A case report: Severe bone marrow suppression caused by 6-mercaptopurin in Crohn's disease patient]

A 23-year-old man was admitted for treatment of acute exacerbation of ileitis and perianal abscess caused by Crohn's disease. After incision and drainage of the abscess, coupled with antibiotic therapy, 6-mercaptopurine (6-MP) was commenced. His white blood cell (WBC) count on day 12 after initiation of 6-MP was not decreased. However, on day 24 he was re-admitted because of severe myelosuppression (WBC: 300/microl), which was complicated by the recurrence of the perianal abscess. Myelosuppression was prolonged and required the administration of granulocyte colony stimulating factor (G-CSF). G-CSF was continued for 17 days to achieve recovery of his WBC count to a normal level.     

Intrapulmonary metastasis developing eighteen years after complete resection of thymoma

We present a case of intrapulmonary metastasis developing 18 years after complete resection of thymoma. An 8 mm nodule in the lower lobe of the left lung was noted on chest X-ray in a 76-year-old woman who had undergone complete resection of Masaoka’s stage II thymoma 18 years earlier. Since the nodule grew to 17 mm during a 2-year follow-up, wedge resection was performed. The lesion was histologically diagnosed as an intrapulmonary metastasis from thymoma. Extremely late recurrence after complete resection of thymoma is discussed.     

Stereoselectivity of a potent calcium antagonist, 1-benzyl-3-pyrrolidinyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Four enantiomers (3a-d) of the title compound, YM-09730 (3), were synthesized by the reaction of (-)- or (+)-5-(methoxycarbonyl)-2, 6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (1a or 1b) with (S)- or (R)-1-benzyl-3-pyrrolidinol (2a or 2b). [3H]Nitrendipine binding affinity and coronary vasodilating activity of these compounds were evaluated. The absolute configuration of the most potent enantiomer (3a) with the longest duration was unequivocally determined to be (S)-1,4-dihydropyridine-C4 and (S)-pyrrolidine-C3 (S,S) by X-ray crystallographic study on 3a X HBr as well as 3a X HCl. The configuration of 1a corresponds to R, and the other enantiomers of 3 were respectively determined by chemical correlation. The potency order of the four enantiomers was (S,S)-3a greater than (S,R)-3b greater than (R,R)-3d greater than (R,S)-3c. Latent chiral characters of nifedipine derivatives with the identical ester groups were assigned by comparison of their puckering modes of 1,4-dihydropyridine (DHP) rings with those found in 3a X HCl or 3a X HBr. On the basis of the assignment, it has been revealed that the (S)-DHP nifedipine derivatives possess the synperiplanar carbonyl group at C5. The conformational restriction may be a factor causing stereoselectivity of antagonism.     

Case of severe ulcerative colitis successfully treated with intravenous cyclosporine without high dose corticosteroid]

A 44-year-old women developed marked myopathy one year earlier, when she was treated with intravenous prednisolone for acute severe exacerbation of ulcerative colitis. When she was admitted to our hospital for another severe exacerbation, intravenous cyclosporine A was administered as monotherapy because she could not tolerate corticosteroid. The treatment was successful and she obtained complete remission. Cyclosporine A monotherapy is considered to be a valuable alternative to proctocolectomy for severe ulcerative colitis patients who cannot tolerate corticosteroid.     

5-HT(2) receptor-mediated phosphoinositide hydrolysis in bovine ciliary epithelium.

The serotonin 2 (5-HT(2)) receptor antagonists, MCI-9042 (Anplag) and ketanserin, have been shown to lower intraocular pressure in rabbits (1) and humans (2). The mechanism of action of these drugs has not been determined, but it is hypothesized that 5-HT(2) receptors, and possibly alpha-adrenergic receptors, (3) may regulate in part aqueous humor production via an intracellular signal transduction pathway in the ciliary body. We therefore examined whether 5-HT(2) receptors were coupled to phosphoinositide hydrolysis in an organ culture system of isolated bovine ciliary epithelium. 5-HT stimulated [(3)H]inositol phosphates ([(3)H]InsPs) accumulation in a dose-dependent manner with a maximum increase approximately twice over the basal level. The mean EC(50) value was 1.1 microM, which was calculated from four dose-response curves. The 5-HT stimulated accumulation of [(3)H]InsPs was inhibited by spiperone (5-HT(2A/1A) and dopamine 2 (D(2)) antagonists), M-1 (a major metabolite of MCI-9042), ketanserin (5-HT(2A) antagonist), SB-206553 (5- HT(2B/2C) antagonist), and mesulergine (5-HT(2C) antagonist and D(2) agonist). It was not inhibited by chlorpromazine, which is a D(2) receptor antagonist. Accordingly, our study demonstrates that 5-HT(2) receptors are coupled to phospholipase C in bovine ciliary epithelium.     

Seasonal variation in the content of a febrifugine and isofebrifugine alkaloid mixture in aerial parts of <Emphasis Type="Italic">Hydrangea macrophylla</Emphasis> var. <Emphasis Type="Italic">Otaksa</Emphasis>, with special reference to its antimalarial activity

Febrifugine and isofebrifugine alkaloid mixtures extracted from the leaves and buds of Hydrangea macrophylla var. Otaksa, collected during different months, in Japan, were quantified using high-performance liquid chromatography. Leaves collected during the flowering season, namely from June to August, contained 0.16–0.31 mg/g of the alkaloid mixture, whereas those collected from September to December had less than 0.03 mg/g of the mixture. However, extracts of buds harvested from October to February contained a consistently larger amount (more than 0.49 mg/g) of the alkaloids. Hot-water extracts from the leaves and buds collected during different seasons were evaluated for antimalarial activity against Plasmodium yoelii 17XL in mice. The extract of leaves collected in August demonstrated high antimalarial activity, and all mice that received the extract survived the infection. In contrast, the extract of leaves collected in December showed little activity. The extract of buds collected in December cleared parasites, but with subsequent mortality to mouse. The present results show that the amount of antimalarial agent—febrifugine and isofebrifugine mixture—in H. macrophylla var. Otaksa is both part- and season-dependent, suggesting that the choice of plant parts and their harvesting season are important factors worth considering in the pharmacological use of medicinal plants.     

Clinical outcome of surgical management for patients with renal cell carcinoma involving the inferior vena cava

BACKGROUND: The objective of this study was to evaluate the clinical outcome after surgical management of renal cell carcinoma (RCC) extending to the inferior vena cava (IVC). METHODS: This study included a total of 55 patients (41 men and 14 women; mean age, 59.3 years) with RCC (39 right- and 16 left-sided tumors) involving the IVC, who underwent radical nephrectomy and tumor thrombectomy between 1983 and 2005 at a single institution in Japan. The level of thrombus was classified as follows: level I, infrahepatic; level II, intrahepatic; level III, suprahepatic; and level IV, extending to the atrium. Clinicopathological data from these patients were retrospectively reviewed to identify factors associated with survival. RESULTS: There were 11 and 18 patients who were diagnosed as having lymph node and distant metastases, respectively. Twenty-two patients had tumor thrombus in level I, 20 in level II, 10 in level III, and 3 in level IV. Pathological examinations demonstrated that 34 and 21 patients had clear cell carcinoma and non-clear cell carcinoma, respectively, 42, 9 and 4 were pT3b, pT3c and pT4, respectively, and 6, 35 and 14 were Grades 1, 2 and 3, respectively. Cancer-specific 1-, 3- and 5-year survival rates of these 55 patients were 74.5%, 51.4% and 30.3%, respectively. Among several factors examined, clinical stage (P = 0.047), lymph node metastasis (P = 0.016), histological subtype (P = 0.034) and tumor grade (P < 0.001) were significantly associated with cancer-specific survival by univariate analysis. Furthermore, multivariate analysis demonstrated clinical stage (P = 0.037) and tumor grade (P < 0.001) as independent predictors of cancer-specific survival irrespective of other significant factors identified by univariate analysis. CONCLUSIONS: In patients with RCC involving the IVC, biological aggressiveness characterized by tumor grade rather than tumor extension would have more potential prognostic importance; therefore, more intensive multimodal therapy should be considered in patients with high grade RCC with tumor thrombus extending into the IVC.