Sensory neuropathy in paraneoplastic leucocytosis.

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) sensitise nerves to mechanical stimuli experimentally and may induce bone and muscle pain when used as supportive drugs. G-CSF and GM-CSF produced endogenously by tumour cells can cause paraneoplastic leucocytosis. Whether paraneoplastic leucocytosis is associated with changes in pain sensitivity is not yet clear. We report on a patient with advanced-stage thyroid cancer who developed extreme leucocytosis within a period of 4 weeks (103 000 white blood cells/mm(3)), composed mostly of neutrophils and eosinophils. Parallel to this leukemoid reaction, allodynia and hyperalgesia developed in the absence of tissue inflammation. The course of disease of an elderly male with advanced stage metastatic thyroid cancer with new onset neuropathic pain followed by the development of extreme leucocytosis in a leukemoid reaction suggests paraneoplastic release of myeloid CSFs. The coincidence of pain sensitisation and extreme leucocytosis suggests a causal contribution of G-CSF and GM-CSF.

Mesenteric panniculitis presenting with acute non-occlusive colonic ischemia.

BACKGROUND: The role of positron emission tomography (PET) of the mesentery as a diagnostic modality in cases of mesenteric panniculitis is unclear. CASE PRESENTATION: A 67-year-old woman presented with rectal bleeding due to nonocclusive colonic ischemia. Abdominal CT showed features of mesenteric panniculitis. PET-CT demonstrated no abnormal fluorine-18 fluordeoxyglucose uptake in the affected mesentery or any surrounding lymph nodes. Laparoscopic biopsies from a thickened segment of mesenteric fat excluded neoplastic infiltration. CONCLUSIONS: In cases of unexplained ischemic colitis, panniculitis should be considered a possible diagnosis. PET-CT may be negative for fluorine-18 fluordeoxyglucose uptake in this condition. As of known false-negative PET-CT results in mesenteric panniculitis, PET-CT has a limited role in the diagnostic work-up.

Class I antiarrhythmics inhibit Na+ absorption and Cl- secretion in rabbit descending colon epithelium.

To clarify the mechanism of the diarrhea associated with the clinical use of antiarrhythmic drugs we assessed the effects of these agents on transepithelial Na+ absorption and Cl- secretion, on basolateral K+ conductance, and on the properties of single basolateral K+ channels of rabbit colon epithelium. Quinidine and propafenone, both at 10 microM, inhibited Na+ absorption by 27 and 38% respectively, compared with 50% with 5 mM Ba2+. The other tested class I antiarrhythmics disopyramide, mexiletine, lidocaine, and flecainide decreased Na+ current by 9-13%. Procainamide and the class III antiarrhythmics N-acetylprocainamide, sotalol, ibutilide, and amiodarone were no or were very weak inhibitors of Na+ absorption. Cl- secretion, stimulated with the adenosine analogue NECA (5'-N-ethylcarboxamide-adenosine), was reduced by 54% with quinidine and by 29% with propafenone compared with 100% with Ba2+. Mexiletine, lidocaine, and flecainide inhibited Cl- secretion by 10-23%, whereas the class III antiarrhythmics were no or were weak inhibitors. Those antiarrhythmics that inhibited Na+ and Cl- transport also reduced basolateral K+ conductance, determined in amphotericin B permeabilized epithelia. The activity of the high-conductance, Ca2+-activated, voltage-dependent K+ (BK(Ca)) channel, which is primarily responsible for basolateral K+ recycling during Na+ absorption, was inhibited by 10-30 microM quinidine or propafenone in the form of a rapidly dissociating block. Mexiletine and flecainide inhibited the single channel conductance at higher concentrations; disopyramide, lidocaine, and procainamide were ineffective. In conclusion, the present evidence suggests that the diarrhea caused by class I antiarrhythmic drugs such as quinidine and propafenone is a result of a reduction in basolateral K+ conductance and inhibition of BK(Ca) channels, thereby impeding transepithelial Na+ and water absorption.