Levetiracetam (LEV), a relatively new antiepileptic drug, is now frequently used for treating partial or generalized seizures. Among the adverse effects of LEV, rhabdomyolysis is rare. We describe here a case of LEV-induced rhabdomyolysis in a 26-year-old woman. The patient’s seizures had been controlled with carbamazepine and phenobarbital for the previous 7 years. However, LEV was initiated at the age of 26 years because her seizures control deteriorated with seizures occurring monthly. She experienced lower limb weakness with a high level of creatine kinase 15 days after starting LEV. When LEV was discontinued, her creatine kinase levels decreased and her symptoms gradually improved. This case provide another example of rhabdomyolysis during the early phase of LEV treatment.
Rhabdomyolysis

Background: Hot spring inhalation and rock bathing are widely practiced in Europe, and immersion in water up to the shoulders is popular in Japanese balneotherapy. We designed a combination therapy of steam rock bathing and immersion in an open-air hot spring pool for allergic rhinitis.Methods: Data were obtained by anonymous questionnaires from 19 participants with perennial allergic rhinitis who underwent the combination therapy for several days during the spring-pollen season. The participants immersed themselves in a sitting position in Saiboku hot spring water (sodium salt hot spring) at 41°C up to the shoulder level for 10 min in the open-air and then lay on a floor paved with small rocks in a supine position for 20 min in a room filled with the steam from hot springs, then immersed themselves again in the hot spring water for 10 min, and finally rested and sat on a chair for 20 min in a comfortable room. The hot spring water circulated through tubes with small holes that were embedded under the floor, which was paved with small rocks consisting of tourmaline and lime stones. Steam from the hot spring water penetrated through the floor and vaporized in the room. The rock bathing room was 40°C in temperature and 75% in humidity.Results: Clinical symptoms were alleviated in 17 of 19 participants. Watery rhinorrhea, eye itching, sneeze, and sore throat were improved in 100%, 75%, 40%, and 100% of the participants, respectively, compared with symptoms during the previous several years. No adverse effects were observed in any participants. Conclusion: Steam rock bathing, combined with immersion in an open-air hot spring pool, is useful in ameliorating the focal and systemic symptoms of allergic rhinitis.

Objective : To find methods to minimize ‘lost to follow-up’ in the long-term follow-up in a pilot study of Prescription-Event Monitoring in Japan (J-PEM) where hypertensive subjects who took losartan or a control drug and gave informed consent to the study were directly followed by researcher for years.
Design : Cohort Study
Methods : We conducted the follow-up survey twice, in which questionnaires were sent to hypertensive patients who had consented to being involved in the survey and returned it by mail. In the questionnaire, we asked about the use of the monitoring drug, change of medical institutions for the treatment of hypertension, significant health-related events. In the second survey, we reminded the non-responders by a letter of reminder and by telephone. When no information was obtained from the subject, we sent a letter, together with a copy of the informed consent given by the subject, to the municipal office where the subject's home was registered to inquire about the subject's current address and related information including the vital status. We calculated Standardized Mortality Ratio (SMR) using the information on death obtained from the mailed questionnaires, telephone and information in the municipal office.
Results : In a pilot study of J-PEM on losartan, 4344 and 3517 questionnaires were sent to pharmacists and doctors, respectively. The doctors handed the informed consent form to the patients and 422 patients agreed to participate the study and sent back the signed form to the study office. In the first and second surveys, a questionnaire was mailed to the subject approximately 1 and 5 years after the first prescription of losartan or a control drug, respectively. The response rate was 73 and 60% in the 1 st and 2 nd survey, respectively. In the manuscript, the results of the 2 nd survey were mainly presented. The reminders by mail and telephone increased the response rate from 60 to 81% and provided the information on the vital status for 86% of the subjects. The response rate was further increased to 84% and the vital status was known for 99% when the information in the municipal office was used. SMR was estimated to be 0.59 (95% CI : 0.34-1.01) before reminding subjects, 0.78 (0.52-1.17) after reminding subjects by a letter and telephone and 0.92 (0.65-1.31) after further addition of the information from the municipal office. During the 5 years of the observation, 21% of 343 subjects who sent back a filled questionnaire did and 70% did not change the clinic/hospital where they received the care for hypertension, while 9% did not answer the relevant question.
Conclusion : The method of the systematic survey may be useful in minimizing the ‘lost to follow-up’ subjects in the long-term pharmacoepidemiology studies in Japan where a patient can change the clinic/hospital for his/her own health care without any letter of reference. In the systematic survey, the researchers may try to follow the subjects by using several methods including reminders like a letter or telephone as well as the use of the information in the municipal office. To facilitate better follow-up, a careful design of the study including the proper design of the informed consent form is essential to maximize the amount and quality of the available information, particularly when the subject has a serious event or dies in a hospital or institution apart from that where the patient has been registered.

We investigated the effect of season or meteorological phenomena, on chief complaints and disorders of outpatients, by way of clarification of relationship between weather and health. This study covered the new outpatients of our division, and carried out on February '03 and June '03 (February: 72 males, 106 females, aged 49.9±18.5, June: 98 males, 109 females, aged 47.6±19.5). We categorized their clinical data into chief complaints (pain, headache, discomforts, fever, cough, vertigo/stagger, palsy) and disorders (gastrointestinal, mental, inflammatory, orthopedic, infection, respiratory, circulatory, tumorous, urinary, autoimmune/allergic, dental/oral, gynecological), then, compared the clinical data of February with June, in terms of seasonal disease. Additionally, we investigated the relationship between weather data and clinical data of February and June, from a perspective of meteoropathy. The average of meteorological phenomena (air pressure, air temperature, relative humidity, velocity of wind, day length, rainfall level) of a week before first visit, were used as weather data. The main results of analysis about seasonal disease, showed that the complaint of discomfort were more frequent in June than February (p=0.005). The orthopedic disorder was more frequent in June than February (p=0.012). Infection was more frequent in February than June (p=0.011). The analyses in terms of meteoropathy, showed that the complaint of cough were more frequent after cold temperature in February (p=0.014). The gastrointestinal disorders were more frequent after humid (p=0.018) and pluvious days (p=0.016) in February. The complaint of headache was liable to be frequent after pluvious weather in June.
The relationship between weather and health is known in the prior an, and our study anew demonstrated the effect of season or meteorological phenomena, on chief complaints and disorders of outpatients, as statistical evidence.

This study investigated the existence of platelet activation before the onset of cerebral infarction, and analyzed the association between the platelet activation and the degree of atherosclerosis. Furthermore, prediction of the risk of cerebral infarction by assessing platelet activation was attempted. Thirteen patients with cerebral infarction, 7 patients with atherosclerosis and 8 healthy subjects were enrolled in this study. Ultrastructural shape change, peroxidase reaction, and fibrinogen content in the platelets were observed and plasma levels of thrombin antithrombin complex, α₂-plasmin inhibitor plasmin complex, β-thromboglobulin and platelet factor-4 were measured in patients with atherosclerosis and cerebral infarction at the acute, subacute and chronic phases. The ultrastructural shape change, peroxidase reaction, and fibrinogen content did not differ among acute, subacute and chronic phases of cerebral infarction. The frequency of platelet shape changes were also increased in patients with atherosclerosis, compared with healthy subjects. Plasma levels of β-thromboglobulin, platelet factor-4, and thrombin antithrombin complex increased only during the acute phase of cerebral infarction. It is suggested that platelet activation occurs before the onset of cerebral infarction and that platelet shape change is associated with the degree of atherosclerosis, or plaque stability. Platelet activation would be derived not from thrombotic event itself but from endothelial damage or pre-existing atherosclerosis. Platelet shape change, therefore, could predict the risk of cerebral infarction. Taken together with our previous reports demonstrating increased blood viscosity, noctural hypotension, increased human atrial natriuretic peptide, decreased fibrinolytic activity, and platelet shape change were observed after very hot hot-spring bathing, cerebral infarction in spa-resort could be caused partly by very hot hot-spring bathing after traveling on a tight schedule and alcohol drinking by elderly patients with atherosclerosis.