Cell cycle homogeneity in bone marrow samples from different sites: flow cytometric evaluation of multiple samples from sheep

The distributions of cells in each of the phases of the cell cycle, determined by flow cytometry (FCM), were compared in multiple marrow trephine biopsy samples from 3 sites (both iliac bones and sternum) in 5 sheep. Within any one animal no significant differences could be found between the proportions of cells in the G0/G1, S or G2 + M phases of the cycle from different sites. Differences between animals were detected and these were consistent for any of the sites sampled. We conclude that the proliferative characteristics of marrow cells as determined by FCM in any one animal at one time are comparable at anatomically distinct marrow sites, and that a sample from one site is representative of the whole.     

Napoleon's illness 1816–1821 in the light of activation analyses of hairs from various dates

Summary The arsenic content has been analysed in millimeter sections of hairs shaved from Napoleon's scalp May 6th, 1821, the day after his death. It appeared that Napoleon was exposed to arsenic on at least 40 occasions between the summer of 1820 and April 1821. So were hairs cut in each of the years 1818, 1817 and 1816 analyzed in centimeter sections. The 1818 hairs disclosed that Napoleon was exposed to arsenic during some three months sometime between January, 1817, and March, 1818. The 1816 hairs showed particularly high concentrations of arsenic which must have been deposited before Napoleon was exiled to St. Helena.     

Osseous metastases from renal cell carcinoma: embolization and surgery for restoration of function. Work in progress

Five patients underwent preoperative embolization of osseous metastases from renal cell carcinoma. The group consisted of four men and one woman who ranged in age from 46 to 79 years. The lesions were located in the pubic ramus and acetabulum, proximal femur, femoral midshaft, proximal humerus, and proximal tibia. All embolizations were performed within 24 hours of surgery. The internal fixation and tumor curettage was accomplished with estimated perioperative blood loss ranging from 10 ml to 1,250 ml. All patients had significant restoration of function following surgery. We suggest that preoperative embolization is an important and efficacious adjunct in the management of hypervascular renal cell osseous metastases.     

Integrating professionalism into the curriculum

Professional values and behaviours are intrinsic to all medical practice yet remain one of the most difficult subjects to integrate explicitly into a curriculum. Professionalism in the twenty-first century raises challenges not only for the adaptation of the medical training programme to changing societal values but also for ensuring that trainees gain the skills for self-directed continuous development and future revalidation. This article is an introduction to the AMEE Guide in Medical Education No 61: Integrating Professionalism into the Curriculum ( www.amee.org ), which is based on the extensive contemporary available literature. An evidence-based approach has been taken throughout the Guide as it focuses on instilling professionalism positively into both undergraduate and postgraduate training. It takes a structured, stepwise approach and sequentially addresses: (i) agreeing an institutional definition, (ii) structuring the curriculum to integrate learning across all years, (iii) suggesting learning models, (iv) harnessing the impact of the formal, informal and hidden curricula and (v) assessing the learning of the trainee. A few well-evaluated case studies for both teaching and assessment have been selected to illustrate the recommendations.     

Craniopharyngiomas

Craniopharyngiomas are rare, mainly sellar/parasellar, epithelial tumors diagnosed during childhood or adult life. Histologically, two primary subtypes have been recognized (adamantinomatous and papillary) with an as yet, unclarified pathogenesis. They may present with a variety of manifestations (neurological, visual, and hypothalamo-pituitary). Despite their benign histological appearance, they often show an unpredictable growth pattern, which, combined with the lack of randomized studies, poses significant difficulties in the establishment of an optimal therapeutic protocol. This should focus on the prevention of recurrence(s), improvement of survival, reduction of the significant disease and treatment-related morbidity (endocrine, visual, hypothalamic, neurobehavioral, and cognitive), and preservation of the quality of life. Currently, surgical excision followed by external beam irradiation, in cases of residual tumor, is the main treatment option. Intracystic irradiation or bleomycin, stereotactic radiosurgery, or radiotherapy and systemic chemotherapy are alternative approaches; their place in the management plan remains to be assessed in adequately powered long-term trials. Apart from the type of treatment, the identification of clinical and imaging parameters that will predict patients with a better prognosis is difficult. The central registration of patients with these challenging tumors may provide correlates between treatments and outcomes and establish prognostic factors at the pathological or molecular level that may further guide us in the future.     

Hypopituitarism following envenoming by Russell's vipers (Daboia siamensis and D. russelii) resembling Sheehan's syndrome: first case report from Sri Lanka, a review of the literature and recommendations for endocrine management

Russell's vipers (Daboia russelii and D. siamensis) inhabit 10 South and South East Asian countries. People envenomed by these snakes suffer coagulopathy, bleeding, shock, neurotoxicity, acute kidney injury and local tissue damage leading to severe morbidity and mortality. An unusual complication of Russell's viper bite envenoming in Burma (D. siamensis) and southern India (D. russelii) is hypopituitarism but until now it has not been reported elsewhere. Here, we describe the first case of hypopituitarism following Russell's viper bite in Sri Lanka, review the literature on this subject and make recommendations for endocrine investigation and management. A 49-year-old man was bitten and seriously envenomed by D. russelii in 2005. He was treated with antivenom but although he recovered from the acute effects he remained feeling unwell. Hypopituitarism, with deficiencies of gonadal, steroid and thyroid axes, was diagnosed 3 years later. He showed marked improvement after replacement of anterior pituitary hormones. We attribute his hypopituitarism to D. russelii envenoming. Russell's viper bite is known to cause acute and chronic hypopituitarism and diabetes insipidus, perhaps through deposition of fibrin microthrombi and haemorrhage in the pituitary gland resulting from the action of venom procoagulant enzymes and haemorrhagins. Forty nine cases of hypopituitarism following Russell's viper bite have been described in the English language literature. Patients with acute hypopituitarism may present with hypoglycaemia and hypotension during the acute phase of envenoming. Those with chronic hypopituitarism seem to have recovered from envenoming but present later with features of hypopituitarism. Over 85% of these patients had suffered acute kidney injury immediately after the bite. Steroid replacement in acute hypopituitarism is life saving. All 11 patients with chronic hypopituitarism in whom the outcome of treatment was reported, showed marked improvement with hormone replacement. Unrecognized acute hypopituitarism is potentially fatal while chronic hypopituitarism can be debilitating. Physicians should therefore be aware of this complication of severe envenoming by Russell's vipers, especially in Burma and South India, so that the diagnosis may be made without delay and replacement started with essential hormones such as hydrocortisone and thyroxine.     

Outcome of transsphenoidal surgery for acromegaly using strict criteria for surgical cure

OBJECTIVE Previous studies of surgical treatment for acromegaly have used varied criteria for ‘cure’, but elevated GH levels are considered to be associated with continuing disease activity. We wished to analyse the results of transsphenoidal pituitary surgery for acromegaly and assess the longer-term outcome for patients not offered further treatment when post-operative levels of GH < 5 mU/l were achieved. DESIGN We studied a retrospective group of patients who underwent transsphenoidal surgery for acromegaly at St Bartholomew’s Hospital between 1985 and 1993. PATIENTS One hundred consecutive patients (53 male, mean age 46 years, range 18–68 years) undergoing transsphenoidal surgery for acromegaly were assessed. The patients were followed for a mean of 3.8 years (range 0.5–8 years) after operation. MEASUREMENTS GH levels are represented as a mean value from a four-point day curve taken at 0830, 1300, 1700 and 1900h. ACTH reserve was assessed basally and, if this was normal, with the insulin tolerance or glucagon tests. TSH, T4, PRL, LH, FSH, testosterone or oestradiol and plasma and urine osmolality were also measured. RESULTS Post-operatively, 42% of patients achieved a mean GH level of < 5 mU/l. The success of surgery was related to the preoperative GH level; 65% of the patients with preoperative GH levels < 20 mU/l but only 18% of the patients with GH levels > 100 mU/l achieved post-operative GH values < 5mU/l. In addition, tumour size influenced the outcome of surgery with 61% of patients with a microadenoma but only 23% of patients with a macroadenoma achieving post-operative GH levels of < 5 mU/l. Of the 42 patients considered in remission postoperatively (mean GH < 5 mU/l), 32 were available for long-term follow-up and were not offered any further treatment: only one of these has shown evidence of mild biochemical recurrence after a mean follow-up of 3.8 years (range 0.5–8). There were no peri-operative deaths. Two patients required surgical repair for CSF leaks and there were eight documented cases of meningitis. Permanent diabetes insipidus was noted in eight patients post-operatively. New anterior pituitary deficiency occurred in 21% of patients following surgery; 73% had unaltered pituitary function and in 6% recovery of partial hypopituitarism was noted. CONCLUSIONS The stated outcome of surgery depends on the criteria adopted. Safe GH levels (mean levels < 5 mU/l) can be achieved in 42% of an unselected series of patients with acromegaly and if the tumour is a microadenoma this figure rises to 61%. Based on the current evidence it is safe not to offer further treatment to those patients in whom post-operative GH < 5 mU/l are achieved.