Effects of sciatic neurectomy on the femur in growing rats: Application of peripheral quantitative computed tomography and Fourier transform infrared spectroscopy

The effects of unilateral sciatic neurectomy (USN) on the development of the femur were studied in 15 growing Wistar-derived rats (age, 5 weeks). The rats were divided into four groups: USN-operated group (right femur), USN-nonoperated group (left femur), sham-operated group (right femur), and sham-nonoperated group (left femur). Bone mineral density (BMD), bone mineral content (BMC), bone area, periosteal circumference, and endosteal circumference were measured by peripheral quantitative computed tomography (pQCT) and the mineral/matrix ratio was evaluated by Fourier transform infrared spectroscopy (FTIR). The USN-operated group showed a significant decrease in cortical BMC, bone area, and periosteal circumference compared with the other groups (P < 0.05). The cortical BMD did not vary significantly between the groups. In the cancellous bone, the USN-operated group showed a significant decrease in BMD and BMC at the metaphysis compared with the other groups (P < 0.05). The mineral/matrix ratio of the cortical bone did not differ significantly between the USN-operated and USN-nonoperated groups. These results suggest that in cortical bone, USN inhibits periosteal bone formation but has no significant effect on the mineral/matrix ratio of cortical bone in femurs. In cancellous bone, USN induces bone loss at the metaphysis. Received: Nov. 19, 1998 / Accepted: Feb. 12, 1999     

Characteristics of bone mineral density and soft tissue composition of obese Japanese women: Application of dual-energy X-ray absorptiometry

We studied the characteristics of bone mineral density (BMD) and soft tissue composition in obese Japanese women using dual-energy X-ray absorptiometry. Eighty-nine women, aged 45–85 years, were divided into three groups according to their body mass index (BMI): a thin group (n = 38; BMI < 21), a standard weight group (n = 31; BMI, 21–25), and an obese group (n = 20; BMI ≥ 25). The mean BMD of the second to fourth lumbar vertebrae and BMD of the lumbar spine, thoracic spine, pelvis, legs, and ribs of the thin group were significantly lower than those of the standard weight group or the obese group (P < 0.05), whereas no significant difference in total body BMD was observed among the three groups. There was a significant difference in total and regional fat mass among the three groups (P < 0.05). Lean mass of legs and total lean mass showed a significant difference between the thin group and the obese group (P < 0.05). The results showed that obesity was associated with higher BMD of weight bearing-bones and ribs, high total and regional fat mass, and high lean mass of bilateral legs and total lean mass. We suggest that obesity may contribute to the prevention of bone loss of weight-bearing bones and ribs and muscular atrophy of the legs. Received: Sept. 30, 1998 / Accepted: Dec. 10, 1998     

Different effects of trypsin inhibitors on intestinal gene expression of secretin and on pancreatic bicarbonate secretion in CCK-A-receptor-deficient rats

The effects of oral administration of two synthetic trypsin inhibitors (camostate and ONO-3403) and soybean trypsin inhibitor (SBTI) on cholecystokinin (CCK), secretin gene expression and pancreatic secretion were examined in CCK-A-receptor-deficient (OLETF) rats. The rats were fed chow containing 0.1% trypsin inhibitors for 7 days. To examine pancreatic secretion, the rats were prepared with cannulae to drain the bile and pancreatic juice separately, a duodenal cannula and an external jugular vein cannula. The animals were maintained in Bollman cages and the experiments were conducted 4 days after surgery. The levels of CCK mRNA were significantly increased by each treatment. The levels of secretin mRNA were significantly increased by camostate and SBTI, but not by ONO-3403. Bicarbonate secretion was significantly increased in rats treated with camostate and ONO-3403, but not SBTI, while protein secretion was not affected by any treatment. These observations suggest that increased bicarbonate secretion produced by synthetic trypsin inhibitors in CCK-A-receptor-deficient rats may not be due to secretin but due to ONO-3403 in the circulation.     

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.     

Role of tachykinins in airway narrowing induced by cigarette smoke in guinea pigs

To investigate the mechanism of the airway narrowing induced by cigarette smoke, anaesthetized guinea pigs were exposed to 200 puffs of smoke for 10 min. Airway narrowing was assessed by monitoring the total pulmonary resistance (R_L). Plasma extravasation was determined by measuring the amount of Evans blue dye extravasated into the trachea and main bronchi. Exposure to cigarette smoke caused a marked airway narrowing and plasma extravasation. Pretreatment with the dual NK₁ and NK₂ receptor antagonist, FK224, abolished such airway narrowing and significantly inhibited the extravasation. While the NK₁ receptor antagonist, FK888, inhibited the extravasation, it had no effect on airway narrowing. Atropine partially inhibited airway narrowing without affecting extravasation. Results suggest that the airway narrowing induced by cigarette smoke is caused by tachykinins, and that a cholinergic pathway is involved. Thickening of the airway walls induced by NK₁ receptor-mediated extravasation may not be involved in such airway narrowing.     

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.