The tolerance to and pharmacokinetics of cefixime, a new oral cephalosporin, were evaluated in healthy volunteers given the drug in single doses of 50, 100 and 200 mg and repeated doses of 200 mg bid for 14 days. In the repeated-dose study, there were mild and transient subjective symptoms such as soft stools, diarrhea, and anorexia, which disappeared without additional treatment during the dosing period. Slight increases in eosinophil and serum amylase levels were also observed. The serum concentrations of cefixime peaked at 0.71, 1.17, and 2.08 micrograms/mL on average, four to five hours after dosing with 50, 100, and 200 mg, respectively, and the half-lives were 2.54, 2.38, and 2.29 hours. Serum concentrations and urinary recoveries after dosing with 100 mg were little affected by food ingestion. There was no evidence of cefixime accumulation in the body by repeated dosing since mean serum concentrations and urinary recoveries were almost the same on the first, third, seventh, and 14th days of dosing.

Adult↗

PubMedDate not supplied

Atrial natriuretic peptide messenger RNA and peptide in rats with aortic valve insufficiency.

To investigate ANP gene expression in diseased hearts of animals without genetic defects, immunoreactive ANP (IR-ANP) and ANP mRNA were measured in a rat with aortic valve insufficiency (AI), which was produced by puncturing one of the aortic valve leaflets with a plastic rod. Plasma IR-ANP concentration was higher in AI rats than in sham rats (p less than 0.05). Decreased atrial concentration of IR-ANP (p less than 0.05) and unchanged atrial ANP mRNA concentration were shown in AI rats. The ventricular concentrations of IR-ANP and ANP mRNA in AI rats were 5.4 and 2.4 times higher than those in sham rats (p less than 0.05, respectively). These results demonstrate that gene expression of ventricular ANP is markedly increased in AI rats while that of atrial ANP is not changed.

Animals↗

PubMedDate not supplied

Measurement of tuberculostearic acid in sputa, pleural effusions, and bronchial washings. A clinical evaluation for diagnosis of pulmonary tuberculosis.

Gas chromatography/mass spectrometry combined with selected ion monitoring was used to measure tuberculostearic acid (TSA), in sputum, pleural effusion, and bronchial washing. The detection limit corresponded to the amount of TSA eluted from as low as 10(3) tubercle bacilli. Sputa were collected from 169 patients with active pulmonary tuberculosis, 35 clinically suspected to be active, 53 with obsolete pulmonary tuberculosis, and 160 with pulmonary diseases other than tuberculosis. TSA was positive in 90% of the patients with active pulmonary tuberculosis (152/169) and 71% of the clinically suspected cases (25/35), respectively. In contrast, less than 10% of the patients with obsolete tuberculosis or other pulmonary diseases had a positive TSA. Pleural effusions and bronchial washings were also collected from patients with active tuberculosis and from those with other diseases, as the controls. TSA in pleural effusions and bronchial washings was detected in 24 of 32 patients and 15 of 22 patients with active tuberculosis, respectively. In those with pulmonary diseases other than tuberculosis, only 8.7% of pleural effusion (4/46) and 4.3% of bronchial washing samples (3/69) showed a positive TSA. Therefore, the measurement of TSA is useful as a rapid and sensitive method for diagnosing pulmonary tuberculosis.

Bronchoalveolar Lavage Fluid↗

PubMedDate not supplied

Clinical evaluation of a new formula of timolol maleate (WP-934 ophthalmic solution). WP-934 Study Group.

We investigated the ocular hypotensive effect and possible adverse reactions of a new timolol maleate formula, WP-934 ophthalmic solution, which is timolol maleate solution dissolved in a reversible thermo-setting gel. Once-daily instillation of 0.25 or 0.5% WP-934 ophthalmic solution was administered in a prospective, randomized manner at 29 institutions for 8 weeks to patients with primary open-angle glaucoma or ocular hypertension, and for another 16 weeks in a limited number of these patients. Patients were closely monitored throughout the study by ophthalmic and systemic examinations, and by continuous evaluation of symptoms. The new timolol formula demonstrated a significant ocular hypotensive effect throughout the study period. Adverse effects were minor. WP-934 ophthalmic solution, timolol maleate dissolved in a reversible thermo-setting gel, has a significant ocular hypotensive effect in eyes with primary open-angle glaucoma and ocular hypertension.

Administration, Topical↗

PubMedDate not supplied

Multiplex sequence-tagged site PCR for efficient screening of microdeletions in Y chromosome in infertile males with azoospermia or severe oligozoospermia.

The multiplex STS-PCR method was used to detect microdeletions in the long arm of the Y chromosome (Yq) of cytogenetically normal men. One hundred infertile men with azoospermia or oligozoospermia were screened with the multiplex PCR method using 58 STSs, which are specific to Yq for detecting microdeletions on this chromosome. Correlations between the microdeletions on Yq and phenotypes of spermatogenetic disturbance were also examined. Ten patients (10%) had microdeletions on Yq. Seven of the 60 azoospermic patients (11.7%), and 3 of the 40 oligozoospermic patients (7.5%) had microdeletions on Yq. None of the patients showed microdeletions in the AZFa region, but 2 had deletions in the AZFb region, another 2 in the AZFc region, including DAZ, and 1 had deletions in both the AZFb and in the AZFc, including RBM and DAZ. Single microdeletions were found in 4 patients, all of them in the AZFc around DAZ, and 1 patient had 2 microdeletions in the AZFb. The improved multiplex STS-PCR method efficiently detected microdeletions in 10% of azoospermic or severe oligozoospermic men who were cytogenetically normal. All of these microdeletions were presented in the AZFb and/or AZFc regions. This suggests that these regions contain candidate genes for spermatogenesis.

Adult↗

PubMedDate not supplied

Salivary production rates fall with age in subjects having anti-centromere, anti-Ro, and/or anti-La antibodies.

OBJECTIVES: To clarify the relationship between a subject's sicca-associated autoantibodies type and changes in salivary production rate (SPR) with age in subjects having any of these antibodies. METHODS: One hundred and eighty-five subjects (female:male = 178:7), who had at least one of the three autoantibodies, anti-centromere (ACA), anti-Ro (SSA), and/or anti-La (SSB), and 65 healthy females were enrolled. The Saxon test was used to measure SPR. RESULTS: SPRs in the seven male subjects were significantly higher than those in the 178 females tested. Therefore, only female subjects were used for the following analyses. Subjects were classified into substantially four groups according to their seropositivities for ACA, anti-Ro, and/or anti-La: group A, subjects having ACA alone; group B, subjects having anti-Ro alone; group E, subjects having anti-Ro and anti-La; group DFG, subjects having ACA with anti-Ro and/or anti-La. The frequency of Sjögren's syndrome (SS) was 74.0-94.1% in these groups. SPR did not decrease with age in normal female controls. By contrast, SPR decreased significantly with age in the groups having sicca-associated antibodies. The degree of SPR decrease compared between groups was: group A group [symbol: see text] B > group E [symbol: see text] group DFG. In the analysis of the subgroup having any of the sicca-associated antibodies but not fulfilling the classification criteria of SS, SPR also decreased with age. CONCLUSION: SPR in subjects having any of the sicca-associated antibodies (ACA, anti-Ro, or anti-La) decreased with age.

Aging↗

PubMedDate not supplied

Clinical significance of anti-citrullinated peptide antibody in Japanese patients with established rheumatoid arthritis.

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Arthritis, Rheumatoid↗

PubMedDate not supplied

Effects of nicardipine, a dihydropyridine calcium antagonist, on regional myocardial blood flow, myocardial oxygen tension, and electrical abnormalities during acute coronary artery occlusion in dogs.

Effects of nicardipine, a dihydropyridine calcium antagonist, on regional myocardial blood flow (RMBF), myocardial oxygen tension (PO2), and excitation and conduction abnormalities during the occlusion of the left anterior descending coronary artery (LAD) were examined in anesthetized dogs, and compared with those of nifedipine and dipyridamole. RMBF was calculated from the H2 gas clearance curves, and PO2 was measured using a membrane-coated Pt wire. Excitation and conduction abnormalities during the LAD occlusion were represented in terms of the degree of ST-T alternans (STTA), TQ depression, and conduction delay, which appeared in epicardial electrograms. Nicardipine and nifedipine in a dose of 10 micrograms/kg increased RMBF and PO2 levels in nonischemic and mildly ischemic tissues, but not in severely ischemic tissues. Nicardipine in a dose of 100 micrograms/kg and nifedipine in a dose of 10 micrograms/kg attenuated the degree of STTA, TQ depression, and conduction delay observed in severely ischemic tissues. In mildly ischemic tissues where only TQ depression was observed without STTA, nicardipine in a dose of 30 micrograms/kg attenuated TQ depression. Dipyridamole in a dose of 1 mg/kg produced only a slight attenuation of STTA and conduction delay. These results suggest that the beneficial effects of nicardipine as well as of nifedipine on myocardial ischemia are due to the increase in the myocardial PO2 levels caused by the increased RMBF and also to direct protecting effects on ischemic myocardial cells. In the severely ischemic tissues, the latter is a main effect of the drugs. In increasing the PO2 level, nicardipine was similarly potent as nifedipine, but in the direct effect, nicardipine was less potent, and dipyridamole was almost ineffective.

Animals↗

PubMedDate not supplied

Expression of thymidine phosphorylase as an effect prediction factor for uterine cervical squamous cell carcinoma after radiotherapy: an immunohistochemical study.

Prognoses in cases of uterine cervical squamous cell carcinoma treated with radiotherapy were investigated in association with immunohistochemical expression of an angiogenic factor, thymidine phosphorylase (TP). Forty-six cases of uterine cervical squamous cell carcinoma mainly treated with radiotherapy during 1992-2001 at our clinic were studied. All were diagnosed as stages IIB to IVA. Paraffin-embedded biopsy specimens excised before radiotherapy were stained immunohistochemically using anti-TP monoclonal antibody. The extent of staining in both tumor and interstitial cells was graded as (-), (+/-), (+), and (2+). Specimens with TP expression levels of (2+) and (+) were regarded as positively stained and those with TP expression levels of (+/-) and (-) as negatively stained. The efficacy of radiotherapy in both groups was analyzed by the Kaplan-Meier method. With tumor cells, 5-year survival rates for the positive (n= 38) and negative (n= 8) staining groups were 73.9% and 42.9%, respectively; the rate being significantly higher for the TP-positive group (log rank, P= 0.0096). Contrarily, with staining for interstitial cells, the 5-year survival rates for the positive (n= 20) and negative (n= 26) staining groups were 74.1% and 64.6%, respectively, with no significant difference (log rank, P= 0.406). The efficacy of radiotherapy in the group with positive staining of tumor cells was significantly better than in the negative staining group. Immunohistochemical expression of TP in tumor cells is suggested as a useful prognostic factor for uterine cervical squamous cell carcinomas treated with radiotherapy. Choosing therapy for individual cases by referring to factors including TP expression should contribute to an improved prognosis.

Aged↗