Intravenous ulinastatin therapy for Stevens-Johnson syndrome and toxic epidermal necrolysis in pediatric patients. Three case reports

BACKGROUND: More effective therapy is needed for the treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The clinical efficacy of intravenous ulinastatin therapy was investigated in 3 Japanese pediatric patients with SJS or TEN. METHODS: Ulinastatin was given to 1 pediatric SJS patient and 2 pediatric TEN patients within 7 days (patient 1; SJS), 6 days (patient 2; TEN), or 4 days (patient 3; TEN) after the onset of the skin rash. Ulinastatin was administered intravenously at a dose of 7,500 U/kg/day (maximum dose: 300,000 U/day). No corticosteroids were given. After the skin lesions resolved, the ulinastatin dose was reduced to between 2,500 and 5,000 U/kg/day as maintenance therapy and then the drug was withdrawn. RESULTS: Erythema, fatigue, and fever improved within 12-36 h of starting the ulinastatin infusion, and the skin lesions resolved completely after 4-7 days of ulinastatin therapy. None of the patients had cutaneous or ocular sequelae. No patient developed secondary infection or relapse and ulinastatin therapy caused no side effects. CONCLUSION: Ulinastatin dramatically reduced the febrile period with no adverse effects and was very safe in this study. Ulinastatin appears to be a useful and effective therapy for controlling SJS and TEN without sequelae.     

Activation of CD44 induces ICAM-1/LFA-1-independent,Ca2+, Mg2+, —independent adhesion pathway in lymphocyte-endothelial cell interaction

We have established an endothelial cell line KOP2.16 from pooled mouse lymph nodes. Resting lymphocytes avidly bound to KOP2.16 and migrated underneath the cytoplasm. The binding was partly mediated by VLA-4 and VCAM-1, but apparently independent of CD44 since anti-CD44 antibody examined failed to inhibit the binding. However, pretreatment of lymphocytes with anti-CD44 resulted in the rapid appearance of Ca²⁺-, Mg²⁺-independent, LFA-1/ICAM-1-, CD2/LFA-3,VLA-4/VCAM-l-independent lymphocyte binding, indicating that a novel adhesion pathway was induced by the anti-CD44 treatment. Interestingly, the elicited adhesion was observed only when anti-CD44 that block hyaluronate recognition of CD44 were used for lymphocyte pretreatment. Neither hyaluronate itself nor non-blocking anti-CD44 up-regulated the adhesion. Fab fragment of the blocking anti-CD44 did not induce the up-regulation unless cross-linked with a second antibody, indicating that cross-linking of surface CD44 is necessary for induction of a novel adhesion pathway. We propose that the agonistic anti-CD44 antibodies induce a novel adhesion pathway by mimicking ligand binding to CD44 on the lymphocyte surface and that non-hyaluronate ligand(s) is involved in regulation of adhesive function of CD44. Potential involvement of such a regulatory mechanism in lymphocyte homing is discussed.     

Establishment and migration pattern of<Emphasis Type="Italic"> Toxocara canis</Emphasis> larvae in chickens

Migrations of Toxocara canis larvae were observed in experimentally infected chickens. Three groups of three chickens were inoculated orally with T. canis eggs. Within each group, individual chickens received either 5,000, 10,000, or 20,000 eggs. A group of infected chickens was then necropsied at either 1, 3 or 6 days post infection (dpi). The entire duodenum, spleen, liver, heart, lungs, right inner pectoral muscle, and brain were subjected to pepsin digestion for larval recovery. Larvae were predominately (>87%) recovered from the liver and lungs, and only a few larvae were seen in other organs or tissues in all chickens, with the exception of the duodenum at 1 dpi of chickens inoculated with 20,000 eggs. The percentage of total larval recovery varied widely among chickens (range: 0.4–16.7%). Similar numbers of larvae were distributed in the liver and lungs at 1 dpi. Subsequently, more larvae were found in the lungs than the liver at 3 dpi, whereas the larval distributions in the liver and lungs were reversed at 6 dpi. These observations suggest that T. canis larvae can migrate by a hepatopulmonary route in the chicken, and reinforces the possibility that chickens harboring migrating T. canis larvae may pose a zoonotic risk, especially if the liver is consumed.     

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.     

Electrophysiological analysis of rhythmic jaw movements in the freely moving mouse

Although rhythmic jaw movement in feeding has been studied in mammals, such as rats, rabbits and monkeys, the cellular and molecular mechanisms underlying it are not well understood. Transgenic and gene-targeting technologies enable direct control of the genetic makeup of the mouse, and have led to the development of a new category of reagents that have the potential to elucidate the cellular and molecular mechanisms of neural networks. The present study attempts to characterize rhythmic jaw movements in the mouse and to demonstrate its relevance to rhythmic jaw movements found in higher mammals using newly developed jaw-tracking systems and electromyograms of the masticatory muscles. The masticatory sequence of the mouse during feeding was classified into two stages, incision and chewing. Small and rapid (8 Hz) open-close jaw movements were observed during incision, while large and slow (5 Hz) open-close jaw movements were observed during chewing. Integrated electromyograms of the masseteric and digastric muscles were larger during chewing than those observed during incision. Licking behavior was associated with regular (8 Hz), small open-close jaw movements with smaller masseteric activity than those observed during mastication. Grooming showed variable patterns of jaw movement and electromyograms depending on the grooming site. These results suggest that there are neuronal mechanisms producing different frequencies of rhythmic jaw movements in the mouse, and we conclude that the mouse is useful for understanding rhythmic jaw movements in higher mammals.     

Elevated nasal mucosal G protein levels and histamine receptor affinity in a guinea pig model of nasal hyperresponsiveness

BACKGROUND: Nasal hyperresponsiveness is a common feature of allergic rhinitis, but the underlying mechanisms have yet to be elucidated. The effects of repeated antigen inhalation on the characteristics of histamine H(1) receptors and expression levels of heterotrimeric guanosine 5'-triphosphate-binding proteins in nasal mucosa were investigated to understand the mechanisms of the pathogenesis of nasal hyperresponsiveness in allergic rhinitis. METHODS: Male Hartley guinea pigs were sensitized by the inhalation of dinitrophenylated ovalbumin antigen (10 mg of protein/ml) and repeatedly challenged by inhaling aerosolized dinitrophenylated ovalbumin antigen for 3 weeks. Twenty-four hours after the last antigen inhalation, in vivo nasal responsiveness to histamine was measured. [(3)H]Mepyramine binding assays and immunoblotting for alpha subunits of the G(q) protein were also performed using membrane preparations of isolated nasal mucosae. RESULTS: The histamine-induced increase in intranasal pressure was significantly augmented after repeated antigen challenge, indicating that nasal hyperresponsiveness was achieved. In saturation binding studies, no significant change was observed in the density and antagonist affinity of H(1) receptors in the hyperresponsive animals. On the other hand, the affinity of histamine for high-affinity agonist binding sites in the hyperresponsive group, measured by histamine competition binding studies, was much greater than that in control animals, and these results were affected by guanosine 5'-O-(3-thiotriphosphate) in both groups. Moreover, Galpha(q) levels in nasal mucosal homogenates were significantly increased after repeated antigen challenge. CONCLUSIONS: Elevated G protein levels in nasal mucosa might induce an increased binding affinity of histamine to its receptors, resulting in an augmented nasal response to histamine, that is, nasal hyperresponsiveness, in guinea pigs.     

Heavy-ion-induced mutations in the gpt delta transgenic mouse: comparison of mutation spectra induced by heavy-ion,X-ray,and gamma-ray radiation

Heavy-ion radiation accounts for the major component of absorbed cosmic radiation and is thus regarded as a significant risk during long-term manned space missions. To evaluate the genetic damage induced by heavy particle radiation, gpt delta transgenic mice were exposed to carbon particle irradiation and the induced mutations were compared with those induced by reference radiations, i.e., X-rays and gamma-rays. In the transgenic mouse model, deletions and point mutations were individually identified as Spi(-) and gpt mutations, respectively. Two days after 10 Gy of whole-body irradiation, the mutant frequencies (MFs) of Spi(-) and gpt were determined. Carbon particle irradiation significantly increased Spi(-) MF in the liver, spleen, and kidney but not in the testis, suggesting an organ-specific induction of mutations by heavy-ion irradiation. In the liver, the potency of inducing Spi(-) mutation was highest for carbon particles (3.3-fold increase) followed by X-rays (2.1-fold increase) and gamma-rays (1.3-fold increase), while the potency of inducing gpt mutations was highest for gamma-rays (3.3-fold increase) followed by X-rays (2.1-fold increase) and carbon particles (1.6-fold increase). DNA sequence analysis revealed that carbon particles induced deletions that were mainly more than 1,000 base pairs in size, whereas gamma-rays induced deletions of less than 100 base pairs and base substitutions. X-rays induced various-sized deletions and base substitutions. These results suggest that heavy-ion beam irradiation is effective at inducing deletions via DNA double-strand breaks but less effective than X-ray and gamma-ray irradiation at producing oxidative DNA damage by free radicals.     

A case of the esophageal candidiasis supposedly caused by rhinenchysis steroid chronic administration before sleep]

In general, steroid is mainly used as anti-inflammatory action in case of allergic diseases. As one of the side effects of inhalation steroid, a report is given below regarding buccal capsule/esophageal candidiasis. The patient came to the hospital with the chief complaint regarding passage dysphagia in the time of deglutition; pharyngitis and esophageal candidiasis were found by endoscopy of upper gastrointestinal tract.The interview after the endoscopy revealed that the patient, a 69-year-old female was diagnosed as chronic perennial allergic rhinitis a few years ago, and had been inhaling rhinenchysis Beclometasone dipropionate (BDP) before sleep every day for the past two years because using this collunarium seemed to mitigate the nasal obstruction and mucus during sleep. The patient did not report this fact before the endocsopy because she did not associate it with her subjective symptom. In this case, it was assumed that nebulized rhinenchysis BDP was accidentally swallowed to the pharynx and esophagus during sleep. As a treatment, rhinenchysis BDP was canceled and instead Azunol mouth washing (gargling/nasal douche) was used. No antifungal agent was used. In two weeks, the patient reported some improvement, and this was confirmed by reexamination of the upper gastrointestinal tract using endoscope in one month and a half. Pharyngitis was improved, and in the digital endoscopic assessment of esophageal candidiasis complicating inhaled steroid therapy the esophageal candidiasis became Grade I (mild grade). As for the later progress, the patient did not report any subjective symptoms such as nasal obstruction and dysphagia. In addition, the inflammation caused by candidiasis and found in the early examination was improved. The patient in this case was under treatment for thrombosis in the vein of lower extremity, but no complications such as diabetes mellitus or immune deficiency syndrome were observed. DISCUSSION: Esophageal candidiasis by chronic administration of inhalation of steroid before sleep for asthmatic patients has been reported. However, there has not been a report of esophageal candidiasis by chronic administration of rhinenchysis steroid before sleep for patients with allergic rhinitis. Similarly, in the case of the use of steroid in the form of collunarium before sleep, steroid stayed in the esophagus via the transendothelial nasal cavity, and that seemed to cause, in the long run, to develop esophageal candidiasis. CONCLUSIONS: One of the implications of the above case is that collunarium can go down, even when it is nebulized in the nasal cavity, to the esophagus via the nasal cavity to buccal capsule. This suggests the necessity for preventative measures in the case of chronic administration of steroid as follows. A. Blowing of the nose just after the use of collunarium B. Daily rinsing (gargling and nasal douche).     

Why is the diverse U letter relationship between embarrassment and psychological distance observed? In view of Schlenker and Leary (1982)'s self-presentation model of social anxiety

The aim of the present study is to explain why there is "the diverse U letter relationship" between embarrassment and psychological distance empirically, in view of Schlenker and Leary (1982)'s self-presentation model of social anxiety. In Study 1, those relationships were observed in three different situations. In Study 2, the main effect of motivation for avoiding rejection and the damage of self-image, and their interaction with embarrassment was examined by hierarchical regression analysis. In the first step, the psychological distance, in the second step, the main effect of both, and in the third step, the interaction was entered. As a result, in the second step, both main effects were significant, but in the third step, only interaction was significant, and both main effects were not significant. This showed that the interaction could predict embarrassment, although the psychological distance was controlled. Finally, this result was discussed in view of social norm.