Ultrasound velocity of the tibia in normal German women and hip fracture patients

One of the latest developments in quantitative ultrasound (QUS) is the measurement of the speed of sound (SOS) of cortical bone of the midtibia. To determine the diagnostic validity of this method we measured 150 healthy women aged 22-94 years. Additionally, we report on first results of patients with hip fracture. Precision in vivo of the tibial QUS expressed as the percentage coefficient of variation (CV) was 0.39% for the first day and 0.45% after repositioning the second day (mean CV = 0.42%). No significant dependency of tibial SOS was found with weight, height, and body mass index in pre- and postmenopausal women. There was a significant decline of SOS with age in postmenopausal women (SOS = 4225 - 5.3 age, r = -0.46, P < 0. 001), whereas premenopausal women showed no decline (SOS = 3906 + 1. 3 age, r = 0.13, ns) Mean SOS values of premenopausal women were significantly higher than those of postmenopausal women (3960 +/- 78.7 m/second and 3898 +/- 120 m/second, respectively, P < 0.001). Postmenopausal women on estrogen substitution had significantly higher mean tibial SOS values than age-comparable postmenopausal women without estrogen substitution (3980 +/- 99 m/second and 3869 +/- 100 m/second, respectively, P < 0.001). Significant difference between age-matched healthy women, n = 11, and hip fracture patients, n = 13, expressed as z-score of -1.4 SD was found. In conclusion, tibial QUS declines with age and detects higher values in premenopausal women and postmenopausal women on estrogen substitution and lower values in hip fracture patients. Further prospective studies are needed to clarify its role in fracture risk assessment.     

Effectiveness of intravenous administration of Fe-gluconate-Na complex to maintain adequate body iron stores in hemodialysis patients

The evolution of body iron stores was prospectively analyzed during a stable erythropoiesis period in 27 subjects (14 males and 13 females) on hemodialysis for more than 2 years in order to clarify the iron requirements of these patients and the effectiveness and safety of the administration of sodium ferric gluconate as a method to maintain adequate body iron stores. All patients had a stable hemoglobin level (variation < 1 g/dl). Sixteen subjects were on maintenance recombinant human erythropoietin therapy at regular doses. All patients received intravenous sodium ferric gluconate for 6 months (62.5 mg/month). The iron requirements were estimated as the difference between the amount of iron administered and the variation of body iron stores (calculated by the empirical formula of Cook and coworkers). The hemoglobin remained stable (basal 10.7 +/- 1.1, at 6th month 10.6 +/- 1 g/dl). Considering all cases, there were no significant variations in body iron stores (basal 457 +/- 273, at 6th month 451 +/- 316 mg). The patients were classified into three groups according to whether their body iron stores decreased (group A, n = 8), remained stable (group B, n = 11), or increased (group C, n = 8). There were no differences among groups concerning sex, age, time on hemodialysis, or erythropoietin therapy. However, there were statistically significant differences concerning their basal body iron stores (group A 457 +/- 228 mg. group B 563 +/- 146, and group C 230 +/- 297 mg; p < 0.05, analysis of variance). The iron needs, considering the total group, were 2.12 +/- 2 mg/day. There were no differences in iron requirements according to sex, but menstruating women had higher iron needs than the nonmenstruating ones (4.29 +/- 2 vs. 2.08 +/- 1.45 mg/day; p < 0.01). The iron requirements in patients on erythropoietin therapy were higher than in those without (2.63 +/- 1.59 vs. 1.88 +/- 1.68 mg/day; p < 0.05). However, excluding the menstruating women, the iron need in patients on erythropoietin were similar to those in subjects without this treatment (2.16 +/- 1.13 vs. 1.88 +/- 1.68 mg/day). All patients showed good compliance with an excellent tolerance. We have observed that in subjects on maintenance erythropoietin therapy, the iron requirements are stable. The administration of sodium ferric gluconate is safe and efficient in maintaining adequate body iron stores.     

Distinct deactivation and desensitization kinetics of recombinant GABAA receptors

The functional role of the large heterogeneity in GABAA receptor subunit genes and its role in setting the properties of inhibitory synapses in the CNS is poorly understood. A kinetic comparison between currents elicited by ultra-rapid application with a piezoelectric translator of 1 mM GABA to mammalian cells transfected with cDNAs encoding distinct GABAA receptor subunits revealed that the intrinsic deactivation and desensitization properties depend on subunit combination. In particular, receptors containing alpha 6 with beta 2 gamma 2 subunits were endowed with a significantly slower deactivation as compared to those receptors containing alpha 1 with beta 2 gamma 2 subunits. While desensitization produced by prolonged GABA applications on alpha 1 beta 2 gamma 2 receptors was characterized by a rapid exponential decay followed by a slower decay and a steady state response, alpha 6 beta 2 gamma 2 receptors lacked desensitization. Furthermore, GABAA receptors lacking the gamma 2 subunit were characterized by a much larger non-desensitization component and a very rapid deactivation. Lastly, analysis of GABA-activated currents in cells cotransfected with alpha 1 and alpha 6 together with beta 2 gamma 2 subunit revealed unique kinetic properties. Our results suggest that distinct subunit composition confers specific deactivation and desensitization properties that may profoundly affect synaptic decay kinetics and the capability to sustain high frequency synaptic inputs.     

The modified Gait Abnormality Rating Scale for recognizing the risk of recurrent falls in community-dwelling elderly adults

BACKGROUND AND PURPOSE: The purpose of this study was to determine the reliability and validity of measurements obtained with a seven-item modified version of the Gait Abnormality Rating Scale (GARS-M), an assessment of gait designed to predict risk of falling among community-dwelling, frail older persons. SUBJECTS: Fifty-two community-dwelling, frail older persons, with a mean age of 74.8 years (SD = 6.75), participated. METHODS: A history of falls was determined from self-report or by proxy report. The GARS-M was scored from videotapes of subjects walking at self-selected paces. Gait characteristics were recorded during a timed walk on a 6-m brown-paper walkway. RESULTS: Scores obtained by three raters for 23 subjects demonstrated moderate to substantial intrarater and interrater reliability. Concurrent validity, as assessed by Spearman rank-order correlation coefficients, was demonstrated for the relationship between GARS-M scores and stride length (r = -.754) and for the relationship between GARS-M scores and walking speed (r = -.679). Mean GARS-M scores distinguished between frail older persons with and without a history of recurrent falls (mean GARS-M scores of 9.0 and 3.8, respectively). CONCLUSION AND DISCUSSION: The GARS-M is a reliable and valid measure for documenting gait features associated with an increased risk of falling among community-dwelling, frail older persons and may provide a clinically useful alternative to established quantitative gait-assessment methods.     

Effects of oleic acid-induced pulmonary edema on lung mechanics

In 25 rabbits anesthetized with pentobarbital sodium and paralyzed with succinylcholine chloride, we investigated the contributions of four factors that might cause the decreased static lung compliance found in oleic acid-induced pulmonary edema: 1) foam, 2) accumulation of fluid in the interstitial spaces, 3) loss of ventilatable units secondary to alveolar flooding, and 4) increased surface tension. Pulmonary edema, reflected by a 115% increase in mean post-mortem extravascular bloodless lung water content, decreased compliance 47% and tripled alveolar-arterial PO2 difference. Removing foam by degassing did not affect compliance measurements. Filling the lungs with saline caused similar changes in control and edematous animals. Because the 38% decrease in functional residual capacity was largely attributable to water accumulation, we concluded that loss of ventilatable units accounted for virtually all the decreased static lung compliance. The role of increased surface tension could not be determined directly but was considered relatively less important.     

Platelet sialic acid and platelet survival after aggregation by ADP

Some investigators have reported recently that platelet surface sialic acid is decreased during ADP-induced aggregation, whereas others have reported an increase. Since removal of sialic acid from the platelet surface shortens platelet survival, we have determined the survival of platelets that have been aggregatad by ADP. We have also measured the amount of sialic acid in the suspending fluid of platelets after ADP-induced aggregation. ADP-induced aggregation did not cause the loss of sialic acid from rabbit platelets (which do not undergo a release reaction in response to ADP) nor from washed human platelets in a medium containing physiologic concentrations of calcium in which granule contents are not released. In a medium without added calcium, ADP caused the release of 14C-serotonin (42.5% +/- 3%) from human platelets, but less than 4% of the sialic-acid-containing material was released. It seems likely that little of the releasable sialic acid of platelets is in the dense granules or the alpha-granules. Thrombin (5 U/ml) released 90.0% +/- 3.4% of the serotonin from human platelets but only 20.6% +/- 7.4% of the total sialic-acid-containing material. Neuraminidase removed 42.3% of the total sialic acid, presumably from the platelet surface. Rabbit platelets that had been aggregated by ADP and deaggregated survived normally when returned to the circulation. This observation also provides evidence that they had not lost membrane sialic acid during aggregation and deaggregation.     

Selective binding and uptake of ribonuclease A and glyceraldehyde-3-phosphate dehydrogenase by isolated rat liver lysosomes

Ribonuclease A (RNase A) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are selectively taken up and degraded by isolated rat liver lysosomes by very similar processes. The uptake and degradation of both of these proteins are stimulated by the heat shock cognate protein of 73 kDa and ATP/Mg2+. Both binding and uptake of RNase A and GAPDH by lysosomes are saturable, and uptake of RNase A and GAPDH requires a protease-sensitive component within the lysosomal membrane. GAPDH competes for binding and uptake of RNase A by lysosomes and vice versa while another protein, ovalbumin, does not compete. RNase S-peptide (amino acids 1-20 of RNase A) also competes for RNase A binding and uptake by lysosomes, while RNase S-protein (amino acids 21-124 of RNase A) does not compete. The uptake of RNase A by lysosomes appears to involve an intermediate step in which approximately 2 kDa of the polypeptide's COOH terminus remains outside lysosomes while the remainder is inside the lysosomal lumen.