Modulation of intestinal transport of 2,4-dinitrophenyl-S-glutathione, a multidrug resistance-associated protein 2 substrate, by bilirubin treatment in rats

The effect of bilirubin treatment on intestinal transport of 2,4-dinitrophenyl-S-glutathione (DNP-SG), a substrate of multidrug resistance-associated protein 2 (MRP2), after application of 1-chloro-2, 4-dinitrobenzene (CDNB), a precursor of DNP-SG, was examined in rat intestine by the in-vitro everted sac, in-situ re-circulating perfusion, and in-situ loop methods. CDNB was taken up rapidly by jejunum and ileum, and the consequent intestinal efflux of DNP-SG, a glutathione conjugated metabolite of CDNB, was significantly higher in jejunum than in ileum in the in-situ and in-vitro studies. Co-administration of bilirubin (100 microM), as well as probenecid (1 mM) or ciclosporin (100 microM), with CDNB decreased the DNP-SG efflux in jejunum significantly, but not in ileum. The suppression of DNP-SG efflux in jejunum was also observed after intravenous administration of bilirubin (85.5 micromol kg-1), in which plasma bilirubin glucuronide levels were approximately 100 microM. In the in-vitro metabolism study, bilirubin exerted no significant effect on CDNB metabolism in the intestinal S9 fraction (supernatant of 9000 g). These results suggested that the diseased states accompanied with hyperbilirubinaemia might have increased the intestinal absorption, or oral bioavailability, of MRP2 substrates by suppressing MRP2 function at the proximal intestinal region.     

Landiolol does not affect bispectral index scale in off-pump coronary artery bypass surgery in patients under fast-track cardiac anesthesia

BACKGROUND: We evaluated the effect of landiolol, a novel ultra-short-acting receptor-selective blocker, on bispectral index scale (BIS). METHODS: Ten patients scheduled for off-pump coronary artery bypass (OPCAB) surgery under fast-track cardiac anesthesia were analyzed. Anesthesia was maintained with appropriate additional administration of fentanyl (total dose: 10-15 microg x kg(-1)) and vecuronium under inhalation of a mixture of oxygen, air and sevoflurane (less than 2%). Landiolol was administered continuously for 5 min, when the heart rate (HR) was 80 or more per minute and the BIS values were kept between 40-60. HR, mean arterial pressure (MAP), cardiac index (CI) and BIS values were recorded at 4 time points (after induction of anesthesia, before administration of landiolol, immediately before comple- tion of administration, and 15 minutes after completion of administration). RESULTS: HR decreased significantly by landiolol administration, but there were no significant changes in MAP, CI and BIS. CONCLUSIONS: This study suggests that landiolol does not affect BIS in OPCAB surgery patients under fast-track cardiac anesthesia.     

Peribronchiolar metaplasia: a common histologic lesion in diffuse lung disease and a rare cause of interstitial lung disease: clinicopathologic features of 15 cases

Peribronchiolar metaplasia (PBM) is a histologic lesion consisting of peribronchiolar metaplasia (PBM) of bronchiolar-type epithelium. Although widely recognized, PBM has received little attention in the pathologic literature and is not known to have clinical significance. We identified 15 cases in which PBM was the only major histologic finding in surgical lung biopsies from patients with interstitial lung disease (PBM-ILD), and we reviewed the clinical, imaging, and pathologic findings. The mean age was 57 years (range, 44-74 years) with 13 females and 2 males. One patient had been a welder with fume and asbestos exposure; another had pigeon exposure. Smoking history was available for 13 patients: three current smokers, one cocaine user, two former smokers, and seven never smokers. Three patients had collagen vascular disease. One had elevated serum antinuclear antibody titers. Pulmonary function data were available for 10 patients: one obstructive, five restrictive, two mixed obstructive and restrictive, and two normal. Computerized tomography in 7 patients showed mosaic attenuation in 3 patients and air trapping in 1 patient; no bronchiectasis, septal lines, or honeycombing were seen in any cases. All 11 patients with available follow-up are alive; 4 of them have experienced symptomatic improvement (follow-up, 0.6-6.9 years; mean, 2.4 years). PBM was found focally in other interstitial lung diseases, which were assessed for this lesion: 59% of usual interstitial pneumonia (17 of 29), 50% of nonspecific interstitial pneumonia (10 of 20), desquamative interstitial pneumonia (3 of 6), hypersensitivity pneumonitis (9 of 18), and 11% of respiratory bronchiolitis (2 of 18). In summary, PBM is a common histologic finding in various interstitial lung disorders. It is rarely the sole major lung biopsy finding in patients presenting with interstitial lung disease (PBM-ILD). Patients are mostly older women, with mild symptoms and CT findings. Survival appears to be favorable.     

Fundamental and clinical investigation of clindamycin-2-phosphate in otorhinolaryngological field (author's transl)]

Some laboratory examinations were made with clindamycin-2-phosphate (CLDM-2-phos.). The drug was applied clinically to several otorhinolaryngological infections and the good results were obtained as follows. 1) Observing by biophotometer, the growth of Staphbylococcus aureus FDA 209P was inhibited well by the serum (diluted 10-fold) 30 minutes, 1, 2, 4 hours after 300 mg of CLDM-2-PHOS. were injected intramuscularly. 2) Serum concentration was determined by thin-layer method with Sarcina lutea ATCC 9341 as the test organism. The peak of serum level was obtained at 1 hour after a single intramuscular injection of 5 mg/kg or 10 mg/kg dosis of CLDM-2-phosphate. The peak of blood concentration was 5.4 mug/ml, 5.6 mug/ml respectively. 3) CLDM-2-phosphate concentration in tissues was estimated one hour after intramuscular injection of CLDM-2-Phosphate. The concentrations in blood and palatine tonsilla were 5.0 mug/ml and 2.9 mug/ml respectively after the intramuscular injection of 10 mg/kg. The concentrations in blood and mucous membrane of maxillar sinusitis were 4.1 mug/ml and 2.5 mug/ml respectively after the intramuscular injection of 10 mg/kg. 4) CLDM-2-phosphate was administered by intramuscular injection into 30 cases with various infections in otorhinolaryngological field. The clinical results were excellent in 22 cases (73.3%), effective in 3 cases (10.0%) and ineffective in 5 cases (16.7%). The effectiveness was 83.3%. 5) No side effects were observed in 30 cases.     

Suicide patterns and characteristics in Akita, Japan

Akita Prefecture currently has the highest rate of suicide in Japan. Given this alarming statistic, investigation of the underlying causes of suicide and identification of strategies for suicide prevention are imperative. Members of the Akita Prefectural Medical Association (APMA) see most of the individuals who commit suicides in Akita Prefecture, so data from the APMA would prove advantageous in any investigation of suicides. In this study, members of the APMA who had attended to individuals who had committed suicide were asked to complete a questionnaire about the case to determine the factors underlying suicide in Akita Prefecture. From 1 July 2001 to 30 June 2002, a total of 138 cases (102 males, 36 females) of suicide were reported. Most suicide cases were of 50-69 year olds. Many cases involved relatively lethal methods (such as hanging). Most suicides were performed at home and at a time when the rest of the family was asleep or absent. The most common complaint appeared to be economic-related problems. Depressive disorder was the most common psychiatric disorder, and many cases displayed high depressive trait scores. The present results do not exclude the possibility that economic-related problems are playing a major role in recent increases in suicide numbers. However, strategies for dealing with depression as well as economic-related problems are considered important.     

The effect of magnesium sulfate on the behavioral activities of fetal goats

OBJECTIVES: To investigate fetal heart rate accelerations, fetal breathing movements, and fetal electrocortical activities during administration of magnesium sulfate to fetal goats. METHODS: The fetal heart rate accelerations, fetal breathing movements, and fetal electrocortical activities during 6 hours of continuous magnesium sulfate infusion into the fetal jugular vein were examined in 8 chronically instrumented fetal goats at 124-131 days of gestation. Fetal breathing movements were defined as repetitive negative fluctuations of the fetal tracheal pressure. Fetal electrocortical activities were assessed by visual analysis of periods of high-voltage and low-voltage electrocortical activities. RESULTS: Continuous infusion of magnesium sulfate for 6 hours significantly increased the fetal plasma magnesium concentration from 2.8 +/- 1.2 to 8.3 +/- 2.6 mg/dL without significant changes in fetal arterial blood gases. The incidence of fetal heart rate accelerations during magnesium infusion was significantly decreased from that found during the control periods. After 2 hours of infusion, the incidence of fetal breathing movements significantly decreased from 33.9% +/- 20.5% to 1.2% +/- 1.4% and remained at this level during the remaining 4 hours of magnesium infusion. The percentage of time that the fetuses were found to have low-voltage electrocortical activities decreased from 51.6% +/- 9.0% to 40.4% +/- 8.2% after 2 hours of infusion but recovered to 49.9% +/- 12.0% by 6 hours of magnesium infusion. CONCLUSION: We concluded that fetal magnesium sulfate administration affected fetal heart rate accelerations and fetal breathing movements continuously but electrocortical activities only temporarily during 6 hours of observations.     

The outcome and a new ISN/RPS 2003 classification of lupus nephritis in Japanese

BACKGROUND: A considerable diversity in prognosis is seen with lupus glomerulonephritis (LGN). Hence, the clinical usefulness of a recent International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification to judge the long-term outcome of human LGN has been investigated. METHODS: We studied retrospectively 60 subjects with LGN (7 males, 53 females, mean age of 33 years old) who underwent renal biopsies and were followed from 1 to 366 months, with a mean of 187 months. We diagnosed renal pathology as classes, active and sclerosing lesions, according to the new and WHO1995 classification of LGN, and analyzed the clinicopathologic factors affecting to the prognosis of LGN. RESULTS: New classification got much higher consensus in the judgment of classes (98% vs. 83%, P = 0.0084). The group of Class IV-S (N = 6) or IV-G (N = 17) at initial biopsies showed higher rate of end-stage renal failure (ESRF) compared with that of Class I, II, III or V (40.9% vs. 2.6%, P < 0.001). The mean 50% renal survival time of Class IV was 189 +/- 29 months, and patients with Class IV-S tended to have a poorer prognosis (95 +/- 22 months for IV-S vs. 214 +/- 35 months for IV-G, P = 0.1495). Class IV was also selected as the most significant risk factor for ESRF by stepwise model (P = 0.002). In subanalysis for ESRF in Class IV (-S or -G), treatment including methylprednisolone pulse therapy was only selected as a significant improving factor for primary outcome (P = 0.034). In addition, activity index was the significant risk factor of death and/or ESRF after initial renal biopsies (P = 0.043). As for actuarial patient death during all follow-up periods, complications with anti-phospholipid syndrome or nephrotic syndrome were significant risk factors (P = 0.013, P = 0.041, respectively). CONCLUSION: New ISN/RPS 2003 classification provided beneficial pathologic information relevant to the long-term renal outcome and the optimal therapy preventing ESRF and/or death in patients with LGN.