Survey of recognition and utilization of guidelines for the diagnosis and management of bronchial asthma in Japan.

BACKGROUND: In Japan in 1993, the Japanese Society of Allergology (JSA) developed guidelines for diagnosis and management of asthma (JGL), which were based on the concept that asthma is a chronic inflammatory disorder of the airway. METHODS: This survey study was intended to investigate the recognition and utilization of JGL among physicians who had treated asthma. The survey comprised two methods: a quantitative mail survey and a qualitative door-to-door survey conducted by trained interviewers. RESULTS: In the mail survey, a total of 1028 physicians responded; 552 members of the JSA and 476 nonmembers. Ninety-four percent of JSA members were aware of adult asthma management guidelines, while 53% of nonmembers were aware of them. Although approximately half of the physicians, both members and nonmembers, found differences between the asthma management policies in JGL and their previous policies, most of them utilized JGL once they read it. In the qualitative door-to-door survey, 80-90% of physicians evaluated JGL as good after they read it. CONCLUSIONS: JGL was recognized and utilized by most JSA members, but only half of nonmember physicians were aware of JGL, although they utilized JGL after they read it. Further action to implement JGL among nonspecialist physicians is needed to improve management of asthma.

Quantification of a very low level of serum human immunodeficiency virus type 1 (HIV-1) RNA using competitive PCR at intervals and the clinical course.

Quantification of human immunodeficiency virus type 1 (HIV-1) genomic RNA levels below the detection limit (400 copies/ml) of commercially available quantification kits is possible by increasing the amount of serum samples using competitive PCR conditions. We evaluated disease prognosis in patients without symptoms for a long period after infection (long-term non-progressors) and patients in whom the virus was controlled to a low level by administration of anti-HIV drugs. For 102 of the 414 serum samples stored at -80 degrees C which showed HIV-1 RNA below 400 copies/ml by competitive PCR using 100 to 200 microl sera, an increase in the sample volume to 500-2000 microl, extraction of HIV-1 RNA, and quantitative detection by competitive PCR was performed. Follow-up quantification of serum HIV-1 RNA from 4 patients indicated that this method is useful in assessing prognosis in the early stage of the disease in patients without symptoms for a long period after infection (long-term non-progressors) and patients in whom the virus in the serum was controlled by administration of anti-HIV drugs to below the detection limit of commercially available quantification kits. Quantification of low level serum HIV-1 RNA was also considered useful as a parameter of treatment.

Genomic alterations in human meningiomas detected by restriction landmark genomic scanning and immunohistochemical studies.

Using restriction landmark genomic scanning (RLGS) methods, 21 samples of human meningioma were analyzed. We found 3 alterations in the genomic DNAs of tumor samples located on chromosomes 5, 14 and 17 which appear to be common to the meningothelial subtype. Two other separate genetic abnormalities located on chromosomes 9-12 and 20 are apparently associated with atypical meningiomas. In addition, the neurofibromatosis type 2 gene is apparently involved in more than half of the tumor samples. There appear to be both common and type-specific genetic mutations associated with the formation and progression of human meningiomas.

Endovascular treatment for ruptured cerebral aneurysms in acute stage.

Since the introduction of endovascular embolization with Guglielmi Detachable Coils (GDC) (1-3) in April 1997, we have performed 56 endovascular treatments for ruptured cerebral aneurysms in the acute stage based on our definition of candidates for this modality. Overall outcomes are as follows. 1) Rebleeding within one year was limited to one case (2.5%). 2) Vasospasm occurrences: four cases (7.1 %) infarction and three cases (5.4%) as transient ischemia. 3) H&K Grade IV: 60% of cases resulted in improved outcomes. 4) H&K Grade II: One case of rupture during an operation. 5) Three out offive older subjects (over 80 years old) resulted in GR or MD. In this study, we reviewed endovascular embolization in acute stage in terms of candidates and technical problems.

[Collaterals after flow alternation in pelvic arteries: precondition for pelvic reservoir therapy].

To determine the best flow alternation in the internal iliac arteries for regional chemotherapy using a reservoir to treat pelvic malignancies, collateral arteries that arose after arterial flow alternation were evaluated on follow-up pelvic angiographies. Follow-up angiographies were obtained in 11 patients with 21 embolized arteries; six male and five female patients including three with urinary bladder cancer, two with prostate cancer, four with uterine cervical cancer and two with bone metastasis. The interval until follow-up angiography ranged from one to-28 months (mean 8.9 months). Three radiologists interpreted the angiographic results and evaluated collateral vessels. Among 21 embolized arteries, 19 were well occluded, while two were not blocked completely. The two arteries with incomplete embolization did not induce collaterals. Eight internal iliac arteries occluded at the proximal portion enhanced retrogradely via collaterals from the ipsilateral external iliac arteries. Collaterals between the bilateral internal iliac arteries were noted only in four of them. In conclusion, embolization at the proximal point of the internal iliac arteries usually induced collaterals from the ipsilateral external iliac arteries and did not always from collaterals between the bilateral internal iliac arteries, which were necessary for regional chemotherapy. This should be considered when pelvic malignancies are treated with reservoirs.

Qualitative and quantitative detection of cytomegalovirus DNA in sera by PCR as a clinical marker.

The amount of human cytomegalovirus (CMV) DNA in sera is considered to be a direct marker for CMV infection. We established conditions for nested PCR that detected one copy of CMV DNA, and for competitive PCR, which detected five or more copies of CMV DNA quantitatively. We tested 50 microl each of 16 freeze-stored and 5 fresh sera from patients, for CMV DNA. In sera obtained from the same patient at different time points, small amounts of CMV DNA were detected before the onset of CMV pneumonia. In sera from certain CMV-infected patients who were treated with the anti-CMV agent, ganciclovir, CMV DNA was not detected. Quantitative PCR detection of CMV DNA seems to be suitable for predicting early recurrent CMV infection and monitoring the efficacy of antiviral therapy. The qualitative nested PCR examination of CMV DNA in 40 cord blood plasma samples was carried out for the purpose of preventing CMV infection by cord blood stem cell transplantation, and they were all negative for CMV DNA.

Quantitative detection of human immunodeficiency virus type 1 (HIV-1) RNA by PCR and use as a prognostic marker and for evaluating antiretroviral therapy.

The amount of human immunodeficiency virus type 1 (HIV-1) genomic RNA in sera is considered to be one of the most direct markers for patient prognosis and monitoring the efficacy of antiretroviral therapy. Quantitative detection of HIV-1 RNA was performed by the dilution endpoint method and competitive PCR. Conditions for detecting one copy of HIV-1 control DNA were examined to decide the dilution endpoint exactly. PCR of the gag region by SK145/SK39 primer pair and seminested PCR by SK145/SK101 primer pair gave the best result. Conditions for competitive PCR of HIV-1 cDNA, which was reverse transcripted from HIV-1 control RNA, were also studied using a SK38/SK39 primer pair in the presence of HIV-PCR MIMIC as a competitor DNA. The detection limit of HIV-1 control DNA by competitive PCR was 10 copies but that of HIV-1 control RNA was 50 copies. Time-course quantitation of HIV-1 RNA in frozen-stored sera from an AIDS patient was carried out and traced back to 1993. The amount of serum HIV-1 RNA markedly decreased when the treatment was changed but increased again before deterioration of his clinical status. It is considered that the quantitation of serum HIV-1 RNA is useful for the prognosis of HIV-infection and the evaluation of the antiretroviral therapy.

Genetic alterations in thyroid carcinomas and adenomas detected by restriction landmark genomic scanning.

Alterations of genomic DNAs in 9 papillary thyroid carcinomas and 3 follicular thyroid adenomas were examined by restriction landmark genomic scanning, a 2-dimensional gel analysis that allows detection of deletions, amplifications and other rearrangements of genomic DNA. DNAs from both thyroid tumors and associated non-tumorous glandular tissues were cleaved with the restriction enzyme NotI end-labeled with P-32 and size-fractionated by 2-dimensional electrophoresis using HinfI in a second digestion. The altered spots in carcinomas and adenomas were compared with those in nontumorous samples. Five and 4 spots were commonly amplified in carcinomas and adenomas, respectively. One amplified spot was apparently specific only for carcinoma and was not detected in any of adenomas examined. In contrast, 12 spots reduced in intensity were frequently observed in tumors, although a subset of 5 were more sporadically affected in adenomas. The results indicate both common and distinct genetic abnormalities occurring in thyroid tumors, which may relate to the different biological behaviors of malignant and benign neoplasms.

[Anesthesia for cesarean section: drug transfer to fetus during anesthesia].

One case of prenatally diagnosed congenital diaphragmatic hernia was reviewed in terms of the anesthetic managements. Concentrations of diazepam, pancuronium and fentanyl were measured in maternal, fetal and umbilical serum. As expectedly, the transition of diazepam through the placenta was large and the concentration of diazepam in the fetal serum was equal to that of maternal serum, but only a small amount of pancuronium was transferred.

Mutagenicity of condensed pyridazines with different substituents.

A total of 24 compounds were prepared by introducing an N-oxide, a hydrazino group, a methoxy group or a chloro group into 3 kinds of condensed pyridazines: pyrido[3,4-d]pyridazines, pyrido[2,3-d]pyridazines and phthalazines. The mutagenicity of these 24 compounds was assessed by the Ames method using two tester strains (Salmonella typhimurium TA98 and TA100). No mutagenic activity was detected with any of the 3 condensed pyridazines without substituents or any of the 5 condensed pyridazines with a methoxy group. The compounds with N-oxide in the pyridazine ring showed no or only very weak mutagenicity. However, when an oxide was introduced into the nitrogen of the pyridine ring, the mutagenicity against strain TA98 was higher than that of any other test compound. All compounds with a hydrazino group were mutagenic against strains TA98 and TA100, irrespective of the presence or absence of S9 mix-induced metabolic activation. 1-Hydrazinophthalazine (hydralazine) which has been clinically used as an antihypertensive agent was weakly mutagenic. The introduction of a chloro group increased the bactericidal effects of the condensed pyridazines, thus hampering the assessment of mutagenicity. A majority of the compounds which were found to be mutagenic in this study required no metabolic activation with S9 mix.

Tumors in domestic animals examined during a ten-year period (1980 to 1989) at Miyazaki University.

During the ten years from 1980 to 1989 inclusive, a total of 468 (16.1%) tumors were found in 2,907 pathological samples from domestic animals, collected from Southern Kyushu, around Miyazaki City. In this study, canine tumors were collected most commonly (340/468 cases, 73%). In small animals, the skin and mammary gland were associated particularly with tumorigenetic hazards. In cattle, high incidence of leukemia and mesothelioma was found. These tendencies were almost the same as those we reported for the preceding ten-year period, although the number of cases of tumor was higher in this study.

Different chemosensitivity of pre and postmenopausal breast-cancer cells.

In order to refine our adjuvant chemotherapy against locally advanced breast cancer, an anticancer drug sensitivity test, using the MTT assay was conducted with biopsy specimens of human breast cancer obtained prior to therapy. Dose-dependent sensitivity was observed with all tested agents: cisplatinum, mitomycin C, methotrexate and doxorubicin. The sensitivity of the premenopausal specimens to the effects of mitomycin C and doxorubicin varied widely. When selecting chemotherapeutic agents to combat breast cancer, this variation in drug sensitivity based on menopausal status and patient age should be considered.

[Detection of myocardial fatty components with ultrafast CT].

Intramyocardial fatty components are sometimes depicted by CT of the thorax. However, no studies have investigated the distribution, frequency and cause of these components by using statistical analysis. Three hundred forty-five patients with various cardiac diseases were examined with an ultrafast CT scanner, and intramyocardial fatty components were detected in 15 (4.3%) of them. The frequency of intramyocardial fatty components in each disease was as follows: 6% in ischemic heart disease, 7% in Kawasaki disease, 11% in hypertrophic cardiomyopathy (HCM), 18% in dilated cardiomyopathy (DCM) and 33% in arrhythmogenic right ventricular dysplasia (ARVD). Except for patients with HCM, the segments of the ventricles, where the fatty components were detected, agreed well with the segments with asynergy in left ventriculography and/or the segments with perfusion defect in T1 myocardial scintigraphy. Thus, ischemic fatty degeneration was considered to be a main factor in the production of intramyocardial fatty components in these diseases. The focus of arrhythmia was sometimes detected in the segments with intramyocardial fatty components in DCM and ARVD cases. It is suspected that intramyocardial fatty components sometimes produce arrhythmia in these diseases.

[Evaluation of pluronic F127 as a base for gradual release of anticancer drug].

The property of pluronic F127 (PLF) as a base for an anticancer agent, mitomycin C (MMC) was evaluated. A weighed amount of PLF and MMC were slowly added to cold water and mixed completely. The solution was warmed to 37 degrees C and MMC containing PLF gel was formed. The cumulative amount of MMC which was released from the gel during a 3-hour period was calculated. 5.5 percent of MMC was released from PLF-MMC gel which contained 20 or 25% PLF and 3.8% MMC from PLF-MMC gel containing 30% PLF. Intraperitoneal (i.p.) administration of large amount of PLF gel alone in rabbits or mouse revealed severe hepatorenal toxicity, and acute i.p. administered LD50 of PLF was supposed to be between 1.7 g and 5.0 g/kg body weight in mouse. Further evaluation of gradual releasing property of PLF is needed.

[Minimal-flow xenon and semiclosed circuit anesthesia for computed tomographic measurement of local cerebral blood flow (LCBF)].

For the purpose of decreasing the volume of expensive xenon, anesthesia with minimal-flow xenon and semiclosed circuit were induced for computed tomographic LCBF measurement. Eighteen patients with ischemic cerebral disease were studied. Anesthesia was induced with minimum dose of thiopental, diazepam and fentanyl. Muscle relaxation was obtained by means of pancuronium bromide. Patients were intubated and ventilated mechanically with flows of 6 l/min. O2 for 20 to 30 minutes to eliminate nitrogen from the system. O2 concentrations in semiclosed circuit were monitored throughout the procedures using galvanic battery. Endtidal CO2 tension was also measured for maintaining normocarbia. Blood gas analyses were carried out before xenon inhalation, during xenon inhalation and immediately before stopping inhalation of xenon-oxygen mixture. Xenon inhalation programs were subdivided into three groups, each of them consisted of 6 patients. The formula for calculating fresh gas flow for low flow semiclosed circuit was introduced according to Shimoji's which was based on the original formula of Foldes. O2 concentration in circuit was predicted to be 25%. Mean xenon uptake for initial 20 minutes was predicted to be 125 ml/min. or 360 ml/min. (Formula: see text) (CRO2: O2% in semiclosed circuit. FO2: fresh O2 flow ml/min. FXe: fresh xenon flow ml/min. VO2: oxygen consumption ml/min. VXe: mean xenon uptake ml/min.) The first group started xenon inhalation during pure xenon inflow into semiclosed circuit for two minutes and followed by about 68% xenon in O2 inhalation for 23 minutes. FXe and VXe were fixed at 700 ml/min and 360 ml/min respectively.(ABSTRACT TRUNCATED AT 250 WORDS)