Local allergic rhinitis in children: identification and characterization in a specialty outpatient clinic.

Summary: Background. Local Allergic Rhinitis (LAR) is a phenotype defined by rhinitis symptoms with negative responses to systemic sensitization tests but with an exclusively nasal allergic inflammatory response. Data on the pediatric age group is scarce, and no Latin American data has been published so far. Methods. Nasal Allergen Challenge (NAC) was performed with Dermatophagoides pteronyssinus and Blomia tropicalis in six- to 18-year-old patients diagnosed with rhinitis and no systemic sensitization. NAC was monitored using subjective parameters and acoustic rhinometry. The study aimed to identify LAR in child and adolescent subjects previously diagnosed with non-allergic rhinitis (NAR) in a Brazilian specialty outpatient clinic (Allergy and Immunology). Results. During the study period, we analyzed 758 skin prick tests (SPT). Of those, 517 (68.2%) were diagnosed with rhinitis. Among those, 18.4% (95/517) had a negative SPT, meeting the criteria for inclusion in the study. Twenty-five patients underwent NAC, and 40% (10/25) of them, previously considered to have NAR, had a positive test and were reclassified as having LAR. Based on the analyzed characteristics, clinically differentiating LAR from NAR was impossible. Conclusions. This study represents the first investigation of LAR in child and adolescent subjects in Latin America, contributing significantly to the understanding of its prevalence and characteristics in this geographic area. Among a subgroup of patients lacking systemic sensitization submitted to NAC, 40% (10/25) demonstrated a positive NAC with Dermatophagoides pteronyssinus and Blomia tropicalis, warranting their reclassification to LAR. NAC with multiple allergens has been proven safe and viable in pediatric populations, affirming its critical role in the accurate diagnosis of LAR.

Acoustic Rhinometry in Nasal Provocation Tests in Children and Adolescents.

OBJECTIVES: To standardize acoustic rhinometry (AR) in nasal provocation tests (NPTs) with histamine in children and adolescents. PATIENTS AND METHODS: We performed a cross-sectional validation to compare AR with anterior active rhinomanometry (AAR) during histamine NPT in 20 children and adolescents with persistent allergic rhinitis and 20 controls. Changes in total nasal resistance (AAR) were compared with changes in nasal volume in the first 5 cm (V5). RESULTS: Compared with controls, patients with rhinitis had significantly higher mean total nasal resistance (0.34 Pa/cm3/s vs 0.21 Pa/cm3/s; P=.01) and lower mean V5 values (8.20 cm3 vs 9.24 cm3; P=.04) at baseline. The mean histamine concentration necessary to increase total nasal resistance by at least 100% was significantly lower in the rhinitis group than in the control group (0.72 mg/mL vs 2.4 mg/mL; P<.001). At the end of the NPT a mean increase of 126% in total nasal resistance and a mean decrease of 24.3% in V5 were observed in the rhinitis group. When compared with the AAR criteria, the highest sensitivity and specificity values were observed for a cutoff represented by a 19%-21% drop in V5. CONCLUSIONS: We found AR to be a feasible and sensitive tool for monitoring nasal response in children and adolescents undergoing histamine NPT. The best AR cutoff for ending the NPT was a 19%-21% drop in V5.

Characterization of yolk sac proteins of Bos indicus cattle embryos.

The yolk sac is an embryonic membrane that is essential for the embryo's initial survival in many mammals. It also plays an important role in the production of proteins necessary for development. We studied proteins of the yolk sac in bovine embryos at up to 40 days of gestation. We examined the yolk sac of 17 bovine embryos at different gestational periods, measuring α-fetoprotein, α-1-antitrypsin, and transferrin. This experiment was carried out by Western blot technique, associated with electrophoresis on a 6% sodium dodecyl sulfate polyacrylamide gel. Mouse monoclonal antibody anti-human-α-fetoprotein, mouse antibody anti-human-transferrin and rabbit polyclonal anti-human-α-1-antitrypsin were used as primary antibodies, and conjugated peroxidase as a secondary antibody. We detected the three proteins in some of the yolk sac samples; however, the bands in some specimens (samples) were weak, maybe a result of poor antigen-antibody reaction, since the antibodies used in this study were not specific to bovine proteins. The fact that weak bands appeared might be due to a weak cross-reaction.

Characterization of 5-hydroxytryptamine-induced contraction and acetylcholine-induced relaxation in isolated chicken basilar artery.

The aim of the present study was to clarify the responsiveness of the chicken basilar artery to 5-hydroxytryptamine (5-HT) and acetylcholine (ACh) and to characterize the related receptor subtypes in vitro. Basilar arteries were obtained from freshly slaughtered broiler chickens. The 5-HT induced concentration-dependent contraction of the arteries. The concentration-response curves for 5-HT were shifted 30-fold to the right by methiothepin (a 5-HT(1) and 5-HT(2) receptor antagonist) and 3-fold to the right by ketanserin (a 5-HT(2) receptor antagonist). In the presence of ketanserin, the concentration-response curve for 5-HT was shifted 10-fold to the right by methiothepin. The pA(2) value for methiothepin was 8.26. The ACh induced concentration-dependent relaxation under conditions of precontraction by 5-HT. The concentration-response curve for ACh was shifted to the right by atropine [a nonselective muscarinic (M) receptor antagonist] and hexahydro-sila-difenidol hydrochloride, a p-fluoroanalog (pFHHSiD, an M(3) receptor antagonist), but not by pirenzepine (an M(1) receptor antagonist) or methoctramine (an M(2) receptor antagonist). The pA(2) value for pFHHSiD was 7.55. Nω-Nitro-l-arginine (a nitric oxide synthase inhibitor) inhibited ACh-induced relaxation by approximately 50%. These results suggest that 5-HT induces contraction via activation of 5-HT(1) and 5-HT(2) receptors and that ACh induces relaxation via activation of the M(3) receptor. The 5-HT(1) receptor might play a dominant role in 5-HT-induced contraction. One of the factors involved in ACh-induced relaxation is probably nitric oxide released from endothelial cells.

Acid hydrolases in leukocytes and platelets of normal subjects and in patients with Gaucher's and Fabry's disease.

Lymphocytes, monocytes, neutrophilic granulocytes and platelets were each separated to greater than 95% purity from six normal subjects, three patients with Gaucher's disease, two heterozygotes for Gaucher's disease, and one patient with Fabry's disease. Activities of the following acid hydrolases were determined: "acid" (pH 4.0) beta-glucosidase, pH 5.0 beta-glucosidase, alpha-galactosidase, alpha-arabinosidase, alpha-mannosidase, alpha-glucosidase, beta-glucuronidase, beta-galactosidase, beta-hexosaminidase, and acid phosphatase. Enzymatic activity varied greatly with cell type and the enzyme being measured; the importance of assaying pure preparations especially for heterozygote detection is emphasized. Gaucher's disease patients' cells were found to be deficient in the pH 4.0 acid beta-glucosidase, variable in the pH 5.0 beta-glucosidase, and normal in all other acid hydrolases tested, including acid phosphatase, the activity of which is known to be elevated in plasma. Blood cells of a patient with Fabry's disease were deficient in alpha-galactosidase and normal in all other acid hydrolases tested.

Clinical significance of intramedullary Gd-DTPA enhancement in cervical myelopathy.

STUDY DESIGN: Prospective multicenter study. OBJECTIVE: To clarify the significance of intramedullary Gd-DTPA enhancement in cervical myelopathy, the prevalence, morphologic features, clinical relevance and postoperative change were investigated. SETTING: Four hospitals in Japan. METHODS: A total of 683 patients with cervical myelopathy who underwent decompressive surgery were consecutively examined. T1, 2 and Gd-DTPA-enhanced MRI were taken before surgery. Fifty consecutive cases without intramedullary enhancement were allocated in the non-enhancement group. The following variables were investigated: prevalence of the enhancement, the morphologic feature, the relationship between the enhancement and T2 high-intensity areas, the change of the Japanese Orthopedic Association (JOA) score for cervical myelopathy and the change of the enhancement after surgery. RESULTS: Intramedullary enhancement was observed in 50 cases (7.3%). The enhancements were observed between the most severely compressed disc and the cranial half of the lower vertebral body. On axial images, they were observed at the posterior or posterolateral periphery of the spinal cord. Enhancement areas were observed within T2 high-intensity areas and smaller than them. The preoperative JOA score was 9.8+/-2.8 points in the enhancement group and 9.8+/-3.3 points in the non-enhancement group (NS). The postoperative JOA score was 12.7+/-2.9 points in the enhancement group and 14.2+/-2.4 in the non-enhancement group (P=0.006). Intramedullary enhancement disappeared in 60% of the patients 1 year after surgery. CONCLUSION: Intramedullary enhancement indicated not the severity of preoperative symptoms, but a sign of a worse prognosis.

Acquired undescended testis and possibly associated testicular torsion in children with cerebral palsy or neuromuscular disease.

INTRODUCTION: Torsion of an undescended testis (UDT) associated with cerebral palsy (CP) and neuromuscular disease (NMD) is an uncommon condition that is not well recognized by primary care physicians or healthcare providers. OBJECTIVE: The objective of this study was to highlight the clinical importance of torsion of a UDT in children with CP and NMD. MATERIALS AND METHODS: Eleven children with testicular torsion of a UDT operated on at the study institute between 1991 and 2015 were identified. The records of seven children (63.6%) associated with CP or NMD were retrospectively reviewed. Clinical findings of testicular torsion were assessed along with the treatment outcome and testicular salvageability. RESULTS: All seven children were not identified with a UDT by public health checkup for infant and young children. No children with CP or NMD had torsion of a descended testis during the present study period. Median age at surgery was 15 years (range, 1-20 years). The testis location was at the external inguinal ring in five patients, in the inguinal canal in one, and in the superficial inguinal pouch in one. Of the contralateral testes, four were a UDT, one was a retractile testis, and two were descended testes. Orchiectomy was performed in six patients (85.7%). In the remaining patients, the testis was preserved but became atrophic. DISCUSSION: This study demonstrated that children with CP or NMD may be affected with torsion of a UDT with peak at around puberty with the poor salvage rate, even if the testes appear descended in infancy and young children. Shortcomings of this study were the retrospective design and a small series of children undergoing surgery for torsion of a UDT. CONCLUSION: Pediatric urologists need to educate primary care physicians and healthcare providers in the recognition of acquired UDTs and possibly associated testicular torsion in children with CP and NMD. Genital examination should be continued regularly until adolescence in these children to detect acquired UDT. These children should be referred to pediatric urologists to promote surgery as soon as the diagnosis of acquired UDT is carried out. It is believed that it is perhaps the best approach to prevent loss of the testis in children with CP and NMD.

One-stage lateral rhachotomy and posterior spinal fusion with compression hooks for Pott's paralysis in the elderly.

PURPOSE: To evaluate the safety and effectiveness of one-stage lateral rhachotomy and posterior fusion with compression hooks, for the treatment of Pott's paralysis in the elderly. METHODS: 11 elderly patients underwent lateral rhachotomy (costotransversectomy and pediculectomy) to debride the tuberculosis focus extending into the epidural space and to decompress the spinal cord. After debridement, the interbody cavity was packed with autologous iliac bone chips. For stabilisation, posterior fusion was performed using a compression lamina hook system. Patients were followed up for at least 2 years for complications. Neurological status was assessed using the Frankel score. The kyphotic deformity was measured on lateral radiographs taken before surgery and at follow-up. RESULTS: During separation of the adhesion around the abscess, a dural tear occurred in one patient and a pleural tear in another. Both tears were successfully repaired. One patient had mild pneumonia after surgery. The Frankel scores of the 11 patients improved from C or D before surgery to D or E after surgery. No relapse of spinal tuberculosis was encountered. The mean deformity angle was 25.5 degrees before surgery and 23.2 degrees at the final follow-up. Spinal fusion was achieved in all patients. CONCLUSION: Without the need of thoracotomy, one-stage lateral rhachotomy with posterior spinal fusion using compression hooks was an effective option for treating Pott's paralysis in the elderly.

New MCA/MR syndrome with generalized hypotonia, congenital hydronephrosis, and characteristic face.

We have observed a newly recognized syndrome in two unrelated Japanese patients. Manifestations include severe mental retardation, growth failure, generalized floppiness, congenital hydronephrosis, cardiac anomalies, cleft palate, and characteristic face. To date, caused genesis is unknown.

Analysis of urinary prostacyclin and thromboxane/prostacyclin ratio in patients with rheumatoid arthritis using gas chromatography/selected ion monitoring.

We investigated production of prostacyclin and the urinary ratio of thromboxane and prostacyclin in patients with rheumatoid arthritis. The prostacyclin production level was assessed according to the level of urinary 2,3-dinor-6-keto-prostaglandin F(1 alpha)measuring by gas chromatography/selected ion monitoring. In patients receiving medication, the prostacyclin level was lower and the thromboxane/prostacyclin ratio was greater compare with that of healthy volunteers. The prostacyclin level in patients without medication was approximately 4-fold higher than that of healthy volunteers and 8-fold higher than those of medicated groups. Although the ratio of the group without medication was similar to that of healthy volunteers, the urinary levels of each prostanoid were higher than those of other groups. Then, the ratios of groups receiving steroids were higher than that of other groups owing to high TX level. The present findings demonstrated that endogenous prostacyclin and thromboxane production increased in patients without medication, and prostacyclin production decreased with medication.

Difference in urinary 11-dehydro TXB2 and LTE4 excretion in patients with rheumatoid arthritis.

Thromboxane and leukotrienes have been implicated in inflammation. However, the production level of these eicosanoids in patients with rheumatoid arthritis is still unclarified. In the present study, endogenous synthesis of thromboxane and cysteinyl leukotrienes in patients was investigated. The production of eicosanoids in patients is assessed by measuring stable urinary metabolites,11-dehydro thromboxane B2 and leukotriene E4, using gas chromatography/selected ion monitoring and liquid chromatography/tandem mass spectrometry. The level of urinary thromboxane in patients was significantly higher than that in healthy volunteers (P < 0.05). Furthermore, we investigated the effects of administered drugs on the production of these eicosanoids. The urinary thromboxane level of the untreated group (1630 +/- 613 pg/mg creatinine) was much higher than that of healthy volunteers (342 +/- 263 pg/mg creatinine). The level in the group receiving NSAID alone was similar to that in healthy volunteers, and the group receiving steroid alone showed slightly lower thromboxane levels than the untreated group. On the other hand, the leukotriene E4 level in patients (280 +/- 360 pg/mg creatinine) was also significantly higher than that in healthy volunteers (59 +/- 54 pg/mg creatinine, P < 0.05). In particular, the group receiving methotrexate (904 +/- 685 pg/mg creatinine) had higher leukotriene levels than not only healthy volunteers but also other medicated groups. These findings demonstrated that endogenous thromboxane and leukotriene production in patients with rheumatoid arthritis are enhanced, and the effects of medication on the production of these eicosanoids differed in thromboxane and leukotriene E4.

Divalent cation, ATP-dependent [3H]leu-enkephalin uptake by synaptic vesicle fraction isolated from bovine caudate nucleus.

The mechanism of [3H]Leu-enkephalin uptake into synaptic vesicle fraction from bovine caudate nucleus was investigated. The simultaneous addition of 2 mM MgCl2, 2 mM CaCl2, and 2 mM ATP stimulated the uptake 22 times over the control, whereas the separate addition of these agents augmented the uptake 2.4 times at most. The addition of 2 mM MGCl2 plus 2 mM ATP and of 2 mM CaCl2 plus 2 mM ATP increased the uptake 6.6 times and 4.5 times, respectively. The cation, ATP-dependent uptake reached its half-maximal level within 10 min after the initiation of incubation at 25 degrees C, and little Leu-enkephalin was taken up at 0 degree C. The apparent Km for the uptake of [3H]Leu-enkephalin was 1.8 x 10(-7) M. Guanosine triphosphate stimulated the uptake as well as ATP, whereas CTP and ITP were only one-fourth effective of ATP. The cation, ATP-dependent uptake was inhibited by 25% and 20% in the presence of 0.1 mM colchicine and 1 microM reserpine, respectively.

Effects of the quantity of water and milk ingested concomitantly with AS-924, a novel ester-type cephem antibiotic, on its pharmacokinetics.

The effect of the quantity of water ingested concomitantly with drugs, on the absorption of AS-924, a novel prodrug-type cephem antibiotic, was studied in five healthy adult volunteers by a cross-over method, using cefteram-pivoxil (CTER-PI) as the control drug. In addition, the effect of milk on the absorption of AS-924 was also investigated. The absorption of CTER-PI was significantly reduced when administered together with 30 ml of water compared with its absorption when administered together with 150 ml of water, whereas no such reduction was found in the case of AS-924. Ingestion of milk did not significantly affect the absorption of AS-924. These results confirm that absorption of AS-924 after oral administration is not likely to be affected by the quantity of water taken concomitantly with the drug, nor by milk.

Growth in width of the metacarpals--an investigation in human fetuses.

The process of growth in width of the human hand during fetal life has never been described. Do metacarpals grow concentrically and separation between the bones occurs through expansion of soft tissues? Or is growth eccentric, a process termed drift by Enlow, a relocation in space of organs? Hands of 10 spontaneously aborted fetuses (age range: between 14.5 and 24 weeks of gestation) were examined paying special attention to the bone bark. A thicker bone bark was taken as an indication of growth in that direction. The thickness of the bone bark was measured at the radial and ulnar sides at the level of the proximal and of the distal physes of the second to fifth metacarpals. A ratio of radial over ulnar bone bark thickness (R/U ratio) was calculated. The third metacarpal grew almost concentrically (R/U ratio 1.12 +/- 0.06). The second metacarpal grew in a radial direction (R/U ratio 3.29 +/- 0.19) and the fourth and more so the fifth metacarpal grew in an ulnar direction (R/U ratio 0.70 +/- 0.04 and 0.42 +/- 0.02, respectively). The differences in R/U ratios between every metacarpal were statistically significant for all comparisons P < or = 0.001. Fetal growth in width of the human metacarpals is eccentric and not concentric. It is concluded that during growth in width the metacarpals move away from the midline of the hand and that growth occurs through eccentric bone apposition rather than through soft tissue expansion.

Problems and solutions of pedicle screw plate fixation of lumbar spine.

Fifty-seven patients with low back pain and sciatica of various causes were reviewed with reference to problems associated with pedicle plate fixation of the lumbar spine. Eleven percent of patients had neurologic problems postoperatively and 3.5% (two patients) had severe sensory impairments. All patients had this complication in the early phases of the study. Of 297 screws, 17 broke, ie, 5.7%. These breakages occurred in 12 of 57 patients (21%). In patients with spondylolisthesis, the degree of slip correction averaged 53% postoperatively, which decreased to 35% at the 1-year follow-up. Slip angle was maintained after correction. Pedicle screw plate fixation is an effective form of immobilization of the lumbar spine used in achieving arthrodesis. The surgeon must be fully trained in methodology. It is recommended that screw and plate materials be improved to prevent screw breakage.

In vivo antibacterial activity of FK041, a new orally active cephalosporin.

The therapeutic activities of orally administered FK041 were evaluated in mouse models of systemic and local infections with a variety of bacteria and were compared with those of cefdinir (CFDN) and cefditoren pivoxil (CDTR-PI). FK041 exhibited potent therapeutic activity against lethal systemic infections induced by intraperitoneally inoculated Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae with 50% effective doses (ED50) in the range of 0.20 to 0.36 mg/kg and was more active than CFDN and CDTR-PI. This result correlated well with its in vitro activity. The therapeutic effects of FK041 and reference drugs on murine local infections were evaluated in an in vivo pharmacokinetic model simulating human plasma concentrations for oral administration of 50 mg, 100 mg, and 200 mg. Against murine subcutaneous abscess induced by S. aureus, FK041 was as effective as CFDN and significantly more effective than CDTR-PI in reducing the number of recoverable viable bacteria in the skin at the infection sites. The efficacy of FK041 against murine pneumonia with H. influenzae was comparable to that of CDTR-PI and was superior to that of CFDN in reducing viable bacteria activity in the lungs. These results strongly suggest that FK041 has potential for clinical use against various bacterial infections.

Animal pharmacokinetics of FK037, a novel parenteral broad-spectrum cephalosporin.

Single-dose pharmacokinetics of FK037 has been investigated in laboratory animals. After bolus intravenous dosing with 20 mg/kg, the elimination half-life of FK037 varied in the species; with values of 0.27, 0.30, 0.97, 1.29 and 1.76 hours in mice, rats, rabbits, dogs and monkeys, respectively. The volume of distribution ranged between 260 ml/kg in rats and 390 ml/kg in dogs. These parameters approximated those of ceftazidime and cefpirome used as reference drugs. The renal clearance of FK037 was almost equal to glomerular filtration rate (GFR) in rabbits. Probenecid did not affect the elimination half-life of FK037 and its clearance ratio to GFR. These findings suggest that FK037 is solely excreted by glomerular filtration. FK037 readily penetrated into the tissues and inflammatory exudate fluid in rats, and the tissue level was highest in the kidneys, and decreased in the following order; lungs > heart > liver > spleen. Penetration of FK037, cefpirome and ceftazidime into the cerebrospinal fluid were determined using induced staphylococcal meningitis in rabbits. The penetration percentage ranged from 14.2 to 16.0% for these drugs with no significant differences. The major route of excretion of FK037 was via the kidney, with more than 74% of the dose being excreted in the urine within 24 hours after dosing to each species. Biliary excretion was low, 0.79% in rats. Bioautograms showed only unchanged drug in the plasma, urine and bile. Serum protein binding was low (8.8 to 17.6%) in all the species studied.

In vitro antibacterial activity of FK037, a novel parenteral broad-spectrum cephalosporin.

FK037 is a new parenteral cephalosporin, which offers some advantages over the commercially available parenteral cephalosporins. It demonstrated potent broad-spectrum activity against clinical isolates of Gram-positive bacteria including methicillin-resistant staphylococci, and Gram-negative bacteria including Pseudomonas aeruginosa. Against clinical isolates of aerobic Gram-positive bacteria, FK037, like cefpirome, demonstrated more potent activity than ceftazidime, cefoperazone and ceftizoxime. It is noteworthy that FK037, on the basis of the MIC90s, was the most active of all the cephalosporins tested against methicillin-resistant Staphylococcus aureus (MRSA). It was similar in activity to cefpirome against methicillin-sensitive S. aureus (MSSA). Against clinical isolates of aerobic Gram-negative bacteria, FK037, like cefpirome, was superior to cefoperazone, similar to ceftazidime and inferior to ceftizoxime in activity. Against P. aeruginosa, FK037 was superior to cefoperazone, similar or slightly superior to cefpirome and inferior to ceftazidime in activity. However, FK037 exhibited significant activity against Citrobacter and Enterobacter which were highly resistant to ceftazidime, cefoperazone and ceftizoxime. FK037 had an advantage in that its bactericidal activity against S. aureus, Escherichia coli and P. aeruginosa at sub-MICs (1/2 or 1/4 the MIC) was much stronger than those of cefpirome and ceftazidime. Moreover, it exhibited potent bactericidal activity against MSSA, MRSA and P. aeruginosa in a pharmacokinetic in vitro model simulating human plasma concentrations after intravenous dosage of 0.125, 1.0 and 1.0 g, respectively. FK037 inhibited essential penicillin-binding proteins (PBPs), 1, 2 and 3 of S. aureus with a 50% inhibitory concentration (I50) of 0.58 micrograms/ml or lower. Of essential PBPs 3, 1a and 1b of E. coli and P. aeruginosa, FK037 inhibited PBP 3 at the lowest I50 (0.03 and 0.04 micrograms/ml, respectively) and PBPs 1a and 1b with I50 values of 2.7 micrograms/ml or lower. FK037, like cefpirome, was highly stable to hydrolysis by various beta-lactamases except Ic cephalosporinase from Bacteroides fragilis, and had extremely low affinity for beta-lactamases. Therefore, FK037 was more potent than ceftazidime in activity against beta-lactamase-producing bacteria except P. aeruginosa and Serratia marcescens. The ability of FK037 to penetrate the outer membrane of E. coli was slightly higher than that of ceftazidime, but slightly lower than that of cefpirome.

In vivo antibacterial activity of FK037, a novel parenteral broad-spectrum cephalosporin.

FK037 has potent therapeutic activity against lethal systemic infections and experimental local infections due to a wide variety of Gram-positive and Gram-negative bacteria such as staphylococci, Streptococcus pneumoniae, Enterobacteriaceae and Pseudomonas aeruginosa in mice. In murine systemic infections, FK037 was the most effective of the cephalosporins and imipenem tested against highly methicillin-resistant Staphylococcus aureus (H-MRSA). It was more effective than ceftazidime against selected strains of S. aureus and Enterobacteriaceae, except Serratia marcescens and P. aeruginosa against which FK037 was as effective as ceftazidime and was as effective as cefpirome against all organisms tested, except MRSA and P. aeruginosa against which FK037 was more effective than cefpirome. These results correlated well with its in vitro activity. In murine local infections, with few exceptions, FK037 was more effective than ceftazidime and cefpirome against Klebsiella pneumonia in ED50 values and against methicillin-sensitive S. aureus (MSSA) subcutaneous abscess, pyelonephritis with Staphylococcus epidermidis, E. coli and P. aeruginosa, intrauterine infections with S. aureus and E. coli in reducing the number of viable bacteria in the abscess, kidneys and uterus. It is noteworthy that the therapeutic effects of FK037 were more potent than had been anticipated from its in vitro activity against local infections with staphylococci and P. aeruginosa when compared with ceftazidime or cefpirome. In addition, the therapeutic effects of FK037 were equipotent or superior to those of cefpirome and ceftazidime against pneumonia due to MSSA, K. pneumoniae and P. aeruginosa in reducing the number of viable bacteria in the lungs in mice using an in vivo pharmacokinetic model simulating human plasma concentrations after drip infusion of usual clinical doses (0.25 to 1.0 g for MSSA, 0.063 to 0.125 g for K. pneumoniae and 1.0 to 2.0 g for P. aeruginosa). FK037 induced an in vivo post-antibiotic effect (PAE) of 3.4 hours against a thigh infection with MSSA in neutropenic mice. These results strongly suggest that it has potential for clinical use against various infections due to bacteria which include staphylococci and P. aeruginosa.