Relation of inflammatory cytokines to atrial fibrillation after off-pump coronary artery bypass grafting.

OBJECTIVE: It has been observed that a systemic inflammatory response after on-pump coronary artery bypass grafting (CABG) participates in the pathogenesis of postoperative atrial fibrillation (AF). In patients undergoing off-pump CABG, it is plausible that inflammation is associated with the development of postoperative AF. The present study examined relation of proinflammatory cytokines, which play an important role in the upstream of inflammatory cascade, to the development of AF after off-pump CABG. METHODS: The present study included 39 patients undergoing off-pump CABG. Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8, were measured by enzyme-linked immunosorbent assay, on anesthetic induction, after sternotomy before anastomoses, at the completion of anastomoses, 3 and 6h thereafter, and on postoperative days (POD) 1-4. C-reactive protein (CRP) was also measured by turbidimetric immunoassay, preoperatively, and on POD 1, 2, 3, 6, 9, and 13. RESULTS: Eleven patients (28%) developed postoperative AF. Patients with postoperative AF were older (70+/-6.4 years vs 60+/-8.8 years, P=0.001); however, there was no difference in other pre- and perioperative variables. TNF-alpha level did not change during the study period. However, IL-8 and CRP levels significantly increased after the surgery, although there was no significant difference between the two groups. IL-6 level also increased after the surgery with its peak at 6h after the completion of anastomoses. IL-6 levels of 3 and 6h after anastomoses were significantly higher in patients with postoperative AF (360+/-143 pg/ml vs 230+/-94 pg/ml, P=0.0047, 435+/-175 pg/ml vs 247+/-102 pg/ml, P=0.0005, respectively). Logistic regression analysis indicated that the highest quartile of IL-6 level immediately after the surgery (odds ratio 7.63; 95% CI, 1.06-54.9; P=0.04) and age (odds ratio 1.18; 95% CI, 1.01-1.39; P=0.04) independently predict postoperative AF. Furthermore, the maximum level of IL-6 immediately after the surgery significantly correlated to age and intraoperative blood loss (r=0.04, P=0.01, and r=0.47, P=0.04, respectively). CONCLUSIONS: Advanced age was a major risk factor for postoperative AF. Furthermore, inflammatory response induced by surgical trauma was also associated with the development of AF after off-pump CABG.     

Inhibitory effect of calcium chloride on gastric carcinogenesis in rats after treatment with N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride.

The effects of calcium chloride on glandular stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride were investigated in male outbred Wistar rats. Animals were given MNNG solution (100 p.p.m.) as drinking water and simultaneously fed a diet supplemented with 5% sodium chloride for 8 weeks. Matched negative controls received neither MNNG nor sodium chloride. Rats were then fed basal diet and given calcium chloride solution (1 or 0.2%) or tap water for the following 52 weeks. The incidences and multiplicities of preneoplastic hyperplasias in the glandular stomachs of rats given MNNG/sodium chloride followed by 1 and 0.2% calcium chloride were significantly lower than those in rats given MNNG/sodium chloride alone. The inhibitory effects of calcium were exerted in a dose-dependent manner. Calcium treatment also showed a tendency to inhibit the development of gastric adenocarcinomas although this was not statistically significant. Rats without carcinogen treatment had neither carcinomas nor preneoplastic hyperplasias in the glandular stomach. Calcium intake also significantly reduced the levels of malondialdehyde, a measure of lipid peroxidation, in the gastric mucosa and urine, the former in a dose-dependent manner. Thus, calcium chloride exerted inhibitory effects when given during the post-initiation phase of two-stage glandular stomach carcinogenesis in rats.     

Effects of caffeine, nicotine, ethanol and sodium selenite on pancreatic carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl)amine.

The modulating effects of caffeine, nicotine, ethanol and sodium selenite on development of N-nitrosobis(2-oxopropyl)-amine (BOP)-initiated pancreatic tumors were investigated. Female Syrian golden hamsters were given s.c. injections of BOP (10 mg/kg body weight) or saline alone once a week for 3 weeks and then administered 2000 p.p.m. caffeine, 25 p.p.m. nicotine, 20% ethanol or 4 p.p.m. sodium selenite in their drinking water for the next 37 weeks. Control animals were given tap water alone after BOP initiation. Only the BOP-treated groups developed pancreatic adenocarcinomas and dysplasias. The multiplicity of pancreatic carcinomas was significantly higher (P less than 0.05) in animals receiving caffeine than in the controls. In addition, caffeine treatment slightly increased the incidence of carcinomas. Nicotine and ethanol also showed tendencies to enhance pancreatic carcinogenesis, although there were statistically no significant differences regarding lesion development. In contrast, sodium selenite administration was associated with a tendency for a decrease in the number of carcinomas and dysplasias. Thus, among these chemicals of obvious significance to human life-style, caffeine enhanced the development of pancreatic tumors when administered during the post-initiation phase in this hamster model.     

Excitatory mechanism of deflationary slowly adapting pulmonary stretch receptors in the rat lung.

The excitatory responses of deflationary slowly adapting pulmonary stretch receptor (SAR) activity to lung deflation ranging from approximately -15 to -25 cm of H(2)O for approximately 5 s were examined before and after administration of flecainide, a Na(+) channel blocker, and K(+) channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The experiments were performed in anesthetized, artificially ventilated rats after unilateral vagotomy. The deflationary SARs increased their activity during lung deflation and its effect became more pronounced by increasing the degree of negative pressure. During lung deflation the average values for the deflationary SAR adaptation index (AI) were below 40%. Intravenous administration of veratridine (50 microg/kg), an Na(+) channel opener, stimulated deflationary SAR activity: one maintained excitatory activity mainly during deflation and the other receptors showed a tonic discharge during both deflation and inflation. Despite the difference in deflationary SAR firing patterns after veratridine administration, flecainide treatment (6.0 mg/kg) blocked veratridine-induced deflationary SAR stimulation and also caused strong inhibition of the excitatory responses of deflationary SARs to lung deflation. Under these conditions, the average values for deflationary SAR AI were over 90%. The responses of deflationary SARs and deflationary SAR AI to lung deflation were not significantly altered by pretreatment with either 4-AP (0.7 and 2.0 mg/kg) or TEA (2.0 and 6.0 mg/kg). These results suggest that the excitatory effect of lung deflation on deflationary SAR activity is mediated by the activation of flecainide-sensitive Na(+) channels on the nerve terminals of deflationary SARs.     

Repeat operations in the management of clival chordomas: palliative surgery.

Some chordomas have a very poor prognosis because of their aggressive growth nature, but the efficacy of repeat operations for these cases has not been well documented. This report concerns 3 patients with aggressive chordoma of the clivus, who underwent operations 6 to 12 times over a period of 8 to 17 years because of symptomatic regrowth. Overall mean interval between repeat operations was 18 months with a range from 5 to 57 months and survival times were 9 to19 years after the first surgery. Main symptoms before each operation were diplopia and visual disturbance. Repeat palliative operations by intentional extradural debulking of the tumour to decompress offending neural structures, as well as maximal removal of the tumour, using appropriate skull base approaches, can mitigate progressive symptoms, and may result in better quality and some prolongation of life, although our patients gradually deteriorated neurologically throughout the clinical course.     

A Case Report of Inflammatory Pseudosarcoma of the Urinary Bladder

A case of inflammatory pseudosarcoma of the urinary bladder in a 35 year-old Japanese male is presented. This benign lesion can easily be mistaken for spindle cell sarcoma since it consists of rhabdomyoblast like elongated strap cells showing infiltrative growth, and whether it is benign or malignant is difficult to determine by microscopic examination. In this case, spindle cell proliferation extended among bundles of the superficial muscle layer. However, no abnormal mitoses, severe nuclear atypia or cellular pleomorphism could be seen, thus indicating inflammatory pseudosarcoma. Although the lesion was not completely resected, no recurrent disease has been clinically observed for two years following transurethral resection. Urologists and surgical pathologists must be able to detect this lesion in order to avoid unnecessary surgical procedures. Acta Pathol Jpn 42: 760 765,1992.     

Clinical evaluation of a potassium nitrate dentifrice for the treatment of dentinal hypersensitivity

Abstract The effectiveness of a 5% potassium nitrate dentifrice as a daily home treatment for dentinal hypersensitivity was evaluated in a double-blind study in 36 Japanese subjects who complained of cold and/or tactile hypersensitivity. The subjects were divided into 2 groups, with 18 being given a 5% potassium nitrate dentifrice (treated group) and the other 18 a vehicle paste (control group). Both groups were instructed to brush their teeth 2 × a day. The hypersensitivity levels of the affected teeth were assessed by 2 stimuli, one tactile and the other cold air, and by the perception of pain. The results of all 3 assessment methods indicated that the potassium nitrate dentifrice significantly decreased the level of hypersensitivity at weeks 4, 8, and 12. In the treated group, a rapid decrease of positive scores for both the cold air stimulus and the subjective symptoms appeared from week 2. Although a significant decrease of the assessment score was also observed in the control group, the reduction rate of the score was much greater in the treated group by ail 3 assessment methods at weeks 4, 8, and 12. Complete relief of subjective symptoms throughout the 12 weeks’examination was noted in 67% of the subjects in the treated group, but in only 6% in the control group. These results suggest the usefulness of a 5% potassium nitrate dentifrice in Japanese patients with dentinal hypersensitivity.     

Retroperitoneal schwannomas simulating adrenal tumors.

Tumors in the area of the adrenal were detected by chance in two patients who underwent a regular physical check-up. On arteriography the tumors were found to be fed by the adrenal artery. The diagnosis was retroperitoneal schwannoma, but in both patients it was difficult to differentiate the schwannoma from an adrenal tumor preoperatively.     

Platelet activating factor (PAF) involvement in endotoxin-induced thrombocytopenia in rabbits: studies with FR-900452, a specific inhibitor of PAF

PAF (1 ug/kg) injected intravenously (i.v.) into anesthetized rabbits resulted in marked loss of circulating platelets and leukocytes. Administration of FR-900452 1-methyl-3-(1-(5-methylthiomethyl-6-oxo-3-(2-oxo-3-cyclopenten-1-y lidene)- 2-piperazinyl) ethyl)-2-indolinone, a specific PAF inhibitor, at a dose of 10 mg/kg i.v. with 10 min prior to the PAF injection significantly prevented both changes. On the other hand, PAF has been considered as a mediator of endotoxin shock. Therefore, in order to determine whether endogenous PAF contributes to the occurrence of thrombocytopenia or leukopenia in endotoxin shock, we assessed the effect of FR-900452 on the thrombocytopenia and the leukopenia following bolus i.v. injection of E.coli endotoxin (0.03 mg/kg) in rabbits. As a result, pretreatment with the compound (10 mg/kg, i.v.) significantly reduced the thrombocytopenia at 60 and 180 min after the endotoxin injection. In contrast, FR-900452 did not reduced the leukopenia at any time of after endotoxin. These results indicate that PAF might be involved in the occurrence of thrombocytopenia in rabbit endotoxemia and the contribution of PAF to the leukopenia is much less extent than that to the thrombocytopenia.