The validity of the MMSE and SMQ as screening tests for dementia in the elderly general population-- a study of one rural community in Japan

OBJECTIVE: To compare the validity of the Mini Mental State Examination (MMSE) and the Short-Memory Questionnaire (SMQ) as screening tests to detect dementia in the elderly general population. SUBJECTS: Six hundred and sixty-two subjects and their informants from the elderly general population sample who had completed these tests. SETTING: One rural community survey in Japan. METHOD: We used receiver-operating characteristic analysis to compare the performance of the MMSE and the SMQ with the clinical diagnosis of dementia according to DSM-III-R. RESULTS: The areas under the receiver-operating characteristic curve of the MMSE and the SMQ were 0.980 (SE = 0.006) and 0.982 (SE = 0.008), respectively. This differed from chance to a highly significant degree for both the MMSE and the SMQ, but the difference between the two scales was not statistically significant. CONCLUSION: As screening tests to detect dementia in the elderly general population, the SMQ which is assessed by informants demonstrates a statistically significant discriminating ability as well as the MMSE.     

Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy.

PURPOSE: To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. PATIENTS AND METHODS: Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 microg/m(2) every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. RESULTS: Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean +/- standard deviation), 1.04 +/- 0.48 ng/mL and 35.6 +/- 16.2 L/h/m(2), respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. CONCLUSION: ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.     

A multicenter trial of mizoribine compared with placebo in children with frequently relapsing nephrotic syndrome

BACKGROUND: The use of corticosteroids or cytotoxic/immunosuppressive agents such as cyclophosphamide, chlorambucil, and cyclosporine for the treatment of frequently relapsing nephrotic syndrome (FRNS) is limited because of their adverse effects. This study was conducted to evaluate the efficacy and safety of mizoribine, a relatively new immunosuppressive drug developed in Japan, in children with FRNS. METHODS: A double-blind, placebo-controlled, multicenter trial was carried out in children, from 2 to 19 years old, with FRNS. At relapse, patients were treated with prednisolone. According to a dynamic allocation, mizoribine or a placebo was concurrently administered to each patient. Prednisolone was gradually tapered and discontinued within 12 weeks. The test drug was maintained for 48 weeks. The primary end point was the relapse rate (the total number of relapses/the total treatment days for all patients). Analyses were performed according to the intention-to-treat principle. RESULTS: The primary analysis was conducted on 99 mizoribine- and 98 placebo-treated patients. The relapse rate was lower in the mizoribine group than in the placebo group (0.0055 vs. 0.0067; ratio 0.81, 95% CI, 0.61 to 1.05, P = 0.12). The hazard ratio of the cumulative remission rate between the two groups was 0.79 (95% CI, 0. 57 to 1.08). In the subgroups consisting of patients 10 years old or younger, the relapse rate ratio between the mizoribine subgroup (54 patients) and the placebo subgroup (57 patients) was 0.66 (95% CI, 0. 44 to 0.94, P = 0.017). The hazard ratio of the cumulative remission rate between the two subgroups was 0.56 (95% CI, 0.37 to 0.85, P = 0. 007). Hyperuricemia was the most common adverse event with mizoribine (16%), but was transient. CONCLUSIONS: Compared with the placebo, mizoribine significantly decreased the relapse rate and prolonged the remission period in the subgroup consisting of patients 10 years old or younger. This drug may be useful in young children with FRNS who generally relapse more frequently than older children.     

Life-table analysis of artificial insemination pregnancy rates for couples with male factor and idiopathic infertility

Background :  In the summer of 2002, standard guidelines for the application of assisted reproductive technology were reported by a research group of the Ministry of Health, Labor and Welfare. The present study aimed to examine the relationship between the number of cycles of artificial insemination and the cumulative pregnancy rates according to the cause of infertility.
Methods :  Patients who experienced their first cycle of artificial insemination during the period of January 1999–December 2002 were included in the study and were divided into a male factor infertility group and an idiopathic infertility group. Cumulative pregnancy rates resulting from artificial insemination with the husband's semen were calculated by the life-table approach.
Results :  During the study period, 139 couples entered the assisted reproduction program and underwent 581 cycles. Significant differences were observed in cumulative pregnancy rates between the two groups.
Conclusion :  It is recommended that couples with male factor infertility and who fail to conceive within six or seven cycles of intrauterine insemination, consider a modification of treatment strategy such as in vitro fertilization, because cumulative pregnancy rates of this group were reached at a plateau within six or seven cycles. In contrast, patients with idiopathic infertility, the cumulative pregnancy rates appeared to increase constantly with each subsequent cycle. It is important to consider modifications of treatment strategy in the light of the cause of infertility. (Reprod Med Biol 2004; 3 : 27–31)     

Ki-67 Labeling Index as a Marker of Malignancy in Ocular Surface Neoplasms

Purpose To evaluate the relationships among histopathological type, clinical malignant grade, and Ki-67 labeling index (LI) in sebaceous gland carcinoma (SGC), conjunctival squamous cell carcinoma (SCC), and conjunctival intraepithelial neoplasia (CIN), with pterygium and normal conjunctiva as controls.Methods This retrospective study was conducted at the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. We used tissue specimens obtained from 20 patients (four SGC, four SCC, four CIN, four pterygium, and four normal conjunctiva). Ki-67 immunohistochemical analysis was performed in all 20 cases.Results The Ki-67 labeling index (LI) was 46.1 ± 3.0% (average ± SD) in SGC, 28.4 ± 4.5% in SCC, 20.0 ± 7.2% in CIN, 9.0 ± 2.2% in pterygium, and 6.8 ± 2.3% in normal conjunctiva. Ki-67 LI was significantly (Mann-Whitney U test, P < 0.05) higher in SGC than in SCC, and higher, but not significantly, in SCC than in CIN. Ki-67 LI was significantly (P < 0.05) higher in SCC and CIN than in pterygium.Conclusions These results suggest that Ki-67 LI may be a sensitive marker for ocular malignant tumor grading. Jpn J Ophthalmol 2004;48:524–529 © Japanese Ophthalmological Society 2004     

Simple smoke ventilation method for uniportal video-assisted thoracoscopic surgery

Fogging of the thoracoscopic lens affects a surgeon’s ability to maintain a clear operating field. In uniportal video-assisted thoracoscopic surgery, the thoracoscopic lens tends to fog when the surgeon does not hold a suction instrument. Thus, a suction instrument needs to be held by the surgeon’s nondominant hand to remove surgical smoke, mist, and moisture. Here, we describe a simple, easy and cost-effective surgical smoke ventilation technique for uniportal video-assisted thoracoscopic surgery using a suction catheter to solve the problem. We present this technique and comment on its advantages, including decreased cost and improved surgical visualization.     

Substituted 3-phenylsulfonylquinazoline-2,4-dione derivatives as novel nonpeptide inhibitors of human heart chymase

A series of 3-phenylsulfonylquinazoline-2,4-dione derivatives have been synthesized and evaluated for their ability to inhibit human heart chymase. The structure-activity relationship studies on these compounds gave the following results. The phenyl moiety of quinazoline participates in a hydrophobic interaction where an optimum size is required. In this moiety, 7-chloroquinazoline is the best moiety for inhibiting chymase, chymotrypsin and cathepsin G. A 3-phenylsulfonyl moiety substituted with hydrophobic electron-withdrawing groups at the 4-position potentiated the activity. Anthranil moiety also enhanced the activity. Pyridylmethyl and N-pyridylacetamide at the 1-position gave an IC50 in the order of 10(-8)M. Molecular modeling studies on the interaction of 7-chloro-3-(4-chlorophenylsulfonyl) quinazoline-2,4(1H, 3H)-dione (4) with the active site of human heart chymase suggested that the phenyl moiety of quinazoline interacts with the hydrophobic P1 pocket, the 3-phenylsulfonyl moiety resides in the S1'-S2' subsites, the moiety at the 1-position locates in the S2-S3 subsites and the 4-carbonyl and 3-sulfonyl group interact with the oxyanion hole and the His57 side-chain of chymase, respectively.