Several of the newer broad-spectrum, potent antibiotics are currently being used for the treatment of meningitis, ventriculitis and shunt-tract infection. The risk of complications following intrathecal administration of some of this newer antibiotics varies considerably. Possible complications of immediate or delayed seizure, cortical electric depression, radiculopathy, transverse myelopathy, and arachnoiditis after intrathecal or intraventricular administration must be weighed against the potential value of this route. These risks may influence the therapeutic management of a specific clinical situation. The author studied the effect of the first generation of cephalosporins(cepalothin, cefazolin, cepharadine, cephapirin), the second generation of cephalosporins(cefamandole, cefmetazole), and the third generation of cephalosporins(cefotaxime, cetriaxone, cefotetan), on electrocortical activity of cerebral cortex. The results are as follows : 1) The topical application of cephalothin, cefazolin, cephapirin 8mg/ml shows electrocortical spike activity. In higher concentration, each cases show intense electrocortical spike activity. The topical application of cephradine 100mg/ml shows electrocortical spike activity and in higher concentration, electrocortical spike activity continued. 2) The topical application of cefamandole 64mg/ml shows electrocortical spike activity first and that of cefmetazole 100mg/ml shows electrocortical spike activity and in higher concentration of each cases, intense electrocortical spike activity continued. 3) The topical application of cefotaxime 16mg/ml shows electrocortical spike activity and that of ceftriaxon 200mg/ml and cefatetan 100mg/ml shows mild electrocortical spike activity. In higher concentration of each cases, electrocortical spike activity continued. In conclusion, the degrees of epileptogenic effect was most severe in the first generation of cephalosporins and the second generation of cephalosporins and the third generation of cephalosporins on the decreasing order.
Anti-Bacterial Agents ; Arachnoid ; Arachnoiditis ; Cefamandole ; Cefazolin ; Cefmetazole ; Cefotaxime ; Ceftriaxone ; Cephalosporins* ; Cephalothin ; Cephapirin ; Cephradine ; Cerebral Cortex* ; Depression ; Meningitis ; Radiculopathy ; Seizures ; Spinal Cord Diseases

An improved method to determine meloxicam (MEL) concentrations in koala plasma using reversed phase high performance liquid chromatography equipped with a photo diode array detector was developed and validated. A plasma sample clean-up step was carried out with hydrophilic-lipophilic copolymer solid phase extraction cartridges. MEL was separated from an endogenous interference using an isocratic mobile phase [acetonitrile and 50 mM potassium phosphate buffer (pH 2.15), 45:55 (v:v)] on a Nova-Pak C18 4-microm (300 x 3.9 mm) column. Retention times for MEL and piroxicam were 8.03 and 5.56 min, respectively. Peak area ratios of MEL to the internal standard (IS) were used for regression analysis of the calibration curve, which was linear from 10 to 1,000 ng/mL (r2 > 0.9998). Average absolute recovery rates were 91% and 96% for MEL and the IS, respectively. This method had sufficient sensitivity (lower quantitation limit of 10 ng/mL), precision, accuracy, and selectivity for routine analysis of MEL in koala plasma using 250-microL sample volumes. Our technique clearly resolved the MEL peak from the complex koala plasma matrix and accurately measured MEL concentrations in small plasma volumes.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*blood ; Chromatography, High Pressure Liquid/methods/*veterinary ; Molecular Structure ; Phascolarctidae/*blood ; Piroxicam/chemistry ; Quality Control ; Reproducibility of Results ; Sensitivity and Specificity ; Thiazines/*blood ; Thiazoles/*blood

An improved method to determine meloxicam (MEL) concentrations in koala plasma using reversed phase high performance liquid chromatography equipped with a photo diode array detector was developed and validated. A plasma sample clean-up step was carried out with hydrophilic-lipophilic copolymer solid phase extraction cartridges. MEL was separated from an endogenous interference using an isocratic mobile phase [acetonitrile and 50 mM potassium phosphate buffer (pH 2.15), 45:55 (v:v)] on a Nova-Pak C18 4-microm (300 x 3.9 mm) column. Retention times for MEL and piroxicam were 8.03 and 5.56 min, respectively. Peak area ratios of MEL to the internal standard (IS) were used for regression analysis of the calibration curve, which was linear from 10 to 1,000 ng/mL (r2 > 0.9998). Average absolute recovery rates were 91% and 96% for MEL and the IS, respectively. This method had sufficient sensitivity (lower quantitation limit of 10 ng/mL), precision, accuracy, and selectivity for routine analysis of MEL in koala plasma using 250-microL sample volumes. Our technique clearly resolved the MEL peak from the complex koala plasma matrix and accurately measured MEL concentrations in small plasma volumes.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*blood ; Chromatography, High Pressure Liquid/methods/*veterinary ; Molecular Structure ; Phascolarctidae/*blood ; Piroxicam/chemistry ; Quality Control ; Reproducibility of Results ; Sensitivity and Specificity ; Thiazines/*blood ; Thiazoles/*blood

OBJECTIVES: Odontogenic keratocysts (OKCs) have a tendency to recur and possess an aggressive nature. the aim of the present study was to evaluate cytokeratin (CK) expression patterns as a method for the differentiation between dentigerous cysts (DCs) and OKCs, as their histomorphologic appearance are often indistinguishable. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissue sections of 43 OKCs and 38 DCs were immunohistochemically analyzed with i-solution in a quantitative manner in order to evaluate the immunoreactivity of CK 10, 16 and 17. RESULTS: CK 10 expression was evident in 79.1% of OKCs but found in only 18.4% of DCs (P<0.05), and CK 10 expression was observed to occur more frequently in OKCs (mean 25.45%) than in DCs (2.19%) (P<0.05). The expression of CK 16 was evident in 79.1% of OKCs but found in only 7.9% of the DCs (P<0.05) and CK 16 expression was observed to occur more frequently in OKCs (mean 4.33%) than in the DCs (0.61%) (P<0.05). The expression of CK 17 was evident in 88.4% of OKCs but seen in only 15.7% of the DCs (P<0.05) and CK 17 expression was observed to occur more frequently in OKCs (mean 31.11%) than in the DCs (2.37%) (P<0.05). CONCLUSION: The immunohistochemical detection of CK 10, 16 and 17 can be utilized as a valuable biomarker for use in distinguishing between OKCs and DCs, which have clinically significant differential diagnoses.
Biomarkers ; Dentigerous Cyst ; Diagnosis, Differential ; Imines ; Keratins ; Odontogenic Cysts ; Thiazines

BACKGROUND: A high proportion of currently isolated gram-negative bacilli are resistant to beta-lactams by producing beta-lactamases. beta-lactam and beta-lactamase inhibitor combinations have been successfully used to overcome the resistance. In this study, in vitro antimicrobial activity of a new combination, cefatrizine-clavulanic acid, was determined against gram-negative bacilli isolated from community-acquired urinary track infections. METHODS: Nonduplicate strains of Enterobacteriaceae, isolated in 2003 from urine specimens of outpatients and inpatients of less than 3 hospital days at Severance Hospital, were tested by the NCCLS agar dilution method. RESULTS: Of a total of 204 isolates, 144 (71%) were Escherichia coli and 30 (15%) were Klebsiella spp. MIC50 and MIC90 of cefatrizine for E. coli were 2 microgram/mL and 16 microgram/mL, respectively. MIC90s of both cefaclor and cefoxitin were also 16 g/mL. MIC50 and MIC90 of cefatrizine-clavulanic acid for E. coli were 1 microgram/mL and 4 microgram/mL, respectively, which were 1/2-1/4 of those of cefaclor and cefoxitin. For Klebsiella spp., MIC90 of cefatrizine was 4 microgram/mL with an MIC range of 1->128 microgram/mL, whereas that of cefatrizine-clavulanic acid was 2 microgram/mL with an MIC range of 0.5-32 microgram/mL. In vitro activity of cefatrizine-clavulanic acid was higher than that of cefatrizine. CONCLUSIONS: Improved in vitro activity of cefatrizine-clavulanic acid against isolates of E. coli and Klebsiella spp. from community-acquired urinary track infection suggested that the combination is useful for an empirical treatment of the infection.
Agar ; beta-Lactamases ; beta-Lactams ; Cefaclor ; Cefatrizine ; Cefoxitin ; Enterobacteriaceae ; Escherichia coli ; Humans ; Inpatients ; Klebsiella ; Outpatients

Cephalosporins are the most important -lactams that induce IgE-mediated reactions. Also, cephalosporins have been known as a causative agent for occupational asthma in pharmaceutical workers. To our knowledge, this is the first report of cephalosporin-induced bronchial asthma in a housewife with no history of occupational exposure. We experienced a 30-year old female who had developed shortness of breath, coughing and itching sensation of the skin since 3 years ago whenever she handled drug powder for upper respiratory infections (URI) prescribed for her two sons with bronchial asthma. She had handled drug powder for 7 years because her sons had experienced frequent URI. Skin prick test with cefadroxil (10mg/ml) and cefaclor (10mg/ml) showed positive reactions. Bronchial challenge test with cefadroxil showed immediate asthmatic reaction, and bronchial challenge with cefaclor showed immediate urticaria and angioedema without significant fall in FEV1. We confirmed cefadroxil-induced bronchial asthma sensitized by intermittent inhalation in a non-occupational setting.
Adult ; Angioedema ; Asthma* ; Asthma, Occupational ; Bronchial Provocation Tests ; Cefaclor ; Cefadroxil* ; Cephalosporins ; Cough ; Dyspnea ; Female ; Humans ; Inhalation ; Occupational Exposure ; Pruritus ; Respiratory Tract Infections ; Sensation ; Skin ; Urticaria

PURPOSE: The aim of this study is to explore non-steroid anti-inflammation drugs (NSAIDs) potency for pelvic floor muscle pain by measuring local concentration in a rat model. MATERIALS AND METHODS: We used nine NSAIDs, including nabumetone, naproxen, ibuprofen, meloxicam, piroxicam, diclofenac potassium, etodolac, indomethacin, and sulindac, and 9 groups of female Wister rats. Each group of rats was fed with one kind of NSAID (2 mg/mL) for three consecutive days. Thereafter, one mL of blood and one gram of pelvic floor muscle were taken to measure drug pharmacokinetics, including partition coefficient, lipophilicity, elimination of half-life (T1/2) and muscle/plasma converting ratio (Css, muscle/Css, plasma). RESULTS: Diclofenac potassium had the lowest T1/2 and the highest mean Css, muscle/Css, plasma (1.9 hours and 0.85+/-0.53, respectively). The mean Css, muscle/Css, plasma of sulindac, naproxen and ibuprofen were lower than other experimental NSAIDs. CONCLUSION: Diclofenac potassium had the highest disposition in pelvic floor muscle in a rat model. The finding implies that diclofenac potassium might be the choice for pain relief in pelvic muscle.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Butanones/therapeutic use ; Chronic Pain/*drug therapy ; Diclofenac/therapeutic use ; Female ; Muscles/drug effects ; Naproxen/therapeutic use ; Pelvic Floor/*pathology ; Pelvic Pain/*drug therapy ; Piroxicam/therapeutic use ; Rats ; Rats, Wistar ; Thiazines/therapeutic use ; Thiazoles/therapeutic use

Acute rhabdomyolysis is a clinical and laboratory syndrome resulting from the breakdown of skeletal muscle, with the release of intracellular contents into the circulatory system, which can cause potentially lethal complications. Here, we present the case of a patient who developed acute rhabdomyolysis after consumption of meloxicam for jaw pain and experienced generalized myalgias in the context of an acute febrile illness with generalized urticaria. Further investigation indicated elevated muscle enzymes and acute renal failure. Serological analysis revealed that the patient was positive for Ross River virus (RRV) IgM. Genetic studies to detect CYP2C9 polymorphisms were negative. Meloxicam was discontinued. He responded to conservative measures within 2 weeks. Oral aspirin challenge was negative, suggesting a drug-specific effect of meloxicam rather than a class effect. Our case indicates a causative role for meloxicam and/or acute RRV in rhabdomyolysis.
Acute Kidney Injury ; Aspirin ; Humans ; Immunoglobulin M ; Jaw ; Muscle, Skeletal ; Muscles ; Rhabdomyolysis ; Rivers ; Ross River virus ; Thiazines ; Thiazoles ; Urticaria

Brinzolamide and dorzolamide are highly specific topical carbonic anhydrase inhibitors (CAIs). They lower intraocular pressure (IOP) by reducing the rate of aqueous humour formation without serious side effects. Although systemic CAIs are the most potent medications for lowering intraocular pressure for conditions with ocular hypertension, many cases with adverse systemic reactions have been reported, including Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN). Here, we report 2 cases of TEN that were associated with topical CAIs rather than systemic CAIs.
Carbon ; Carbonic Anhydrase Inhibitors ; Carbonic Anhydrases ; Epidermal Necrolysis, Toxic ; Intraocular Pressure ; Ocular Hypertension ; Stevens-Johnson Syndrome ; Sulfonamides ; Thiazines ; Thiophenes

The association rate constant and dissociation rate constant are important parameters of the drug-cyclodextrin supermolecule systems, which determine the dissociation of drugs from the complex and the further in vivo absorption of drugs. However, the current studies of drug-cyclodextrin interactions mostly focus on the thermodynamic parameter of equilibrium constants (K). In this paper, a method based on quantitative high performance affinity chromatography coupled with mass spectrometry was developed to determine the apparent dissociation rate constant (k(off,app)) of drug-cyclodextrin supermolecule systems. This method was employed to measure the k(off,app) of meloxicam and acetaminophen. Firstly, chromatographic peaks of drugs and non-retained solute (uracil) on β-cyclodextrin column at different flow rates were acquired, and the retention time and variance values were obtained via the fitting the peaks. Then, the plate heights of drugs (H(R)) and uracil (H(M,C)) were calculated. The plate height of theoretical non-retained solute (H(M,T)) was calculated based on the differences of diffusion coefficient and the stagnant mobile phase mass transfer between drugs and uracil. Finally, the k(off,app) was calculated from the slope of the regression equation between (H(R)-H(M,T)) and uk/(1+k)2, (0.13 ± 0.00) s(-1) and (4.83 ± 0.10) s(-1) for meloxicam and acetaminophen (control drug), respectively. In addition, the apparent association rate constant (k(on,app)) was also calculated through the product of K (12.53 L x mol(-1)) and k(off,app). In summary, it has been proved that the method established in our study was simple, efficiently fast and reproducible for investigation on the kinetics of drug-cyclodextrin interactions.
Acetaminophen ; chemistry ; Chromatography, Affinity ; Drug Interactions ; Kinetics ; Mass Spectrometry ; Thermodynamics ; Thiazines ; chemistry ; Thiazoles ; chemistry ; beta-Cyclodextrins ; chemistry