Four new polymorphic forms of suplatast tosilate.

We found four new polymorphic forms (γ-, ε-, ζ-, and η-forms) of suplatast tosilate (ST) by recrystallization and seeding with ST-analogous compounds; three polymorphic forms (α-, ß-, and δ-forms) of ST have been previously reported. The physicochemical properties of these new forms were investigated using infrared (IR) spectroscopy, solid-state nuclear magnetic resonance (NMR) spectroscopy, differential scanning calorimetry, and powder X-ray diffractometry. The presence of hydrogen bonds in the new forms was assessed from the IR and solid-state NMR spectra. The crystal structures of the ε- and η-forms were determined from their powder X-ray diffraction data using the direct space approach and the Monte Carlo method, followed by Rietveld refinement. The structures determined for the ε- and η-forms supported the presence of hydrogen bonds between the ST molecules, as the IR and solid-state NMR spectra indicated. The thermodynamic characteristics of the seven polymorphic forms were evaluated by determining the solubility of each form. The α-form was the most insoluble in 2-propanol at 35°C, and was thus concluded to be the most stable form. The ε-form was the most soluble, and a polymorphic transition from the ε- to the α-form was observed during solubility testing.

Cross-sectional study on relationship between constipation and medication in consideration of sleep disorder.

Constipation can be caused by adverse drug reactions as a result of many drugs and might be induced by sleep disorders; however, the relative risk of its occurrence with individual drugs and the influence of sleep conditions have not been clarified. To clarify the relationship between constipation and various drugs in consideration of sleep disorders, we investigated the self-reported bowel habits, use of laxatives, and the Athens Insomnia Scale (AIS, a self-administered psychometric instrument to measure insomnia) in 344 inpatients on admission. They were divided into a constipation group (self-reported bowel habits of "Constipation" or "Occasional constipation" and/or use of laxatives, n=161) and a non-constipation group (both "Normal" and the non-use of laxatives, n=183). A comparison of the backgrounds of the two patient groups revealed significant differences in age, gender, number of used drugs, AIS score, hypothyroidism, chronic obstructive pulmonary disease, use of diuretics, coronary vasodilators, thyroid hormones, non-steroidal anti-inflammatory drugs, proton pump inhibitors, antidepressants, anti-anxiety drugs, and hypnotics. Multiple logistic regression analysis using these fourteen factors as autonomous variables showed that age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.04; p=0.007), female gender (OR, 1.96; 95% CI, 1.21-3.18; p=0.006), the AIS score (OR, 1.10; 95% CI, 1.02-1.18; p=0.010), and the use of hypnotics (OR, 2.33; 95% CI, 1.30-4.16; p=0.004) were significantly related to constipation; therefore, as hypnotics appear more likely to cause constipation than other drugs, they should be used with caution.

Case-controlled study on risk factors for the development of constipation in hospitalized patients.

Constipation is a common problem in hospitalized patients; however, the relative risks of its development with various factors have not been clarified. To clarify the risk factors associated with constipation, we performed a case-controlled study of 165 hospitalized patients who were not laxative users on admission. They were divided into case (n=35) and control (n=130) groups according to laxative administration during hospitalization. Comparison of the patient backgrounds in the two groups revealed significant differences in the activities of daily living, length of fasting, rest level on admission, cerebrovascular disease, and administration of hypnotics. Multiple logistic regression analysis using these five factors as autonomous variables showed that administration of hypnotics (odds ratio, 2.79; 95% confidence interval, 1.10-7.06; p=0.031) was significantly related to laxative use. Therefore, the administration of hypnotics may be the principal cause of constipation development in hospitalized patients and they should be used with caution.

[Penicillium marneffei isolated from a Thai AIDS patient with fungemia].

Penicillium marneffei was isolated from three blood cultures of a Thai woman with AIDS and then identified as such. The patient, 41 a year-old female from northeast Thailand came to Japan 10 years ago and married a Japanese man. She was reportedly the third patient infected with this fungal species in Japan, and considered to be the first case from whom the causative fungus was successfully cultured, which led to the diagnosis of penicilliosis marneffei. The colony of the isolate, which was cultured on Sabouraud dextrose agar at 25-27 degrees C, was initially white and pannose, gradually turned in color from yellow to yellow-green, and diffused a deep red pigment into the medium. Conidial heads were divergent, and chains of conidia were formed from phialides. Colonies of the isolate, which was cultured on brain-heart infusion agar at 35 degrees C, had a grayish white, membranous yeast-like form with fine plicae and microscopically consisted of short hyphae. Furthermore, 560 bases of the internal transcribed spacer (ITS) region of the ribosomal RNA gene including the 5.8S region (ITS1-5.8S-ITS2) (DDBJ accession number AB298970) were sequenced and allowed an unequivocal species identification.

[Antimicrobial susceptibility and beta-lactamase productivity of recent clinical isolates during the period between December 1999 and February 2000].

Antimicrobial susceptibility testings of 24 antimicrobial agents against 605 clinical strains belonging to 10 species were carried out according to the micro-broth dilution method of NCCLS M7-A4. The productivity of beta-lactamase was also determined against them isolated at 8 medical facilities in Nagano prefecture, Japan during the period between December 1999 and February 2000. When applied the nitrocefin method, beta-lactamase productivity was demonstrated to be positive for 89.2% of 74 S. aureus, 4.3% of 94 H. influenzae, and 100% of 69 M. (B.) catarrhalis isolates. On the other hand, when used the acidometry method, penicillinase/cephalosporinase were found to be positive for 21.2%/9.6% of 52 E. coli, 29.0%/3.2% of 31 K. pneumoniae, 53.2%/100% of 47 E. cloacae, 0%/11.1% of 99 S. marcescens, and 25.9%/55.6% of 54 P. aeruginosa isolates, respectively. Among the beta-lactamase-producers including P. aeruginosa isolates, only 2 E. coli isolates were found to be ESBL-producers. Besides, 9.6% (9/94) of H. influenzae isolates were proved to be BLNAR strains.