CHEMOTACTIC ACTIVITY FOR POLYMORPHONUCLEAR AND MONONUCLEAR LEUKOCYTES IN RHEUMATOID SYNOVIAL FLUIDS

In order to why polymorphonuclear leukocytes (PMNs) are predominant and mononuclear leukocytes (MNLs) are few in rheumatoid synovial fluids, chemotactic factor(s) for PMNs and MNLs were studied in the synovial fluids of rheumatoid arthritis (RA-SF) and osteoarthritis (OA-SF) using both Boyden's and agarose methods. The RA-SF showed strong chemotactic activity for human peripheral blood PMNs compared with non-rheumatoid OA-SF. The chemotactic activity for PMNs was well correlated with the number of PMNs in RA-SF, suggesting that it was a natural mediator for PMN emigration into rheumatoid joint cavity. The major chemotactic factor for PMN in RA-SF was of apparent molecular weight of 14,000 and its activity was suppressed to less than 10 percent by anti-C5a antibody, but it failed to show any anaphylatoxin activity which was an attribute of C5a. It was, therefore, suggested to be C5a-like molecule but not C5a itself. The possibility that the factor may be a C5a des-Arg was discussed. On the contrary, the chemotactic activity for MNLs was not found neither in RA-SF nor OA-SF. These findings may explain the fact that PMNs are predominant in rheumatoid synovial fluids.     

Clinical studies on cefminox in pediatric field

Clinical studies on cefminox (CMNX, MT-141) were conducted and the following results were obtained. Twelve cases of bacterial infections were treated with CMNX with a satisfactory result of "excellent" in 9 and "good" in 3. Antibacterial activity was examined in 7 cases. Pathogenic organisms which were S. aureus, beta-Streptococcus, H. influenzae, S. pneumoniae and P. morganii were eradicated in all the cases. Mean maximum serum concentrations of CMNX after intravenous injection of 10, 20 and 40 mg/kg were 54.5 mcg/ml, 102.3 mcg/ml and 202.4 mcg/ml, respectively which were obtained 15 minutes after each injection. Mean half-lives of each dose group were 1.60, 1.13 and 1.51 hours, respectively. Mean urinary excretion rates of CMNX at 6 hours after intravenous injection in 10, 20, 30 and 40 mg/kg groups were 73.5%, 80.9%, 92.6% and 66.5%, respectively. Side effects were not observed clinically, but anemia in 1 case and eosinophilia in 2 cases were noted in laboratory examination.     

Amiodarone pharmacokinetics. I. Acute dose-dependent disposition studies in rats

Single intravenous bolus doses of amiodarone hydrochloride of 30, 60, 90 and 120 mg/kg were administered to male Sprague-Dawley rats to determine the effects of dose on amiodarone pharmacokinetics. Serial blood samples and total urine were collected over 48 hr and assayed for amiodarone and desethylamiodarone by HPLC. The blood amiodarone concentration-time curves for the four doses were best described by a triexponential equation with terminal half-lives (t _1/2 ) ranging from 17 to 20 hr. Over the dose range studied, no changes in , t _1/2 , or central compartment volume (Vc=1.2–1.4 L/kg) were observed. On the other hand, reductions in amiodarone clearance (CL and steady-state volume of distribution (V _ss of 44% (17.7 to 10.0 ml/min per kg) and 50% (16.4 to 8.2 L/kg), respectively, were noted as the dose of amiodarone increased. The conversion of amiodarone to desethylamiodarone (fm was dose-independent and amounted to approximately 10% of each amiodarone dose. No amiodarone or desethylamiodarone was detected in the urine of any of the treated animals. The blood-to-plasma concentration ratio of amiodarone was concentration-independent and therefore did not account for the dose-dependent changes in V_ss and CL observed. The data suggested that the dose-dependent changes noted were due to an alteration in the volume (s) of the peripheral tissue compartment(s).Supported by a Grant-in-Aid from the American Heart Association, Nebraska Affiliate.     

ADAMANTINOMA OF THE TIBIA A Case Report and a Statistical Review of Reported Cases

A case of adamantinoma of the tibia is reported. A 70-year-old man complained of a painful swelling over the lower front of the right tibia. Roentgenograms showed an oval well-circumscribed, multilocular cystic lesion. Curettage and bone grafting were performed, and 17 months later the patient is in good condition. Microscopically the tumor tissue consisted mainly of epithelial Islands with a palisading at the periphery and a loose reticular pattern in the center of the tumor cell nests, showing a close resemblance to the ameloblastoma of the jaw bones. Electron micrographs revealed the epithelial nature of the tumor cells, i.e., a continuous basal lamina, desmosomes and bundles of microfilaments, probably tonofilaments. One hundred fifty six cases of this peculiar primary skeletal bone tumor previously reported in the literature were reviewed and discussed.     

The effects of butorphanol on baroreflex control of heart rate in man

The effects of butorphanol injection on baroreflex control of heart rate were investigated using both pressor and depressor tests in eighteen adult patients. Baroreflex sensistivity was attenuated after butorphanol injection in the pressor test using phenylephrine, whereas it was unchanged in the depressor test using nitroglycerine. No resetting of the baroreflex occurred after butorphanol injection. After the administration of butorphanol, plasma epinephrine and norepinephrine levels increased. These results suggest that it is safe to use butorphanol clinically even when a reduction in blood pressure due to hypovolemia or unclamping of the major artery is expected and that it is disadvantageous to administer the drug when an increase in blood pressure due to cross-clamping of the major artery is predicted.(Wajima Z, Inoue T and Ogawa R: The effects of butorphanol on baroreflex control of heart rate in man. J Anesth 7: 411--418, 1993)     

Effects of gelonin immunoconjugate of monoclonal antibody MSN-1 to endometrial adenocarcinoma on antigen-producing tumor cells in vitro

Missile therapy, which destroys cancer cells specifically, has been considered to be an effective modality for treatment of carcinoma. We have developed a monoclonal antibody MSN-1 (immunoglobulin class: IgM), of which the immunogen is the endometrial adenocarcinoma cell line SNG-II, which strongly reacts with endometrial adenocarcinomas. We describe an immunoconjugate consisting of the MSN-1 and a plant hemitoxin named gelonin which has revealed to assume selective cytotoxicity against the SNG-II in a colony formation assay in vitro. The results of our study suggest that the 'inhibitory concentration' or IC50, of the MSN-1-gelonin immunoconjugate against the SNG-II was 188 fold that of gelonin alone. These results indicated that the MSN-1-gelonin immunoconjugate exhibited highly selective cytotoxicity to endometrial adenocarcinoma, which expressed an epitope against the MSN-1, and it is suggested that the MSN-1-gelonin immunoconjugate has possibility of clinical application to treatment of endometrial adenocarcinomas.