Initial steroid bolus injection promotes vigorous CD8+ alloreactive responses toward early graft acceptance immediately after liver transplantation in humans.

We have found that steroid bolus withdrawal prior to graft reperfusion increased the incidence of acute cellular rejection (ACR). This study aims to clarify how initial steroid bolus (ISB) injection at reperfusion influences the kinetics of CD8(+) alloreactive immune responses immediately after living donor liver transplantation (LDLT). A total of 49 hepatitis C virus (HCV)-infected recipients were classified into 3 groups according to hierarchical clustering by preoperative CD8(+)CD45 isoforms. The naive T cell proportion was considerably higher in Group I than in Groups II and III, whereas Group II recipients had the highest effector memory (EM) T cells and Group III the highest effector T cells. The frequency of ACR was significantly higher in recipients without ISB than in those with ISB. In particular, the ACR rates were the highest in Group II without ISB. Following ISB, the proportion of effector T cells was promptly upregulated within 6 hours after graft reperfusion, simultaneously with the upregulation of CD27(-)CD28(-) subsets, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha and perforin expression, which significantly correlated with increasing interleukin (IL)-12 receptor beta 1 cells. These were then downregulated to below preoperative levels by tacrolimus (Tac) administered at 24 hours. These changes did not occur in the absence of ISB. In Group II without ISB, the downregulation of IL-12Rbeta1(+) cells was the greatest, consistent with the highest rates of ACR and mortality (60%). In conclusion, ISB must be done in place, especially in Group II with preexisting high EM T cells, to enable the development of early allograft acceptance.     

Clinical and fundamental studies on intravenous drip infusion of gentamicin in the pediatric field. Pediatric study group of gentamicin

A multiclinic study of gentamicin (GM) given by intravenous drip infusion was carried out by the Gentamicin Pediatric Study Group. The results are summarized as follows: 1. Upon intravenous drip infusion of GM at a dose range of 2.0-2.5 mg/kg over a period of 0.5-1 hour, therapeutically effective serum concentrations of 4-12 micrograms/ml were obtained. These values are similar to reported values in previous studies using GM intramuscular injection. 2. High urinary concentrations were observed up to 6 hours after administration, and the urinary recovery rate was approximately 60%. 3. Of a total of 142 cases collected, 117 cases were evaluated. Efficacy rates by diseases were: 100% in pneumonia (30/30), 98.3% in urinary tract infections (59/60), and 92.3% in other infections (skin and soft tissue) (12/13), with an overall efficacy rate of 94.9% (including 77 "excellent" cases). 4. Bacteriological examinations showed high eradication rates with the use of GM; i.e., 80% with Staphylococcus aureus (8/10), 60% with Pseudomonas aeruginosa (3/5), 100% with Haemophilus influenzae (7/7) and 97.8% with Escherichia coli (44/45), achieving an overall eradication rate of 92.4%. In mixed infections, the eradication rate was 85.7% (6/7). 5. No ototoxicity, nephrotoxicity or allergic reactions was observed. Abnormal laboratory findings observed were: GOT elevation in 3.1% of cases, GPT elevation in 3.9%, platelet increase in 1.5% and eosinophil increase in 0.8%, thus an overall rate of the appearance of abnormality was 5.6%. The above results indicate that an intravenous drip infusion of GM is a useful method for treating infections in pediatrics.     

Chymase participates in chronic dermatitis by inducing eosinophil infiltration

An epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) to a mouse ear caused a transient skin swelling, and the repetition of the challenge enlarged the contact dermatitis. The repeated challenge with DNFB also induced eosinophil infiltration on the application site. Administration of a chymase inhibitor significantly inhibited the ear swelling as well as eosinophil accumulation. An intradermal injection of human chymase to the mouse ear also elicited transient skin swelling and eosinophil infiltration, both of which were augmented in proportion to the number of injections. Human serum albumin and heat-inactivated chymase failed to induce such skin reactions, suggesting the participation of proteolytic activity of the enzyme. In addition, chymase stimulated eosinophil migration in vitro in a concentration-dependent manner. Taken together, these observations suggest that mast cell chymase may contribute to development of the DNFB-induced dermatitis, probably by promoting eosinophil infiltration. It is therefore possible that chymase plays a role in pathogenesis of chronic dermatitis such as atopic dermatitis.     

An ambulatory respirometer (Hotmate) as a tool for screening of sleep apnea syndrome

The gold standard diagnostic method for sleep apnea syndrome(SAS) is overnight polysomnography(PSG), but is costly in terms of time and money. We studied the usefulness of a 24-hour ambulatory respirometer equipped with oximeter(Hotmate) for screening of SAS. Seventy-six cases of suspected SAS were enrolled(68 males and 8 females, mean age 51). The correlation between data from Hotmate and PSG was evaluated in 24 cases who underwent both of the tests for the final diagnosis of SAS. There was a good correlation between the two parameters of the data obtained by Hotmate(H) (H-apnea index(AI) vs H-desaturation index(DI)). Among 24 cases who underwent both Hotmate and PSG, there was a good correlation between the data from PSG and Hotmate(PSG-AI vs H-AI: r = 0.80, p < 0.001). Both sensitivity and specificity were highest when screening criteria of H-DI > 15 was utilized(sensitivity = 91.7%, specificity = 66.7%). Our findings suggest that the respiromonitor with oximeter is useful for the screening the patients with SAS.     

Effects of Alkyl Alcohols and Related Chemicals on Rat Liver Structure and Function: III. Physicochemical Properties of Ethanol-, Propanol- and Butanol-treated Rat Liver Mitochondrial Membranes

The physicochemical properties of mitochondria in liver tissue obtained from rats given 32% ethanol, 32% propanol or 6.9% butanol in drinking water for up to 3 months were investigated using differential scanning calo-rimetry and fluorescence polarization measurements. The results obtained were as follows: 1) Phospholipids extracted from mitochondria showed increases in the relative amounts of phosphatidylcholine, phosphatidylinositol and phosphatidylserine, and a decrease in the relative amount of phosphatidylethanolamine. An increase in the unsatu-rated/saturated fatty acid ratio of phospholipids was also observed. 2) Elevation of the thermotropic lipid phase transition temperature with a decrease in the enthalpy value (δ H ) was revealed by differential scanning calo-rimetry. 3) The elevation of the lipid phase transition temperature was detected also by fluorescence polarization measurements using 1,6 diphenyl 1, 3, 5 hexatriene (DPH) as a probe. Elevation of mitochondrial membrane fluidity was found in some of the experimental animals, but most showed no changes in comparison with the control. A possible role of membrane fusion in the mechanism of formation of ethanol-, propanol- and butanol induced hepatic megamitochondria is discussed on the basis of these results. Acta Pathol Jpn 42: 549–557, 1992.     

Infective endocarditis caused by Granulicatella elegans originating in the oral cavity

We studied the pheno- and genotypes of an oral Granulicatella elegans strain in comparison with those of a blood-derived isolate which caused infective endocarditis. The two isolates exhibited identical biochemical characteristics and had the same drug MICs. Their genotypes were indistinguishable, indicating that these were from the same clone. The transmission of G. elegans from the oral cavity thus should be noted as a possible cause of infective endocarditis.     

Effects of nocturnal bright light on saliva melatonin, core body temperature and sleep propensity rhythms in human subjects

Nine healthy male volunteers (mean age of 24) participated in two experimental sessions of random crossover design: a bright light (5000 lux for 5 h from 00:00 to 05:00 h) session and a dim light (10 lux for 5 h from 00:00 to 05:00 h) session. Subsequently participants entered an ultra-short sleep-wake schedule for 26 h, in which a sleep-wake cycle consisting of 10-min sleep EEG recording on a bed and 20-min resting awake on a semi-upright chair were repeated. Saliva melatonin level and core body temperature was measured throughout the experiment. Bright light significantly delayed rhythms of melatonin secretion (01:58 h), core body temperature (01:12 h) and sleep propensity (02:00 h), compared as dim light session. Significant positive correlation was found between bright light-induced phase change in core body temperature and that in sleep propensity rhythm. Light-induced melatonin suppression significantly positively correlated with the phase change in core body temperature and that in sleep propensity rhythm. Assuming that light-induced melatonin suppression represents an acute impact of light on the circadian pacemaker, our results suggest that such an impact may be directly reflected in phase changes of sleep propensity and core body temperature rhythms rather than in melatonin rhythm.