Protective effects of ONO-5046*Na, a specific neutrophil elastase inhibitor, on postperfusion lung injury

Background. Polymorphonuclear neutrophil elastase might contribute to postperfusion lung injury, so we evaluated the protective effect of ONO-5046·Na, a specific inhibitor of polymorphonuclear neutrophil elastase, against such an injury.

Methods. The study was done using 8 mongrel dogs that received ONO-5046·Na (15 mg/kg per hour) (group O) and 8 control dogs (group C), all of which had 1 hour of partial bypass and 5 hours of observation.

Results. The respiratory index showed no significant changes in group O, but increased significant in group C (1.4 ± 2.0 versus 5.1 ± 4.7, p = 0.0047). Pulmonary extravascular water volume increased markedly in group C but only slightly in group O (group C 20.6 ± 8.7, group O 11.2 ± 2.7 mL/kg; p = 0.0005). Blood concentrations of polymorphonuclear neutrophil elastase and interleukin-6 showed more than a tenfold increase in group C (PMN elastase, group C 12.9 ± 12.8, group O 2.4 ± 1.3 ng/mL; IL-b, group C 11.0 ± 9.3, group O 2.9 ± 3.8 pg/mL; p < 0.05) but were only slightly higher in group O. Histologic examination revealed interstitial and intraalveolar edema in group C, but group O was virtually normal.

Conclusions. ONO-5046·Na inhibits polymorphonuclear neutrophil elastase and maintains better pulmonary function, so it should reduce postperfusion lung injury.     

Life span of Japanese male medical doctors

There have been few reports with regard to the life spans of medical doctors. The status of the medical doctors graduating from 1926 to 1974, alive or dead as of October 1996, was ascertained on the basis of the list of graduates from the School of Medicine, Hokkaido University. Excluding data on female doctors and those who died in battle during World War II, data on a total of 3,982 doctors were available for study. Their mortality as of October 1996 decreased in parallel with the graduation year. Their mean future life span at graduation was estimated to be about 52.88 years (95% CI, 52.45-53.31) through linear regression (r = 0.992). Their mean age at graduation was 25.17 years. This was not different from the future life expectancy at 25 years of age of the general population (52.35 years). The future life span of surgeons and gynecologists-obstetricians was shorter than that of the doctors of basic medical sciences and internal medicine. This difference might be accounted for by factors peculiar to each speciality (e.g., exposure to blood) or by the degree of stress from work.     

High inducibility of Epstein-Barr virus replication in B lymphocytes in Vogt-Koyanagi-Harada disease]

PURPOSE: The role of Epstein-Barr virus (EBV) reactivation in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease was examined. MATERIAL AND METHODS: Using B lymphocytes obtained from 8 patients with VKH disease and 10 patients with other types of uveitis, immortarized lymphoblast lines were established and infected with EBV. The degree of EBV activation in each lymphoblast line, in the presence and absence of various stimuli, was assessed by measuring the expression of 3 different antigens involved in replication by immunofluorescent staining and western blot analysis. Quantification of EBV DNA in cell culture supernatants was done by polymerase chain reaction. RESULT: Cell lines established from VKH patients expressed more viral antigens that those established from patients with other types of uveitis. There were greater amounts of EBV DNA in the VKH cell lines. CONCLUSION: B lymphocytes from VKH patients may be more susceptible to EBV activation, and the reactivation of EBV may be involved in the pathogenesis of VKH.     

Monophosphoryl lipid A provides biphasic cardioprotection against ischaemia-reperfusion injury in rat hearts

1 We utilized a rat model of myocardial infarction to investigate whether cardioprotection by monophosphoryl lipid A (MLA) is provided in the early and late phases, as well as to determine whether this cardioprotection may be related to the activation of manganese superoxide dismutase (Mn-SOD), an intrinsic radical scavenger. 2 Pretreatment with MLA (0.5 or 1.0 mg kg-1, i.v.) 24 h prior to 20-min left coronary artery (LCA) occlusion and 48-h reperfusion significantly decreased the incidence of ventricular fibrillation (VF) during ischaemia, as well as infarct size. Pretreatment with lower concentrations of MLA, however, was ineffective. 3 When we examined the time course of MLA (0.5 mg kg-1)-induced cardioprotection, both infarct size and the incidence of VF were significantly reduced in rats pretreated with MLA 0.5 h and 24 h before occlusion. We observed no differences, however, 2 and 72 h after MLA treatment. 4 The activity of Mn-SOD paralleled the cardioprotective effects of MLA. Mn-SOD activity in the myocardium was significantly enhanced in rats pretreated with MLA (0.5 mg kg-1) 0.5 and 24 h before. Mn-SOD activity was not altered, however, in rats pretreated 2 or 72 h before. Lower MLA concentrations were not effective even 24 h after the treatment. 5 We conclude that MLA treatment induced a biphasic pattern of cardioprotection. The pattern of Mn-SOD activity suggests that this enzyme may play a major role in the acquisition of cardioprotection against ischaemia-reperfusion injury.     

Lactonamycin, a new antimicrobial antibiotic produced by Streptomyces rishiriensis MJ773-88K4. II. Structure determination.

The absolute structure of a new antibiotic lactonamycin is described. The NMR studies deduced one of four possible structures for the aglycon attached by a rhodinose through glycosidic bond. The stereochemistry of the sugar obtained by an acid hydrolysis was determined to be L-form by measuring optical rotation. The stereochemistry of the aglycon was determined by X-ray crystallographic analysis.     

The Studies of the Attacks of Abnormal Eye Movement in a Case of Infantile Spasms

We observed the attacks of nystagmus in a case of infantile spasms and carried out overnight sleep polygraphy. The following findings were obtained:

• 1 Awake time was prolonged to 56% of TIB, while sleep time was markedly shortened to 44% of TIB. Also REM sleep time was reduced to 20% of SPT and deep slow sleep (stage N3) was absent.
• 2 Attacks of nystagmus were observed only during wakefulness. At first, fast wave bursts appeared in the right occipital area, and were followed by left-upward deviations of eyeballs, and then the attacks of counterclockwise right-downward rotatory nystagmus. Also the fast wave bursts were succeeded by spreading of fast waves to adjacent areas. At the same time, EMG exhibited elevated muscle action potentials of mentalis and biceps fernoris. During the attacks of nystagmus, there was alteration of respiratory movements.

In NREM sleep, both fast wave bursts and the attacks of nystagmus were not observed. In REM sleep, the fast wave bursts and eye movements were observed but the attacks of nystagmus did not appear. During the fast wave bursts, alteration of respiratory movements were observed. From the results of this study, it was presumed that the brain lesions of this case were extended with severe degree of damage in the great parts of brain containing Cerebral cortex and brain stem.     

Evaluation and selection of normal range calculation methods]

There are many methods for normal range calculation, and they give different values even with the same normal data sample. I proposed three parameters, accuracy, precision and robustness, for evaluating the calculation methods. A complicated calculation method, the distribution selection method, seems to be theoretically correct, but it shows unstable precision and inadequate robustness when the normal data contain a small amount of abnormal data. A method called "Clinical reference range program (CRRP)" is a robust method, and is applicable to the data which contains abnormal data. I also proposed a condition which defines the sample size required for the calculation using the precision parameter.     

Effects of synchronous pulsatile extracorporeal membrane oxygenation in an endotoxin-induced shock model: an experimental study

A synchronous pulsatile venoarterial device for extracorporeal membrane oxygenation (ECMO) was designed to accomplish more effective circulatory support for neonates. The effect of this device was studied using an endotoxin-induced shock model, compared with conventional nonpulsatile ECMO. Twenty puppies weighing 1.6 to 4.0 kg were given endotoxin (5 mg/kg) intravenously. Thirty minutes after the administration of endotoxin, 10 were placed on pulsatile ECMO, and the others were placed on nonpulsatile ECMO, and they were studied for an additional 180 min. Peak blood pressure, arterial pH, base excess, and renal blood flow were significantly higher in the pulsatile group than in the nonpulsatile group. Serum lactate and serum noradrenaline were significantly lower in the pulsatile group than in the nonpulsatile group. These results indicate that pulsatile ECMO may provide more effective cardiopulmonary support in the treatment of neonates with serious circulatory failure that has failed to be supported by nonpulsatile ECMO.     

Effects of isoflurane and halothane on the calcium ion-tension curve in rat myocardium

In order to clarify the interaction of volatile anesthetics and extracellular calcium ion on the myocardial contraction, effects of both isoflurane (1.0%) and halothane (0.5%) on the extracellular calcium ion concentration ([Ca²⁺]_O)-tension curve were studied. Increasing [Ca²⁺]_O enhanced the myocardial contraction response, and the maximal response was obtained at [Ca²⁺]_O of 3.0mM. Halothane depressed the maximal value of the tension development in response to increasing [Ca²⁺]_O, while isoflurane did not (P 0.01). The probit response of the developed tension to the changes in [Ca²⁺]_O indicated that isoflurane increased the median effective concentration (EC₅₀) of [Ca²⁺]_O significantly from 0.484 ± 0.051 (mean ± SEM) to 0.870 ± 0.056mM (P = 0.001), but halothane did not (P = 0.018). Therefore, 1.0% isoflurane was concluded to move the [Ca²⁺]_O-tension curve to the right, while a downwards shift occurred with 0.5% halothane.(Saeki S, Hirakawa M, Shimosato S: Effects of Isoflurane and Halothane on the Calcium Ion-tension Curve in Rat Myocardium. J Anesth 6: 172–175, 1992)