Concentric structure of thalamic lesions in acute necrotizing encephalopathy.

Acute necrotizing encephalopathy of childhood (ANE) is characterized by multiple, symmetrical brain lesions affecting the bilateral thalami, putamina and cerebral white matter, which often show a concentric structure on CT and MRI. To reveal the pathological substrate of this finding, comparison was made between CT and necropsy findings of three fatal cases of ANE. Cranial CT demonstrated a concentric structure of the thalamocerebral lesions in one patient who died 3.5 days after the onset of encephalopathy, but not in the other two patients who died within 30 h. Neuropathological examination of postmortem brains revealed laminar changes of vascular and parenchymal pathology in all the cases. Excessive permeability of blood vessels and resultant vasogenic edema became more prominent with increasing depth from the cerebral surface. The deep portion of the lesions showed severe perivascular hemorrhage, accounting for the central high density on the CT images of one patient.

[The relation between the severity of bronchial asthma and the treatment points in children].

The treatment points and score for definition of the asthma severity were initially introduced in the guideline for pediatric asthma treatment and management on 1998. We studied the relationship between the severity of clinical symptoms for children with bronchial asthma and the treatment points from July 1998 to November 1999 in our hospital. One hundred twenty five patients (one to 15 years of age, 77 boys and 48 girls) were retrospectively investigated. The treatment points and scores were associated with the clinical symptom score. However, there was no relationship in some patients. In order to define the severity of bronchial asthma, we should investigate not only the severity in terms of the clinical symptoms; the number and degree of asthma attacks, but also the treatment points and score. Furthermore, we should pay attention to the seasonal variation of the treatment points.

Ultrasonographic detection of very thin percutaneous central venous catheter in neonates.

To assess the ability of ultrasonography to detect the tip of a very thin (0.4 mm outer diameter) percutaneous central venous catheter (PCVC) in neonates, the PCVC tip location was assessed by ultrasonography (US) and compared to the location estimated by standard radiography for 57 PCVCs in 44 neonates. Of 57 occasions, the examiner could not find the PCVC tip in three cases (5%). In the remaining 54 instances, in 87% of cases, the PCVC tip position was consistent with the location implied by skeletal landmarks on standard radiographs. On 24 occasions we also assessed catheter tip dislodgement according to flexion and extension of the infant's arm. US could detect 78% of cases of catheter tip dislodgement. The PCVC tip was sometimes visualized as a dot and parallel lines as well as mere parallel lines. In a large population of cases, US is a reliable method for detection of a thin PCVC tip. US provides precise information about the PCVC tip position in relation to vascular structure and contributes to safer positioning of the PCVC than traditional radiography alone.

Craniotubular dysplasia with severe postnatal growth retardation, mental retardation, ectodermal dysplasia, and loose skin: Lenz-Majewski-like syndrome.

The heterogeneous group of craniotubular dysplasias is characterized by modeling errors of the craniofacial and tubular bones. Some conditions in this category cause not only skeletal abnormalities but also a variety of mesoectodermal dysplasias, as exemplified in Lenz-Majewski syndrome (MIM 151050), which comprises craniodiaphyseal dysplasia, failure to thrive, mental retardation, proximal symphalangism, enamel hypoplasia, and loose skin. We report on a boy with a hitherto unknown multisystem disorder, including skeletal changes that were regarded as a form of craniotubular dysplasia. The patient had a large head, exophthalmos, a broad nasal root, anteverted nostrils, large auricles, thick lips, micrognathia, severe postnatal growth retardation with emaciation, severe mental retardation, sparse hair growth, enamel hypoplasia, and thin, loose skin with hyperlaxity. Skeletal changes consisted of thickened calvaria, sclerosis of the skull base and facial bones, thick ribs, and metaphyseal undermodeling of the tubular bones. In addition, generalized osteopenia was evident. The present disorder overlaps phenotypically with Lenz-Majewski syndrome; nevertheless, the absence of diaphyseal hyperostosis and proximal symphalangism in the present patient was not consistent with Lenz-Majewski syndrome.

Pharmacological profile of alminoprofen among four writhing models of mice caused by kaolin, zymosan, acetylcholine and phenylquinone.

The effects of alminoprofen and other non-steroidal antiinflammatory drugs (NSAIDs) on the writhing reaction caused by kaolin, acetylcholine, phenylquinone and zymosan were studied. Aspirin, indomethacin, ibuprofen and diclofenac-Na, as cyclooxygenase inhibitors, showed similar potency ratios on four writhing tests, although, alminoprofen exhibited a somewhat rather higher potency ratio on kaolin- and zymosan-induced writhing models than on acetylcholine- and phenylquinone-induced writhing models. All NSAIDs, cyclooxygenase inhibitors except alminoprofen showed similar shapes in illustrations of potency ratio when the potency of aspirin was expressed as 1.0. The potency of alminoprofen produced a figure unlike those of other cyclooxygenase inhibitors. These results suggest that alminoprofen has a different pharmacological profile from other general NSAIDs in terms of analgesic action. This combination method with potency ratios for writhing reactions caused by the above four inducers could be a simple method for classification of pharmacological profiles of the analgesic actions of NSAIDs.

[Isolation of Legionella spp. from cooling tower water and the effect of microbicides].

Legionella spp., the causative organism of legionnaires' disease, were isolated from more than 80% of water samples in cooling towers before washing. Therefore, we evaluated the effect of microbicide treatment of cooling tower water on Legionella spp., other bacteria and protozoa. 2-Bromo-2-nitropane-1,3-dial, 2,4-dibromo-5,5-dimethylhydantoin or silver nitrate-treated silica gel was added to cooling tower water. The isolation rate of Legionella spp. in the cooling tower water was 50% after microbiocide treatment with 2-bromo-2-nitropane-1,3-dial being the most effective. The microbicide treatment had no effect on other bacteria or protozoa. These findings indicated the importance of regular washing and water exchange of cooling tower water with microbicide treatment.

Kaolin-induced writhing in mice, a new model of possible bradykinin-induced pain for assessment of analgesic agents.

Kaolin induced a clear and reproducible writhing reaction when intraperitoneally injected into mice. A simultaneous injection (i.p.) of soybean trypsin inhibitor (SBTI) significantly suppressed the kaolin-induced writhing reaction. This writhing reaction was markedly potentiated by a simultaneous injection (i.p.) of captopril. In an in vitro experiment kaolin caused kinin-release in mouse plasma, possibly through the activation of prekallikrein. This activation of plasma prekallikrein and kinin-release were inhibited in the presence of SBTI. Some non-steroidal anti-inflammatory agents inhibited the kaolin-induced writhing reaction dose-dependently. These results suggest that kaolin-induced writhing reaction may be caused by the released bradykinin through activation of the plasma kallikrein-kinin system. This model is a novel and simple tool for assessment of analgesic agents.

Pharmacological studies on EB-382, a new non-steroidal antiinflammatory agent: mode of action of the antiinflammatory effects.

The mode of action of (+/-)-2-[p-[(2-methylallyl)amino]phenyl]propionic acid (EB-382) was studied in terms of its antiinflammatory effect. EB-382 displayed a more potent inhibitory effect than that of ibuprofen on carrageenin-induced paw edema in rats, and its inhibitory action was unaffected by adrenalectomy. EB-382 had a less potent inhibitory effect than that of ibuprofen on the prostaglandin E2 biosynthesis of 3T6 mouse fibroblast cells. EB-382 displayed a much more potent inhibitory effect than that of ibuprofen on carrageenin-induced pleurisy in rats. EB-382 exhibited a dose-dependent and significant inhibitory effect on the bradykinin and prostaglandin contents released into the pleural cavity in rat pleurisy induced by carrageenin, and its potency was much higher than that of ibuprofen. EB-382 strongly inhibited the leukocyte emigration into the pleural cavity, and its potency was almost equal to that of indomethacin. EB-382 did not affect the kinin-forming enzyme and kininase activities of rat plasma in vitro. The above results suggest that the antiinflammatory effect of EB-382 was probably due to inhibition of the production of bradykinin and prostaglandins derived from emigrating leukocytes in the local inflamed tissue besides a weak inhibitory effect on prostaglandin biosynthesis.

A new writhing model of factor XII activator-induced pain for assessment of non-steroidal anti-inflammatory agents. I. Kaolin-induced writhing in mice.

The writhing reaction in mice induced by kaolin, a factor XII activator, was studied. An intraperitoneal injection of kaolin clearly induced a writhing reaction in a dose-dependent fashion, and the reaction disappeared about 10-15 min later. The writhing reaction reached a peak at 5-10 min after the injection of kaolin (0.5 ml/mouse, i.p.; 5 mg/ml saline). A simultaneous intraperitoneal injection of soybean trypsin inhibitor (SBTI, 2.5 mg/mouse) almost completely suppressed the writhing reaction caused by kaolin (2.5 mg/mouse) for the first 10 min. The kaolin-induced writhing reaction was markedly potentiated by a simultaneous intraperitoneal injection of captopril (50 micrograms/mouse). At 60 min after kaolin injection during the disappearance of the writhing reaction, the reaction reappeared when captopril was injected, but reactions observed at this later stage were completely blocked by SBTI. Indomethacin, ibuprofen and alminoprofen inhibited the writhing reaction dose-dependently. Kaolin thus induces a clear and reproducible writing reaction, which might be mainly dependent on the action of bradykinin via activation of factor XII, and should prove to be a simple and convenient model of bradykinin-induced pain for the assessment of analgesic actions.

Pharmacological studies on EB-382, a new non-steroidal antiinflammatory agents: mode of action of the analgesic effects.

The analgesic mechanism of (+/-)-2-[p-[(2-methylallyl)amino]phenyl]propionic acid (EB-382), a new non-steroidal antiinflammatory agent, was studied. EB-382 exerted a potent analgesic effect on yeast-induced hyperalgesia in rats and bradykinin-induced writhing in mice, and its potency was superior to that of ibuprofen. EB-382 had a comparatively weak inhibitory effect on the prostaglandin E2 production from arachidonic acid in sheep seminal vesicle microsomal fraction in vitro. EB-382 exhibited a dose-dependent inhibitory effect on the phospholipase A2 activity in 3T3 mouse fibroblast cells with a different mechanism from steroidal agents, although indomethacin and ibuprofen did not reveal any significant inhibition. EB-382 did not affect the bradykinin-induced contraction of isolated rat uterus. Intracisternal injection of EB-382 did not affect the acetic acid-induced writhing response in mice. From these results, it is suggested that the analgesic effect of EB-382 in inflammation is exerted through its direct peripheral action, and inhibition of prostaglandin biosynthesis via phospholipase A2, rather than cyclooxygenase.