Dose-dependency in the exsorption of theophylline and the intestinal dialysis of theophylline by oral activated charcoal in rats

The elimination half-life of theophylline in serum after intravenous (i.v.) administration of aminophylline increased with increase in dose. Exsorption of theophylline from blood to the gastrointestinal tract was investigated after i.v. administration of aminophylline (10-50 mg kg-1) to rats by the in-situ single-pass perfusion technique. The exsorption rate of theophylline into the intestinal lumen also increased with increase in dose. When the dose of aminophylline was increased five-fold from 10 to 50 mg kg-1, the amount of theophylline exsorbed in 120 min was proportionally increased from 450 to 2300 micrograms. The average extent of theophylline exsorbed into the intestinal lumen was 12-15% after doses from 10-50 mg kg-1, while the extent of the drug excreted into the bile varied from 0.17-0.30% after doses from 10-50 mg kg-1. However, intestinal and biliary clearance of theophylline did not change significantly in the range 10 to 50 mg kg-1. Oral administration of multiple doses of activated charcoal reduced the serum theophylline levels after i.v. administration of aminophylline (50 mg kg-1) to rats. The serum half-life and the area under the serum concentration-time curve of theophylline were decreased to 52 and 50% by the charcoal treatment, respectively, while the total body clearance of the drug was increased to 188% compared with the corresponding control experiments. The volume of distribution was not significantly different between treated and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bone loss of the radius in rheumatoid arthritis Comparison between 34 patients and 40 controls

We measured bone mineral density (BMD) in the radius by dual energy X-ray absorptiometry in 34 patients with rheumatoid arthritis (RA) and in 40 healthy controls. The BMD in RA patients in their fifties and sixties, but not in their forties and seventies, was significantly lower than that in the control subjects. The decrease in total radial BMD correlated with grip strength, RA activity and RA stage. The de crease in distal radial BMD correlated with RA activity, but not with grip strength. The levels of serum parathyroid hormone, alkaline phosphatase, and urinary hydroxyproline/creatinine were significantly higher in the patients. From these findings, we suggest that the bone loss in RA patients is affected by severity of inflammation, disuse, postmenopausal osteoporosis and secondary hyperparathyroidism.     

A case of primary pulmonary sporotrichosis

We report the first case of primary pulmonary sporotrichosis in Japan. A 53-year-old man was admitted to our hospital for further examination of the abnormal shadows on chest X-ray film. Six months before admission, he was admitted to another hospital because of alcoholic liver disease and diabetes mellitus. Since the initial chest film showed cavities with infiltration in the left upper lung field, he was treated with antituberculous drugs despite negative sputum cultures for mycobacterium. In spite of the medication, his chest X-ray film revealed another cavitary lesion, so he was referred to our hospital. He had been asymptomatic during this period. Chest X-ray on admission disclosed multiple cavities in the left upper lobe and a cavity in the right lower lobe. Repeated sputum specimens, bronchial washings and brushings for cytology and cultures were all negative. In an attempt to clarify the pathogen, percutaneous lung aspiration (PLA) was performed. The PLA sample yielded a positive culture of Sporothrix shenckii. After the diagnosis, S. schenckii was also cultured from sputa. A sporothrix skin test and yeast agglutination test for S. schenckii were positive. In the absence of a history for skin lesion, the patient was diagnosed as a primary pulmonary sporotrichosis. As iodide therapy was ineffective, he was started on a regimen of intravenous amphotericin B. However his renal function progressively deteriorated, so amphotericin B was discontinued. Now he receives miconazole intravenously and is still under careful observation. As far as we know, this is the first report of primary pulmonary sporotrichosis in Japan. The possibility of sporotrichosis should be considered in any cases of undiagnosed cavitary lung diseases.     

Short stature in a girl with partial monosomy of the pseudoautosomal region distal to DXYS15: further evidence for the assignment of the critical region for a pseudoautosomal growth gene(s)

This report describes a 12 year 10 month old girl with short stature and a non-mosaic 46,X,Xp+ karyotype. Her height remained below −2 SD of the mean, and her predicted adult height (143 cm) was below her target height (155·5 cm) and target range (147·5 cm−163·5 cm). Cytogenetic and molecular studies showed that the Xp+ chromosome was formed by an inverted duplication of the Xp21.3−Xp22.33 segment and was missing about 700 kb of DNA from the pseudoautosomal region distal to DXYS15. The results provide further support for the previously proposed hypothesis that the region between DXYS20 and DXYS15 is the critical region for a pseudoautosomal growth gene(s).