Fifty-Six Years after Acrylic Hemiarthroplasty and after Then: A Case Report of Revision THA.

We revised an acrylic femoral hip prosthesis to a total hip prosthesis for an 86-year-old female. The implant was made of dental resin and had functioned for 56 years in situ, though its stem had broken. Because of no osteolytic reaction, the reconstruction was relatively easy. From the result of histologic and radiologic examination, the bio-inertness of material and uncemented fixation seemed to contribute the minimum bone loss and to the favorite spontaneous arthrodesis after providing good joint function in her middle age.

Ceramic on Ceramic Bearings for Dysplastic Hips: Analysis of Uncemented 2,861 THAs.

We analyzed 2,861 uncemented primary total hip arthroplasties (THAs) with ceramic on ceramic bearing couple (C on C) for dysplastic hips followed up at least one year. The age at THA was 58 and the follow-up period was 6.8 (maximum of 21.4) years. Those belonged to Crowe's classification I were 76.4%, II were 14.6%, III were 7.0%, and IV were 2.0%. Two types of C on C were used: alumina on alumina (A on A) for 1979 hips and zirconia toughened alumina on zirconia toughened alumina (ZTA on ZTA) for 882 hips. Osteolysis was not detected. Dislocation occurred in six (0.2%) hips and the prevalence did not differ between A on A and ZTA on ZTA. Two liner fractures occurred only in A on A. Joint noise was detected in 79 (2.8%) hips. The prevalence of the noise was lower in ZTA on ZTA than in A on A. The revision rate was 0.5% and had no difference between A on A and ZTA on ZTA. All revisions in ZTA on ZTA were performed early after the initial surgery, while there was only one early revision in A on A. Taking endpoint as revision for any reason, the final survival rate was 97.2% for all C on C. At nine years after THA, the survival rate was higher in A on A than in ZTA on ZTA. Preventing the early failure by careful surgical procedure is essential to expect the same long-term durability of ZTA on ZTA as that of A on A.

Adherence to changing from brand-name to generic atorvastatin in newly treated patients: a retrospective cohort study using health insurance claims.

BACKGROUND: Effect of statin therapy has been reported to be associated with patient's adherence. Atorvastatin was available in Japan as a brand-name product beginning in 2000. The first atorvastatin generics were introduced in Japan in November 2011. The objective of this study was to analyze whether changing from a brand-name atorvastatin to a generic product would affect patient adherence. METHODS: We conducted a retrospective cohort study that included adult patients who received newly prescribed brand-name atorvastatin between June 1, 2011 and May 31, 2012, using a health insurance claims database in Japan. Patients were classified by the presence or absence of changing to a generic during the 6 months from December 1, 2011 to May 31, 2012 (the index period). The first prescription date for the generic or brand product during the index period was defined as the index date. Adherence to therapy was assessed by the proportion of days covered (PDC) and persistence of treatment by time to discontinuation. RESULTS: There were 135 patients changing to generic atorvastatin and 147 continuing with the brand-name product. There was no significant difference in decrease of PDC from pre- to post-index date between the changed cohort and continued cohort (-8.6% vs -10.3%, respectively; P = 0.443). After adjusting for baseline covariates, including adherence in pre-index date, no statistically significant differences were observed in the adjusted odds of adherence between the cohorts (adjusted odds ratio = 0.83, 95% confidence interval (CI) = 0.46-1.53). There was also no significant difference in persistence between two cohorts in the 180-day after post-index date. After analysis of a Cox proportional hazard regression model controlling for baseline covariates, including adherence in pre-index date, no statistically significant differences were observed for the hazard of non-persistence between the cohorts (adjusted hazard ratio = 0.96, 95% CI = 0.60-1.53). CONCLUSIONS: Changing from a brand-name atorvastatin to generic product did not affect adherence for patients newly treated with atorvastatin.

Enantioselective disposition of clenbuterol in rats.

Clenbuterol is a long-acting ß2-adrenoceptor agonist and bronchodilator that is used for the treatment of asthma, but the desired activities reside almost exclusively in the (-)-R-enantiomer. This study examined enantioselectivity in the disposition of clenbuterol following administration of clenbuterol racemate to rats. Concentrations of clenbuterol enantiomers in plasma, urine and bile were determined by LC-MS/MS assay with a Chirobiotic T column. This method was confirmed to show high sensitivity, specificity and precision, and clenbuterol enantiomers in 0.1 ml volumes of plasma were precisely quantified at concentrations as low as 0.25 ng/ml. The pharmacokinetic profiles of clenbuterol enantiomers following intravenous and intraduodenal administration of clenbuterol racemate (2 mg/kg) in rats were significantly different. The distribution volume of (-)-R-clenbuterol (9.17 l/kg) was significantly higher than that of (+)-S-clenbuterol (4.14 l/kg). The total body clearance of (-)-R-clenbuterol (13.5 ml/min/kg) was significantly higher than that of the (+)-S-enantiomer (11.5 ml/min/kg). An in situ absorption study in jejunal loops showed no difference in the residual amount between the (-)-R- and (+)-S-enantiomers. Urinary clearance was the same for the two enantiomers, but biliary excretion of (-)-R-clenbuterol was higher than that of the (+)-S-enantiomer. The fractions of free (non-protein-bound) (-)-R- and (+)-S-clenbuterol in rat plasma were 48.8% and 33.1%, respectively. These results indicated that there are differences in the distribution and excretion of the clenbuterol enantiomers, and these may be predominantly due to enantioselective protein binding.

Gosha-jinki-gan reduced oxaliplatin-induced hypersensitivity to cold sensation and its effect would be related to suppression of the expression of TRPM8 and TRPA1 in rats.

Peripheral neuropathy is a common side effect of the chemotherapeutic agent oxaliplatin (Oxp), and is associated with hypersensitivity to cold sensation in the acute stage. Recently, gosha-jinki-gan (GJG), a Japanese herbal medicine, was reported to improve Oxp-induced cold hypersensitivity. However, the mechanism for this effect was not elucidated. We hypothesized that the effect of GJG on Oxp-induced cold hypersensitivity may be associated with the expression of the transient receptor potential melastatin 8 (TRPM8) and transient receptor potential ankyrin 1 (TRPA1) channels, which are cold-gated ion channels. To assess this hypothesis, we examined alteration of the withdrawal response to cold stimulation following coadministration of GJG and Oxp in rats, and the relationship between this altered withdrawal response and the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG). Assessment of cold hypersensitivity was performed at 4 and 10°C using a cold plate. Compared with Oxp administration alone, coadministration of GJG (oral dose: 1 g/kg/day for 12 days) and Oxp (intraperitoneal dose: 4 mg/kg twice a week) significantly reduced the withdrawal response to cold stimulation. On the 12th day of drug administration, the L4-L6 DRG were removed and the expression of TRPM8 and TRPA1 mRNA was determined using RT-PCR. The expression of TRPM8 and TRPA1 in the DRG of rats that were coadministered GJG and Oxp decreased significantly compared with that in the rats administered Oxp alone. These results suggest that coadministration of GJG may improve Oxp-induced cold hypersensitivity by suppressing the overexpression of TRPM8 and TRPA1 mRNA.

[Face-to-face questionnaire survey on the use of multiple antipsychotics and the manifestation of side effects in outpatients with schizophrenia].

We investigated the use of multiple antipsychotics and the manifestation of side effects in outpatients with schizophrenia and compared the results of patients who received 1 antipsychotic (monotherapy) with those of patients who received more than 1 antipsychotic (multidrug therapy). To achieve this, we visited 8 community life-support centers and conducted a face-to-face questionnaire survey with 47 outpatients. Sixteen (34%) of these patients had received monotherapy and 31 (66%), multidrug therapy. Complaints involving the central nervous system, anticholinergic symptoms, metabolic symptoms (weight gain, increase in blood glucose, etc.), and extrapyramidal symptoms were seen across the patients. The average incidence of side effects was 2.2 per person in the monotherapy group and 4.8 in the multidrug-therapy group. The number of nonantipsychotic drugs used concomitantly in the monotherapy group was also smaller than that used in the multidrug-therapy group (2.3 and 5.0 per person, respectively). Further, we analyzed the 47 patients as described above; 20 patients received typical antipsychotics (TA group), 10 patients received atypical antipsychotics (AA group), and 17 patients received both typical and atypical antipsychotics (MIX group). The average incidence of side effects in the TA, AA, and MIX groups was 2.8, 3.2, and 5.5 per person, respectively, and the number of nonantipsychotic drugs used concomitantly was 2.2, 3.2, and 6.1, respectively. On the basis of our results, it can be suggested that monotherapy with an atypical antipsychotic can reduce both the number of nonantipsychotic drugs used concomitantly and the average incidence of side effects.

Causative agent of vascular pain among photodegradation products of dacarbazine.

The photodegradation products of the anticancer drug, dacarbazine, cause adverse reactions including local venous pain when injected intravenously. In this study, we attempted to identify which of these products is responsible. We synthesized or purchased five photodegradation products of dacarbazine (dimethylamine, 5-diazoimidazole-4-carboxamide (Diazo-IC), 4-carbamoylimidazolium-5-olate, 5-carbamoyl-2-(4-carbamoylimidazol-5-ylazo)imidazolium-5-olate and 2-azahypoxanthine) and examined the pain reaction induced by their intraperitoneal administration in mice using an abdominal stretching or constriction assay. Only Diazo-IC clearly induced pain reaction in mice in a dose-dependent manner, the other products caused no pain reaction. The threshold concentration for pain reaction in mice was estimated to be about 0.1 mg mL-1. While diclofenac sodium significantly reduced acetic-acid-induced pain reaction in mice, it did not influence those induced by Diazo-IC. This result suggests that the mechanism of Diazo-IC-induced pain is different from that of acetic-acid-induced inflammatory pain. Dacarbazine itself produced marked relaxation of rat thoracic aorta strips in a concentration-dependent manner, but there was no difference between the activity of dacarbazine and its photo-exposed solution, so constriction or relaxation of blood vessels is unlikely to be a factor in the pain reaction. In conclusion, Diazo-IC generated by photodegradation of dacarbazine solution causes the side-effect of venous pain. Dacarbazine solution that has turned pink should not be used, because Diazo-IC is an intermediate in the formation of the reddish product, 5-carbamoyl-2-(4-carbamoylimidazol-5-ylazo)imidazolium-5-olate. Drip infusion preparations of dacarbazine should be shielded from light.

Modulation of mdr1a and CYP3A gene expression in the intestine and liver as possible cause of changes in the cyclosporin A disposition kinetics by dexamethasone.

We investigated the effect of dexamethasone (DEX) on the disposition kinetics of cyclosporin A (CyA) and the mechanism of this drug interaction. Rats were treated with DEX (1 or 75mg/kg per day, i.p.) once a day for 1-7 days, and the blood concentration of CyA was measured after an i.v. or p.o. dose of CyA (10mg/kg) at 1.5hr after the last DEX treatment. In rats treated with a low dose of DEX (1mg/kg), the blood concentration of CyA after i.v. administration was unchanged compared with that of untreated rats, whereas the blood concentration after oral administration was significantly decreased, and this decrease was dependent on the duration of DEX administration. The total clearance (CL(tot)) of CyA was unchanged, but the bioavailability was significantly decreased to about one-third of that in DEX-untreated rats after 7 days of DEX treatment. At this time, the expression of mdr1a mRNA and P-gp in the liver and intestine was increased, whereas CYP3A2 was unaffected at both the mRNA and protein levels. In rats treated with a high dose of DEX (75mg/kg), the blood concentration of CyA was significantly decreased after both i.v. and p.o. administrations compared with those of untreated rats. The bioavailability of CyA was decreased, and the CL(tot) was significantly increased. The P-gp and CYP3A2 in the liver and intestine were increased at both the mRNA and protein levels. Our results indicate that the drug interaction between CyA and DEX is a consequence of modulation of P-gp and CYP3A2 gene expression by DEX, with differential dose-dependence.

[Investigation of actual use of laxatives and application to the active drug information offer in drug control guidance].

On the therapy of constipation, there are few reports that surveyed the actual circumstance of patients taking laxatives and the effectiveness of the drug. In this study, we investigated the contents in prescription, the actual conditions of administration of laxatives, and the subjective symptoms of inpatients in all wards of Kanazawa University hospital (2000. 12.1-2000. 12. 10). As a result of the investigation, the percentage of patients prescribed some laxatives was found to be about 31.5% (274) of all hospitalized patients (871), and among them about 16% (43) of the patients had some problems in defecation control. One of the causes leading to the problems for some patients (11) among them seemed to be due to the lesser amount of magnesium oxide taken per day. Then, in the ophthalmology ward we further investigated the proper use of laxatives and the defecation condition of the patient using a questionnaire paper and a record paper (20 cases). Patients became constipated by hospitalization, and although being administered some laxatives, they were often insufficient to control the defecation. Some patients (7) with changeable defecation control could be improved by change or addition of prescription. Pharmacist concerned 5 cases of patients with change or addition of prescription. This study indicates that pharmacists should actively offer information and rational usage of laxatives to doctors and patients.