No abstract

A report of germline mutations of CBL in three patients with JMML is presented here, confirming the existence of an unreported inheritable condition associated with a predisposition to JMML.

Summary Objective  Glucagonoma is a pancreatic neuroendocrine tumour that arises from alpha cells in the pancreas and is often accompanied by a characteristic clinical syndrome. Design  In this report, we present the cumulative experience and clinical characteristics of six patients diagnosed with glucagonoma and the glucagonoma syndrome and treated at our centre during the past 25 years. Results  Although the course of the disease was variable, some features were similar. The median age at diagnosis was 53·5 years; the median time from onset of symptoms to diagnosis was 39 months. Presenting symptoms were as follows: weight loss 5/6 (83%), necrotizing migratory erythema (NME) 5/6 (83%), diabetes mellitus 4/6 (66%) and diarrhoea, weakness and thrombosis 2/6 (33%). Plasma glucagon was elevated in all patients upon diagnosis (range 200–10 000 pm; N < 50). Skin biopsy was diagnostic only in 1/6 specimens obtained, even after revision. Metastatic disease developed in all patients; 4/6 initially presented with hepatic metastasis. All patient symptoms responded to somatostatin analogue therapy. In 4/6, the NME responded to amino acid solutions. Other modes of therapy were as follows: surgery in 3/6 patients, peptide receptor radioligand therapy with 90Y‐DOTATOC (PRRT) in 3/6 patients (two responses) and chemotherapy in three patients (two responded). Four out of six patients died of the disease, and median survival time was 6·25 years (range 2–11) from diagnosis and 8 years (range 8–16) from initial symptoms. Five‐year survival was 66%. Conclusion  Our data indicate that somatostatin analogues and an aggressive surgical approach offer symptom relief and tumour control. Among other available treatment modalities, PRRT seems to hold the most promise.

Although ⁶⁸Ga-DOTA-NOC and OCT images were similar, in this study, ⁶⁸Ga-DOTA-NOC demonstrated more true positive tumor foci and was better tolerated by patients. This direct comparison supports replacement of OCT with ⁶⁸Ga-DOTA-NOC-PET/CT in the evaluation of NETs.

SUMMARY1. In human blood, heroin is rapidly hydrolysed by sequential deacylation of two ester bonds to yield first 6-monoacetylmorphine (6-MAM), then morphine.2. Serum butyrylcholinesterase (BuChE) hydrolyses heroin to 6-MAM with a catalytic efficiency of 4.5/min per mol/L, but does not proceed to produce morphine.3. In vitro, human erythrocyte acetylcholinesterase (AChE) hydrolyses heroin to 6-MAM, with a catalytic efficiency of 0.5/min per mol/L under first-order kinetics. Moreover, erythrocyte AChE, but not BuChE is capable of further hydrolysing 6-MAM to morphine, albeit at a considerably slower rate.4. Both hydrolysis steps by erythrocyte AChE were totally blocked by the selective AChE inhibitor BW284c51 but were not blocked by the BuChE-specific inhibitor, iso-OMPA (tetraisopropylpyrophosphoramide).5. The brain synaptic form of AChE, which differs from the erythrocyte enzyme in its C-terminus, was incapable of hydrolysing heroin.6. Heroin suppressed substrate hydrolysis by antibodyimmobilized erythrocyte but not by brain AChE.7. These findings reveal a new metabolic role for erythrocyte AChE, the biological function of which is as yet unexplained, and demonstrate distinct biochemical properties for the two AChE variants, which were previously considered catalytically indistinguishable.