Effects of a 2-substituted adenosine derivative, 2-(p-methoxyphenyl)-adenosine (CV-1674) on coronary and cardiohemodynamics, and myocardial energetics

In dogs, intracoronary doses of CV-1674, adenosine ( ADS) and 2-Cl-ADS for doubling coronary flow were estimated as 5.0, 2.0 and 0.4 microgram/dog, and i.v. doses 31, 71 and 2.5 microgram/kg, respectively. ADS and 2-Cl-ADS decreased, while CV-1674 increased LV dp/dt. Intravenous infusion (30 min) of CV-1674 (10 microgram/kg per min) and ADS (700 microgram/kg per min) decreased coronary resistance to approximately the same extent. Decreases in blood pressure, total peripheral resistance and myocardial O2 concumption with ADS were more prominent than those with CV-1674. ADS produced a marked bradycardia that was not evident with CV-1674. Neither agent had a significant influence on myocardial efficiency. In guinea pig atria, ADS and 2-Cl-ADS exerted negative effects while those with CV-1674 were positive inotropic and chronotropic. In cats, intraduodenal ADS (10 mg/kg) produced no effects on cardiohemodynamic parameters. CV-1674 (250 and 500 microgram/kg) increased myocardial tissue blood flow (MBF) with a slight hypotension in a dose-dependent manner, whereas 2-Cl-ADS (100, 250 and 500 microgram/kg) increased MBF only with the highest dose concomitantly with marked hypotension and bradycardia. These results suggest that CV-1674 induces selective coronary vasodilation with less depression on cardiohemodynamics, and is relatively well absorbed from the intestinal tract. The pharmacological profile of the compound, therefore, differs from that of ADS and 2-Cl-ADS.     

Intrahepatic arterial chemotherapy with 5-fluorouracil and intramuscular interferon-alpha for a patient with diffuse type of hepatocellular carcinoma

We report a case of diffuse type advanced hepatocellular carcinoma (HCC), which was successfully treated by a combination therapy of interferon-alpha (IFN) and 5-fluorouracil (5-FU). A 74-year-old man underwent distal gastrectomy 6 years ago for gastric cancer. In April 2002, an increased serum alpha-feto-protein (AFP) level was noted and a computed tomography (CT) of the abdomen revealed a diffuse type of HCC. He was treated with a combination therapy of IFN (5x10(6) units/body i.m., days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26) and 5-FU (500 mg/body/day i.a., days 1-5, 8-12 continuously). The treatment was repeated every 4 weeks with a maximum of five cycles. After 5 cycles, serum AFP levels fell from 665 ng/ml to a normal level. CT showed a reduced size of the tumor. He has been well and continue to receive IFN (3x10(6) units/body i.m., two times a week) and 5-FU (500 mg/body/day i.a., once a week) at the outpatient clinic for the last 16 months.     

An improved method for estimating the heart-to-mediastinum ratio from cardiac sympathetic nerve imaging with low-energy high-resolution collimators

Background

Septal penetration causes underestimation of the heart-to-mediastinum (H/M) ratio in cardiac ¹²³I-metaiodobenzylguanidine (MIBG) imaging with a low-energy high-resolution (LEHR) collimator. We aimed to improve the method of estimating the H/M ratios using the LEHR collimator.

Methods and Results

4 hours after ¹²³I-MIBG injection, 40 patients were imaged successively with the medium-energy (ME) and LEHR collimators using gamma cameras having 3/8-inch crystals. Severe underestimation of the H/M ratios was observed with the LEHR collimator when compared to the ME collimator. Narrowing the energy window width did not reduce the underestimation. Application of ¹²³I-dual-window (IDW) correction using a narrow or wide subwindow reduced the underestimation substantially but not entirely. The H/M ratios estimated from the LEHR images with or without IDW correction were corrected based on their correlations with the ratios estimated from the ME images. This empiric correction removed systematic underestimation, and residual errors were reduced when the H/M ratios after IDW correction were converted using the empiric equation. The conversion equation was successfully applied to the correction of the H/M ratios determined in another 40 patients using a 5/8-inch crystal.

Conclusions

In estimating the H/M ratios using an LEHR collimator, empiric correction combined with IDW correction improves concordance with ME-based values in comparison with empiric correction alone.     

Health-Related Quality of Life Among Japanese Women With Iron-Deficiency Anemia

Iron-deficiency anemia (IDA) is a common disease in females of childbearing age. Although iron supplementation quickly improves laboratory-measured parameters, its effect on health-related quality of life is unknown. Here, we conducted a prospective follow-up study to evaluate health-related quality of life in pre-menopausal women diagnosed with IDA. A convenience sample of 92 patients who visited Tokai University Hospital and three other affiliated hospitals were asked to fill out the Medical Outcome Study 36-item short-form health survey (SF-36) during the course of treatment (baseline, and 1 and 3 months after the start of treatment). At baseline, vitality and general health scores were significantly lower than the Japanese national norms. After the start of therapy, however, a significant improvement was seen in all domain scores except role emotional (RE), and at 3 months all eight scores were comparable to or greater than the national norms. In particular, physical functioning and vitality scores of patients with a lower hemoglobin level ( < 9.0 g/dl) at baseline showed a dramatic improvement. Iron supplementation in IDA patients improves not only hemoglobin levels, but also physical function, vitality, and general health perception. Address for correspondence: Kiyoshi Ando, Department of Hematology and Oncology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan Phone: +81-463-93-1121; Fax: +81-463-92-4511 E-mail: andok@keyaki.cc.u-tokai.ac.jp     

A novel human B-lymphocyte antigen shared with lymphoid dendritic cells: characterization by monoclonal antibody.

A novel cell-surface antigen (L25) expressed on human B cells was identified using a B cell-reactive monoclonal antibody (TB1-4D5). This L25 antigen was expressed on most B-lineage cells but not other cell types including thymocytes, T cells, granulocytes and monocytes. Thus, L25 existed on the majority of normal B cells present in the blood and lymphoid tissues, on cultured cell lines derived from normal and malignant B cells, and on neoplastic cells isolated from patients with B cell-derived malignancies. Though L25 was persistently expressed on B cells until 7 days after their activation with pokeweed mitogen (PWM), neither normal nor neoplastic plasma cells expressed L25. Moreover, L25 was present on cultured as well as freshly isolated leukaemic cells with common acute lymphatic leukaemia (CALL) antigen, which have been thought to correspond to the early B-cell ontogeny. Besides pan-B cell reactivity of TB1-4D5 antibody, it apparently cross-reacted with so-called dendritic or interdigitating cells located in the thymic-dependent areas of peripheral lymphoid organs, which have been presumably ascribed to those associated with accessory-cell function. Functional studies showed that anti-L25 (TB1-4D5) antibody had inhibitory effect on induction of immunoglobulin synthesis by PWM-stimulated B cells.     

Photocrosslinkable chitosan as a dressing for wound occlusion and accelerator in healing process.

Application of ultraviolet light (UV-) irradiation to a photocrosslinkable chitosan (Az-CH-LA) aqueous solution resulted in an insoluble, flexible hydrogel like soft rubber within 60 s. The chitosan hydrogel could completely stop bleeding from a cut mouse tail within 30 s of UV-irradiation and could firmly adhere two pieces of sliced skins of mouse to each other. In order to evaluate its accelerating effect on wound healing, full thickness-skin incisions were made on the back of mice and subsequently an Az-CH-LA aqueous solution was added into the wound and irradiated with UV light for 90 s. Application of the chitosan hydrogel significantly induced wound contraction and accelerated wound closure and healing. Histological examinations also have demonstrated an advanced granulation tissue formation and epithelialization in the chitosan hydrogel treated wounds. The chitosan hydrogel due to its accelerating healing ability is considered to become an excellent dressing for wound occlusion and tissue adhesive in urgent hemostasis situations.