Effect of etidronate on aortic calcification and bone metabolism in calcitriol-treated rats with subtotal nephrectomy

The present study was undertaken to determine the effects of etidronate (ED) on calcitriol-induced aortic calcification and bone metabolism in rats with renal failure. Severe aortic calcification was induced by treatment with calcitriol for 3 weeks in rats in which 5/6 of the kidneys were removed (SNx group). Treatment of ED (10 mg/kg) together with calcitriol after subtotal nephrectomy (SNx) significantly inhibited thoracic and abdominal aortic calcification 3 weeks after the operation; however, ED (2 mg/kg) was ineffective. The serum levels of osteocalcin and pyridinoline decreased in ED (10 mg/kg) treated-renal failure rats compared with SNx rats. Total bone mineral density (BMD) in the SNx group was lower than that in the sham group, in which animals were treated with calcitriol after a sham operation. The total BMD value in the ED (10 mg/kg)-treated group was similar to that in the SNx group, whereas the levels of cancellous BMD were low in the ED (10 mg/kg)-treated rats. Our data show that ED at a dosage that suppresses bone metabolism markedly inhibits vascular calcification in rats with renal failure.     

Allergic airway eosinophilia is suppressed in ovalbumin-sensitized Brown Norway rats fed raffinose and alpha-linked galactooligosaccharide

We recently found that dietary raffinose suppressed allergic airway eosinophilia in ovalbumin-sensitized Brown Norway rats. Using this model in the present study, we compared the efficacy of other oligosaccharides with that of raffinose. Brown Norway rats were immunized s.c. with ovalbumin on d 0 and exposed to aerosolized ovalbumin on d 20; broncho-alveolar lavage fluid was obtained on d 21. In Expt. 1, rats were fed a control diet or diets supplemented with different oligosaccharides (50 g/kg diet, raffinose, alpha-linked galactooligosaccharide, fructooligosaccharide, and xylooligosaccharide). The number of eosinophils in the fluid was significantly lower in rats fed raffinose and alpha-linked galactooligosaccharide diets than in those fed the control diet. Dietary fructooligosaccharide and xylooligosaccharide did not affect airway eosinophilia. In Expt. 2, i.p. administration of raffinose and alpha-linked galactooligosaccharide, but not fructooligosaccharide and xylooligosaccharide, suppressed airway eosinophilia in rats fed the control diet. In Expt. 3, suppression of airway eosinophilia by dietary alpha-linked galactooligosaccharide occurred in cecectomized rats administered neomycin. Reduced levels of interleukin (IL)-4 and IL-5 mRNA in lung tissue were associated with the suppression of airway eosinophilia. We propose that indigestible oligosaccharides differ in their suppressive effect on allergic airway eosinophilia in ovalbumin-sensitized Brown Norway rats and that the effect appears not to be mediated by intestinal microflora.     

Case-mix payment in Japanese medical care

The Japanese medical care system, highly rated internationally, has recently experienced a crisis that has placed a burden on all of its citizens, providers, and payers, due to the expansion of medical expenditures in rapidly aging society with the stagnant economy. To address this, in April 2003, Japan implemented a case-mix payment system, instead of conventional fee-for-service payment, based on an original case classification with 2552 groups (Diagnosis Procedure Combination: DPC), with inpatients from 82 special functioning hospitals. This system contains two parts: per diem prospective payment for hospital's fee with a three-level step down according to average length of stay for each diagnosis group, which is adjusted to secure the previous year's remuneration in each hospital; fee-for-service payment for doctor's fee based on national fee schedule. The payment system reduced average length of stay, but did not change inpatient expenditures and increased outpatient expenditures. The in-hospital mortality rate, although un-adjusted, did not changed, but the readmission rate increased mainly through an increase in planned, not accidental, readmissions. For the expansion of this system, ongoing program refinement, reflecting the results of data analysis, is indispensable.     

Evaluation of the relationship between periapical lesions/sclerotic bone and general bone density as a possible gauge of general health among 80-year-olds

OBJECTIVES: To evaluate the incidence among 80-year-olds of periapical lesions as detected on panoramic radiographs and to determine the relationship between sclerotic bone around the periapical lesions to heel bone density, body height, and hand-grip strength. STUDY DESIGN: Six hundred fifty-nine panoramic radiographs (262 males, 397 females), obtained from 80-year-old residents of Fukuoka Prefecture, Japan, were used for evaluation of periapical lesions. These findings were correlated with physical examination results to determine the relationship to general health. RESULTS: Of 659 panoramic radiographs, 31 (5%) were noted to have periapical lesions. Average size of the 31 periapical lesions was 6.1 +/- 2.2 mm. Of the 31 periapical lesions, 21 (68%) were accompanied by linear or diffuse types of sclerotic bone. Of the 21 sclerotic bones, 10 (48%) were of a linear type of sclerotic bone and 11 (52%) of a diffuse type of sclerotic bone. Of the 11 diffuse types of sclerotic bone, 10 (91%) were in the mandible and 1 (9%) in the maxilla. Periapical lesions in the mandible were more frequently accompanied by a diffuse type of sclerotic bone than those in the maxilla (P < .01). The hand-grip strength of those having periapical lesions, accompanied by a diffuse type of sclerotic bone, was stronger than those having no periapical lesions (P < .01) and those accompanied by a linear type of sclerotic bone (P < .03). However, there was no relationship between presence of sclerotic bone and heel bone density or body height. CONCLUSIONS: Periapical lesions accompanied by a diffuse type of sclerotic bone were more frequently seen in the mandible of 80-year-olds. To evaluate the clinical significance of sclerotic bone around periapical lesions in 80-year-olds, further study to evaluate the significance of endodontic treatment needs to be done.     

Renal oncocytosis

Renal oncocytosis is a rare disorder in which numerous oncocytic nodules develop in the kidney. An additional case is reported here. The patient was a 51-year-old woman who had received hemodialysis for 27 years. Nineteen years previously she had developed a tumorous lesion in the right kidney, which had been diagnosed as oncocytoma with laparotomic biopsy. Recently the kidney was removed because of enlargement of the tumor. The renal parenchyma was entirely replaced with numerous brownish nodules. Histologically, the nodules were composed of nests of uniform oncocytic cells. Ultrastructurally, the oncocytic cells contained numerous mitochondria. Immunohistochemical features of the nodules were identical to those of sporadic oncocytomas, that is, immunophenotypes similar to the distal nephron and reactivity with antimitochondrial antigen. Based on these findings, the lesion was diagnosed as renal oncocytosis. It was not possible to determine whether the larger nodules should be diagnosed as oncocytoma or a part of oncocytosis. Additionally, the germ line mutation of the Birt-Hogg-Dubé (BHD) syndrome gene was examined using the genomic DNA obtained from the peripheral lymphocytes, which failed to show any gene alteration. Despite the rare occurrence pathologists and urologists should be aware of renal oncocytosis, as a precursor lesion of renal oncocytoma and chromophobe renal cell carcinoma.     

Effect of flumazenil on hypoglossal and phrenic nerves activities in rabbits

BACKGROUND: Upper airway obstruction and inadequate ventilation often arise during sedation and anesthesia by benzodiazepines (Bz). Flumazenil antagonizes these effects of active benzodiazepines on the central nervous system. To estimate the influence of flumazenil on the endogenous Bz system related respiratory control, we studied the effect of flumazenil and diazepam on the neural activity and the respiratory response caused by a brief (60 sec) respiratory arrest (RA) manifested in the hypoglossal nerve (HG) and the phrenic nerve (PH) activities in rabbits. METHODS: Experiments were performed on adult rabbits which were vagotomized, paralyzed and artificially ventilated with 50% N2O, 50% oxygen and 0.5% sevoflurane. We evaluated and compared the effects of the sequential administrations of flumazenil and diazepam on the peak amplitude (AMP) as well as the root mean square (RMS) of HG and PH, and respiratory cycle (Tc). RESULTS: Flumazenil by itself increased HG activity more than PH activity with no influence on Tc. But it was not dose-related. Previous administration of flumazenil in total dose of 0.25 mg x kg(-1) could not prevent the anticipated respiratory depression caused by diazepam 2.0 mg x kg(-1). These depressions are greater in HG activity than in PH activity. Additional flumazenil 0.15 mg x kg(-1) following the administration of diazepam promptly reversed these inhibitory effects on HG activity beyond the control level. The same dose of flumazenil, however, did not reverse PH activity sufficiently. RA response was characterized by raised AMPs and augmented RMSs (deltaAMPs, deltaRMSs) with marked prolongation in Tc (deltaTc). Flumazenil and diazepam did not seem to have any influence upon these RA responses. There was a significant change in cardiovascular parameters with the tested dosages of flumazenil and diazepam, but the change was in the normal physiological range. CONCLUSIONS: These results suggest the possibility that the endogenous benzodiazepine system is likely to play an inhibitory role in the regulation of respiration, especially in the maintenance of upper airway patency but the system is unrelated to the chemosensitive-respiratory control.     

Characteristics of patients with chronic hepatitis C who develop hepatocellular carcinoma after a sustained response to interferon therapy

BACKGROUND: The objective of the current study was to determine the characteristic features of sustained responders who develop hepatocellular carcinoma after treatment with interferon for chronic hepatitis C. METHODS: This study included 3626 patients with chronic hepatitis C who had received interferon monotherapy. Cox proportional hazards analysis was used to compare sustained responders who did and did not develop hepatocellular carcinoma, and nonsustained responders who developed hepatocellular carcinoma in a multicenter, retrospective cohort study. RESULTS: Among 1197 sustained responders, 27 patients developed hepatocellular carcinoma (2.3%). Compared with sustained responders who did not develop hepatocellular carcinoma, patients who developed disease more often were male (P = 0.0212), were older (P = 0.0068), and had advanced-stage histologic disease before interferon therapy (P = 0.0345). Conversely, compared with patients with hepatocellular carcinoma who were not sustained responders, patients who were sustained responders tended to be older at the time of the initiation of interferon therapy (P = 0.0552) and at the time hepatocellular carcinoma was detected (P = 0.0593), and they also were predominantly male (P = 0.0507). The histologic staging and serum aminotransferase levels at the initiation of interferon therapy, the interval to the detection of tumor, and the tumor size showed no significant differences between the two groups. CONCLUSIONS: Sustained responders in the group at high risk for developing hepatocellular carcinoma after interferon therapy were older, more often were male, and had more advanced histologic disease stage. Such patients should be followed carefully periodically for > 10 years after they complete interferon therapy.