly worse physical, role, emotional and social function than those surviving 2 years and significantly more problems with appetite loss (P < 0·001). The notable exception in both groups was dysphagia, which improved after operation. This improvement was maintained until death or for the duration of the study. Conclusion Patients dying within 2 years of operation suffer an irreversible loss of QL, except that dysphagia is relieved. Further work is needed to assess whether additional postoperative support or the use of multimodality adjuvant treatment can improve the outcome for this group of patients.

Editor—I C Cameron and colleagues raise two important issues: whether surgeons wish to see duplicate presentations of research at national meetings and whether dual publication of abstracts should be prevented.1 The British Journal of Surgery has published abstracts for the Association of Surgeons of Great Britain and Ireland, a general surgical meeting, since 1996. The proceedings of the Vascular Surgical Society of Great Britain and Ireland are also published (59 abstracts from the …

EDITOR,—Deborah A Simon and colleagues' study provides further evidence supporting the role of community based clinics in the management of leg ulcers.1 These specialised local clinics provide skill in managing leg ulcers close to patients' homes and have influenced healing and cost effectiveness.2 Our only concern with this study is that no patient was referred for venous investigation or surgery. We, like others, have shown that superficial venous disease alone is present in about half of patients with venous ulceration. …

Definition The radial arm maze, originally developed by David Olton, is an apparatus that taps into natural foraging abilities of rodents and can be used to test different types of memory, including short-term (working), longterm (reference), nonspatial and spatial memory. The arena consists of a number of arms (typically ranging from 4 to 16) that extend from a central hub, and food is placed in the ends of some or all of the arms. The food cannot be seen from the central platform. Versions that test spatial memory require rats or mice to navigate through the environment using allocentric spatial cues placed around the maze. Thus, animals must recall which arms had been entered or remain to be entered using the location of each arm relative to the different cues around the maze. Numerous studies have shown that rats do indeed use a spatial strategy to solve this task, as elaborate control experiments have been used to ensure that the rats do not simply use their sense of smell either to sense unclaimed food objects or to sense their own tracks.

A sensitive single-stranded hybridisation probe for the oestrogen receptor mRNA was synthesised using T3 polymerase from oestrogen receptor cDNA cloned in the Bluescript vector. This probe was used to measure oestrogen receptor mRNA in total RNA extracted from breast tumours. Oestrogen receptor mRNA was detected in 41 of 47 (87%) tumours whereas cytosolic oestrogen receptor protein was detected in only 18 out of 39 (46%). There was a significant correlation between the levels of the oestrogen receptor, as measured by 3H-oestradiol binding, and the oestrogen receptor mRNA. Oestrogen receptor mRNA was detected in 15 of the 21 tumours that did not contain detectable oestrogen receptor protein. This suggests that detection of the mRNA is a more sensitive means for establishing oestrogen receptor status than the radioligand oestrogen receptor assay. Oestrogen receptor mRNA was found in all histological tumour types examined. Its level was related to tumour differentiation. All the tumours that did not contain oestrogen receptor mRNA and most of the tumours that contained only low levels of oestrogen receptor mRNA were classified as grade III according to Bloom and Richardson: the median of the oestrogen receptor mRNA levels was significantly lower in this group. Images Figure 2 Figure 3

Dispersed canine pancreatic grafts were cryopreserved and the in vivo function was studied following intrasplenic autotransplantation. Four protocols were employed, examining the effects of cooling and thawing rates and cryoprotectant (dimethylsulfoxide) concentration on graft survival. The degree of graft injury by each protocol was assessed by examining the requirement for exogenous insulin following transplantation. Cooling at 5 degrees C/min and thawing at 80 degrees C/min allowed three successful grafts from seven when thawed at 80 degrees C/min using 1.4 or 2 M Me2SO but only one success from eight when thawed at 8 degrees C/min. Of the seven experiments where successful preservation was achieved graft injury was estimated as less than 50% in four but for three it was probably greater than 50%. Each protocol exhibited considerable variability of islet survival. When sufficient islet mass was transplanted to restore fasting euglycaemia, graft function, as assessed by glucose-stimulated insulin release and intravenous glucose disposal, was identical to fresh grafts. Successful graft implantation, however, does not guarantee indefinite survival as six of seven grafts in this study became exhausted within 13 months of implantation.

The abnormal glucose tolerance seen in experimental diabetic animals receiving pancreatic transplants has been assumed to be due to a reduced functional islet mass.

Islet cell transplantation is a potential treatment for insulin-dependent diabetes (IDD), assuming that physiological hormone release results in biochemical normality which, in turn, reduces the incidence of long-term diabetic complications. These experiments sought to create a metabolic model of IDD in a large animal and investigate the effects of insulin therapy and islet transplantation. After demonstrating the success of transplantation, further studies examined the feasibility of creating multiple grafts from a single donor and their long-term preservation. The totally pancreatectomized dog, treated with suboptimal insulin therapy was biochemically identical to human IDD and, when more appropriate doses of insulin were administered, metabolic improvements occurred without restoring normality. Islet cell autotransplants rendered such animals metabolically normal apart from persisting impairment of glucose tolerance. The isolation technique permitted the production of at least two recipient grafts and some success was achieved after graft cryopreservation. The experiments confirm the theoretical background to islet transplantation and demonstrate its applicability in a large animal model before allotransplantation.

A teenage girl is described who had an osteogenic sarcoma of the tibia at 11 years of age, a pulmonary metastasis at 13 years, and an intestinal leiomyosarcoma at 15 years. She remains well at the age of 18 years. Leiomyosarcoma is extremely rare in children either as a primary or secondary tumor.