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Multicenter, double-blind study of intravenous milrinone for patients with acute heart failure in Japan. Japan Intravenous Milrinone Investigators.

OBJECTIVES: Milrinone is a phosphodiesterase F-III inhibitor with positive inotropic and vasodilating activities. We investigated the hemodynamic response and pharmacokinetics of intravenous milrinone in patients with acute heart failure. DESIGN: Double-blind studies: a prospective, multicenter, double-blind, dose-finding study and a placebo-controlled, double-blind, comparative study. SETTING: Patients with acute heart failure (pulmonary artery occlusion pressure of > or = 18 mm Hg), who were hospitalized in the cardiac care units of 33 institutes in Japan, were entered into the study. PATIENTS: Fifty-four patients with acute or decompensated heart failure in the dose-finding study and 52 patients in the placebo-controlled, double-blind, comparative study. INTERVENTIONS: The present multicenter study consisted of a double-blind, dose-finding study (50-micrograms/kg intravenous loading dose, followed by 0.25, 0.5, or 0.75 microgram/kg/min of a continuous infusion of milrinone for 6 hrs, n = 54), and a placebo-controlled, double-blind, comparative study (50-micrograms/kg loading dose, followed by 0.5 microgram/kg/min of a continuous infusion of milrinone vs. placebo treatment, n = 52). We investigated the effects on cardiovascular hemodynamics, subjective symptoms, physical findings, and the pharmacokinetics of intravenous milrinone in a total of 106 patients with acute heart failure. MEASUREMENTS AND MAIN RESULTS: In the double-blind, dose-finding study, dose-dependent inotropic/vasodilating hemodynamic effects were documented for percent changes in cardiac index (+21.2%, +25.8%, and +30.9%, respectively) and pulmonary artery occlusion pressure (-12.8%, -17.0%, -41.3%, respectively) vs. plasma drug concentration at the equilibrium state (6 hrs after starting continuous infusion; 97 +/- 13, 197 +/- 22, and 284 +/- 28 ng/mL, respectively). Throughout the 6-hr infusion period, subjective symptoms were improved in 40%, 46.2%, and 70% of patients, respectively, for the three continuous infusion rates (0.25, 0.5, and 0.75 microgram/kg/min). In the placebo-controlled, double-blind, comparative study, the milrinone group exhibited marked improvement in cardiovascular hemodynamics (pulmonary artery occlusion pressure: from 26 +/- 6 to 15 +/- 3 mm Hg; cardiac index: from 2.6 +/- 0.9 to 3.3 +/- 1.1 L/min/m2) within 15 mins after starting drug administration. However, the placebo group showed no significant hemodynamic changes. Subjective symptoms and physical findings of acute heart failure improved in 47.6% and 40%, respectively, of patients within 60 mins after starting milrinone. The placebo group, however, showed no improvement providing inotropic/vasodilating (both 0%). CONCLUSION: Continuous infusion of milrinone (0.25 to 0.75 microgram/kg/min) after a 50-micrograms/kg loading dose is effective for inotropic/vasodilating hemodynamic support in patients with acute or decompensated heart failure.

Acute Disease↗

p53 gene mutations in human prostate cancers in Japan: different mutation spectra between Japan and western countries.

The involvement of p53 mutations in prostate cancers in Japan was investigated. To evaluate any possible clinicopathological significance, p53 mutations in 40 samples from 36 Japanese prostate cancers of different stages (five cases of latent tumors, three of stage A cancers, 10 of stage B, five of stage C and 13 of stage D), including four lymph node metastases of stage D cases, were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and sequencing. Mutations were detected in five of 40 samples (12.5%); four were in primary cancers and the other in a lymph node metastasis from one of them. All mutation-positive cases were in stage D, and the mutation frequency in stage D cases was 31%. This result indicates that p53 mutations may play a role in the progression of a subgroup of prostate cancers in Japanese, as observed for Americans and Europeans. However, a difference was noted between Japanese and Americans in the p53 mutational spectrum (at CpG site), presumably arising from variation in the underlying etiologic factors.

Aged↗

Twelve-month use of mental health services in four areas in Japan: findings from the World Mental Health Japan Survey 2002-2003.

The aim of the present study was to provide basic descriptive data regarding utilization of 12-month mental health services in the Japanese community population. Face-to-face household surveys were carried out in four areas (two urban cities and two rural municipalities), and a total of 1663 persons participated (overall response rate: 56.4%). For data collection, the structured psychiatric interview, World Mental Health version of the World Health Organization Composite International Diagnostic Interview (WMH-CIDI) was used, allowing DSM-IV diagnoses, severity, and service utilization. It was found that 7.3% of total respondents had received any service, either professional or non-professional, in the past 12 months, including 20.0% of those with 12-month DSM-IV disorders and 6.2% of those without. Thirty-three percent of those with any mood disorder used any service, and 26.8% of those used some type of health care. The probability of people with 13-15 years of education receiving mental health treatment was fourfold higher than those with >or=16 years of education. Gender, age, or income were not found to contribute to utilization of mental health services. The results confirm that the majority of people with a recent psychiatric disorder have not used mental health care or other support systems. The mental health care system in Japan has improved over the past decade, but not enough for people suffering from mental disturbances.

Adult↗

A statistical analysis of lung cancer registered in the Annual of Pathological Autopsy Cases in Japan between 1958 and 1987, with special reference to the characteristics of lung cancer in Japan.

Autopsy cases of lung cancer, 41,988 in males and 13,818 in females, consecutively registered between 1958 and 1987, were analysed statistically and compared with other case materials and mortality statistics. Cases of malignant tumor showed a gradual increase, and now comprise 60% of the total male and 55% of the total female autopsy cases. The percentage of lung cancer cases among the total autopsy cases was 9% for males and 5% for females. The percentage of lung cancer cases among total cases of malignant tumor was about 17% for males and 9% for females. Among fatal malignant tumors, gastric cancer and lung cancer showed the highest frequency. The relative incidence of gastric cancer was seen to decrease, whereas that of lung cancer increased. Of the histological types of lung cancer in both sexes, adenocarcinoma was the most frequent, followed by squamous cell carcinoma. During the period studied the peak age of patients with lung cancer shifted from the seventh to eighth decade, and a significant elevation of mean age was demonstrated for all of the major histological types in both sexes. The male:female ratio for all lung cancer cases was 3.0, which was much lower than those for the United States and Europe, but very similar to the ratios of mortality statistics in Japan and other Asian countries. As a result of a previous autopsy study at the University of Tokyo, it was also confirmed that the male:female ratio relative to age in each country reflects very well the histological distribution.

Adenocarcinoma↗

Protection against pertussis by acellular pertussis vaccines (Takeda, Japan): household contact studies in Kawasaki City, Japan.

To evaluate the vaccine efficacy of an acellular pertussis vaccine which has been in clinical use in Japan since 1981, a retrospective study was performed by a questionnaire survey of secondary pertussis attacks through family contact in 146 children with pertussis diagnosed in the period from January 1981 through May 1988. In this study, acellular vaccine made by Takeda Pharmaceutical Company, which contains a high level of FHA (filamentous hemagglutinin), a low level of PT (pertussis toxin) and a small amount of agglutinogen, was evaluated. Secondary pertussis attacks through family contact were found in 17 of 29 siblings (58.6%) not immunized with pertussis vaccine. On the other hand, 27 siblings immunized with Takeda's acellular vaccine were exposed to pertussis through family contact and a secondary attack was seen in only one of them (3.7%). The present study revealed an efficacy rate of 93.7% for Takeda's acellular pertussis vaccine.

Child↗

Natural history and prognosis of epilepsy: report of a multi-institutional study in Japan. The group for the study of prognosis of epilepsy in Japan.

A multi-institutional study on the prognosis of patients with epilepsy was performed in Japan from 1975 to 1977, including 20 institutions. The outcome of epileptic seizures and social adjustment 10, 5, and 3 years after the onset of the illness was studied in three different groups of epileptic patients, respectively. The number of successfully followed-up cases was 1,868 in total, follow-up rate being 42%. The data were analyzed statistically by use of analysis of variance. The rate of remission of seizures in all was 58.3% and the rate of normal social adjustment 62.6%. The remission rate showed no significant difference among the 10-, 5-, and 3-year outcome groups. The study on the outcome of seizure control indicated that the prognosis of seizure control is more favorable (a) in idiopathic than in residual or symptomatic epileptics; (b) in patients with onset before 10 years of age than in those with onset after 10 years; (c) in patients with less frequent seizures; (d) in sleep epilepsy than in waking and diffuse epilepsies; (e) in patients who started treatment within 1 year of onset of seizure; (f) in patients with single-type partial seizures than in those with partial seizures combined with tonic-clonic seizures; (g) in patients without high grade EEG background abnormality; and (h) in patients without neurological symptoms, intellectual deficits, personality disturbances, or psychotic symptoms. Factors that determine the prognosis of social adjustment were almost similar to those for remission of seizures. There was a close correlation between the outcome of seizure control and that of social adjustment. Correlation coefficient between follow-up rate and remission rate in 15 of the 20 collaborated institutions was 0.55 (p less than 0.05), showing a tendency that the remission rate becomes higher as the follow-up rate is raised.

Adolescent↗

Recent status in the occurrence of leukemia in growth hormone-treated patients in Japan. GH Treatment Study Committee of the Foundation for Growth Science, Japan.

The Foundation for Growth Science in Japan has monitored the safety and efficacy of GH treatment in GH-deficient patients since 1975. Data were collected from more than 32,000 patients up to December 31, 1997. New leukemia was observed in 14 patients and myelodysplastic syndrome (MDS) in one patient. The types of leukemia were acute lymphocytic leukemia (n = 6; 40%), acute myelocytic leukemia or MDS (n = 7; 47%), and chronic myelocytic leukemia (n = 2; 13%). Leukemia developed in 9 patients during GH treatment and in 6 after the cessation of GH treatment. Six patients had known risk factors for leukemia, such as Fanconi's anemia and previous radiation or chemotherapy. Patient-years of GH therapy was defined as the time from the first dose of GH to the date of the last visit during GH therapy, and patient-years of risk was defined as the time from the first dose of GH to December 31, 1997. The incidence of leukemia of patient-years of GH therapy and patient-years of risk in GH-treated patients without risk factors was 3.0/100,000 and 3.9/100,000, respectively, a figure similar to the incidence in the general population aged 0-15 yr. We conclude that the incidence of leukemia in GH-treated patients without risk factors is not greater than that in the general population aged 0-15 yr, and a possible increased occurrence of leukemia with GH treatment appears to be limited to patients with risk factors.

Adolescent↗

Dietary risk factors of stroke and hypertension in Japan -- Part 3: Comparative study on risk factors between farming and fishing villages in japan.

General medical examinations were performed in two rural areas of Shimane Prefecture in Japan, one was a farming village and the other a fishing village where incidences of death due to stroke differed, higher in the former and lower in the latter. Comparisons were made on salt and protein intake by analyzing the fasting single spot urine collected in the morning and by blood tests. Urine samples were analyzed for sodium (Na), potassium (K), urea nitrogen (UN), inorganic sulfate (SO4) and creatinine (Cr) and blood samples for cholesterol (Chl), triglyceride (TG), hematocrit (Ht) and hemoglobin (Hb). Blood pressure, Na/Cr, Na/K and Ht were higher in the farming village and K/Cr, UN/Cr, SO4/Cr, SO4/UN, Chl and TG were higher in the fishing village. These findings indicate the higher salt intake and lower intake of K, animal protein and fat in the farming village. This typical dietary pattern of the Japanese may explain the higher incidence of hypertension and stroke in the farming village.

Adult↗

Changes of serum total cholesterol and triglyceride levels in normal subjects in Japan in the past twenty years. Research committee on familial hyperlipidemia in Japan.

Serum lipid levels of 10,977 normal Japanese subjects in 1980 were determined by a joint study of 14 institutions, specializing in lipid research, located in 9 districts of Japan. The data obtained were compared with those in 1960 and 1970. Total cholesterol (TC) levels in 1980 increased with age except for the 1st decade and reached maximum (205 mg/dl) at the 7th decade. The mean value in any age was higher than that of 20 years ago by 10-15 mg/dl. Triglyceride (TG) levels also increased with age and reached maximum (130 mg/dl) at the 7th decade. The mean values of subjects over the 5th decade were higher than those of 10 years ago by 10-20 mg/dl. In contrast with TC and TG, HDL-cholesterol levels were highest at the 1st decade and declined gradually with age. TC and TG levels of younger age (1st to 3rd decade) were equal to or even higher than those of Americans in 1972-76. It was concluded that serum lipid levels of Japanese have increased in the past 20 years and approached to the levels of Europeans and Americans.

Adolescent↗

An epidemic of echovirus 18 in 1988 in Japan--high association with clinical manifestation of exanthem. A report of the National Epidemiological Surveillance of Infectious Agents in Japan.

Laboratory reports of isolation of echovirus serotype 18 (E18) slightly increased in the summer of 1987 followed by a sharp increase with a peak in July, 1988. A total of 1,094 isolations were reported during these two years from 39 laboratories participating in the National Epidemiological Surveillance of Infectious Agents in Japan. When compared with the previous E18 outbreaks, a higher proportion of children at two years of age or under (58.3%) and a much higher incidence of exanthem (46.4%) were remarkable. Meningitis-associated isolations were reported in 30.6%, less than half of the percentage of the previous epidemic.

Age Factors↗

Herpangina surveillance in Japan, 1982-1989. A report of the national epidemiological surveillance of infectious agents in Japan.

In Japan, herpangina cases increase every summer with an incidence peak in July. During the past eight years from January, 1982 to December, 1989, a total of 3,974 viruses from herpangina cases were reported from 47 participating laboratories, and coxsackie A (CA) viruses accounted for most of them, 3,055 (76.9%). The major types associated with herpangina were, in order of frequency, CA4, 10, 5, 6, 2 and 3, representing 87.2%-80.8% of total isolations reported for each respective type in this period. Eighty-four point four percent of the total virus isolations were from children at four years of age or younger. More than 80% of total CA virus isolations were from nasopharyngeal specimens and nearly 90% of the viruses were isolated in mice.

Adolescent↗

Enteroviral aseptic meningitis in Japan, 1981-1991. A report of the National Epidemiological Surveillance of Infectious Agents in Japan.

In Japan, aseptic meningitis cases due to enterovirus infections increase every summer in various degrees with an incidence peak usually in July. During the past 11 years from 1981 through 1991, a total of 8,595 enterovirus isolations from aseptic meningitis cases were reported from 54 participating laboratories. Eight enterovirus types caused large epidemics; more than 100 isolations of each type from aseptic meningitis cases were reported for every epidemic year of the respective type. They were coxsackievirus (C) types B3 and B5, echovirus (E) types 4, 6, 7, 9, 18 and 30. Among these, the highest meningitis-associating frequency was reported for E30, representing 82.6% of the total isolations reported for the type during this period, followed by E4, 71.1%. The frequencies of E9, E7, E6 and CB5 were in a range from 54.5% to 44.4%, while that of E18 was 37.7% and that of CB3 21.0%. During the epidemics, enterovirus-associated meningitis was most frequently reported among children of 4-7 years of age. High frequencies were also shown in infants less than 1-year of age in some types. A total of 4,240 enteroviruses were isolated from cerebrospinal fluid of aseptic meningitis cases, representing 49.3% of the cases with enterovirus isolation.

Adolescent↗

Trend of adenovirus type 7 infection, an emerging disease in Japan. A report of the National Epidemiological Surveillance of Infectious Agents in Japan.

The program of the National Epidemiological Surveillance of Infectious Diseases under the auspices of the Ministry of Health and Welfare started in 1981 apprehended in 1995 emergence of adenovirus type 7 in Japan. We analyzed the reported data of type 7 comparing with those of type 3, both belonging to the same subgenus B, and the following results were obtained: After 1981, the main serotypes in the reports of adenovirus isolation/detection were types 3, 2, and 1 in this order. The reports of isolation of adenovirus type 7 used to be extremely few, however, suddenly increased in 1995. In 1997, reports of isolation of adenovirus type 3 decreased and those of type 7 acquired the third place after those of types 2 and 3. Type 7 infection occur almost every month, but most frequently during May-September. The ages of cases from which type 7 was isolated were 0-4 years accounting for 55%, 5-9 years 35%, teens 6.3% and adults 4.0%, being similar proportions to those yielding type 3. Clinical diagnoses of cases yielding adenovirus type 7 were pharyngo-conjunctival fever (PCF) and influenza-like illness, these two accounting for half. The symptoms were severe, being characterized by higher maximum body temperature during the feverish period and severe pneumonia. Encephalitis and arthro-muscular pain were seen in only type 7-infected cases, although such cases were few.

Adenoviridae Infections↗

[C. P. Thunberg and his voyage to Japan (2): medical studies conducted before arrival in Japan].

C. P. Thunberg (1743-1828) stayed in Japan for about 16 months as a doctor attached to the Dutch trading post. He taught medicine, pharmaceutical science and natural history to Japanese doctors and interpreters during his stay. In order to determine his educational, mainly medical, background, I made inquiries to the university and other facilities where he studied, as well as programs he followed. ...

Education, Medical↗

[C. P. Thunberg and his voyage to Japan (3): medical articles written before arrival in Japan].

Three medical articles written by Thunberg before his visit to Japan were reviewed. "De venis resorbentibus" is an article on the lumph duct written in Latin under the guidance of Professer Linné. ... "De ischiade" is a thesis written in Latin under the guidance of Prof. Sidrén. This thesis, examined in public on June 28, 1770, lists 8 major causes of lumbago and explains therapies for lumbago in each cause. ... "Händelse, at Blybvitt af förseende blif vit brukadt i mat" is a short article published in the Kungliga Vetenskaps Academiens Handlingar, 1773. It relates his own experience of acute lead poisoning during his travel from Holland to South Africa by ship in January 1772. ...

Academic Dissertations as Topic↗

[Annual study of perioperative mortality and morbidity for the year of 1999 in Japan: the outlines--report of the Japan Society of Anesthesiologists Committee on Operating Room Safety].

Anesthetic mortality and morbidity in Japan Society of Anesthesiologists (JSA) Certified Training Hospitals (CTH) for the year 1999 were reported as continuation of annual studies started in 1993. The JSA Committee on Operating Room Safety (CORS) sent confidential questionnaires to 774 CTH and received valid responses from 60.3% of hospitals. A total number of 793,840 anesthetics were documented. The respondents were asked to report all cases of cardiac arrests and other critical incidents (serious hypotension, serious hypoxemia and others), and their outcomes (death in operating room, death within 7 days, transfer to vegetative state and rescue without sequelae) as well as one principal cause for each incident from list of 52 items. They were also requested to submit the tabulation of patients by ASA physical status, age distribution, surgery sites and anesthetic methods. Analysis was made by total incidents under anesthesia/surgery, and also by incidents totally attributable to anesthetic management (AM), due to preoperative complications (PC), due to intraoperative pathological events (IP) and due to surgery (SG), with special reference to each of four tabulation groups and the whole group of patients. This paper focused analysis on all patients, as analyses with special reference to ASA physical status, age distribution, surgery sites and anesthetic methods were previously reported. Total incidence of cardiac arrest under anesthesia/surgery was 6.53 per 10,000 anesthetics. PC, IP and SG represented principal causes in 42.9%, 22.0% and 21.4% causes of total cardiac arrest cases, respectively. AM was noted as the principal cause in 12.0% of cases, with an incidence rate of 0.78 per 10,000. In 52 more detailed classification of principal causes, the most frequent cause of cardiac arrest was preoperative hemorrhagic shock, 20.3% of all cardiac arrests. The second cause was massive hemorrhage and/or hypovolemia due to surgical procedures (13.1%), and the third was intraoperative myocardial infarction/coronary ischemia/coronary spasm (9.5%). Prognoses of cardiac arrest cases declined due to PC: 71.1% of cardiac arrests died in the operating room or within 7 days after surgery and only 19.8% survived without sequelae. The best prognoses were found in cardiac arrest cases due to AM: 69.4% survived without sequelae and 12.9% died. The mortality rate post-cardiac arrest was 3.44 per 10,000 anesthetics, of those 0.10 due to AM, 0.57 due to IP, 1.99 due to PC and 0.76 due to SG. The mortality rate after critical incidents other than cardiac arrest such as severe hypotension and severe hypoxemia was 3.75, of those 0.03 due to AM, 0.28 due to IP, 2.31 due to PC and 1.13 due to SG. The final mortality rate attributable to anesthesia/surgery including deaths post-cardiac arrest and after other critical incidents was 7.19 per 10,000 anesthetics and very close to 7.18 [6.22, 8.13], that of mean [95% C.I.] in 1994-1998. The final mortality rate totally attributable to anesthesia was 0.13 per 10,000 anesthetics, which was significantly improved from 0.21 [0.15, 0.27], that of mean [95% C.I.] in 1994-1998. IP, PC and SG showed the final mortality rate of 0.84, 4.30 and 1.89, respectively. Five major causes of all critical incidents were massive hemorrhage due to surgical procedures (20.8%), preoperative hemorrhagic shock (10.7%), surgical technique (8.0%), inappropriate airway management (5.2%) and intraoperative myocardial infarction and coronary ischemia (4.5%). Drug overdose or selection error (3.9%) and overdose of main anesthetic (2.9%) as a result of human error occupied the 7th and 10th places. As far as anesthetic management to reduce mortality and morbidity related to anesthesia is concerned, we should increase vigilance to avoid human errors in addition to improving preanesthetic preparations and assessment of cardiovascular status as well as intraoperative management of cardiovascular events.

Anesthesia↗

[Surveillance of antimicrobial resistance of Streptococcus pneumoniae isolates from the Kinki Region of Japan during 2003/2004. The Surveillance Program of Bacterial Resistance in the Kinki Region of Japan; SBRK].

Three hundred seventy five isolates of Streptococcus pneumoniae were collected from 14 medical institutions in the Kinki region of Japan between November 2003 and February 2004. We determined the minimum inhibitory concentration (MIC) of penicillin G (PCG) and 25 of other antimicrobial agents against these isolates according to the National Committee for Clinical Laboratory Standards (NCCLS). Overall, 71.5% of all isolates were resistant to PCG (intermediate and resistant categories were 51.7% and 19.8%, respectively). For the carbapenems and penem, the rank order of activity was PAPM (MIC90, 0.12 microg/ml) > IPM (0.25 microg/ml) > MEPM (0.5 microg/ml) = FRPM (0.5 microg/ml). For the cephems, the overall rank order of activity was CPR (MIC90, 0.5 microg/ml) = CDTR (0.5 microg/ml) > CTRX (1 microg/ml) = CTX (1 microg/ml) = CZOP (1 microg/ml) = CFPN (1 microg/ml). Rank order activity for six of fluoroquinolones was TFLX = MFLX (MIC90, 0.25 microg/ml) > GFLX (0.5 microg/ ml) = SPFX (0.5 microg/ml) > LVFX (1 microg/ml) > PZFX (4 microg/ml). The rate of resistance to fluoroquinolones per the NCCLS criteria were very low, ranging from 0.7% to 2.6%. Rate of resistance to other antimicrobiotics were CAM, 77.0%; CLDM, 41.7%; TEL, 0%; VCM, 0%; ST, 32.7%, and CP, 21.4%.

Drug Resistance, Bacterial↗

[Reports on medico-legal data from the massive-investigation performed by the Medico-Legal Society of Japan--a statistical study of death by poisoning. Investigation Committee of the Medico-Legal Society of Japan].

A statistical study was made on the fatal poisoning cases examined by forensic pathologists in Japan, in the period of 1975-1984. The total number of the cases was 1559:29.9% were poisoning by carbon monoxide, 10.9% by the other gases (cyanide, liquefied petroleum gas, hydrogen sulfide and freon), 10.9% by alcohol (mean blood ethanol level was 4.27 mg/ml), 9.3% by medicines (bromvalerylurea, barbiturates, chlorpromazine etc.), 9.2% related to burning (mean CO-Hb level was 47.9%), 7.4% by pesticides (organophosphate, paraquat, carbamate, chlorinated hydrocarbon etc.), 3.5% by methamphetamine and 11.2% by the others, including 4.9% by oxygen deficiency. These cases were found most frequently in winter and 41% of the victims died within 30 minutes after ingestion or inhalation. With regard to age distribution, the peak of frequency was 41 to 45 in male, and not characteristic in female. Samples were mainly the blood, urine and stomach contents, and analyzed by gas chromatography, spectrophotometry, ultraviolet spectrometry, thin-layer chromatography, atomic absorption spectrometry and gas chromatography-mass spectrometry.

Adolescent↗