Age-associated declines in muscle mass, strength, power, and physical performance: impact on fear of falling and quality of life.

UNLABELLED: This 3-year longitudinal study among older adults showed that declining muscle mass, strength, power, and physical performance are independent contributing factors to increased fear of falling, while declines of muscle mass and physical performance contribute to deterioration of quality of life. Our findings reinforce the importance of preserving muscle health with advancing age. INTRODUCTION: The age-associated loss of skeletal muscle quantity and function are critical determinants of independent physical functioning in later life. Longitudinal studies investigating how decrements in muscle components of sarcopenia impact fear of falling (FoF) and quality of life (QoL) in older adults are lacking. METHODS: Twenty-six healthy older subjects (age, 74.1 ± 3.7; Short Physical Performance Battery (SPPB) score ≥10) and 22 mobility-limited older subjects (age, 77.2 ± 4.4; SPPB score ≤9) underwent evaluations of lower extremity muscle size and composition by computed tomography, strength and power, and physical performance at baseline and after 3-year follow-up. The Falls Efficacy Scale (FES) and Short Form-36 questionnaire (SF-36) were also administered at both timepoints to assess FoF and QoL, respectively. RESULTS: At 3-year follow-up, muscle cross-sectional area (CSA) (p < 0.013) and power decreased (p < 0.001), while intermuscular fat infiltration increased (p < 0.001). These decrements were accompanied with a longer time to complete 400 m by 22 ± 46 s (p < 0.002). Using linear mixed-effects regression models, declines of muscle CSA, strength and power, and SPPB score were associated with increased FES score (p < 0.05 for each model). Reduced physical component summary score of SF-36 over follow-up was independently associated with decreased SPPB score (p < 0.020), muscle CSA (p < 0.046), and increased 400 m walk time (p < 0.003). CONCLUSIONS: In older adults with and without mobility limitations, declining muscle mass, strength, power, and physical performance contribute independently to increase FoF, while declines of muscle mass and physical performance contribute to deterioration of QoL. These findings provide further rationale for developing interventions to improve aging muscle health.

Lower extremity muscle mass predicts functional performance in mobility-limited elders.

OBJECTIVES: This study examined the influence of lower extremity body composition and muscle strength on the severity of mobility-disability in community-dwelling older adults. METHODS: Fifty-seven older males and females (age 74.2 +/- 7 yrs; BMI 28.9 +/- 6 kg/m2) underwent an objective assessment of lower extremity functional performance, the Short Physical Performance Battery test (SPPB). Participants were subsequently classified as having moderate (SPPB score 7: n = 38) or severe mobility impairments (SPPB score

Model development for O(2) and N(2) permeation rates through CZ-resin vials.

The headspace of vials containing oxygen-sensitive formulations is filled with a nitrogen blanket. This paper presents the development of a mathematical model to predict the oxygen and nitrogen permeation rates through the walls of plastic CZ-resin vials. The model estimates the time required for a nitrogen-filled vial to reach ambient nitrogen and oxygen levels. The permeation of oxygen and nitrogen through the vial is governed by Fick's law and may be described by an exponential equation. Using the values for oxygen and nitrogen permeation through CZ-resin vial, the half-lives for the decrease in nitrogen level and increase in oxygen level was found to be 150 days and 15 days, respectively. This result can be attributed to the greater permeability of CZ-resin vial to oxygen (79.06 cm(3)-mm/m(2)-24 h-atm) when compared with nitrogen (12 cm(3)-mm/m(2)-24 h-atm). The ingress of oxygen into CZ-resin vials was determined experimentally and it was found to verify the model. These results indicate that CZ-resin vials may be inappropriate for packaging oxygen-sensitive formulations even in the presence of a nitrogen-filled headspace.

A dynamic test of lower extremity function following anterior cruciate ligament reconstruction and rehabilitation.

It is essential to assess the functional status of patients with surgically reconstructed and rehabilitated anterior cruciate ligaments prior to discharge. This study established a testing paradigm for functional force production and absorption. Data were obtained from 100 healthy subjects for maximal hops, controlled leaps, and hopping and leaping symmetry. Only 10% of symptomatic patients met maximal hopping criteria, while 15% achieved controlled leaping norms. Ninety-five percent of these patients failed to reach both hopping and leaping symmetry norms. Asymptomatic patients were 63% successful in meeting hopping criteria, and 57% were successful in meeting leaping criteria. Hop symmetry and leap symmetry were achieved at rates of 70% and 60%, respectively. The performance of both groups fell significantly below that of normal subjects (p < .05). Data suggest that this protocol does accurately assess functional and dysfunctional knees, and that force absorption may be more critical than force production in the determination of functional capacity.

The endocrine investigation of disorders of sodium and water homeostasis.

This article reviews critically the investigation of polyuric states, hyponatremia with particular emphasis on the syndrome of inappropriate antidiuretic hormone secretion, and primary hyperaldosteronism. Details of some essential tests are given with comments on interpretation of results.

Osmoregulation of vasopressin and thirst: comparison of 20% mannitol with 5% saline as osmotic stimulants in healthy man.

OBJECTIVE: Osmoregulation is normally studied using a 5% saline infusion. This may be deleterious in fluid overloaded patients. Twenty per cent mannitol is another osmotic stimulant. This study aimed to compare 20% mannitol infusion with 5% saline as an osmotic stimulant to thirst and vasopressin secretion in normal volunteers. DESIGN AND PATIENTS: Eight healthy volunteers studied on 2 occasions in random order. Each study involved a 2-hour infusion period of either hypertonic (5%) saline (0.06 ml/kg/h) or hypertonic (20%) mannitol (0.07 ml/kg/h). MEASUREMENTS: Plasma vasopressin (pVp), plasma sodium, plasma osmolality (pOsm), haematocrit (HCT), blood pressure, thirst, blood glucose and volume drunk at end of infusion. RESULTS: Five per cent saline infusion stimulated significantly higher levels of pOsm, pVp and thirst than 20% mannitol. Plasma sodium rose significantly during 5% saline infusion and fell during 20% mannitol infusion. HCT fell and mean arterial pressure rose in both infusions but the changes were not clinically significant. Piecewise linear regression analysis defined the overall threshold for pVp release for the two solutions as 5% saline, 292 mosm/kg and 20% mannitol, 291 mosm/kg, and the post threshold slope as 5% saline, 0.46 pmol/l pVp per mosm and 20% mannitol, 0.30 pmol/l pVp per mosm. The threshold for thirst onset was 5% saline, 291 mosm/kg and 20% mannitol, 290 mosm/kg, and the post threshold slope, 5% saline, 0.58 cm thirst per mosm and 20% mannitol, 0.28 cm thirst per mosm. The differences between the calculated osmotic thresholds and slopes post threshold for the two infusions were not significant for the pVp versus pOsm relationship. The difference between the cumulative volume drunk following the two infusions did not reach statistical significance. Mannitol caused a significant diuresis. CONCLUSIONS: Twenty per cent mannitol infusion is an effective osmotic stimulant to thirst and vasopressin release in normal individuals, but is less potent than 5% saline infusion.

Physicochemical stability of crystalline sugars and their spray-dried forms: dependence upon relative humidity and suitability for use in powder inhalers.

Lactose, trehalose, sucrose, and mannitol were purchased in crystalline form and fractionated by sieving. Coarse (125-212 microns) and fine (44-74 microns) free-flowing fractions were selected as typical of drug carriers in dry-powder inhalers. In addition, one batch of each sugar was spray-dried to form a respirable powder (> 50% [w/w], < 5 microns). Both fractions and the spray-dried powders were characterized before and after storage for 30 days at < 23%, 23%, 52%, 75% and 93% relative humidity (RH) at 25 degrees C. Moisture uptake was determined by thermogravimetric analysis (TGA) validated by Karl Fischer titration. Sieve fractions (before storage at different RHs) and spray-dried materials (before and after storage) were further characterized by differential scanning calorimetry (DSC) and x-ray powder diffraction (XRPD). All crystalline sieve fractions (except sucrose at 93% RH) were stable at 25 degrees C and showed insignificant moisture uptake when exposed to each relative humidity for 30 days. Sucrose dissolved in sorbed moisture at 93% RH. Spray-dried lactose, sucrose, and trehalose, which were collected in the amorphous form, showed moisture uptake, without recrystallization, when held for 30 days at 23% RH. These sugars recrystallized as sintered masses and became undispersible at > or = 52% RH. Spray-dried mannitol was apparently 100% crystalline when collected directly from the spray-dryer; it did not show humidity-induced changes. The physicochemical behavior of each sugar form is discussed as it relates to the sugar's suitability as a powder-inhaler excipient, with both conventional and protein drugs.

Optimized inhalation aerosols. II. Inertial testing methods for particle size analysis of pressurized inhalers.

Pressurized metered dose inhaler (MDI) output from three different albuterol formulations was characterized using three inertial separation devices. Results were compared for the Delron six-stage cascade impactor (DC16), the Andersen Mark II eight-stage impactor (AC18), and Copley's twin-stage liquid impinger (LI). None of the devices tested in this study was ideal in all respects. All devices could differentiate between formulations in terms of respirable doses (albuterol amount with aerodynamic diameters less than 5.5 through 6.4 microns). Only the high-flow rate LI could differentiate among all three formulations when data were presented in terms of respirable percentage (RP) of drug collected. Values for RP were in excellent agreement for the independently calibrated impactors when the same evaporation chamber was used atop the impactors. The LI appeared to overestimate values for RP in vivo. Results are discussed in light of the debate surrounding the revision of USP aerosol testing requirements. Rigorous specifications for evaporation chambers and methodologies are necessary for meaningful inter- and intra-laboratory comparison of results when any of these devices are used.