Staphylococcus aureus is the most common islolate from skin both in infectious and noninfectious inflammation. We review the involvement of this microorganism in skin infections and atopic dermatitis. S. aureus causes disease by direct invasion or through exotoxins produced at a distant focus. S.aureus strains feature coagulase type, exotoxin production, binding to fibronectin and fibrinogen, and the production of exfoliative toxins (ET). We studied and reviewed the ET mechanism in inducing subcorneal blisters. Biofilm-related diseases in dermatology are also described and the roles of S. aureus in atopic dermatitis reviewed.

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When the in vitro activity of ampicillin (ABPC), cefotaxime (CTX), meropenem (MEPM), panipenem, imipenem (IPM) and biapenem was assayed using ABPC-susceptible, β-lactamase-producing, and βlactamase-nonproducing ABPC-resistant (BLNAR) Haemophilus influenzae isolated recently, the ratio of IPM-resistant BLNAR isolates (MIC: 8μg/mL) was 50% due to following to the NCCLS breakpoint. Against these organisms the MIC₉₀ of MEPM was 1/4 and that of CTX was 1/64 of ABPC-susceptible organisms. The in vivo activity of ABPC, CTX, meropenem/cilastatin (MEPM/CS) panipenem/betamipron, imipenem/cilastatin and BIPM was evaluated using murine respiratory infection models due to ABPC-susceptible H.influenzae and β-lactamase-nonproducing ABPC-resistant H.influenzae. On intravenous injection of each drug at 20mg/kg (ABPC and CTX; 40 mg/kg) twice a day for 3 days in mice infected with H.influenzae, MEPM/CS and CTX showed the best efficacy among test drugs. MEPM is thus a representative intravenous drug of potential use in fighting H.influenzae infection.

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Caffeine is known of inhibit DNA repair of cancer cells. The anticancer effects of caffeine increase when it is used in combination with anticarcinogenic agents. We examined the clinical and side effects of treating oral squamous cell carcinoma with intravenous (IV) drips of cisplatin (CDDP), etoposide (VP-16), bleomycin hydrochloride (BLM), and caffeine as a neoadjuvant. CDDP (25mg) was infused by IV for 2 hours, VP-16 (100mg) 1 hour, and BLM (20mg) 16 hours. Caffeine (1, 000mg) was them infused by IV for 18 hours. Subjects were 17 patients with oral squamous cell carcinoma, of these 14 underwent post treatment surgery, and cancer regression was seen in 8 of the 14 (57%). Side effects in the 17 patients were appetite loss (53%), leukopenia (47%), and nausea (29%). Insomnia did not occur. Other side effects were fever (2 cases), paleness (1 case), lip erosion (1 case) and skin eruption (1 case). This regimen has proven useful in treatment, but further work is necessary to determine the most efficacious doses.

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Purpose: To evaluate the efficacy and toxicity of a novel cisplatin derivative, nedaplatin (CDGP), for cisplatin-resistant advanced esophageal cancer patients. Method: CDGP was administered at a dose of 100mg/m² intravenously over 1 hour every 4 weeks. Results: Nineteen patients were enrolled in this study from August 1995 to January 1997. Of these, 13 had no change and 1 developed progressive disease. No response was obtained and the median time to progression and overall survival time were 90 days and 105 days, respectively. Adverse events in this trial were leukopenia (G 3; 16%), neutropenia (G3; 11%, G 4; 5%), thrombocytopenia (G3; 21%, G4; 11%), and nausea/vomiting (G1; 53%, G2; 11%), renal dysfunction (G1; 21%, G2; 11%), liver dysfunction (G1; 11%, G2; 5%), hearing loss (G1; 16%), and peripheral neuropathy (G1; 47%, G2; 11%). We observed severe allergic reactions in 2 patients (11%). Conclusions: Since it appears that there was clinical cross-resistance between CDDP and CDGP, CDGP should be used for chemotherapy-naive esophageal cancer patients. Care must to be taken to determine allergic reactions.

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Serum concentrations produced from initial dosing of vancomycin (VCM) using Moellering's nomogram were studied retrospectively using data collected in routine therapeutic monitoring in 30 patients (April 1995-July 2000). Creatinine clearance (Ccr) was estimated by the Cockcroft-Gault (C-G) equation. Steadystate troughs were within the therapeutic range of 5-15μg/mL in 25 patients (83.3%), while 4 (13.3%) showed troughs below 5μg/mL. Only 1 patient had a trough was in the toxic range (23.9μg/mL). Peaks were within the therapeutic range of 20-40μg/mL in 8 patients (31%) and below the minimum of 20μg/mL in 18 (69%). Mean average concentration in all patients was 14.5μg/mL, agreeing well with the desired mean steady-state concentration of 15μg/mL based on Moellering's nomogram, 9 patients needed to have initial VCM dosage adjusted for effective treatment. VCM treatment was effective in 85.7%. Nephrotoxicity was observed in 1 patient who showed a toxic trough caused by overdosing. The C-G equation apparently overestimated Ccr for this patient. Our study on the effect of body mass index (BMI) to the serum VCM concentration showed the C-G equation overestimates Ccr for patients with BMI less than 14μg/m². Patients with BMI of less than 14μg/m² should have 24-h Ccr measured for safe and effective initial dosing. If clinical data on measured Ccr is limited, appropriate Ccr is estimated using the C-G equation after modifying the patient's weight multiplied by a factor of 1/(15-BMI).

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Two-hundred and seventy-four strains belonging to 6 species (Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pyogenes and Streptococcus agalactiae) were clinically obtained from sputum, bronchoalveolar lavage fluid, nasal discharge and miscellaneous samples at St. Marianna University Hospital between August 1998 and December 1999. These species represent the main causative organisms of respiratory tract infections (RTI). The antimicrobial activity of 5 β-lactams, ampicillin (ABPC), cefazolin (CEZ), cefotiam (CTM), ceftriaxone (CTRX) and meropenem (MEPM) against these strains were evaluated using microdilution methods to assess the recent incidence of resistant strains. All strains of S. pyogenes, S. agalactiae and K.pneumoniae were susceptible to CTM, CTRX, and MEPM, except for one strain of K. pneurnoniae that was resistant to CTRX but susceptible to MEPM. MEPM was the most active of the 5 tested agents against S. pneumoniae, including penicillin resistant S. pneumoniae (PRSP). However, the activity of CTRX was almost the same as that of MEPM. CTRX was the most active agent against H. influenzae, including β- lactamase negative ampicillin resistant H.influenzae (BLNAR). The MIC₉₀S of CTRX was 0.125μg/mL for BLNAR and ≤0.06μg/mL for other strains of H. influenzae.

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A post-marketing surveillance study on the practical use of cefditoren pivoxil (CDTR-PI) was performed between October 1999 and September 2000. The purpose of this study was to investigate the recent occurrences of penicillin-resistant Streptococcus pneumoniae (PRSP), and beta-lactamase negative ampicillin-resistant Haemophilus influenzae (BLNAR) and to determine the susceptibility of these resistant organisms to CDTR-PI in Japan. At the same time, several clinical signs of these infections were investigated, and the clinical effectiveness and safety of CDTR-PI chemotherapy was evaluated by the physicians. The following findings were obtained:
(1) In this study, 92.6% of all patients consisted of nursing infants under the age of 6 years, the majority of whom were only 1-year old (including a 4-month-old nursing baby).
(2) S.pneumoniae was detected in 188 patients, H.influenzae in 157 patients and both organisms were detected in 99 patients, out of a total of 248 patients.
(3) S. pneumoniae with alterations in 1 or 2 pbp genes (PISP) was detected by PCR in 81 strains (43.1%) and alterations in 3 pbp genes (PRSP, pbp 1a, pbp 2x and pbp 2b), were detected in 89 strains (47.3%). Out of the H.influenzae clinical isolates, in 67 strains (42.7%) were BLNAR and contained a mutation in penicillin-binding protein 3 (PBP 3), encoded by the ftsI gene; 7 strains (4.5%) produced TEM-type beta-lactamase. In addition, 5 strains (3.2%) were BLNAR and produced TEM-type beta-lactamase.
(4) PSSP was detected at a lower frequency (4.0%) in patients with a history of chemotherapy than in patients without a history (11.5%); this difference was significant. On the other hand, PRSP was detected at a higher frequency (60.0%) in patients with a history of chemotherapy than in patients without a history (40.5%).
(5) Most of the patients had a fever of 38ºC or over that persisted for 3 days or longer. The presence or absence of purulent pituita and its grade could be used as an index for intractability. Most of the patients had otitis media complications.
(6) The presence or absence of a fever, puruloid pituita and improvement of severe otitis media symptoms were the main criteria used to judge clinical efficacy.
(7) The efficacy rate based on the clinical evaluations of effectiveness by the physicians was 85.1%(211/248). The efficacy rates in patients from whom S. pneumoniae and H.influenzae were detected were 81.9%(154/188) and 87.3%(137/157), respectively.
(8) Adverse drug reactions occurred in 5.60%(15/269) of the patients, which is a nearly identical rate to that present at the time of the approval of this antibiotic. The main adverse drug reactions were Gastrointestinal system disorders. None of the adverse drug reactions were serious, and none of the reactions were reported to the regulatory authority as adverse drug reactions or infections.

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Nonspecific mucosal immune responses in infants and children during acute phase of RS virus infection were analyzed. The first step of host defence mechanisms and immune responses during viral infection has been thought to be functional and organic reactions in virus-infected host cells, that is, in other words transcritional changes of host cellular genes which charge a variety of functions. Using in vitro RS virus infection system, it has been clarified that the transcriptional level of inflammatory cytokine (IL-1 β, IL - 6, TNF-α), and chemokine gene (IL-8, RANTES) increased in RS virus infected respiratory cells. In addition, a transcriptional activation of apoptosis-associated proteases and inducible nitric oxide synthase (iNOS) genes were also confirmed. These activation were associated with the upregulation of nuclear transcriptional activator, such as IRF-1 and NF-KB. These results suggest that, also in vivo setting, the cytokines and chemokines produced at the airway attract and activate several inflammatory cells in local infection site, in addition they activate endothels of airway blood vessel and submucosal gland. As a result a whole feature of respiratory tract inflammation may be formed. The first step of mucosal immune responses should be started through these inflammation processes.

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