Comparison of preoperative chemotherapy using docetaxel, cisplatin and fluorouracil with cisplatin and fluorouracil in patients with advanced carcinoma of the thoracic esophagus.

We retrospectively compared preoperative docetaxel, cisplatin, and fluorouracil (DCF) with cisplatin and fluorouracil (CF) in patients with esophageal cancer. The study included patients with advanced thoracic esophageal carcinoma (excluding T4 tumors) receiving preoperative chemotherapy. In the DCF group, five patients received two courses of treatment every 4 weeks, and 33 patients received three courses every 3 weeks. In the CF group, 38 patients received two courses of treatment every 4 weeks. Patients underwent curative surgery 4-5 weeks after completing chemotherapy. Patient demographic characteristics did not differ between the two study groups. The incidence of a grade 3 or 4 hematologic toxicity was significantly higher in the DCF group (33 patients) than in the CF group (five patients; P < 0.001). Curative resection was accomplished in 79% of patients in the DCF group and 66% in the CF group (P = 0.305). There were no in-hospital deaths. The incidence of perioperative complications did not differ between the groups. A grade 2 or 3 histological response was attained in a significantly higher proportion of patients in the DCF group (63%) than in the CF group (5%; P < 0.001). Progression-free survival and overall survival were significantly higher in the DCF group (P = 0.013, hazard ratio 0.473; P = 0.001, hazard ratio 0.344). In conclusion, a grade 3 or 4 hematologic toxicity was common in the DCF group but was managed by supportive therapy. Histological response rate, progression-free survival, and overall survival were significantly higher in the DCF group compared with the CF group.

Discovery and structure-activity relationship of N-(ureidoalkyl)-benzyl-piperidines as potent small molecule CC chemokine receptor-3 (CCR3) antagonists.

Structure-activity relationship (SAR) studies of initial screening hits from our corporate library of compounds and a structurally related series of CCR1 receptor antagonists were used to determine that an N-(alkyl)benzylpiperidine is an essential pharmacophore for selective CCR3 antagonists. Further SAR studies that introduced N-(ureidoalkyl) substituents improved the binding potency of these compounds from the micromolar to the low nanomolar range. This new series of compounds also displays highly potent, in vitro functional CCR3-mediated antagonism of eotaxin-induced Ca(2+) mobilization and chemotaxis of human eosinophils.

[Fluoroscopic contrast medium percutaneous ethanol injection therapy (FCM-PEIT): newly developed clinical useful method for injecting ethanol into nodules of hepatocellular carcinoma].

We have performed fluoroscopic contrast medium percutaneous ethanol injection therapy (FCM-PEIT) total 266 times to 82 hepatocellular carcinoma (HCC) nodules in 44 HCC cases: FCM-PEIT is the newly developed method that HCC nodules are punctured by a needle and injected with ethanol mixed with water-soluble contrast medium (Iopamidol containing 370 mg/ml iodine) (vol/vol: 7/3) under the fluoroscopic observation as well as ultrasonic diagnostic equipment (US). Autopsy analyses have demonstrated nearly complete tumor necrosis by FCM-PEIT. We analyzed the detectable rate (%) of the contrast medium-mixed ethanol (CME) leakage out of HCC nodules by US-alone, fluoroscope-alone, and US-fluoroscope observation. The detectable rate of the leakage was 63% by US-fluoroscope, while was only 32% by US-alone. Particularly, all leakages into intra hepatic bile duct were missed by US-alone. The maximal CME-amount for injection without any leakage was not uniform and not related to the size of HCC nodules. The present results suggest that FCM-PEIT is clinically more useful method for the treatment of HCC compared to general PEIT that HCC nodules are injected with ethanol under the US-alone observation, since it is easy to confirm whether ethanol can be sufficiently injected into HCC nodules without any leakage.

[Acute leukemia with active hemophagocytosis, positive immunologic markers for the megakaryocyte-platelet lineage, and translocation (16; 21) (p11; q22].

We report a case of infantile acute leukemia with t(16; 21) (p11; q22). The patient was a phenotypically normal one-year-old girl without lymphadenopathy or hepatosplenomegaly. Her peripheral blood at diagnosis showed anemia, thrombocytopenia, and many circulating blasts. Bone marrow blasts were monocytoid with fine reticular nuclear chromatin, abundant grayish-blue cytoplasm with occasional pseudopods or cytoplasmic projections and active hemophagocytosis. Serum levels of lysozyme and ferritin were normal. These blasts were not stained with butyrate esterase and immunologic study showed KOR-P77+ (anti-megakaryocyte monoclonal antibody), MY9+, Ia-. Electron microscopic examination failed to show platelet peroxidase activity. Remission was not induced by mini-COAP or VP-16 and the patient died of measles pneumonitis. The patient's blasts took typical appearance of megakaryoblasts later in the course, although some of them retained the ability of hemophagocytosis observed in the original blasts. This case is considered to be quite atypical since leukemic cells with active hemophagocytosis, megakaryoblastic appearance and t(16; 21) (p11; q22) have not been reported in the literature.

Childhood acute megakaryoblastic leukemia with internalization of hemic cells.

Two atypical cases of acute megakaryoblastic leukemia (AMKL) in infants diagnosed by immunophenotying are described. In both cases, the leukemic cells at diagnosis resembled monoblasts with reniform nuclei, fine reticular chromatin, and abundant grey-blue cytoplasm with pseudopods. In addition, these blasts frequently showed internalization of hemic cells. Therefore, the diagnosis of acute monocytic leukemia (AMOL) or malignant histiocytosis (MH) was initially suggested. However, alpha-naphthyl butyrate esterase stain was negative and immunologic studies determined megakaryocytic lineage of the blasts. Our observation in two consecutive cases of AMKL implies that there is a potential risk of misdiagnosing AMKL as AMOL or MH in infants. The incidence and significance of internalization of hemic cells by blast cells of AMKL in infancy are unknown and we cannot be certain whether these cases constitute a subgroup of AMKL in infancy.

Basic study of fluoride-releasing adhesive resin for prevention of root caries: 1. Transfer of fluorine from the resin to dentin.

Release of fluoride ion from a newly-developed fluoride-releasing resin (F-resin) into phosphate buffer and incorporation of fluorine by the dentin were studied in vitro. The rate of fluoride release (amount of daily release) from a pellet of cured F-resin showed rapid decrease to 1/2 of the initial value by day 6, and then moderate decrease to 1/4 of the initial by day 30. However, the pellet continued to release fluoride at a low but constant rate for more than 520 days. In the first 30 days after F-resin was applied to the dentin surface, large amount of fluorine was concentrated within 100 mu of the subsurface dentin. With longer incubation period, the peak concentration of fluorine at the dentin surface decreased but the depth of penetration increased to about 180 mu by day 180.

Basic study of fluoride-releasing adhesive resin for prevention of root caries: 2. Enhancement of acid resistance of the dentin.

The human root dentin was covered with a fluoride-releasing resin (F-resin) and incubated for various periods up to 180 days in phosphate buffer. After removal of the F-resin, resistance of the dentin to decalcification by acetic acid--sodium acetate buffer was assessed by measuring both the amount of calcium dissolved during decalcification and the knoop hardness of dentin after decalcification. The acid resistance progressively increased for 90 days when assessed by measurement of calcium dissolution and for 30 days by measurement of the knoop hardness. The percent inhibition of calcium dissolution achieved by 30 days of incubation was about 90% of the maximal inhibition obtained by incubation in concentrated sodium fluoride solution (2.4 x 10(-2) M). The enhancement of acid resistance was not induced by the resin infiltrated layer of the surface dentin but by the fluoride released from the F-resin into the dentin.

Determination of prednisone and prednisolone in human serum by high-performance liquid chromatography--especially on impaired conversion of corticosteroids in patients with chronic liver disease.

A reliable and rapid method is described for the determination of prednisone and prednisolone in human serum by high-performance liquid chromatography, using a Zorbax-SIL column with dichloromethane-ethanol (92.5:7.5) as eluent, with UV detection at 254 nm. Metabolites and endogenous hydrocortisone did not interfere with the determination of prednisone and prednisolone. The alteration of corticosteroid concentrations in serum from patients with chronic liver diseases was studied following a single oral administration of prednisone or prednisolone (30 mg). The proposed method showed good separation of several corticosteroids and was time-saving, suitable and reliable for the routine analysis of corticosteroids in human serum.