Kikuo Takano

Serum Albumin for Estimating Creatinine Clearance in the Elderly with Muscle Atrophy

The present study was conducted to develop a special formula to predict creatinine clearance (CCr, ml/min) in the elderly with chronic muscle atrophy using serum albumin (Alb, g/dl). We obtained 90 data sets including actual body weight (BW, kg), urinary creatinine excretion (UCr, mg/24 h), serum creatinine (SCr, mg/dl), and Alb from 90 inpatients aged 60-92 years. Regression equations were determined between the dependent variable of UCr/BW and the explanatory variable of Alb as follows: For males Ucr/BW = 2.695 Alb + 4.665 For females Ucr/BW = 1.827 Alb + 4.146. Then, the new predictive formula was derived from the equations: For males CCr = (19Alb + 32)BW/(100 x SCr) For females CCr = (13Alb + 29)BW/(100 x SCr). Evaluations for the predictive error (predicted CCr- measured CCr) showed that the new formula could provide more accurate and less biased estimates of CCr than the Cockcroft and Gault formula could, even in patients with renal insufficiency and in those with Alb < or = 2.8 g/dl.

The Effect of Anti-Platelet Aggregation to Prevent Pressure Ulcer Development: A Retrospective Study of 132 Elderly Patients

Background: As the number of bedridden elderly patients increases, prevention of pressure ulcers is becoming a more important issue. However, an approach to this problem using medication has not been considered sufficiently in the clinical context. Objective: To test the hypothesis that anti-platelet aggregation therapy administered to the elderly patients may be helpful in preventing pressure ulcer formation, the medical records of 132 bedridden elderly patients were analyzed. In addition, the propensity of platelets to aggregate was also measured in some of the bedridden patients. Methods: Patients were divided into two groups, with pressure ulcers (group P, 52 patients) and without (group N, 80 patients). Subsequently, six factors defining the clinical characteristics age and gender, underlying disease, cause of being bedridden, level of consciousness, mobility and activity as defined on the Braden scale, and frequency of anti-platelet aggregation medication were investigated in groups P and N. In addition, physical findings (three factors): body mass index, blood pressure (BP), and heart rate were investigated in both groups. Furthermore, laboratory data (seven factors): total protein (TP), albumin, total cholesterol, hemoglobin (Hb), hematocrit (Hct), platelets, and platelet aggregation were compared between two groups. Results: There were no significant differences in clinical characteristics between the two groups with the exception of the frequency of anti-platelet aggregation medication (23.1% of group P vs. 40.0% of group N, χ2 = 4.06, p < 0.05). There was also no significant difference in physical findings except a difference between systolic and diastolic BP (48.4 mm Hg in group P vs. 57.1 mm Hg in group N, p < 0.01). Values of TP, albumin, Hb, and Hct in both groups were lower than the normal range, but there was no significant difference between the two groups. The platelet count was significantly greater in group P than in group N after lying supine (p < 0.03), and platelet aggregation in group P was significantly higher compared with group N (p < 0.03). Conclusions: Although our hypothesis must be tested by a randomized prospective trial, these results indicate that increased platelet aggregation is possibly associated with the development of pressure ulcers; therefore anti-platelet aggregation therapy may prevent their occurrence in bedridden elderly patients.

Pharmacokinetic characteristics of minocycline in debilitated elderly patients.

A pharmacokinetic study of minocycline was performed in 12 debilitated elderly patients who had suffered from acute bacterial respiratory infections. Serial intravenous administrations of 100 mg minocycline were performed at least 10 times (infused for 1 hour, every 12 hours). Blood samples were obtained at 0, 1, 3, and 10 hours after initiating the first and fifth dose and 1 hour after the ninth dose (total, 9 points). The serum concentrations of unchanged minocycline were measured using high-performance liquid chromatography. The obtained data were analyzed using a two-compartment model in 11 cases and a one-compartment model in 1 case. Other clinical data were also collected simultaneously. The mean age of the subjects was 82 +/- 6 years. The elimination half-lives at beta-phase averaged 25.0 +/- 16.4 hours, the volume of distribution averaged 32.9 +/- 13.4 L, and the total clearance averaged 1.14 +/- 0.49 L/h. The correlation coefficient between the expected trough concentration of minocycline in steady-state and the dose per 1 kg body weight was.54 (P =.06), suggesting that dosage should be adjusted by body weight when administered to debilitated elderly patients. The present data are considered to be important and clinically useful because little information is available concerning the pharmacokinetics of minocycline in elderly patients.

Rapid and Accurate Estimation of Creatinine Clearance in the Muscle-Wasted Elderly by Computed Tomography

To develop a new method for accurately predicting creatinine clearance (Ccr) in the debilitated elderly without urine collections, the total muscle volume of both thighs (MV thigh), as a new predictive parameter, was calculated using computed tomography in 68 debilitated patients aged 61-92 years. A regression line between 24-hour urinary creatinine excretion and MV thigh was divided by serum creatinine (Scr), and then the following formula was derived: Ccr (ml/min) = 9 x [MV thigh (cm3) - 100]/[1,000 x Scr (mg/dl)] Predicted Ccr by the new method more closely correlated with measured Ccr (r = 0.862) than did predicted Ccr by Cockcroft and Gaults method (the C-G method) (r = 0.727). Statistical analysis of prediction error (= predicted Ccr-measured Ccr) suggested that the new method could provide more accurate and less biased estimations of Ccr than did the C-G method, even in patients with renal insufficiency. By using computed tomography, we have proposed a more accurate method for predicting Ccr of the debilitated elderly than the C-G method, although the new method has inherent disadvantages of radiation exposure and high cost.

Digoxin-like immunoreactive substance in the elderly patient and its impact on the TDx digoxin assay.

This study was undertaken to examine the impact of endogenous digoxin-like immunoreactive substance (DLIS) on the therapeutic drug monitoring of digoxin in elderly patients. Serum digoxin concentrations were detected by TDx digoxin assay in 220 patients 65 years of age and older who were not administered cardiac glycosides, spironolactone, or canrenone. The influence of clinical factors and laboratory parameters on the presence of DLIS was also evaluated. The concentration of DLIS averaged .07 ng/ml (range, 0-0.74 ng/ml), and in 25 subjects DLIS was observed over the detection limit of the assay. None of the parameters demonstrated a significant contribution to the presence of DLIS except one: continuous intravenous drip infusion therapy with a sodium-containing solution (DIV). The frequency of DLIS was significantly higher in the elderly subjects than in 121 control subjects younger than 35 years of age (p = 0.01). However, the difference became insignificant when subjects administered DIV were excluded from the analysis (p = 0.15). It was suggested that DIV may be clinically important in indicating the presence of DLIS.

News from the IAG

This year marks the 50th anniversary of the International Association of Gerontology. To celebrate this watershed occasion, the IAG Executive, Regional Chairs and Presidents of member associations will have the opportunity to meet in December and consider future strategic directions for the association and contribute to a United Nations’ project, ‘Research Agenda on Ageing for the 21st Century’ (RAA-21). Invitations to the meeting have been distributed. The Salsomaggiore Therme has generously offered to provide full accommodation and board for delegates for the 3 days of the IAG meeting and travel grant assistance is being provided by the Novartis Foundation for Gerontology for presidents whose travel cannot be funded by their associations. A full day will be devoted to discussion of future strategic directions for the IAG. The next half day will be a joint consultation when the IAG representatives and a panel of experts with an ongoing involvement in developing the Research Agenda will convene. Participants will also include the Officer in Charge, Dr. Alexandre Sidorenko, and others from the UN Office on Ageing. The UN and Expert Panel will continue their deliberations for a further 2 days in order to draft the final Research Agenda. The United Nations Research Agenda project is supported by the Novartis Foundation for Gerontology and is convened by the IAG in support of the UN Programme on Ageing. The Second Congress Planning Committee Meeting for the 2001 Vancouver Congress convened by Dr. Gloria Gutman, President-Elect of IAG, will precede the gathering of presidents and regional chairs. Hence the 50th anniversary of the IAG will represent an occasion when it will be possible to build upon the proud history of the association and vigorously pursue the further development and achievements of national and global gerontological activities into the opening years of the new century. An agenda will be set for the meeting in Salsomaggiore, Italy, that we are confident will engender vigorous and positive consideration and debate about the IAG’s future directions and will set goals and objectives to guide the organization through the coming years.

Accuracy of a recently proposed method for estimating creatinine clearance in elderly debilitated patients

The present study was conducted to evaluate accuracy of a recently proposed method for estimating creatinine clearance (CLcr, ml/min) from actual body weight (ABW, kg), serum creatinine (Scr, micromol/l), and serum albumin (Alb, g/l) in elderly patients with muscle atrophy (the debilitated elderly). The recent method (Alb method) is CLcr=(1.6*Alb+28)*(ABW/Scr) for males and CLcr=(1.1*Alb+25)*(ABW/Scr) for females. In 46 debilitated elderly inpatients (64-96 years of age), CLcr was actually measured, and it was estimated by Cockcroft and Gaults method (C-G method), the C-G method corrected by lean body weight (LBW method), and the Alb method. The accuracy was accessed by mean prediction error (ME, ml/min) and mean squared error (MSE, [ml/min](2)). The C-G method yielded ME=7.39 and MSE=448.3, the LBW method gave ME=6.33 and MSE=385.9, and the Alb method provided ME=3.66 and MSE=196.1. The Alb method was found the most accurate in the debilitated elderly.