Severe Case of Peripheral Leukocytosis Initially Diagnosed as Myelodysplastic Syndrome/Myeloproliferative Neoplasm, Unclassifiable, but Possibly Prefibrotic Primary Myelofibrosis

Leukocytosis is occasionally seen in patients with presumptive but undiagnosed myeloproliferative disorders (MPD). A 74-year-old woman was admitted to our hospital for tarry stools, anemia, and marked peripheral leukocytosis of 1.4×105/μL. Gastroenteroscopy revealed an acute gastric and duodenal mucosal lesion that was treated successfully via endoscopic hemoclipping. Bone marrow aspiration revealed marked megakaryocyte proliferation with atypia of naked nuclei and marrow hypercellularity (90% cellularity). A fluorescence in situ hybridization test could not detect the BCR-ABL fusion gene. Bone marrow aspiration later revealed further abnormalities of megakaryocytes. The patient died from cerebral bleeding. The present case fulfilled 2 of the 3 major criteria of primary myelofibrosis according to the World Health Organization 2008 classification:namely, megakaryocytic hyperplasia with hypercellular marrow and granulocytic hyperplasia. However, the megakaryocytic abnormality was not strictly compatible with the criteria. Instead, we considered prefibrotic primary myelofibrosis as a possibility, although myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U) was technically the correct diagnosis. The present case shows that MPN diagnosis remains difficult and suggests that other cases of peripheral leukocytosis with diagnosed MDS/MPN-U might include similar findings

Diuretic effect of cilazapril and dopamine system in the spontaneously hypertensive rat.

&lt;p&gt;To assess the role of the kidney dopamine system on the diuretic state induced by angiotensin-converting enzyme (ACE) inhibitors, we examined the changes in urinary excretion and plasma level of dopamine, and kidney dopamine receptors in spontaneously hypertensive rats (SHR) treated with cilazapril, an ACE inhibitor. We administered cilazapril 10 mg/kg orally to 13-week-old SHR daily for 21 days (CILAZA group). Systolic blood pressure was significantly decreased in the CILAZA group on Day 6 compared with that in vehicle-treated SHR (control group). The urine volume was three- to fivefold higher in the CILAZA group, and total urinary dopamine secretion was also increased compared with the control group. There was no significant difference in affinity and number of kidney dopamine receptors between the CILAZA and the control groups. In conclusion, the diuretic effect caused by cilazapril is partly mediated by inhibition of the water reabsorption via the increase of dopamine production in the kidney.&lt;/p&gt;</p

Effects of beta-adrenergic blocking agents on specific binding of [3H]D-Ala2-Met5-enkephalinamide and [3H]naloxone.

To gain further insight into the central nervous system (CNS)-action of beta-adrenergic blocking agents (beta-blockers), we examined the effects of various kinds of beta-blockers on opioid receptors (Op-Rs) using radiolabeled receptor assay (RRA). We demonstrated that beta-blockers are competitively bound to Op-Rs in the CNS. Sodium index of beta-blockers in [3H]naloxone binding study indicated that beta-blockers had the mixed agonist-antagonist activity of opiates. The relative potency of beta-blockers in opioid RRA was negatively correlated with their membrane stabilizing activity. Neither beta-blocking activity nor intrinsic sympathomimetic activity was correlated with IC50 values of beta-blockers in opioid RRA. While it is widely accepted that beta-blockers have a tranquilizing activity, a part of the tranquilizing action of beta-blockers may be mediated through Op-Rs in the CNS. Although beta-blockers may have effects on their own receptors (beta-receptors) in the CNS, the more precise mechanisms of central action of these drugs must be further investigated.</p