Lower-Extremity Torque Capacity and Physical Function in Mobility-Limited Older Adults.

OBJECTIVES: Skeletal muscle weakness and an increase in fatigability independently contribute to age-related functional decline. The objective of this study was to examine the combined contribution of these deficiencies (i.e., torque capacity) to physical function, and then to assess the functional implications of progressive resistance training (PRT) mediated-torque capacity improvements in mobility-limited older adults. DESIGN: Randomized controlled trial. SETTING: Exercise laboratory on the Health Sciences campus of an urban university. PARTICIPANTS: Seventy mobility-limited (Short Physical Performance Battery (SPPB) ≤9) older adults (~79 yrs). INTERVENTION: Progressive resistance training or home-based flexibility 3 days/week for 12 weeks. MEASUREMENTS: Torque capacity was defined as the sum of peak torques from an isokinetic knee extension fatigue test. Relationships between torque capacity and performance-based and patient-reported functional measures before and after PRT were examined using partial correlations adjusted for age, sex, and body mass index. RESULTS: Torque capacity explained (P<0.05) 10 and 28% of the variance in six-minute walk distance and stair climb time, respectively. PRT-mediated torque capacity improvements were paralleled by increases (P<0.05) in self-reported activity participation (+20%) and advanced lower extremity function (+7%), and associated (P<0.05) with a reduction in activity limitations (r=0.44) and an improved SPPB score (r=0.32). CONCLUSION: Skeletal muscle torque capacity, a composite of strength and fatigue, may be a proximal determinant of physical function in mobility-limited older individuals. To more closely replicate the musculoskeletal demands of real-life tasks, future studies are encouraged to consider the combined interaction of distinct skeletal muscle faculties to overall functional ability in older adults.

Midazolam for continuous sedation in Japanese critical care patients: phase II study.

This prospective study was undertaken to evaluate the efficacy and safety of midazolam as a sedative agent in 14 critically ill patients without coma admitted to the intensive care unit at Nihon University Itabashi Hospital, Japan. Adequate sedation (sedation score [SS] 4-6) was induced with 0.058- 0.372 mg/ kg midazolam and maintained with a dose range of 0.03-0.4 mg/kg per h. Most burn or trauma patients required higher midazolam doses than patients with cardiovascular disease. The most frequent adverse events observed were hypotension, heart-rate fluctuation and electrocardiogram abnormalities. Pharmacokinetic analysis of the population suggested that lower drug clearance rates correlated with presence of complications. Plasma concentrations (EC50) of SS 5, estimated by logistic regression analysis, varied among patients (mean 194 ng/ml). Midazolam infusion achieved successful sedation in this critical care setting, but the optimum dose differed by patient and was influenced by the presence of complications.

Midazolam for continuous sedation in Japanese patients in the critical care setting: phase II study.

This prospective, phase II study was carried out to evaluate the efficacy and safety of midazolam as a sedative agent in nine critically ill Japanese patients without coma who had been admitted to an intensive care unit. An adequate level of sedation (sedative score [SS] 4-6) was induced by midazolam 0.14 - 0.39 mg/kg and maintained with a dose range of 0.08 - 0.24 mg/kg per h. One patient was excluded from the efficacy analysis since optimum sedation was not maintained by continuous infusion. The percentage of time during which SS 5 was achieved varied among the patients. The most frequent adverse events were hypotension, partial pressure of carbon dioxide elevation and premature ventricular contraction. Population pharmacokinetic analysis suggested that lower drug clearance rates were correlated with the presence of complications. The 50% of effective concentration values of SS 5, estimated by logistic regression analysis, varied greatly (mean, 251 ng/ml). In conclusion, midazolam infusion achieved successful sedation in this critical care setting. The optimum dose differed among the patients, however, and was influenced by the presence of complications.

Removal of soluble selenium by a selenate-reducing bacterium Bacillus sp. SF-1.

In order to develop a biological process for removal of selenium from industrial wastewater, Bacillus sp. strain SF-1 was isolated from selenium-contaminated sediment. The bacterium reduces selenate to selenite and subsequently to nontoxic insoluble elemental selenium using lactate as an electron donor and selenate as an electron acceptor in an anaerobic condition. Elemental selenium transformed from soluble selenium was deposited both inside and outside of the cells. Since the selenate reduction rate of the strain SF-1 was higher than the selenite reduction rate, selenite was transiently accumulated. In an experiment of the repeated soluble selenium reduction by strain SF-1, 0.5 mM of selenate was sequentially treatable with a cycle of one day. Thus, our sequential system for removal of soluble selenium is very useful.

Factors affecting soluble selenium removal by a selenate-reducing bacterium Bacillus sp. SF-1.

High concentrations of soluble selenium, selenate and selenite, have acute and chronic toxicity toward living things. With the aim of developing a biological process for selenium removal, the effects of a variety of parameters on the reduction of soluble selenium by a Bacillus sp. strain SF-1, which is capable of reductively transforming selenate into selenite and, subsequently, into nontoxic insoluble elemental selenium, were studied. The bacterial strain could effectively reduce 20 mM of selenate to selenite and 2 mM of selenite to elemental selenium in the presence of an appropriate carbon source and in the absence of oxygen. The reduction rate of selenate to selenite was much higher than that of selenite to elemental selenium, resulting in the transient accumulation of selenite during selenate reduction. The selenate reduction rate increased with increases in the selenate concentration up to 20 mM, while the rate of selenite reduction decreased sharply at selenite concentrations of more than 2 mM. The elemental selenium transformed from selenate via selenite was found both inside and outside the cells. Bacillus sp. SF-1 was able to utilize a variety of organic acids or sugars as a carbon source in selenate reduction. Although the copresence of sulfate did not inhibit selenate reduction, it was completely inhibited by some other oxyanions, including nitrate. A model sequencing batch system using the bacterial strain was developed and exhibited good performance in the treatment of wastewater containing high concentrations of selenate.

Invasive infection due to Trichosporon cutaneum in patients with hematologic malignancies.

BACKGROUND: Invasive infection due to Trichosporon is a rare but often fatal disease in immunocompromised patients. In this study, data on patients with hematologic malignancies who had an invasive infection due to Trichosporon diagnosed at the Tokyo Metropolitan Komagome Hospital in Tokyo, Japan, were analyzed. METHODS: Positive blood cultures obtained between 1986 and 1996 were reviewed. Medical records of all patients who were positive for Trichosporon in their blood culture or autopsy material were then examined. RESULTS: A total of nine patients with hematologic malignancies were reported positive for Trichosporon cutaneum in their blood culture or at the time of autopsy. The average age was 52 years, and all patients except 2 had acute leukemia. All 8 patients with positive blood cultures were neutropenic, and the average duration of neutropenia before the positive blood cultures were obtained was 43 (range, 0-101) days. For prophylaxis of fungal infection, eight patients were kept in a laminar air flow room and also received nebulization with amphotericin B. Five patients received oral amphotericin B. All 9 patients died of the infection an average of 9 days after their blood cultures turned positive. Minimal inhibitory concentrations were evaluated in six available strains obtained from the patients. They were all resistant to amphotericin B and azoles. CONCLUSIONS: More effective antifungal agents are required for the treatment of infections with this organism.

Pharmacological properties of YM17E, an acyl-CoA:cholesterol acyltransferase inhibitor, and diarrheal effect in beagle dogs.

YM17E (1,3-bis[[1-cycloheptyl-3-(p-dimethylaminophenyl)ureido]methyl]ben zene dihydrochloride) was found to be a potent inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT) in rabbit liver and intestine microsomes. Dixon plot analysis revealed that YM17E inhibited microsomal ACAT in a non-competitive manner. YM17E induced a marked decrease in serum cholesterol, especially in non-high-density lipoprotein (HDL) fractions, in cholesterol-fed rats and rats fed normal chow. Measurement of bile secretion after oral administration of YM17E in cholesterol-fed rats showed that the drug markedly accelerated the secretion of bile acids and neutral sterols. Furthermore, absorption of [3H]cholesterol from the gut of cholesterol-fed rats was significantly inhibited by YM17E. From these results, the hypocholesterolemic activity of YM17E in these animals resulted from both a decrease in cholesterol absorption from the gut and the stimulation of excretion of cholesterol from the liver into bile. However, YM17E caused secretory diarrhea in beagle dogs at near lipid lowering doses. When YM17E was administered at the same total dosage but divided into 5 daily administrations, the incidence of diarrhea was significantly reduced while its cholesterol lowering effect became stronger. These results suggest that the inhibition of intestinal and/or liver ACAT increases the risk of diarrhea development which, however, can be avoided by controlled drug administration in beagle dogs.

Candidemia in non-neutropenic patients with an intravenous hyperalimentation catheter: good prognosis of Candida parapsilosis infection.

Positive blood cultures reported between 1986 and 1993 at the Tokyo Metropolitan Komagome Hospital were evaluated and all patients with an intravenous hyperalimentation catheter who developed candidemia, a total of 94 patients, were analyzed further, while patients with neutropenia were excluded. The primary diagnosis was malignancy in 87.2% of the cases, and Candida albicans and C. parapsilosis were the main organisms detected. A total of 17 patients died from candidemia. The patients who were positive for C. parapsilosis, however, all survived in spite of the fact that their main treatment was only removal of the catheter (20/32 cases), while eight of 25 patients who developed fungemia due to C. albicans died from the fungemia (p = 0.001). There were no significant differences in their risk factors. Because of the better outcome for the patients who developed candidemia due to C. parapsilosis, we might be able to consider less aggressive treatment for such patients.