Quantitative and qualitative abnormalities in HIV-1-specific T cells.

OBJECTIVE: To assess the characteristics of CD4 and CD8 T cells specific for HIV-1 and cytomegalovirus (CMV) antigens in untreated and treated HIV-1-infected patients. METHODS: Antigen-specific T cell frequencies were determined by flow cytometric detection of antigen-induced intracellular cytokines. RESULTS: In untreated patients, HIV-1-specific CD4 T cell counts in peripheral blood were less than one tenth of CMV-specific CD4 T cell counts, while the number of specific CD8 T cells was approximately the same for both HIV-1 and CMV. In patients treated with highly active antiretroviral therapy (HAART) for less than 1.5 years, HIV-1-specific CD4 and CD8T cell counts were significantly lower than those in untreated patients. Perforin expression in HIV-1-specific CD8 T cells was significantly lower than that in CMV-specific CD8 T cells. CONCLUSION: These data indicate that HIV-1-specific T cells in HIV-1-infected patients have quantitative and qualitative abnormalities.

Gene structure and promoter for Crad2 encoding mouse cis-retinol/3alpha-hydroxysterol short-chain dehydrogenase isozyme.

Cis-retinol/androgen dehydrogenase type 2 (CRAD2) has been shown to catalyze the dehydrogenation of retinols, including 9-cis retinol, and also to exhibit 3alpha- and 17beta- hydroxysteroid dehydrogenase activities. To examine the function of this enzyme and regulation of its gene, the Crad2 gene was cloned from a mouse genomic DNA library and characterized. The complete mouse CRAD2-coding region was found in four exons spanning an approximately 5kb region. The nucleotide sequences of the exons encoding 316 amino acids were identical to those of the previously reported mouse Crad2 cDNA. Primer extension analysis and RNase protection assay were used to map the major transcription initiation sites to the positions lying 87 and 89 base pairs upstream of the ATG translation start codon. The region proximal to the initiation sites exhibited the absence of both TATAA and CAAT boxes. This region had hepatocyte nuclear factor binding sites, consistent with its predominant expression in the liver. Computer analysis of an approximately 7.5kb 5'-flanking region also suggested the presence of binding sites for AP-1, SREBP1, HSF2, c-Rel, c-Myc, CREBP, GATA, Ets, E2F, and Oct-1, suggesting that various factors including retinoic acid, cholesterol, various kinds of stress, the cell cycle, and cyclic AMP may regulate the expression of this gene. Fluorescence in-situ hybridization analysis showed that Crad2 is located at the terminus of mouse chromosome 10, an area that corresponds to band 10D3, suggesting that RDH-related SDRs may be located together in the cluster locus. Northern blot hybridization and RT-PCR analysis demonstrated that CRAD2 was expressed not in early embryonic stages, and not in embryonic stem cells, but instead in the gastrointestinal tract during later embryonic development and adult stage. In conclusion, we have presented the first complete structural analysis, including that of the promoter and chromosomal location, of a member of the retinol/androgen dehydrogenase subfamily of the group of the short-chain dehydrogenase/reductase (SDR) isozymes. Our findings will provide the basis for in-vitro or in-vivo studies concerning the regulation of retinol and androgen metabolism and enable determination of the mechanism of diseases related to retinol, retinal, retinoic acid, and androgen.

Minor structural changes in nicotinoid insecticides confer differential subtype selectivity for mammalian nicotinic acetylcholine receptors.

The major nitroimine insecticide imidacloprid (IMI) and the nicotinic analgesics epibatidine and ABT-594 contain the 6-chloro-3-pyridinyl moiety important for high activity and/or selectivity. ABT-594 has considerable nicotinic acetylcholine receptor (AChR) subtype specificity which might carry over to the chloropyridinyl insecticides. This study considers nine IMI analogues for selectivity in binding to immuno-isolated alpha1, alpha3 and alpha7 containing nicotinic AChRs and to purported alpha4beta2 nicotinic AChRs. Alpha1- and alpha3-containing nicotinic AChRs (both immuno-isolated by mAb 35, from Torpedo and human neuroblastoma SH-SY5Y cells, respectively) are between two and four times more sensitive to DN-IMI than to (-)-nicotine. With immuno-isolated alpha3 nicotinic AChRs, the tetrahydropyrimidine analogues of IMI with imine or nitromethylene substituents are 3-4 fold less active than (-)-nicotine. The structure-activity profile with alpha3 nicotinic AChRs from binding assays is faithfully reproduced in agonist potency as induction of 86rubidium ion efflux in intact cells. Alpha7-containing nicotinic AChRs of SH-SY5Y cells (immuno-isolated by mAb 306) and rat brain membranes show maximum sensitivity to the tetrahydropyrimidine analogue of IMI with the nitromethylene substituent. The purported alpha4beta2 nicotinic AChRs [mouse (Chao & Casida, 1997) and rat brain] are similar in sensitivity to DN-IMI, the tetrahydropyrimidine nitromethylene and nicotine. The commercial insecticides (IMI, acetamiprid and nitenpyram) have low to moderate potency at the alpha3 and purported alpha4beta2 nicotinic AChRs and are essentially inactive at alpha1 and alpha7 nicotinic AChRs. In conclusion, the toxicity of the analogues and metabolites of nicotinoid insecticides in mammals may involve action at multiple receptor subtypes with selectivity conferred by minor structural changes.

Irradiation with ultrasound of low output intensity increased chemosensitivity of subcutaneous solid tumors to an anti-cancer agent.

Ultrasound is a possible mechanical method to deliver small molecules into target cells. In order to evaluate the therapeutic potentials provided by ultrasound irradiation, we compared anti-tumor effects of electroporation- and ultrasound-mediated chemotherapy and efficacy of gene transfer by the two methods. Electric pulses (5 Hz, 100 V/cm, 8 square-wave/100 microsec) or ultrasound (1 MHz, 2 W/cm(2), 5 min) was delivered to subcutaneous solid tumors of murine lymphoma after the tumor-bearing mice received an intraperitoneal injection of bleomycin (BLM) (2.5 mg) or intratumoral injection of plasmid DNA containing the luciferase reporter gene. Administration of BLM alone did not affect the subsequent tumor growth but additive treatment with ultrasound irradiation suppressed the growth to the same level as electroporation. The luciferase activity of the DNA-injected tumors showed that ultrasound irradiation achieved better transfection efficiency than plasmid DNA injection alone but the efficacy was not as great as that by electroporation. The low energy level of ultrasound that is currently used for a diagnostic purpose and physical therapy in clinical fields can thereby increase the in vivo chemosensitivity of treated tumors but further modifications are necessary to achieve better efficacy of the ultrasound-mediated gene transfer.

[125I]Azidonicotinoid photoaffinity labeling of insecticide-binding subunit of Drosophila nicotinic acetylcholine receptor.

The novel synthetic nicotinoid insecticide imidacloprid is a high affinity ligand for the insect nicotinic acetylcholine receptor (nAChR). The goal of this study is to identify the ligand- and insecticide-binding subunit of Drosophila nAChR with a novel [125I]azidonicotinoid ([125I]AN) photoaffinity probe modeled on imidacloprid. [125I]AN photoaffinity labels a single polypeptide in Drosophila head membranes corresponding in molecular mass to 66 kDa at a specific site inhibited by various cholinergic ligands including (-)-nicotine, cytisine, carbachol, alpha-bungarotoxin and d-tubocurarine as well as the insecticides imidacloprid and acetamiprid, pharmacologically consistent with the ligand- and insecticide-binding subunit. The Drosophila nAChR, isolated with three putative subunits (69, 66 and 61 kDa) using a nicotinoid-agarose affinity column, is labeled by [125I]AN primarily at the 66 kDa subunit and secondarily at the 61 kDa subunit. Clearly, the novel synthetic nicotinoid insecticides are valuable contributors in exploring the structure and function of the Drosophila nAChR.

Relative biological effectiveness of carbon ions for causing fatal liver failure after partial hepatectomy in mice.

To evaluate the acute phase damage to liver by carbon ions, BALB/c mice were irradiated with carbon ions or X-rays after two-thirds partial hepatectomy, and their survival was followed. The 50% lethal dose within 60 days (LD50/60) was 42.2 +/- 0.25 Gy (standard error) for X-rays, and 22.7 +/- 0.25 Gy for carbon ions. The relative biological effectiveness (RBE) of carbon ions was 1.86 (95% confident limits: 1.69-2.04) as calculated from the LD50/60. Mice irradiated at much higher doses, 60 Gy of X-rays or 24 Gy of carbon ions, showed significantly higher serum ammonia levels and lower serum albumin levels than normal, suggesting hepatic failure as a cause of death. Hepatocytes showed karyorrhexis and karyolysis in carbon ion irradiated and spotty necrosis in X-ray irradiated mice, suggesting nuclear damage. Mice irradiated with LD50 of X-rays or carbon ions had a remarkably lower bromodeoxyuridine (BrdU) labeling index and mitotic index than control. Treatments with both BrdU and vincristine showed that none of the hepatocytes that synthesized DNA after irradiation completed mitosis, indicating G2 arrest. The liver weight of irradiated mice significantly decreased depending on the dose. Carbon ions as well as X-rays damaged hepatocytes directly and suppressed liver regeneration leading to fatal liver failure.

Etiological analysis of focal nodular hyperplasia of the liver, with emphasis on similar abnormal vasculatures to nodular regenerative hyperplasia and idiopathic portal hypertension.

Pathological studies were performed on 23 cases of focal nodular hyperplasia (FNH) under the hypothesis that FNH is a hyperplastic lesion caused by abnormal vasculatures of portal tracts within the nodule. For a comparison of the histological features of portal tracts, nodular regenerative hyperplasia (NRH), idiopathic portal hypertension (IPH), chronic hepatitis and so-called normal liver were used as control tissues. Extranodular areas of FNH nodules were also examined. Clinical data were briefly summarized. Most of the portal tracts within FNH nodules showed various abnormal findings, such as dilatation and/or stenosis of portal vein, muscular thickening of arterial wall with dilated or stenotic lumina, lymphocyte infiltration, and bile ductule proliferation. However, portal vein thrombi were not found. These findings were not thought to represent compensatory reaction to portal vein thrombosis. Similar abnormal features were also observed in extranodular areas of FNH although to a milder degree. These abnormal features resembled those of NRH and IPH. Moreover, the characteristic scar-like tissues within FNH nodules were proved to be abnormally large portal tracts including large feeding arteries, portal veins and bile ducts. It has been believed that septa and scar-like tissue within FNH nodules are not portal tracts and that arterial malformation independent of portal tracts are related to the development of FNH. In addition, venous structures within FNH modules have until now not been considered to be portal veins. However, this study revealed that severe anomaly of portal tracts including portal veins and hepatic arterial branches existed in FNH nodules. Moreover, portal tracts in extranodular areas were also abnormal. Clinically, only one patient had a history of oral contraceptives. Based on these findings, congenital anomaly of the portal tracts histologically resembling the abnormal portal tracts of NRH and IPH may be related to the pathogenesis of FNH.

Neonicotinoid insecticides: molecular features conferring selectivity for insect versus mammalian nicotinic receptors.

The favorable selective toxicity of neonicotinoid insecticides (represented here by imidacloprid, thiacloprid, and a nitromethylene analogue) for insects versus mammals is not shared by three of their N-unsubstituted imine derivatives or by nicotine or epibatidine. The same selectivity pattern is evident at the receptor level, i.e., the insect nicotinic acetylcholine receptor (nAChR) versus mammalian nAChR subtypes (alpha1, alpha3, alpha4, and alpha7) assayed independently. The insect-selective compounds are not protonated with a nitroimine, cyanoimine, or nitromethylene group and the mammalian-selective compounds are ionized at physiological pH. We propose that the negatively charged tip of the nitro or cyano group (not a partial positive charge at imidazolidine N-1 as suggested earlier) interacts with a putative cationic subsite of the insect nAChR. This contrasts with the mammalian nAChRs where the iminium cation (+C-NH2 <--> C =+NH2) of the neonicotinoid imine derivatives or ammonium nitrogen of nicotine or epibatidine interacts with the anionic subsite.

Effect of sugars-addition on the survival of vitrified bovine blastocysts produced in vitro.

We investigated the effect of addition of sugars to a vitrification solution on the survival rate of bovine blastocysts produced in vitro. In vitro-matured (IVM) and in vitro-fertilized (IVF) bovine Day-6 to Day-8 bovine blastocysts were classified into 3 developmental stages: early blastocysts, blastocysts and expanded blastocysts. The blastocysts were cryopreserved in 1 of 3 vitrification solutions: 1) 25% glycerol25% ethylene glycol (GE); 2) 20% glycerol20% ethylene glycol3/4 M sucrose (GES); and 3) 20% glycerol20% ethylene glycol3/8 M sucrose3/8 M dextrose (GESD). The basic solution was Dulbecco's PBS supplemented with 20% of fetal calf serum. Embryos were exposed to each vitrification solution in 3 steps, and after loading into 0.25-ml straws, were plunged into liquid nitrogen. After warming in water bath at 20 degrees C, cryoprotectants were diluted in 1/2 M and 1/4 M sucrose each for 5 min. Equilibration and dilution procedure except warming were conducted at room temperature (23 to 27 degrees C). After dilution, the embryos were cultured in Ham's F10 medium0.1 mM beta-mercaptoethanol20% fetal calf serum. Survival rates of embryos at 48 h of incubation of each of the 3 developmental stages (early blastocysts, blastocysts and expanded blastocysts) exposed to the 3 types of the vitrification solutions (GE, GES and GESD) were 23.5, 33.3, 65.8% (early blastocysts, blastocysts and expanded blastocysts respectively) in GE, 55.6, 71.9, 90.5% in GES and 84.6, 83.3, 95.8% in GESD respectively. These results indicate that a mixture of 25% glycerol25% ethylene glycol is not suitable for vitrification of early bovine blastocysts; however, addition of sugars to the solution significantly (P<0.01) improved the survival rate of the vitrified blastocysts, independently of their stage of development.

Structure and diversity of insect nicotinic acetylcholine receptors.

The nicotinic acetylcholine receptor (nAChR) is an agonist-regulated ion-channel complex responsible for rapid neurotransmission. The vertebrate nAChR, assembled from five homologous subunits, penetrates the synaptic membrane. Different subunit combinations lead to receptor subtypes with distinctive pharmacological profiles. In comparison with mammalian nAChRs, the insect receptor is poorly understood relative to functional architecture and diversity. Several genes for Drosophila, Locusta and Myzus encoding insect nAChR subunits have been identified, although the functional assembly and presence of different subtypes of these receptors are not defined. The insect nAChR is the primary target site for the neonicotinoid insecticides, thereby providing an incentive to explore its functional architecture with neonicotinoid radioligands, photoaffinity probes and affinity chromatography matrices. This review considers the current understanding of the structure and diversity of insect nAChRs based mainly on recent studies in molecular biology and protein biochemistry.

[Double-blind comparative study of roxithromycin (RU 28965) and midecamycin acetate (MOM) in the treatment of pneumonia].

The clinical efficacy and safety of Roxithromycin (RU) were compared with those of Midecamycin acetate (MOM) in patients with pneumonia in a double blind study. RU and MOM were administered orally for 14 days with daily doses of 300 mg (150 mg b.i.d.) and 600 mg (200 mg t.i.d.), respectively. The following results were obtained. 1. RU and MOM were administered to a total of 204 patients (RU: 101, MOM: 103). The clinical efficacy was judged in 150 patients (RU: 70, MOM: 80), with 54 of the patients excluded from the total by the committee. 2. The clinical efficacy rates were 81.4% for RU and 70.0% for MOM on the basis of the committee's judgement. There was no significant difference between the two groups. In the evaluation of the clinical efficacy by the doctors in charge, the efficacy rates were 81.4% for RU and 67.5% for MOM, which constitutes a significant difference between the two groups (p less than 0.05). 3. No significant difference was found between the two drugs in bacteriological efficacy. 4. No significant differences were observed in either the incidence of side effects between RU (4.3%) and MOM (4.0%) or in abnormal changes in the laboratory findings. 5. Regarding the clinical usefulness judged by the committee, RU showed a significantly higher rate than MOM (79.2% vs. 67.9%). There was no significant difference in the judgement by the doctors in charge. From the above results, it was concluded that a daily dosage of 300 mg of RU was equal in usefulness to 600 mg daily of MOM in the treatment of mild to moderate pneumonia.

[Clinical evaluation of SM-4300, a new human immunoglobulin preparation].

Clinical efficacy and safety of SM-4300, a newly developed human immunoglobulin preparation for intravenous use, were evaluated in 11 patients with severe infectious disease which are resistant to antibiotic therapy in the combined use with the antibiotics. Clinical effects of SM-4300 wee excellent in 1 case, good in 5 cases, fair in 1 case, poor in 1 case and unevaluable in 3 cases. The efficacy rate was summarized as 75%. Bacteriological responses were eradicated in 1 case and unknown in 10 cases. No side effects and abnormal laboratory findings due to SM-4300 were observed in this investigation.

[Clinical studies on tobramycin using intravenous drip infusion (author's transl)].

Clinical studies and serum levels on tobramycin (TOB) using intravenous drip infusion were carried out and the following results were obtained. 1. Clinical results Nineteen patients with various infections including 11 respiratory tract infections, 7 urinary tract infections and a wound infection were treated with TOB 20-60 mg b.i.d. and t.i.d. by intravenous drip infusion and for 1 hour during 4 to 16 days. Clinical effects were excellent in 10 cases, good in 4 cases, fair in 2 cases and failure in 3 cases. It was 73.7% of the efficacy rate of the drug. Side effects were observed in 2 cases of oliguria and increase in BUN, S-creatinine and S-potassium. 2. Serum levels of TOB Serum levels of TOB administrated 30 or 60 mg intravenous drip infusion for 1 hour were measured in first and final administration of 8 patients. The peak serum levels were 3.1-5.0 micrograms/ml at the end of infusion in first 60 mg administration of the drug, and 3.8-5.3 micrograms/ml in final 60 mg administration of the drug.

[Studies on the intravenous administration of sulbenicillin (author's transl)].

Basic and clinical investigation on the intravenous administration of sulbenicillin in moderate dose (510g daily) was carried out to evaluate its clinical effect in systemic infections due to gram-negative bacilli. The following results were obtained. (1) In human subjects received 5 g intravenous drip infusion, the peak blood levels were found at the end of infusion. In 6 cases with normal renal function (Ccr greater than or equal to 70ml/min.) the peak blood level was 181 mcg/ml on the average and the half-life 1.1 hours, while in 3 cases with impaired renal function (Ccr less than 70 ml/min.) the peak level 216 mcg/ml and the half-life longer than 2 hours. The height of the peak level seemed to be subjected to the duration of infusion. The renal excretion of sulbenicllin was 55.2% on the average both in cases with normal and impaired renal functions. (2) Sulbenicillin, 510g daily divided in 2 doses, was administered to 15 cases including 6 cases with acute pyelonephritis, 3 with acute cystitis, 3 with biliary tract infection, 2 with respiratory tract infection and 1 with acute prostatitis. All the cases except 3 cases with acute pyelonephritis had underlying diseases. Escherichia coli was isolated from 10 cases, Klebsiella from 2, Pseudomonas aeruginosa from 1, and unidentified gram-negative bacilli from 1. Eleven cases responded to the treatment, but 4 cases failed. In 11 cases with susceptible bacteria, 8 cases responded bacteriologically (2 cases recurred), and 3 cases failed to respond. A case with biliary tract infection due to E. coli did not respond to 5 g daily treatment, but responded to 5 g twice daily. Two cases due to organisms which were not inhibited by 200mcg/ml in vitro did not respond to the treatment. (3) A moderate decrease in red blood cell number and hemoglobin content was observed in one case. A transient increase in transaminase and alkaline phosphatase level was observed in other cases.

[Antimicrobial susceptibility of Pseudomonas aeruginosa isolated in Fukushima Prefecture].

We investigated the susceptibility of Pseudomonas aeruginosa (isolated from the sputum of patients with respiratory infection in 4 medical institutions in Fukushima Prefecture) to 8 beta-lactam antibiotics including three carbapenems and relationships among MICs of antibiotics tested. The MIC90 values for a total of 216 strains were 6.25 micrograms/ml for meropenem, 12.5 micrograms/ml for imipenem and ceftazidime, 25 micrograms/ml for panipenem and cefsulodin, 50 micrograms/ml for cefpirome and over than 200 micrograms/ml for cefoperazone and piperacillin. The frequency of resistance of these strains to each antibiotic was as follows: The resistant strains were 19 (8.8%) for meropenem, 34 (15.7%) for imipenem and ceftazidime, 50 (23.1%) for cefsulodin, 72 (33.3%) for panipenem, 76 (35.2%) for piperacillin and 90 (41.7%) for cefpirome. Eighteen strains (18.3%) of 19 meropenem resitant straisn were resistant to imipenem and panipenem, but 16 strains of the 34 imipenem-resistant strains and 54 strains of the 72 panipenem-resistant strains were susceptible to meropenem. In investigation of isolation of multi-resistant Pseudomonas aeruginosa, the susceptibility of strains tested to 7 antibiotics except cefoperazone was as follows: The strains susceptible to all the 7 antibiotics were 92 strains (42.6%), and 33 strains (15.2%) were resistant to 2 antibiotics, 31 strains (14.4%) were resistant to 1 antibiotic, 21 strains (9.7%) were resistant to 3 antibiotics, 13 strains (6.0%) were resistant to 5 antibiotics, 9 (4.2%) were resistant to 4 and 7 antibiotics, and 8 strains (3.7%) were reistant to 6 antibiotics. Since the emergence of these multi-resistant strains is closely related to frequent use of antibiotics for nosocomial infections, special attention should be paid to the antimicrobial susceptibility of Pseudomonas aeruginosa and the situation of antibiotic resistant strains.

[A comparative study of tazobactam/piperacillin and piperacillin in bacterial pneumonia].

The efficacy, safety and usefulness of tazobactam/piperacillin (TAZ/PIPC), in bacterial pneumonia and lung abscess were determined with PIPC as the control in a multi-institutional comparative study a penicillin antibiotic for injection prepared by combining a newly developed beta-lactamase inhibitor, tazobactam (TAZ), with a broad spectrum penicillin antibiotic, piperacillin (PIPC), at a ratio of 1:4. TAZ/PIPC was intravenously injected at a dose of 2.5 g (titer) twice a day, and PIPC at a dose of 2.0 g (titer) twice a day as a rule for 14 days. The following results were obtained: 1. The efficacy rates for bacterial pneumonia and lung abscess were 94% (80/85) in TAZ/PIPC group and 89% (70/79) in PIPC group, showing no significant difference between the two groups. 2. In a comparison of degrees of improvement in clinical symptoms, signs and laboratory findings, there were no significant differences between the two groups except for results on thoracic rales after three days of administration. 3. As for bacteriological effects, the elimination rates of causative organisms were 98% (40/41) in the TAZ/PIPC group and 80% (28/35) in the PIPC group. Thus, the TAZ/PIPC group was significantly superior to the PIPC group. The TAZ/PIPC group showed significantly better eradication of bacteria as well. Bacteria considered to be pyogenic were detected in 80 patients (43 administered TAZ/PIPC and 37 administered PIPC), but beta-lactamase production was confirmed in only 11 patients of each group. There were no significant differences in bacteriological effects among these patients. Minimum inhibitory concentrations of TAZ/PIPC against beta-lactamase producing organisms were distinctly superior to those of PIPC. 4. Side effects occurred in 10% (10/96) of the TAZ/PIPC group and 7% (7/95) of the PIPC group. Abnormal clinical laboratory test values were observed in 22% (20/92) of the TAZ/PIPC group and 18% (17/93) of the PIPC group. Thus, there were no significant differences between the two administration groups. 5. The usefulness rate in the TAZ/PIPC group was 87% (75/86) and it was 85% (67/79) in the PIPC group, showing no significant difference between them. The results suggest that TAZ/PIPC administered at a dose of 2.5 g (titer) twice a day is more useful than PIPC administered at a dose of 2.0 g (titer) twice a day in the treatment of bacterial pneumonia.

[Pharmacokinetics and clinical evaluation of amoxicillin sustained release preparation].

C-AMOX--long acting amoxicillin preparation (gastro coating 3, enterocoating 7)--has been investigated to give following results. A pharmacokinetic study of C-AMOX was conducted in 6 healthy male volunteers in postprandial state (30 minutes after light mean). The levels of 1.8--2.5 micrograms/ml in blood was detected for 6 hours after 500 mg dose orally. It was seemed to be long acting amoxicillin in blood levels. And, the calculated data of AUC of C-AMOX was 15.17 micrograms . hr/ml administered 500 mg dose, and 14.33 micrograms . hr/ml of AMPC twice 250 mg doses, respectively. The urinary excretion rate was 56.1% of the dose during 10 hours. Sixty-six patients with respiratory tract infections, urinary tract infections and others were treated with C-AMOX 0.5 g twice daily for 4--7 days mainly. Thirty one patients of all were cured excellent, 27 were good, 4 were fair and 4 were poor. The global efficacy rate was 87.9%. Only 1 patient was occurred diarrhea, and no abnormal laboratory finding was observed.

[Clinical evaluation of BMY-28100 for bacterial pneumonia in comparison with cefaclor in a double-blind study].

The efficacy, safety and usefulness of BMY-28100 for the treatment of bacterial pneumonia were compared with those of cefaclor (hereinafter referred to as CCL) in a double-blind study. The daily dosages were 750 mg for BMY-28100 and 1,500 mg for CCL, divided into 3 administrations daily. These drugs were administered orally for at least 14 days. A total of 172 cases were enrolled in this study. Of these, cases which deviated from the protocols were excluded from evaluations. Thus, clinical efficacy was evaluated in 124 cases, adverse reactions were evaluated in 160 cases, and abnormal laboratory test values were evaluated in 146 cases. The following results were obtained. 1. Efficacy rates ("good" or better responses) in bacterial pneumonia cases as evaluated by the subcommittee were 81.7% (49/60) in the BMY-28100 group and 89.1% (41/46) in the CCL group, thus no significant difference was found between the 2 groups. 2. Efficacy rates ("good" or better responses), as evaluated by investigators, in the same bacterial pneumonia cases which were subjected to the evaluation by the subcommittee were 83.3% (50/60) in the BMY-28100 group and 88.9% (40/45) in the CCL group, thus no significant difference between the 2 groups was found also. 3. Bacteriological response rates in bacterial pneumonia cases were 86.2% (25/29) in the BMY-28100 group and 85.7% (18/21) in the CCL group with no significant difference between the 2 groups. 4. Incidences of subjective/objective clinical adverse symptoms were 3.5% (3/85) in the BMY-28100 group and 1.3% (1/75) in the CCL group, and no significant difference was observed between the 2 groups. No significant difference was also found between the 2 groups in incidences of abnormal laboratory test values, as abnormalities were found in 21.1% (16/76) of the cases in the BMY-28100 group and 25.7% (18/70) in the CCL group. 5. As for overall usefulness of the drug in bacterial pneumonia cases, utility rates ("useful" or better evaluations) as evaluated by the subcommittee were 83.6% (46/55) in the BMY-28100 group and 90.5% (38/42) in the CCL group, and the rates as evaluated by investigators in cases judged as evaluable by the subcommittee were 78.3% (47/60) and 82.2% (37/45), respectively. There were no significant differences between the 2 groups. The utility rates as evaluated by investigators in cases in which diseases were diagnosed as bacterial pneumonia or lung abscess by investigators were 78.3% (47/60) in the BMY-28100 group and 82.2% (37/45) in the CCL group.(ABSTRACT TRUNCATED AT 400 WORDS)

[Comparison of in vitro antibacterial activities of new cephems against clinical organisms (isolated between June 1983 and January 1984)].

We compared the in vitro antibacterial activities of ceftizoxime (CZX), cefotaxime (CTX), cefmenoxime (CMX), cefoperazone (CPZ), ceftazidime (CAZ), latamoxef (LMOX) and cefotetan (CTT) against 2,729 strains of 11 organisms freshly isolated from 10 medical institutions in Japan between June 1983 and January 1984 and obtained the following results: Against S. pyogenes, LMOX and CTT, which have the methoxy group at the 7 position, were less active than the other drugs. LMOX inhibited 80% of S. pyogenes at 0.78 micrograms/ml; CTT, at 1.56 micrograms/ml; but CZX and CTX inhibited 100% at 0.025 micrograms/ml or lower; CMX, at 0.05 micrograms/ml; and CPZ and CAZ, at 0.20 micrograms/ml. Against H. influenzae, E. coli, K. pneumoniae, P. mirabilis and indole-positive Proteus, these test antibiotics, especially CZX, CTX and CMX, which have the aminothiazolyl methoxyimino group, were potently active. Against S. marcescens CZX and CAZ were more active than the other drugs and against P. aeruginosa CAZ was more active than the other drugs. The test organisms did not tend to acquire resistance to these cephems when our results were compared with the results obtained at the development period.

[Extracalvarial meningioma--report of a case (author's transl)].

A case of extracalvarial meningioma was reported. 75-year-old man was admitted to our department on November 11, 1974 because of a slowly growing tumor in the right frontoparietal area. The tumor was ovoid and 15x13 cm in size, protruding 5 cm above the skin level, and covered by the normal scalp. Neurological and electroencephalographic examination were negative. Spinal tap showed an opening pressure of 90 mm of water and clear CSF with 62 mg/dl of protein content. Plain roentgenogram and laminagram of the skull revealed both osteolytic and osteoblastic change in the outer and inner table of the skull just beneath the tumor. A right external carotid angiography disclosed a homogeneous extracalvarial tumor stain supplied by the superficial temporal artery and draining into the superficial temporal vein. A right carotid angiogram showed a 1 cm thick avacular area. The segmentally occluded superior sagittal sinus was displaced inward together with bridging collateral channels. Radiologically these picture corresponded to "intracranial non-globoid shape or avascular meningioma" discussed by Huckman et al. The tumor was well-circumscribed, encapsulated and loosely adherent to the periosteum and the skull except for a small portion through which the tumor was communicated with its intracranial part. Histological examination revealed that it was a typical endotheliomatous meningioma. This case should be allocated to the transitional or intermediate type between Lopez II and III type. In the schematical presentation (Fig. 6) we tried to readjust the rather confusing concept and classification of the extracalvarial meningioma.