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1. Cyclic GMP phosphodiesterase-5 inhibitors have been shown to alter blood flow in specific tissues by potentiating local NO-dependent vasodilatory mechanisms. Since the haemodynamic effects of physiologic insulin, particularly capillary recruitment, may be critical for muscle glucose uptake in vivo and are blocked by inhibitors of nitric oxide synthase, we have explored the acute effects of the specific cGMP phosphodiesterase-5 inhibitor T-1032 on physiologic insulin action in anaesthetized healthy rats in vivo. 2. Whole-body glucose infusion (GIR), femoral blood flow (FBF), hind leg vascular resistance (VR), hind leg glucose uptake (HGU), 2-deoxyglucose uptake into muscles of the lower leg (R'g), hind leg metabolism of infused 1-methylxanthine (1-MX), a measure of capillary recruitment, and muscle cGMP were determined. The experimental groups were T-1032 (10 microg min-1 kg-1) infused for 1 h before and during a euglycaemic insulin clamp (3 mU min-1 kg-1 x 2 h), T-1032 infused for 3 h with saline, T-1032 during a 2 h clamp, T-1032 with saline for 2 h, and a 2 h saline control. 3. Insulin increased GIR from zero to 13 mg min-1 kg-1, HGU from 0.1+/-0.01 to 0.43+/-0.05 micromol min-1, R'g and 1-MX, marginally increased FBF, and had no effect on blood pressure or heart rate. T-1032 alone had no effect on blood pressure, heart rate, FBF, VR, HGU, R'g or 1-MX, but increased muscle cGMP. T-1032 1 h before and during insulin completely blocked GIR (1 h), HGU (2 h), R'g (2 h), and 1-MX (2 h). T-1032 commenced with insulin had only partial blocking activity against insulin. 4. We conclude that T-1032 is a potent acutely acting inhibitor of the muscle effects of physiologic insulin on capillary recruitment and glucose uptake in vivo. These, together with inhibition of whole-body glucose infusion during insulin, may caution against the use of isoenzyme-5-specific cyclic GMP phosphodiesterase inhibitors as therapeutic agents.

This case report is of a 68 year old woman who presented with post menopausal bleeding. Uterine curettings showed an adenocarcinoma with high grade features favouring a clear cell carcinoma. Subsequent hysterectomy showed a FIGO Grade 3 adenocarcinoma with predominant areas of clear cell differentiation and minor endometrioid adenocarcinoma component. Two years later, the patient presented with lung metastases. A core biopsy of lung was obtained which showed features of an adenocarcinoma with dirty necrosis, no evidence of clear cell carcinoma and immunophenotype more suggestive of a colorectal carcinoma. The original uterine tumour was then subjected to a histological review and immunohistochemical analysis. The histological features were of a high grade adenocarcinoma with areas of clear cell differentiation. In some areas, glandular differentiation with intraluminal necrosis was observed. Immunoperoxidase markers suggested a metastatic adenocarcinoma of gastrointestinal origin, whilst the immunomarkers for mullerian tract origin were negative. Gastroscopy and colonoscopy showed no evidence of a lesion. The patient meanwhile has been commenced on oral chemotherapy. This case highlights an unusual profile for an endometrial adenocarcinoma. Negative mullerian tract markers however, do not exclude a primary endometrial adenocarcinoma. It is important to know the origin of the tumour for the purpose of choosing appropriate chemotherapy for the patient.

Fibrillary-immunotactoid glomerulonephritis is a relatively newly identified form of immune-mediated glomerular disease found only in 0.6–1% of native renal biopsies. Most patients rapidly progress to renal failure. A Congo red stain for amyloid is negative. The diagnosis is established by electron microscopy based on arbitrary ultrastructural criteria regarding fibril size and/or organisation. We describe two cases of fibrillary-immunotactoid glomerulonephritis and discuss the controversies and recent development on the nomenclature of fibrillary glomerulopathy.

We describe a 49-year-old female who presented with watery diarrhoea, palpitations, intense anxiety and headaches. Her blood pressure was 135/85 mmHg and there was no history of hypertension. Computed tomography (CT) and magnetic resonance imaging (MRI) confirmed a 6 cm right adrenal tumour. Endocrine profile showed increased plasma metanephrine, normetanephrine and vasoactive intestinal peptide (VIP). Laparoscopic adrenalectomy was performed with complete resolutions of symptoms as well as biochemical abnormalities. Histopathology confirmed a ‘composite phaeochromocytoma’ with the non-phaeochromocytoma component as ganglioneuroma. Composite phaeochromocytoma is the coexistence of a phaeochromocytoma with another tumour type of the same embryonic origin in a single adrenal tumour. Its incidence is estimated to be 3%. The occurrence of a functional VIP and catecholamine co-secreting tumour is even more obscure. To date there are only five cases of clinically significant VIP secreting composite tumours reported in the literature. Secretion of functionally active VIP not only can confound the clinical presentation but can also lead to suboptimal perioperative management that may produce adverse outcomes. We present a case report followed by a literature review of this rare entity.

Aim To determine the presenting symptoms and histological changes in a large series of intestinal biopsies showing spirochaetosis. Methods A multicentre retrospective review of cases diagnosed as spirochaetosis was performed. Results A total of 113 cases were retrieved from the archives, comprising 97 colorectal specimens and 16 appendices. In only 25 cases was the presenting symptom recorded as diarrhoea. Of the colorectal specimens 87 (90%) showed no mucosal abnormality (apart from the spirochaetes); 10 showed mucosal inflammation, but six of them had a diagnosis of another inflammatory disease process accounting for the inflammatory changes. Five appendices showed acute appendicitis;the other 11 were unremarkable. Conclusion Spirochaetosis in an unselected general population is unlikely to be of pathological significance.