Kazuyo Kuzume

Before-birth climatologic data may play a role in the development of allergies in infants.

While an exacerbation in allergic symptoms corresponding to seasons has long been reported, few studies have investigated the association between the season of birth and allergic disorders. The aim of this study was to investigate whether the climatologic data before and after birth affected the incidence of atopic dermatitis (AD) and the results of allergy‐related blood tests in early infancy. From February 1995 to January 2000, 2136 infants were tested for AD and followed for 12 months. AD patients were tested by using allergy‐related blood tests. Data were compared according to the month of birth and the climatologic data using a computed statistical software package. Six hundred and thirty infants had AD before 12 months old, and significant differences were found according to the season of birth (p < 0.0001). Infants born in spring showed the lowest (22.3%) incidence, while those born in autumn showed the highest (34.6%). In 369 patients, total serum IgE levels, and serum specific IgE levels with egg white at 3 months old were also different according to the season of birth. All of these levels were lower in patients born in spring and summer, and higher in patients born in autumn and winter. Furthermore, the cumulative sunshine amount during the 3 months before and after birth was inversely correlated, while the average temperature over the 3 months before birth was positively correlated to the incidence of AD according to the month of birth. The climatologic data around birth may play an important role in whether an infant develops allergies.

Adenosine A1 receptor blockage mediates theophylline-associated seizures.

Theophylline‐associated seizures (TAS) often progress to prolonged or treatment‐resistant convulsions. Theophylline is a nonselective adenosine receptor antagonist. Adenosine is an endogenous anticonvulsant that can terminate seizures. Fever and young age have been reported to be risk factors for TAS. To elucidate the mechanism of TAS, we investigated the effect of theophylline and adenosine receptor ligands on hyperthermia‐induced seizures in juvenile rats. The treatment dose of theophylline or control saline was injected intraperitoneally 1 h before hyperthermia‐induced seizures. The seizure threshold in the theophylline group was significantly lower and seizure duration was significantly longer than those in the control group. The addition of a selective adenosine A1 receptor agonist and an adenosine kinase inhibitor completely counteracted the effects of theophylline. Moreover, a selective A1 antagonist caused a significantly longer seizure duration compared with the control. These findings suggest that blockage of the adenosine A1 receptor is the main cause of TAS.

Bupivacaine Inhibits Baroreflex Control of Heart Rate in Conscious Rats

Background Because exposure to intravenously administered bupivacaine may alter cardiovascular reflexes, the authors examined bupivacaine actions on baroreflex control of heart rate in conscious rats. Methods Baroreflex sensitivity (pulse interval vs. systolic blood pressure in ms/mmHg) was determined before, and 1.5 and 15.0 min after rapid intravenous administration of bupivacaine (0.5, 1.0, and 2.0 mg/kg) using heart rate changes evoked by intravenously administered phenylephrine or nitroprusside. The actions on the sympathetic and parasympathetic autonomic divisions of the baroreflex were tested in the presence of a muscarinic antagonist methyl atropine and a &bgr;-adrenergic antagonist atenolol. Results Within seconds of injection of bupivacaine, mean arterial pressure increased and heart rate decreased in a dose-dependent manner. Baroreflex sensitivity was unaltered after administration of 0.5 mg/kg bupivacaine. In addition, 1 mg/kg bupivacaine at 1.5 min depressed phenylephrine-evoked reflex bradycardia (0.776 ± 0.325 vs. 0.543 ± 0.282 ms/mmHg, P < 0.05) but had no effect on nitroprusside-induced tachycardia. Bupivacaine (2 mg/kg), however, depressed reflex bradycardia and tachycardia (phenylephrine, 0.751 ± 0.318 vs. 0.451 ± 0.265; nitroprusside, 0.839 ± 0.256 vs. 0.564 ± 0.19 ms/mmHg, P < 0.05). Baroreflex sensitivity returned to prebupivacaine levels by 15 min. Bupivacaine (2 mg/kg), in the presence of atenolol, depressed baroreflex sensitivity (phenylephrine, 0.633 ± 0.204 vs. 0.277 ± 0.282; nitroprusside, 0.653 ± 0.142 vs. 0.320 ± 0.299 ms/mmHg, P < 0.05). In contrast, bupivacaine did not alter baroreflex sensitivity in the presence of methyl atropine. Conclusions Bupivacaine, in clinically relevant concentrations, inhibits baroreflex control of heart rate in conscious rats. This inhibition appears to involve primarily vagal components of the baroreflex–heart rate pathways.

Histological characterisation of visceral changes in a patient with type 2 Gaucher disease treated with enzyme replacement therapy.

Gaucher disease is a lysosomal storage disease caused by deficiency of glucocerebrosidase and accumulation of glucocerebroside. Three major sub-types have been described, type 2 is an acute neurological form that exhibits serious general symptoms and poor prognosis, compared with the other types. This case was a girl diagnosed with type 2 Gaucher disease at 12months of age who presented with poor weight gain from infancy, stridor, hypertonia, hepatosplenomegaly, trismus and an eye movement disorder. Enzyme replacement therapy (ERT) was administered, but she had frequent myoclonus and developmental regression. She needed artificial ventilation because of respiratory failure. She died at 11years of age. An autopsy demonstrated infiltrating CD68-positive large cells containing abundant lipids in alveoli, while in the liver, kidney and bone marrow CD68-positive cells were small and round. In the bone marrow, myelodysplastic changes were present without Gaucher cells. The infiltration of Gaucher cells in alveoli was marked, suggesting that ERT was relatively ineffective in pulmonary involvement, particularly intra-alveolar. Additional treatments are necessary to improve the neurological and pulmonary prognosis of type 2Gaucher disease.

Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan

Introduction Fatty acid oxidation disorders (FAODs) are rare diseases caused by defects in mitochondrial fatty acid oxidation (FAO) enzymes. While the efficacy of bezafibrate, a peroxisome proliferator-activated receptor agonist, on the in vitro FAO capacity has been reported, the in vivo efficacy remains controversial. Therefore, we conducted a clinical trial of bezafibrate in Japanese patients with FAODs. Materials and methods This trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in 6 patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and 2 patients with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 8.2 years; ranging from 5.8 to 26.4 years). Bezafibrate was administered for 6 months following a 6-month observation period. The primary endpoint was the frequency of myopathic attacks, and the secondary endpoints were serum acylcarnitines (ACs, C14:1 or C16 + C18:1), creatine kinase (CK) levels, degree of muscle pain (VAS; visual analog scale) during myopathic attacks, and quality of life (QOL; evaluated using validated questionnaires). Results The frequency of myopathic attacks after bezafibrate administration decreased in 3 patients, increased in 3, and did not change in 2. The CK, AC, and VAS values during attacks could be estimated in only three or four patients, but a half of the patients did not experience attacks before or after treatment. Changes in CK, AC, and VAS values varied across individuals. In contrast, three components of QOL, namely, physical functioning, role limitation due to physical problems (role physical), and social functioning, were significantly elevated. No adverse drug reactions were observed. Conclusion In this study, the frequency of myopathic attacks and CK, AC, and VAS values during the attacks could not be evaluated due to several limitations, such as a small trial population. Our findings indicate that bezafibrate improves the QOL of patients with FAODs, but its efficacy must be examined in future investigations.

EVALUATION OF DYSFUNCTION IN BLOOD COAGULATION IN CHILDREN WITH URTICARIA

INTRODUCTION Recently, an association between coagulation dysfunction and the pathology of urticaria has been reported, but research in children is scarce. PATIENTS AND METHODS We measured levels of prothrombin fragments 1+2 (PTF1+2), fibrin degradation product (FDP), D-dimer, and mean platelet volume (MPV) in 32 children with urticaria. The study cohort comprised 18 cases of chronic and active urticaria, 7 cases of chronic and inactive urticaria, and 7 cases of acute urticaria. RESULTS PTF1+2 levels in the chronic and active urticaria group were higher than those in the chronic and inactive urticaria group (p<0.01). PTF1+2 levels in the acute urticaria group were higher than those in the chronic and inactive group (p<0.05). No significant difference was observed in the levels of FDP, D-dimer, and MPV among the three groups of the patients. Levels of PTF1+2, FDP, and D-dimer decreased as symptoms improved. CONCLUSION Plasma levels of PTF1+2 may be useful for assessment of the activity of urticaria.