[Clinical effectiveness of intra-arterial chemotherapy combined with degradable starch microspheres (DSM) for liver metastases and prediction of effectiveness by diagnostic imaging].

The aim of this study was to evaluate the clinical effectiveness of intra-arterial chemotherapy combined with degradable starch microspheres (DSM) for liver metastases and the possibility of predicting the effectiveness of the chemotherapy by pretreatment diagnostic imaging. The subjects were 67 patients with metastatic liver cancer, treated with Seldinger method via the left brachial artery, and tumor selective hepatic injection using a micro-catheter. The early response rate was 38.7% for colorectal cancer, 42.8% for gastric cancer, 16.7% for bile tract cancer and 80% for uterine cancer. The relationship between effectiveness and the tumor occupation rate in the liver estimated from pretreatment CT images was not significant, but the degree of tumor stain in the early phase of contrast enhancement CT correlated well with early responsiveness of the liver metastases for this treatment. This suggests the possibility of pretreatment prediction of the effectiveness of intra-arterial chemotherapy combined with DSM for metastatic liver tumors.

Alginate hydrogel linked with synthetic oligopeptide derived from BMP-2 allows ectopic osteoinduction in vivo.

Bone morphogenetic proteins (BMP) are unique molecules with a specific biological activity for inducing ectopic bone formation when implanted with a suitable carrier matrix. However, incorporation of BMP into the carrier has disadvantages, including early burst release and protein degradation in biological environments. Therefore, we considered that the next greatest challenge in achieving successful clinical use was the development of a carrier system for site-specific delivery of the morphogenetic signal of BMP. In this study, a novel BMP-2-derived oligopeptide, NSVNSKIPKACCVPTELSAI, was coupled covalently to alginate. Then NSVNSKIPKACCVPTELSAI-linked alginate hydrogel composites were implanted into the calf muscle of rats and harvested 3 or 8 weeks after surgery. Ectopic bone formation was observed in alginate hydrogel linked with BMP-2-derived peptide. It is suggested that alginate hydrogel linked with an oligopeptide derived from BMP-2 might provide an alternative system for topical delivery of the morphogenetic signal of BMP-2.

cps1+, a Schizosaccharomyces pombe gene homolog of Saccharomyces cerevisiae FKS genes whose mutation confers hypersensitivity to cyclosporin A and papulacandin B.

The Schizosaccharomyces pombe cps1-12 (for chlorpropham supersensitive) mutant strain was originally isolated as hypersensitive to the spindle poison isopropyl N-3-chlorophenyl carbamate (chlorpropham) (J. Ishiguro and Y. Uhara, Jpn. J. Genet. 67:97-109, 1992). We have found that the cps1-12 mutation also confers (i) hypersensitivity to the immunosuppressant cyclosporin A (CsA), (ii) hypersensitivity to the drug papulacandin B, which specifically inhibits 1,3-beta-D-glucan synthesis both in vivo and in vitro, and (iii) thermosensitive growth at 37 degrees C. Under any of these restrictive treatments, cells swell up and finally lyse. With an osmotic stabilizer, cells do not lyse, but at 37 degrees C they become multiseptated and multibranched. The cps1-12 mutant, grown at a restrictive temperature, showed an increase in sensitivity to lysis by enzymatic cell wall degradation, in in vitro 1,3-beta-D-glucan synthase activity (173% in the absence of GTP in the reaction), and in cell wall biosynthesis (130% of the wild-type amount). Addition of Ca2+ suppresses hypersensitivity to papulacandin B and septation and branching phenotypes. All of these data suggest a relationship between the cps1+ gene and cell wall synthesis. A DNA fragment containing the cps1+ gene was cloned, and sequence analysis indicated that it encodes a predicted membrane protein of 1,729 amino acids with 15 to 16 transmembrane domains. S. pombe cps1p has overall 55% sequence identity with Fks1p or Fks2p, proposed to be catalytic or associated subunits of Saccharomyces cerevisiae 1,3-beta-D-glucan synthase. Thus, the cps1+ product might be a catalytic or an associated copurifying subunit of the fission yeast 1,3-beta-D-glucan synthase that plays an essential role in cell wall synthesis.

Varioliform mucosal polypoid lesions in intestinal tract in a patient with adult T-cell leukemia.

We describe a case of adult T-cell leukemia (ATL) with intestinal infiltration. In the early clinical stage, the endoscopic findings for the intestine were similar to those of amebic enterocolitis, i.e., varioliform mucosal polypoid lesions, and amebic cyst was detected with stool examination. Although no specific pathological factor could be identified on biopsy, the patient was treated for amebiasis as a diagnostic therapy. The findings of varioliform mucosal polypoid lesions were detected in the duodenum on endoscopic examination, but the lesions eventually disappeared during the treatment for amebiasis. We then suspected lymphoma partially masked by the amebiasis. Immunological staining of a specimen of the colonic mucosa revealed T cell invasion and Southern blotting demonstrated adult T-cell leukemia provirus invasion. Thus, ATL cell infiltration of the intestinal tract was confirmed. It is suggested that systemic disease should also be considered when varioliform mucosal polypoid lesions are found on colonoscopic examination.

[The essays of Keizou Tanba and Ougai Mori about separation of dispensary from medical practice].

Keizou Tanba wrote an article on separation of dispensary in Chugai-iji-shinpo in June, the year 23 of Meji Era. It was said that separation of dispensary had to be carried out and it brought many advantages. First, a pharmacist can examine the prescription and correct it if there are any mistakes. He will be able to give an advice to a doctor that the side effects will perhaps occur due to preparation of medicine. Secondly, a pharmacist can superintend whether unnecessary medicine is prescribed or not. He will check surplus prescription in such a case that a patients will be cured by observing dietary or exercise. According to Tanba's opinion, if we will get people to know what separation of dispensary is, it is easy to be carried out. Ougai Mori wrote an essay separation of dispensary in the same period. His opinion was opposite, basically. It caused to impose a burden on a patient. As the number of pharmacist were not enough, it was impossible to carry it out. A conflict of opinion also remains among people related to medicine at present. The circumstances on separation of dispensary have not been changing during one hundred years.

[A simple and rapid method capable of detecting methicillin-resistant Staphylococcus aureus (MRSA) by single culture on an agar plate].

A novel simple agar plate capable of detecting methicillin-resistant Staphylococcus aureus (MRSA) by single culture was developed. The agar plate included 1) mannitol and a pH indicator, and 4-methylumbelliferyl phosphoric acid, both for identification of Staphylococcus aureus by its ability to digest mannitol and produce phosphatase; detection of the former by change in color of pH indicator and the latter by fluorescence of 4-methylumbelliferone, 2) oxacillin at a minimum concentration just to eliminate methicillin-sensitive Staphylococcus aureus (MSSA), and 3) phenylethyl alcohol to inhibit growth of most gram negative rods. The method was simple, sensitive, time-saving, and quite effective in the identification of MRSA directly from clinical specimens. Neither false positive nor false negative results were observed by the present method.

[The essay on separation of dispensary from medical practice written by Yukichi Fukuzawa].

In November 1891, the union of pharmacists submitted the petitions letter on revision of the Law No. 10 issued on March 15, 1889, because by this law physicians acquired the right to dispense medicine rather than to give prescriptions to their patients. Yukichi Fukuzawa criticized the above mentioned problems and he contributed essays to the famous newspaper, Jiji-shin-pou in december 1891. Principles of his essays were as follows: 1) separation of dispensary from medical practice widely done in western countries were important from scientific viewpoint; 2) however, both physicians and patients had no concept on total medical fee which was consistent with consultation fee and charge for medicines. Thus, patients in Japan have been receiving medicines from physicians customarily over several hundred years; 3)introduction of new system on separation of dispensary from medical practice would cause troubles, because additional payment at the pharmacy should be required other than payment for physicians; 4)he was aware that opportunities to commit sick persons to doctor's care would be decreased especially in case of poor persons. Compared the public opinion to the separation of dispensary from medical practice of present day, there was found no difference on the attitude of Japanese people in these hundred years.

Action of Escherichia coli heat-stable enterotoxin II on isolated sections of mouse ileum.

When Escherichia coli STII was applied to the serosa of the ileum at a concentration of 40 micrograms/ml, an acceleration of the spontaneous motility and a weak contraction were induced 2-3 min later. The induction was not affected by the addition of atropine (10(-6) M), but was abolished by the addition of papaverine (10(-4) M). When STII was applied to the mucosa, the acceleration of the spontaneous motility appeared 7-8 min later, but a contraction was not induced. These results suggest that STII acts directly on muscle cell of the ileum and enhances the spontaneous motility of the intestine.

[The advertisements of drug in newspaper by Ginkou Kishida].

Ginko Kishida, who was a journalist formerly, took advantage of newpaper to publicize ophthalmicus. He put an advertisement expressed by only characters in Yokohama-mainichi-shinbun just founded. After that, he employed advertisement with illustration. In the beginning, the advertisement laid stress on spreading the name of the ophthalmicus, "Seikisui." The advertisement published in Meiji 8th, appealed variation of ophthalmic diseases and their causes, besides it expressed effective of "Seikisui." His contributions to convey the information of drug were difficult to distinguish between advertisement and articles. Nowadays, advertisement of drug imitating the articles are popular. Needless to say, Ginko Kishida was the pioneer of the style of present advertisement of drug.

[Comparative study of medicament culture between Japan and Occident].

Needless to say, cultural background of the medicines are dependent on traditions and systems of medical care of each country. Until Edo-Era in Japan, Wakanyaku (local phytotherapy), which was developed under the influence of Chinese culture was popular. In the Meiji-Era synthetic medicines beat the local one in accordance with the introduction of occidental culture. However, people are still attracted to Wakanyaku. At present many medical doctors are using Kampou-medicines consisting of Wakanyaku. In the Occident, Kampou-medicines are not much appreciated due to lack of scientific approval. Medicines differ with cultures. From the end of Edo-Era to the beginning of the Meiji-Era, occidental diplomats including physicians came to Japan and reported their observations on medical environment and cultural background. In their literal works they pointed out heterogeneity. For instance, people always kept Moxa at hand for unexpected disease. They felt strange that people treated themselves with Moxa without any knowledge of anatomy. Furthermore, they also mentioned that physicians of Kampou administered medicines without any chemical knowledge.

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1988)].

Isolated bacteria from respiratory infectious diseases were collected in cooperation with institutions located throughout Japan, since 1981, and Ikemoto et al. have been examining sensitivities of the isolates to various antibacterial agents and antibiotics, relationships between the isolates and the backgrounds of the patients and so forth each year. We report here the research results for the year 1988. In 18 institutions around the entire Japan from October 1988 to September 1989, 554 strains of bacteria were isolated mainly from the sputa of 439 patients with respiratory infectious diseases and assumed to be the etiologic bacteria. MICs of various antibacterial agents and antibiotics against 68 strains of Staphylococcus aureus, 102 strains of Streptococcus pneumoniae, 120 strains of Haemophilus influenzae, 86 strains of Pseudomonas aeruginosa, 65 strains of Branhamella catarrhalis, 18 strains of Klebsiella pneumoniae and so forth, were determined, and the drug sensitivities of these strains were examined except for the strains which died during transportation. The drug sensitivities of the main strains were almost the same as those determined last year for each drug. However, S. aureus strains for which MICs of methicillin were higher than 12.5 micrograms/ml (methicillin-resistant S. aureus) accounted for 38.2%, and the frequency of drug resistant bacteria increased over last year's 18.2%. Also, we examined changes in the backgrounds of patients, the infectious diseases, and the etiologic bacteria and so forth. As to patient backgrounds, there were many infectious diseases found in a high age bracket, and the patients over age 60 accounted for 57.2% of the diseases. In the distribution by disease, bacterial pneumonia and chronic bronchitis accounted for greatest numbers of cases 32.1% and 31.4%, respectively, followed by bronchiectasis and bronchial asthma. As for frequencies of etiologic bacteria by disease, S. aureus (22.5%) and S. pneumoniae (15.4%) in pneumonia, S. pneumoniae (25.7%) and H. influenzae (24.1%) in chronic bronchitis, H. influenzae (32.5%) and P. aeruginosa (23.8%) in bronchiectasis, and H. influenzae (31.4%), S. pneumoniae and B. catarrhalis (20.0%) in bronchial asthma were the most frequent. Regarding effects of administration of antibiotics and isolates obtained on each day after infection, those bacteria which were isolated before antibiotic administration and which decreased after administration included S. pneumoniae, H. influenzae, and B. catarrhalis. Frequencies of S. aureus and P. aeruginosa, however, increased after antibiotic administration. Also, when dosing continued for more than 15 days, the frequency of P. aeruginosa increased rapidly.

[A case of renovascular hypertension accompanied by focal segmental glomerulosclerosis like lesion in the contralateral kidney].

A 19-year-old female patient with renovascular hypertension accompanied by focal segmental glomerulosclerosis like lesion in the contralateral kidney is described. She was admitted to our hospital for uncontrollable hypertension which was first pointed out at check-up when she was 18 years old. On admission physical examination revealed remarkable hypertension and a bruit around the umbilical region. Laboratory findings disclosed renal dysfunction and slight proteinuria (0.8-1.1 g/day). Arteriography revealed severe narrowing of the right renal artery suggesting fibromuscular dysplasia. Taken together, renovascular hypertension was diagnosed. She underwent an operation to reconstruct the artery with autotransplantation of the ipsilateral kidney in the pelvic cavity, and sections were taken from both kidney for histological evaluation during the procedure. After the operation her blood pressure normalized and proteinuria decreased. And interestingly, the kidney specimens revealed that the left side consisted of focal segmental glomerulosclerosis like lesion whereas the right was only of ischemic change. Hyperfiltration theory has recently been highlighted experimentally. And the etiology of the renal findings in this case may be based on such hemodynamic alteration as has been described in animal models. We present the case so that it may be of some help to understand how focal segmental glomerulosclerosis is brought about in humans.

[Effects of EDTPO on hard tissues in rats. 2. Changes of serum components and morphology of hard tissues due to various doses of EDTPO].

Dose dependent effects of EDTPO on morphology and mineralization of hard tissues as well as calcium (Ca), inorganic phosphorus (IP) and alkaline phosphatase (ALP) levels in serum were examined in growing rats. Five groups of male S.D. rats weighing 110-120g were received s.c. injections of 0 (control), 1, 2, 4, and 8mg P/kg body wt. of EDTPO once daily (at noon) for 10 days respectively. Tetracycline (Tc.) were i.p. injected three times, one day before drug treatment (1st), 5th (2nd) and 10th (3rd) day of experimental period. All rats were received i.p. injection of 185kBq (5 microCi) of 45Ca six hours after the 10th injection of EDTPO. On the next day, blood samples were taken from the carotid artery. Then the animals were killed and both tibias, submandibular teeth and right femur were removed. Serum Ca, IP and ALP were determined by spectrophotometry. Wet, dry and ash bone weight were measured and bone calcium was determined by atomic absorption method. 45Ca activity was counted by the liquid scintillation counter. Serum Ca levels revealed decreasing tendency at the dose of 1mg P/kg and 2mg P/kg of EDTPO but increasing tendency at 4mg P/kg and significant increase at the dose of 8mg P/kg. Specific activity of 45Ca in serum increased slightly at 2mg P/kg, but at the dose of 8mg P/kg increased five times compared to that of control. Decrease of IP and increase of ALP level were observed only at the dose level of 8mg P/kg. Wet, dry, and ash weight, and Ca content of femur and 45Ca activity were decreased dose-dependently. In histological examination, changes of tibia and teeth were observed at the dose of 2mg P/kg and following dose increase these changes were more significantly. Ultraviolet line of Tc. appeared three in proximal metaphysis of tibia and dentin at the dose of 1mg P/kg and 2mg P/kg, but at the dose of 4mg P/kg and 8mg P/kg 2nd and 3rd line could not be detected. These result indicated that the effects of EDTPO on serum ingredients, long bone and teeth are initiated at the dose of 2mg P/kg, appeared at the dose of 4mg P/kg significantly, and at the dose of 8 mg P/kg severely. In addition, increase of the ratio of 45Ca specific activity between serum and bone observed at the dose of 4mg P/kg and 8mg P/kg suggested that these effects of EDTPO would be due to inhibitory action on mineralization.

[Clinical and bacteriological studies in four cases of pulmonary infection caused by Protomonas extorquens].

A novel bacterium, Protomonas extorquens was isolated from sputum, pleural effusion and ascitis in four cases of pulmonary infection by buffered charcoal yeast extract agar (B-CYE) which was generally used for Legionella spp. Three cases were so-called immunocompromised hosts (2 malignant diseases, 1 renal failure), and they died from underlying diseases. Protomonas extorquens was newly named by Komagata in 1984, which was characterized by production of pink pigment, growth in methanol medium and positive production of oxidase and catalase. This organism is ordinarily isolated from soil and dead leaves. This is the first report for isolation of P. extorquens from clinical specimens in Japan and it seems to have a significant role in immunocompromised hosts.

[A case report of superior vena cava reconstruction using a heparin-coated temporary bypass tube].

A 56-year-old woman with stage IIIB (c-T1N3M0) small cell lung cancer was treated with combination chemotherapy (CAVE). After five cycles of chemotherapy a surgical resection was performed. As mediastinal lymph nodes (#2, 3, 3a) had invaded to the superior vena cava, a heparin-coated tube was inserted into the left innominate vein and the right auricular appendage as a temporary bypass. Advantages of a heparin-coated tube for the temporary SVC bypass are as follows. 1) simple operative procedure. 2) enough flexibility to be kept out of the operative field. 3) no need for anticoagulants, consequently less bleeding resulted.

[Susceptibility of bacteria isolated from patients with lower respiratory tract infections to antibiotics (1987)].

Since 1981, in cooperation with research institutions across the nation, Ikemoto, et al. have been collecting clinical isolates from patients with respiratory tract infections and conducting an annual retrospective survey of patients' background factors and of isolated strains and their sensitivities to various antibacterial agents and antibiotics. In the period from October, 1987 to September, 1988, 17 institutions participated in the survey and a total of 706 strains which were demonstrated to be causative organisms were isolated from 562 patients with respiratory tract infections. Strains were mostly isolated from the sputum. The taxonomic breakdown of these strains was: Staphylococcus aureus (69 strains), Streptococcus pneumoniae (120), Haemophilus influenzae (170), Mucoid-producing Pseudomonas aeruginosa (42), Non-mucoid-producing P. aeruginosa (87), Escherichia coli (11), Klebsiella pneumoniae (35), Brahamella catarrharis (72), etc. Of these strains, 629 were used to determine MICs of various antibacterial agents and antibiotics for susceptibility analyses. Relationships between patient backgrounds and diagnoses and between infections diseases and causative organisms were also investigated. Most of the major causative organisms, such as H. influenzae and P. aeruginosa, showed no substantial changes from previous years, with regard to their sensitivities to antibiotic agent, but S. aureus, particularly methicillin/cephem-resistant strains of S. aureus (MCRSA) showed somewhat lower sensitivity to beta-lactams, and as in recent years, to ofloxacin, a new quinolone drug, as well. Regarding background factors of patients, the age distribution was heavily concentrated in age brackets of 50 years and older, thus patients in these age group accounted for 75.2% of all the patients, which was comparable to 73.5% in 1985 and 77.9% in 1986. Among infections encountered, bacterial pneumonia was most frequent at 28.3%, followed by chronic bronchitis (27.2%) and bronchiectasis (16.0%). Bacterial pneumonia was actually the most frequent, throughout the entire age groups accounting for 34.3% of patients up to 29 years, 26.6% in the group of 30-69 years and 30.7% in patients aged 70 years and older. Chronic bronchitis was next most frequent and accounted for 20.0%, 26.4% and 30.7% among the three age groups, respectively. Breaking down clinical isolates by diagnosis, H. influenzae, S. pneumoniae and P. aeruginosa were isolated frequently from most of the infectious diseases.(ABSTRACT TRUNCATED AT 400 WORDS)

[Susceptibility of bacteria isolated from patients with lower respiratory tract infections to antibiotics (1986)].

Enlisting the help of various research institutions across the nation, Ikemoto et al. have been pooling cultures of clinical isolates of respiratory tract infections and mapping out the correlations between patient backgrounds and the causative bacteria and the changes in the sensitivity spectra of the bacteria to various antibacterial and antibiotic agents annually since 1981. The following is a report of the 1986 findings. During the period from September, 1986 to March, 1987, 558 cases of respiratory infections were reported at 17 institutions across the nation and a total of 657 apparent causative strains were isolated from sputum samples. Of these strains, 75 strains of Staphylococcus aureus, 108 of Streptococcus pneumoniae, 150 of Haemophilus influenzae, 107 of Pseudomonas aeruiginosa (non-mucoid production type), 21 of P. aeruginosa (mucoid production type), 32 of Klebsiella pneumoniae, 8 of Escherichia coli, and 55 of Branhamella catarrhalis were subjected to MIC determination of various antibacterial and antibiotic agents to map drug sensitivities. In addition, diagnoses, age distributions by diagnoses, frequencies of infectious diseases, types of isolated bacteria, and usage statuses of the antibacterial and antibiotic agents the times of at isolation were also investigated. MIC determinations were carried out to investigate susceptibilities of causative organisms of respiratory tract infections to various antibacterial and antibiotic agents. From the 558 cases of respiratory tract infections, 657 strains were detected at concentrations not less than 10(4-6)/ml and identified to be the causative organisms. Of these strains, 603 could be used for MIC determination. An overwhelming majority of major causative bacteria, inclusive of H. influenzae and S. pneumoniae, showed sensitivity patterns similar to the sensitivity patterns found a year earlier, P. aeruginosa alone, however, showed some increase in its susceptibility to penicillin and cephem antibiotics. Regarding patient backgrounds, the age distribution was heavily biased towards the higher end of the scale, which patients with ages of 50 or higher accounting for 77.9%, compared to 73.5% in 1985. When the patients were classified by diagnoses, chronic bronchitis, bacterial pneumonia and bronchiectasis accounted for the majority of the infections: 28.7%, 23.3%, and 19.0%, respectively. The percentages of chronic bronchitis and bacterial pneumonia 28.7% and 23.3%, respectively, were somewhat higher in 1986 than in 1985. The disease which was comparatively frequent in all age groups was bronchiectasis, which accounted for 44.0% in patients with ages 29 years or lower, 18.4% in patients between 30 years and 69 years, and 16.7% in patients with ages 70 years or higher. The next most frequent infection was bacterial pneumonia.(ABSTRACT TRUNCATED AT 400 WORDS)