Allopurinol and thiazide effects on new urinary stone formed after discontinued therapy in patients with urinary stones

We treated 87 patients with calcium-containing urinary stones with either allopurinol alone (44 patients) or in combination with thiazide (43 patients) and studied new stone formation before, during, and after the discontinuation of the drug therapy. The number of stones formed were 1.18, 0.24, and 0.13 before, during, and after discontinuation of the drug therapy, respectively, in the patients treated with allopurinol alone and 1.32, 0.20, and 0.09 in those treated in combination with thiazide. No differences were observed in these values and the duration of each observation period between the two groups. Decreases in the incidence of stone formation even after interruption of drug therapy suggested that recurrence-preventive effects observed following administration of these drugs include the effects of medical guidance. However, allopurinol therapy was effective in preventing recurrence in patients with hyperuricosuria.     

Multiglycosidorum tripterygii versus Tacrolimus for rat tracheal allografts.

OBJECTIVE: Several other immunosuppressive agents still need to be found for rejection as alternatives to Tacrolimus in lung transplantation. We tried to elucidate the treatment effect of Multiglycosidorum tripterygii on tracheal allografts in comparison to that of Tacrolimus. Methods: Treatment effect of agents on tracheal allografts, undergoing incomplete immunosuppression for 12 weeks after transplantation, was investigated using a heterotopic rat tracheal transplantation model. Treatments with Tacrolimus (1.0 or 1.5mg/kg per day), Multiglycosidorum tripterygii (150 or 225mg/kg per day) and a combination of Tacrolimus (1.0mg/kg per day) and Multiglycosidorum tripterygii (150mg/kg per day) were applied as a therapy for allografts. Four weeks after administering this therapy, the effect of each treatment was investigated by the morphologic assessment of transplants. RESULTS: Treatment group with high doses of Multiglycosidorum tripterygii demonstrated a significantly better graft patency and lower cartilage dislocation than that without any treatment and tended to show better morphological findings than the other treatment groups, in addition to being safe. Some of allografts with high doses of Tacrolimus or Multiglycosidorum tripterygii therapy had a viable epithelium and viable tracheal glands in part, whereas the allografts with other treatments showed almost a completely denuded epithelium. High doses of Multiglycosidorum tripterygii therapy demonstrated less infiltration of mononuclear cells into the allografts, whereas other therapies showed a higher infiltration of such cells. CONCLUSIONS: We conclude that high doses of Multiglycosidorum tripterygii may be a useful alternative to Tacrolimus as an immunosuppressant for rat tracheal allografts.     

A case of pancreatic ductal adenocarcinoma with rapid progress in a young man]

A 17-year-old man was admitted to hospital because of epigastric pain. Various imaging studies showed a solid tumor (4cm in diameter) in the tail of the pancreas, multiple hypovascular tumors in liver. Serum levels of DUPAN2, SPAN1 and NSE were elevated slightly. Biopsy of hepatic tumor demonstrated that tumor cells had eosinophilic cytoplasm generally and unevenly distributed polymorphic nucleus. These data suggested that this tumor is poorly differentiated pancreatic carcinoma originated from the epithelium. Therefore, we administered 5-fluorouracil and cisplatin, combined with gemcitabine. The clinical status improved temporarily by the treatment, however, worsened rapidly. He died 81days after the treatment. Final diagnosis of autopsy was pancreatic ductal adenocarcinoma. Pancreatic ductal adenocarcinoma in the young patients is rare, and we reported this case in addition to consideration on literature.     

Effect of cadmium on the bone collagen metabolism of rat

Effects of various metals on the chick bone lysyl oxidase activity have been studied. Cadmium and zinc at 5 × 10^?4min vitro inhibited the oxidase activity by approximately 62 and 69%, respectively. Iron, magnesium, and copper did not affect the lysyl oxidase activity, whereas manganese and mercury slightly enhanced the activity.When young rats were fed a diet containing 50 ppm cadmium for 6 weeks or 100 ppm for 8 weeks, the bone lysyl oxidase activity was inhibited by approximately 40 and 89%, respectively. The ratio of the amount of soluble bone collagen to that of the total collagen in cadmium-treated rats (50 ppm for 52 weeks) significantly increased compared with that of the control group. These results indicate an inhibitory effect of cadmium on the crosslinking of collagen. However, the lysyl oxidase activity remained unchanged when 50 ppm zinc was administered for 6 weeks to the rats. Cadmium accumulated in small amounts but significantly in the bones of cadmium-treated rats, particularly in the epiphyses rather than diaphyses. Cadmium was also found in the bone extracts prepared from epiphyses of the cadmium-treated rats. A remarkable decrease in the serum copper level was observed in the cadmium-treated rats but the copper contents of both bone and its extract did not change. Histological studies of the bone of cadmium-treated rats (100 ppm for 8 weeks) revealed thin cortices in the tibiae and unusual proliferation, irregular arrangements of resting cartilage cells, and shortening of cartilage cell columns in the epiphyseal plates of the bones.     

Posthepatectomy Liver Failure Affects Long-Term Function After Resection for Hepatocellular Carcinoma

Background

This study examined whether the severity of posthepatectomy liver failure (PLF) affected the long-term postoperative liver recovery of patients with hepatocellular carcinoma (HCC).

Methods

We performed a retrospective cohort study of 395 HCC patients who underwent hepatectomy from 2004 to 2012 at the Kyoto University Hospital. The severity of PLF between postoperative days 5 and 10 was categorized according to the International Study Group of Liver Surgery criteria. We compared the Child-Pugh (C-P) score, platelet count (PLT), and the ratio of future remnant liver volume (FRLV) to the total liver volume (%RLV) at 3, 6, and 12 months after hepatectomy in the non-PLF, grade A, and grade B groups.

Results

The non-PLF, grade A, and grade B groups contained 272, 63, and 56 patients, respectively. The C-P score in the grade A group recovered from 5.37 points before hepatectomy to 5.38 points at 12 months after hepatectomy. The C-P score in the grade B group increased from 5.51 to 6.81 points at 3 months and was significantly higher (6.00 points) at 12 months than in the non-PLF group (5.47 points). The PLT significantly decreased at 12 months in the grade B group compared with the non-PLF group. The %RLV at 12 months in the non-PLF, grade A, and grade B groups were 84, 83, and 78 %, respectively. The remnant liver hypertrophy in the grade B group was significantly slower than that in the non-PLF group.

Conclusions

PLF severity affects long-term liver function recovery and remnant liver hypertrophy after hepatectomy.

     

Intercellular junctions in odontoblasts of the rat incisor studied with freeze-fracture

The morphology and distribution of various types of intercellular junctions were investigated in young odontoblasts. Gap junctions were found between odontoblasts as well as between odontoblasts and fibroblasts in the dental pulp. The junctions between odontoblasts were larger and more numerous than those between odontoblast and fibroblast, suggesting that the former may play an important role in regulating cellular activity and the latter may provide a pathway of low electrical resistance between odontoblast and nerve fibres. Irregularly-shaped gap junctions appeared as small aggregations of particles associated with a particle-free area and may indicate that the junction might not yet have been completely assembled. Tight junctions were observed at the distal ends of the young odontoblasts, arranged to form small maculae or faciae occludentes rather than belt-like zonulae. It is therefore not likely that the junction contributes to barrier function in the young odontoblasts. Although structures resembling typical desmosome were recognizable, this type of junction in odontoblasts is properly termed a desmosome-like junction from its morphological peculiarities.     

Proposal of membrane transport mechanism of protein-unbound ulifloxacin into epithelial lining fluid determined by improved microdialysis

Microdialysis method (MD) is useful for sampling protein-unbound substances in vivo. Generally in the MD, a reference compound is used to correct differences in drug permeation clearance through a dialysis membrane in vivo and in vitro. No reference compound was, however, used for determination of a protein-unbound drug concentration in the epithelial lining fluid (ELF). In this study, we firstly examined the propriety of endogenous urea as a reference compound to determine the protein-unbound ulifloxacin concentrations in rat ELF by MD. Endogenous urea was used to correct differences in the permeation clearance in vivo and in vitro which reflect the differences in the extent of contact between a tip probe and ELF in vivo and in vitro. The results showed that our MD is applicable to determine the various concentrations of ulifloxacin and urea, and that we can use endogenous urea as a reference compound even if the extent of the contact between a tip of the probe and the ELF is small. In addition, use of urea concentrations does not affect drug distribution from plasma to ELF because we used endogenous urea. These results support usefulness of endogenous urea as a reference compound to determine protein-unbound drug concentration in ELF by MD. In addition, our results also suggest the existence of certain distribution mechanisms which cause the high penetration ulifloxacin into ELF. Our MD can help progress in pharmacokinetic-pharmacodynamic analysis of various antibiotics in the case where the concentrations in ELF are not equal to that in plasma.     

Association between unmet needs for medication support and all-cause hospitalization in community-dwelling disabled elderly people

OBJECTIVES: To clarify the association between unmet medication management need and 3-year mortality and hospitalization for community-dwelling older people with various levels of disabilities.
DESIGN: Prospective cohort study (the Nagoya Longitudinal Study for Frail Elderly).
SETTING: Community-based.
PARTICIPANTS: One thousand seven hundred seventy-two community-dwelling elderly subjects (611 men, 1,161 women).
MEASUREMENTS: Data included the clients' demographic characteristics, a rating for basic and instrumental activities of daily living (ADLs), number of prescribed medications and physician-diagnosed chronic diseases, medication adherence, ability to manage medication, and presence or absence of medication assistance. Cox proportional hazard models and the Kaplan-Meier method were used to assess the association between the medication management at baseline and mortality or hospitalization during a 3-year period.
RESULTS: Of 1,772 participants, 681 reported no difficulty with self-medication management, and 1,091 experienced difficulty with self-medication. Of participants with difficulty with self-medication management, 929 had medication assistance, and 162 did not. During a 3-year follow up, 424 participants died, and 758 were admitted to hospitals. The baseline data demonstrated that participants not receiving medication assistance were younger and had better ADL status and fewer comorbidities. Multivariate Cox regression models adjusting for potential confounders showed that the lack of assistance in those who needed medication assistance was associated with hospitalization but not mortality during the study period.
CONCLUSION: In community-dwelling disabled elderly people, lack of medication assistance in those needing medication support was associated with higher risk of hospitalization.