Twenty-four-hour venoarterial extracorporeal membrane oxygenation without systemic heparinization in dogs

Venoarterial extracorporeal membrane oxygenation (ECMO) was performed in five dogs without systemic heparinization to assess the feasibility of heparin-free ECMO. The surfaces of the inverted hollow-fiber-type oxygenator and circuit of the ECMO system were coated with heparin by the endpoint-attached (covalent-bonded) technique. No heparin was administered to the animal except for a small dose to maintain patency of the arterial line (1 IU/h). ECMO was run for 24 h at a pump flow of 50 ml/kg · min and was successful throughout the experiment in four of the five dogs. Scanning electron microscopy did not detect any blood clots in the oxygenator or circuit except for inside and outside the cannulas that were not coated with heparin in the carotid artery and jugular vein. Activated clotting time (ACT), fibrinogen, and anti-thrombin III (AT-III) activity remained within the normal physiological range. Serum heparin concentrations were low throughout the experiment, indicating minimal heparin release. Platelet levels decreased and fibrinopeptide B 15–42 (FPB 15–42) increased significantly after 6 h ECMO. D-dimer levels did not change throughout the experiment. ECMO was discontinued in one case after successful a 23-h run because of macroscopic clot formation at the oxygenator blood inlet. ACT had suddenly increased to 160 s approximately 1 h prior to this clot formation. These results suggest that the amount of systemic heparinization required can be substantially reduced by a heparin-coated ECMO system. Total abolishment of heparin administration in pediatric venoarterial ECMO may be possible by refinement of this technique. Monitoring of AT-III and FPB 15–42 in addition to ACT may be useful for early diagnosis of latent but ongoing coagulopathies during ECMO.     

Micro-mainframe-link Personal Clinical Research System

We constructed a micro-mainframe-link clinical research system for personal use (Personal Clinical Research System). This system was developed with both a mainframe computer and a personal computer (PC). The prepared programs included a database manager (on the mainframe computer), a user interface program (on the PC), and a communication control program that connected the mainframe computer with the PC. The database on the mainframe computer was constructed by two methods. The first method was to transmit data from the PC to the mainframe computer. The second method was to extract data from the patient information database. Using this system, a physician is able to construct a personal research database that contains interesting data for the physician. In addition, the physician is able to accumulate data on a special field using this system. A discharge summary system is now in operation as an example of this system.     

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.     

Bipolar II disorder and its premorbid personality

This study psychopathologically analyzes and compares the premorbid personalities associated with bipolar II disorder and unipolar depression. Using Cloninger's tridimensional personality theory, we evaluated 14 inpatients with bipolar II disorder and 14 inpatients with unipolar depression. The results indicate that the premorbid personality associated with bipolar II disorder is characterized as 'the reward-dependent, passive-avoidant/dependent tendency of personality' or 'the dependent tendency of personality'. We also clarified that atypical symptoms of bipolar II disorder, such as the hypomanic state and the mixed state, were induced by the mingling of this tendency with the melancholic personality type (Tellenbach) or the cycloid personality type (Kretschmer), both of which are based on syntony (Minkowski), categorized by the use of an obsessional defense mechanism to maintain stable social relations. When an insufficiency in the obsessional defense weakens the syntony, the dependent tendency engenders the symptoms stated above. Although few serious problems associated with the dependent tendency may have occurred previously, it may have resulted in conflicts with others after onset of the bipolar II disorder. Therefore, psychotherapy for these conflicts is necessary along with the administration of mood stabilizers.     

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