Chemiluminescence response of whole blood in patients undergoing urological operations

Polymorphonuclear leukocytes (PMNs) are one of the most important components of the defence mechanisms against bacterial infection. The functions of PMNs are believed to be impaired in patients during the perioperative period. Bactericidal function of PMNs was investigated together with the luminol-dependent chemiluminescence (CL) reaction of whole blood in 23 patients, 12 undergoing open surgery and 11 undergoing endoscopic surgery. Blood samples were collected one day before surgery (day-1) and 2 hours (day 0), 24 hours (day 1) and 7 days (day 7) after surgery. Counts of whole white blood cells (WBCs), PMNs and lymphocytes were not different between the two surgery groups. CL responses in the open surgery group were increased on days 0, 1 and 7. In the endoscopic surgery group, CL response was increased on day 1, but not on day 0 or day 7. These results suggest that the PMN function during the perioperative period was not impaired, but increased just after surgery, mainly due to an increasing number of WBC caused by the surgical intervention.     

Clinical study of asymptomatic microscopic haematuria

A clinical statistical survey was performed on 355 patients with asymptomatic microscopic haematuria. Urologic lesions were detected in 19.4% of the patients. Urologic lesions requiring surgical treament were found in only two patients with bladder carcinoma and with renal calculus. With the exception of glomerulonephritis, the proportion of those over 40 years who had urologic lesions was higher. It is suggested that an initial evaluation based on excretory urography, cystoscopy and ultrasonography is more important for patients over 40 years.     

Functional and metabolic effects of mexiletine in the rat heart-lung preparation.

The effects of mexiletine on cardiac function and myocardial metabolism were assessed in the isolated rat heart-lung preparation. Mexiletine 1, 2, 4 or 8 micrograms ml-1 was administered 5 min after the start of perfusion. Heart rate decreased in the 2, 4 and 8 micrograms ml-1 groups significantly following the drug administration. The highest dose of mexiletine reduced cardiac output significantly, and this dose was associated with a higher incidence of dysrhythmias than the other groups. Although there was no significant difference in myocardial glycogen concentration among groups, ATP contents in the 4 micrograms ml-1 and 8 micrograms ml-1 groups were significantly less than in the control group. Lactate contents in the 4 micrograms ml-1 and 8 micrograms ml-1 groups were significantly higher than in the control group. Generally, the therapeutic plasma concentration of mexiletine is 0.5-2.0 micrograms ml-1. These results suggest that mexiletine may have a lesser margin of safety than lignocaine.     

Protective effects of the fractions extracted from the callus of Acer nikoense Maxim. on alpha-naphthylisothiocyanate induced liver injury]

It has been reported that the methanol extract from the bark of Acer nikoense MAXIM. (AN) and the fractions separated from this extract showed the protection for liver injuries induced by carbontetrachloride (CCl4) in rat. On the other hand, the evidence manifested that the fractions of the callus of young branches from AN were recognized to have protective effects on the CCl4-induced liver injuries in rat. In this study, the protective activities of the fractions extracted from the callus of AN were investigated on the alpha-naphthylisothiocyanate (ANIT)-induced liver injuries in rat. The protectively active principles on the ANIT-induced liver injuries were found in the ether soluble fraction. The components of the protective effect were purified by repeated silica gel chromatographies. One of the protective substances in this fraction was identified to be beta-sitosterol. The protective fractions on the ANIT-induced liver injuries showed the protective effects on ANIT-induced cholestasis, but did not show cholagogic effects.     

Synthesis and antiallergic activity of 11-(aminoalkylidene)-6,11-dihydrodibenz[b,e]oxepin derivatives.

A new series of 11-substituted 6,11-dihydrodibenz[b,e]oxepin-2-carboxylic acid derivatives was synthesized and demonstrated to be orally active antiallergic agents. These compounds are structurally related to 1 (KW-4994), which we had reported previously to be a new antiallergic agent. Most compounds synthesized exhibited potent inhibitory effects on 48-h homologous passive cutaneous anaphylaxis (PCA) in rats and on IgG1-mediated bronchoconstriction in guinea pigs. Additionally, compounds possessing a terminal carboxyl group at the 2-position of the dibenz[b,e]oxepin ring system exhibited inhibitory effects on specific [3H]pyrilamine binding to guinea pig cerebellum histamine H1 receptors, whereas these demonstrated negligible effects on specific [3H]QNB binding to rat striatum muscarinic acetylcholine M1 receptors. Structure-activity relationship studies revealed that the following key elements were required for enhanced antiallergic activities: (1) a 3-(dimethylamino)propylidene group as the side chain at the 11-position, (2) a terminal carboxyl moiety at the 2-position, and (3) a dibenzoxepin ring system. Among the compounds synthesized, (Z)-11-[3-(dimethylamino)propylidene]-6,11-dihydrodibenz [b,e]oxepin-2-acetic acid hydrochloride (16) was selected for further evaluation. It had an ED50 value of 0.049 mg/kg po in the PCA test in rats and an ID50 value of 0.030 mg/kg po in inhibiting anaphylactic bronchoconstriction in guinea pigs. Furthermore, it had a Ki value of 16 +/- 0.35 nM for the histamine H1 receptor, while it exhibited negligible CNS side effects up to a dose of 600 mg/kg po. Compound 16 is now under clinical evaluation as KW-4679.     

Prognostic factors and value of adjunctive nephrectomy in patients with stage IV renal cell carcinoma

We reviewed 57 cases of Stage IV renal cell carcinoma to clarify the factors influencing prognosis and to evaluate the value of nephrectomy. Cumulative survival from the initial diagnosis was analyzed with respect to the patients' age, sex, side of primary tumor, initial performance status (PS), site of metastasis, and nephrectomy. Overall survival for the patients was 51 percent at one year, 22 percent at three years, and 11 percent at five years. Age, sex, and side of primary tumor had no influence on survival. Improved survival was correlated with good PS, metastases limited to single organ, and removal of the primary tumor. With regard to histopathologic features in nephrectomized patients, low grade and stage were correlated with longer survival. These factors should be considered in the analysis of results of future clinical trials of metastatic renal cell carcinoma.     

Expression of Recombination Activating Genes in Germinal Center B Cells: Involvement of Interleukin 7 (IL-7) and the IL-7 Receptor

Mouse germinal center (GC) B cells have been shown to undergo secondary V(D)J (V, variable; D, diversity; J, joining) recombination (receptor editing) mediated by the reexpressed products of recombination activating gene (RAG)-1 and RAG-2. We show here that interleukin (IL)-7 as well as IL-4 was effective in inducing functional RAG products in mouse IgD⁺ B cells activated via CD40 in vitro. Blocking of the IL-7 receptor (IL-7R) by injecting an anti– IL-7R monoclonal antibody resulted in a marked suppression of the reexpression of RAG-2 and subsequent V(D)J recombination in the draining lymph node of immunized mice, whereas RAG-2 expression was not impaired in immunized IL-4–deficient mice. Further, these peripheral B cells activated in vitro or in vivo were found to express IL-7R. These findings indicate a novel role for IL-7 and IL-7R in inducing receptor editing in GC B cells.     

The effects of bradykinin agonists and antagonists on visceral polymodal receptor activities

The endogenous algesic agent bradykinin (BK) is a consistent stimulant for the polymodal receptor, a type of nociceptor. Two types of BK receptor, B1 and B2, have been proposed in smooth muscles by Regoli. The type of BK receptor mediating the BK response of the polymodal receptor was studied using 3 BK analogs, des-Arg9-BK (a B1 agonist), des-Arg9-[Leu8]-BK (a B1 antagonist), and [Thi5,8, D-Phe7]-BK (a B2 antagonist). Single- and multi-fiber activities from testicular polymodal receptors were recorded in vitro using testis-spermatic nerve preparations excised from dogs anesthetized with pentobarbital (30 mg/kg, i.v.). Neither des-Arg9-BK, des-Arg9-[Leu8]-BK, nor [Thi5,8,D-Phe7]-BK induced discharges in nociceptors at concentrations up to 9.4 x 10(-6) M. Des-Arg9-[Leu8]-BK (up to 9.4 x 10(-6) M) did not suppress responses to BK (9.4 x 10(-8 approximately -9) M), whereas [Thi5,8,D-Phe7]-BK (above 2.8 x 10(-7) M) suppressed the BK response in a concentration-dependent manner and shifted the concentration-response curve of BK to the right. It was ascertained that [Thi5,8,D-Phe7]-BK had no effect on responses to noxious heat and high K+ solution. These results suggest that the BK receptor mediating the nociceptor response to BK is of the B2 type.     

ANCA-associated systemic vasculitis in Japan: clinical features and prognostic changes

Background

This study was conducted to standardize treatment and determine patient and renal outcome in Japanese anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis/rapidly progressive glomerulonephritis (AAV/RPGN) patients, because the prognosis of AAV/RPGN patients in Japan had been poor compared with that of other countries.

Methods

The participants in this retrospective cohort study were 824 ANCA-positive RPGN patients, 705 of whom were only myeloperoxidase (MPO)-ANCA positive.

Results

Among the early-years cohort (group?A; cases diagnosed between 1988 and 1998), patients frequently died due to opportunistic infection. Therefore, we recommended a reduced dose of prednisolone (oral prednisolone dose <0.8?mg/kg/day) with or without cyclophosphamide for initial treatment of Japanese RPGN patients. After this recommendation, 1-year survival of the patients improved: 75% in group?A, 79% in group?B (between 1999 and 2002), and 81% in group?C (after 2003). During the entire observation period, average serum creatinine level at the start of treatment decreased, and improvement of 1-year renal survival was also found (72% in group?A, 83% in group?B, and 83% in group?C), while the recurrence rate was significantly increased in group?C (0.05/patient-year in group?A, 0.07/patient-year in group?B, and 0.13/patient-year in group?C).

Conclusions

Oral prednisolone dose <0.8?mg/kg/day with or without cyclophosphamide as an initial treatment could improve patient survival in older Japanese AAV/RPGN patients. However, maintenance treatment avoiding relapse should be established to improve renal outcomes.