We examined the changes in pharmacokinetics of an oral sustained-release theophylline preparation (Theolong^®) during attacks of bronchial asthma. Ten patients (4 males and 6 females) were studied. They were admitted to the hospital because of attacks of bronchial asthma despite administration of an oral sustained-release theophylline preparation in the emergency outpatient clinic. After admission, serum concentrations of theophylline during the attack and during remission were measured in each patient, and the pharmacokinetic parameters at both stages were analyzed bythe Bayesian method. The serum concentrations of theophylline were 14.4±0.7μg/ml during the attack and 18.1±3.2μg/ml during remission; hence, the serum concentration of theophylline was decreased during the attack. The systemic clearance of theophylline was 0.044±0.0151/kg/hr during the attack, and 0.037±0.0181/kg/hr during remission; hence, clearance of theophylline was elevated during the attack. The volume of distribution (Vd) was 0.429±0.0241/kg during the attack and 0.399±0.0461/kg during remission; hence, an increased volume of distribution was noted during the attack. Furthermore, there was a correlation (r=-0.65) between the volume of distribution and the arterial pH level. Theophylline shows pH-dependent protein binding, so there is a possibility that the volume of distribution was increased by the protein binding rate which was affected by the changes in arterial pH level. No significant difference was noted in absorption lag time between the two stages. During the course from attack to remission, pharmacokinetics of theophylline undergo changes and affect serum concentrations, thus inducing easier development of adverse reactions. The above results suggest the importance of modifying doses when necessary after the attack stage while monitoring serum concentrations of theophylline.

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In this paper we describe the current situation regarding out-of-hospital cardiopulmonary arrest (OHCPA) based on 2 years of experience with doctor-car operation and will clarify differences from conventional DOA reports. The subject of this study was 463 cases of OHCPA encountered during operation of the doctor car over the two-year period begining April 1, 1993. We assessed incidence, age, sex, type, premorbid profile of the patients, the time and place of the OHCPA, presence of bystanders, and circumstances at the time of arrival at the scene. 1) Incidence: The incidence of OHCPA was 50.6-59.8 persons/year per 100, 000 population. 2) Age: The aged accounted for a very large proportion of the cases, with 43.7% being 71 years of age or older. 3) Type: Endogenous CPA accounted for 65.0% of the cases, exogenous CPA for 21.4%, and in 13.6% the cause was unknown. 4) Premorbid profile: In 11.4% of the cases the patient was already confined to bed for chronic diseases or terminal cancer. 5)Time of occurrence: The most common times of occurrence, in decreasing order, were evening, daytime working hours and the middle of the night. 6) Place: Almost all of the endogenous and etiology-unknown cases of CPA occured at home, and 16.8% of the patients were found in the bathtab. 7) Witnessed cases: Witnessed cases accounted for only 38.9% of the total incidence. 8) Circumstances at the time of arrival at the scene: In 26.3% of the cases postmortem changes were already evident. The ECG findings showed standstill in 78.3%, ventricullar fibrillation in 12.8%, electromechanical dissociation in 3.1%, and bradycardia in 5.8%. The patients with OHCPA differed from the DOA cases reported earlier in the following ways: 1) There was a higher proportion of aged and a lower percentage of young persons, and postmortem changes observed in many more cases. 2) There were fewer witnessed cases. 3) There were fewer cases of exogenous CPA. 4) DOA included cases in which CPA had occurred in the ambulance. As there is a clear disparity between the actual circumstances regarding OHCPA and DOA, it is difficult to compare the outcome in each group. Further comparison of the results of each pre-hospital care system should be made using uniform terms and definitions regarding OHCPA in Japan.

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To elucidate the progressive pathology of burned dermal lymphatics, present study shows three-dimensional reconstruction images of the lymphatics in rat dermis subjected second degree scald burns were constructed, and the volume of the lymphatics per skin area measured. Local scald burns were inflicted by applying 70°C hotwater for 5 seconds on the abdominal wall of female Wistar rats. Burned skins were harvested at 1, 2, 4, 8, and 12 hours, and 1, 2, 4, 7, and 14 days postburn. Rats were anesthetized with ethylether during any intervention. Specimens were embedded in epoxy-resin. Semithin 300 sections 2μm were serially cut from each resin block. Every third section was examined and photographed. Each lymphatic image in a series of 100 pictures were taken with a CCD camera, and three-dimensional reconstruction figures were made by computer (using OZ soft; RIZE company Japan). Dermal lymphatic volumes were also measured. Unburned rats were prepared as controls. In normal dermis several lymphatics running at the sebaceous gland level, to which a few subepidermal lymphatics descended were seen. The lymphatics developed several hours postburn, markedly at 4 hours postburn, to well-expanded subepidermal lymphatics, with a lymphatic network that formed a plexus in the mid-dermis, and further descending lymphatics. On and after 1 day postburn, lymphatics in the upper dermis gradually disappeared and the continuity of dermal lymphatics decreased. Consequently, the structure of lymphatics in the mid/deep dermis remained from 4 to 14 days postburn. Volumes expanded significantly from 1 hour to 2 days (the volumes between 4-12 hours increased to 7∼9-fold that of normal animal). Measurement of burned dermal lymphatic volume is thought to reflect the extent of lymphatic distention, and these results correlate with previous physiological findings. This study outlined the actual morphological changes in dermal lymphatics over the postburn period.

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