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Hemodynamics of hemorrhage in the conscious rat and chicken.

Hemodynamic responses to hemorrhage in conscious chicks (n = 10, 233 g) and rats (n = 10, 309 g) were compared. The animals were fitted with miniature pulsed Doppler aortic flow probes 2 days (chickens) or 5 days (rats) before catheterization, and the experiment began 1 (chickens) or 2 (rats) days later. Mean arterial pressure (MAP) and cardiac output (CO) were recorded continuously and simultaneously digitized to compute total peripheral resistance (TPR). MAP, CO, and TPR values were graphed on-line by a microcomputer and stored for later analysis. A 4-ml hemorrhage reduced MAP and CO by 25 and 43% in the rat, and 15 and 4% in the chickens, respectively. The fall in CO in the rat was due to reduction of stroke volume (SV) unlike the birds where SV was well maintained. TPR was elevated 65% in the rats and fell 13% in the chickens. The minimal fall in CO and SV in these conscious birds suggests that anesthetic agents used previously (i.e., urethane, paraldehyde, phenobarbital, and pentobarbital sodium) suppressed cardiac function. However, they do not account for the lack of a peripheral vascular response during hemorrhage. The chicken apparently maintains MAP by a volume regulating mechanism operating independently of peripheral vascular tone inasmuch as circulating fluid volume restitution is rapid and occurs without vasoconstriction. The rat maintains MAP through reflex cardiac and peripheral vascular responses which eventually may contribute to transvascular fluid loss and the ultimate collapse after prolonged hemorrhagic hypotension.

Animals↗

Mechanical loading-induced gene expression and BMD changes are different in two inbred mouse strains.

Our goal is to evaluate skeletal anabolic response to mechanical loading in different age groups of C57B1/6J (B6) and C3H/HeJ (C3H) mice with variable loads using bone size, bone mineral density (BMD), and gene expression changes as end points. Loads of 6-9 N were applied at 2 Hz for 36 cycles for 12 days on the tibia of 10-wk-old female B6 and C3H mice. Effects of a 9-N load on 10-, 16-, and 36-wk-old C3H mice were also studied. Changes in bone parameters were measured using peripheral quantitative computed tomography, and gene expression was determined by real-time PCR. Total volumetric BMD was increased by 5 and 15%, respectively, with 8- and 9-N loads in the B6, but not the C3H, mice. Increases of 20 and 12% in periosteal circumference were reflected by dramatic 44 and 26% increases in total area in B6 and C3H mice, respectively. The bone response to bending showed no difference in the three age groups of B6 and C3H mice. At 2 days, mechanical loading resulted in significant downregulation in expression of bone resorption (BR), but not bone formation (BF) marker genes. At 4 and 8 days of loading, expression of BF marker genes (type I collagen, alkaline phosphatase, osteocalcin, and bone sialoprotein) was increased two- to threefold and expression of BR marker genes (matrix metalloproteinase-9 and thrombin receptor-activating peptide) was decreased two- to fivefold. Although expression of BF marker genes was upregulated four- to eightfold at 12 days of training, expression of BR marker genes was upregulated seven- to ninefold. Four-point bending caused significantly greater changes in expression of BF and BR marker genes in bones of the B6 than the C3H mice. We conclude that mechanical loading-induced molecular pathways are activated to a greater extent in the B6 than in the C3H mice, resulting in a higher anabolic response in the B6 mice.

Alkaline Phosphatase↗

Adaptations to free-fall impact are different in the shafts and bone ends of rat forelimbs.

Impact exercise can have beneficial effects on the growing skeleton. To understand what changes it promotes in the shafts and ends of weight-bearing bones, we measured the effects of impact from repetitive free falls in growing rats. Fischer 344 female rats, 6.5 wk old, were assigned to one of three groups (n = 10 each). Controls were not dropped, whereas those subjected to impact were dropped from 30 or 60 cm. Rats in both free-fall groups were dropped 10 times per day for 8 wk. Leg bones were mechanically tested, and their cross-sectional area (CSA), cross-sectional moments of inertia, and volumetric bone mineral density (BMD) were measured by peripheral quantitative computed tomography. In the shafts of the forelimbs, but not the hindlimbs, free-fall impact resulted in greater ultimate breaking force, minimum and maximum second moments of area, and CSA but not BMD. In the bone ends of the forelimb and tibial bones, trabecular BMD increased but CSA did not. Landing from 30 and 60 cm produced peak impact forces of 12.0 and 16.7 times the standing forefoot weight for each front leg and of 4.5 and 7.7 times the standing hind foot weight for each hind foot. Overall, free-fall impact affected the forelimbs by increasing trabecular bone density in the bone ends and improving the strength at the shaft as a result of geometric improvements. These results indicate that adaptation to impact may occur by different mechanisms in bone end and shaft regions.

Adaptation, Physiological↗

Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats.

This study was designed to determine the effects of 28 days of hindlimb unloading (HU) on the mature female rat skeleton. In vivo proximal tibia bone mineral density and geometry of HU and cage control (CC) rats were measured with peripheral quantitative computed tomography (pQCT) on days 0 and 28. Postmortem pQCT, histomorphometry, and mechanical testing were performed on tibiae and femora. After 28 days, HU animals had significantly higher daily food consumption (+39%) and lower serum estradiol levels (-49%, P = 0.079) compared with CC. Proximal tibia bone mineral content and cortical bone area significantly declined over 28 days in HU animals (-4.0 and 4.8%, respectively), whereas total and cancellous bone mineral densities were unchanged. HU animals had lower cortical bone formation rates and mineralizing surface at tibial midshaft, whereas differences in similar properties were not detected in cancellous bone of the distal femur. These results suggest that cortical bone, rather than cancellous bone, is more prominently affected by unloading in skeletally mature retired breeder female rats.

Animals↗

Effects of physical training on cortical bone at midtibia assessed by peripheral QCT.

Effects of long-term exercise on volumetric bone mineral density (vBMD), bone mineral content, bone geometric properties, and the strength indexes of bone were examined in a cross-sectional study of athletes and controls. Tibias of 25 jumpers (13 women), 30 swimmers (15 women), and 25 controls (15 women), aged 18-23 yr, were scanned at midsite by using peripheral quantitative computed tomography. The cortical vBMD of female athletes was lower than that of the controls (2.00 +/- 0.05, 1.90 +/- 0.08, and 1.92 +/- 0.12 g/cm3, respectively, for controls, swimmers, and jumpers). On the other hand, periosteal areas of male jumpers and female athletes were greater than that of controls (460 +/- 50, 483 +/- 46, and 512 +/- 55 mm2, respectively, for male controls, swimmers, and jumpers, and 283 +/- 52, 341 +/- 73, and 378 +/- 75 mm2, respectively, for female controls, swimmers, and jumpers). The endocortical area of female swimmers was greater than that of controls (103 +/- 29, 148 +/- 52, and 135 +/- 54 mm2, respectively, for controls, swimmers, and jumpers). The polar moment of inertia and strength strain index of male jumpers and female athletes were significantly greater than those of controls, except for the difference in strength strain index between male jumpers and controls. We conclude that the improvement of mechanical properties of young adult bone in response to long-term exercise is related to geometric adaptation and not to vBMD.

Absorptiometry, Photon↗

Musculoskeletal plasticity after acute spinal cord injury: effects of long-term neuromuscular electrical stimulation training.

Maintaining the physiologic integrity of paralyzed limbs may be critical for those with spinal cord injury (SCI) to be viable candidates for a future cure. No long-term intervention has been tested to attempt to prevent the severe musculoskeletal deterioration that occurs after SCI. The purposes of this study were to determine whether a long-term neuromuscular electrical stimulation training program can preserve the physiological properties of the plantar flexor muscles (peak torque, fatigue index, torque-time integral, and contractile speed) as well as influence distal tibia trabecular bone mineral density (BMD). Subjects began unilateral plantar flexion electrical stimulation training within 6 wk after SCI while the untrained leg served as a control. Mean compliance for the 2-yr training program was 83%. Mean estimated compressive loads delivered to the tibia were approximately 1-1.5 times body weight. The training protocol yielded significant trained versus untrained limb differences for torque (+24%), torque-time integral (+27%), fatigue index (+50%), torque rise time (+45%), and between-twitch fusion (+15%). These between-limb differences were even greater when measured at the end of a repetitive stimulation protocol (125 contractions). Peripheral quantitative computed tomography revealed 31% higher distal tibia trabecular BMD in trained limbs than in untrained limbs. The intervention used in this study was sufficient to limit many of the deleterious muscular and skeletal adaptations that normally occur after SCI. Importantly, this method of load delivery was feasible and may serve as the basis for an intervention to preserve the musculoskeletal properties of individuals with SCI.

Adult↗

Spatial memory and path integration studied by self-driven passive linear displacement. I. Basic properties.

According to path integration, the brain is able to compute the distance of a traveled path. In this research we applied our previously reported method for studying memory of linear distance, a crucial mechanism in path integration; our method is based on the overt reconstruction of a passive transport. Passive transport is a special case of navigation in which no active control is performed. Blindfolded subjects were first asked to travel 2 m forward, in darkness, by driving with a joystick the robot on which they were seated. The results show that all subjects but two undershot this distance, i.e., overestimated their own displacement. Then, subjects were submitted to a passive linear forward displacement along 2, 4, 6, 8, or 10 m, and had to reproduce the same distance, still blindfolded. The results show that the distance of the stimulus was accurately reproduced, as well as stimulus duration, peak velocity, and velocity profile. In this first condition, the imposed velocity profile was triangular and therefore stimulus distance and duration were correlated. In a second condition, it was shown that distance was correctly reproduced also when the information about stimulus duration was kept constant. Here, different velocity profiles were used as stimuli, and most subjects also reproduced the velocity profile. Statistical analyses indicated that distance was not reproduced as a consequence of duration, peak velocity, or velocity profile reproduction, but was uniquely correlated to stimulus distance. The previous hypothesis of a double integration of the otolith signal to provide a distance estimate can explain our results. There was a large discrepancy between the accuracy with which the subjects matched the velocity profiles and that of distance reproduction. It follows that, whereas the dynamics of passive motion are stored and available to further use, distance is independently estimated. It is concluded that vestibular and somatosensory signals excited by passive transport can be used to build a dynamic as well as a static representation of the traveled path. We found a close quantitative similarity between the present findings on distance reproduction and those obtained from active locomotion experiments in which the same paradigm was used. This resemblance suggests that the two types of navigation tasks draw on common physiological processes and extends the relevance of our results to naturally occurring path integration.

Acceleration↗

Relation of PvuII site polymorphism in the COL1A2 gene to the risk of fractures in prepubertal Finnish girls.

Genetic susceptibility to fractures may be detectable in early childhood. We evaluated the associations between the polymorphic PvuII site of the COL1A2 gene and bone properties assessed by different modalities (dual-energy X-ray absorptiometry; peripheral quantitative computed tomography; gel coupling scanning quantitative ultrasonometry; ultrasound bone sonometry), bone turnover markers, and the occurrence of fractures in 244 prepubertal Finnish girls. Tanner stage and physical characteristics did not differ significantly among girls with different COL1A2 genotypes. The polymorphism was not significantly associated with different bone properties or any of the bone turnover markers when girls at Tanner stage I (prepuberty) and stage II (early puberty) were considered together, but there was a significant association with spine bone mineral content (BMC) and bone mineral density (BMD), as well as with speed of sound (SOS) (P < 0.05), when girls at Tanner stage I were considered separately, as a purpose to avoid the confounding effect that the pubertal growth spurt has on skeletal development. The distribution of fractures was different between the three genotype groups (P = 0.023). The P alleles were over-represented in girls who had been fractured at least once; 88% of them had at least one copy of the P allele (either PP or Pp). Girls with the PP genotype had 4.9 times higher relative risk for fractures than girls with the pp genotype (95% CI, 1.4 to 17.4; P = 0.015). No significant difference was found between fractured and nonfractured girls in anthropometric measurements, physical activity, or bone mass. However, BMD of the spine and SOS at the radius and tibia were significantly lower in the fractured girls. We conclude that the COL1A2 polymorphism is associated with nonosteoporotic fractures in prepubertal girls independently of bone density.

Binding Sites↗

The development of the skeletal system in children and the influence of muscular strength.

In a study on 14 healthy children aged from 6 to 13 years, the volumetric spongiosa bone density (SBD), cortical bone density (CBD), bone cross-sectional area (BCSA), cortical area (CA), and bone strength index (BSI) at the distal radius were analyzed using peripheral quantitative computer tomography (pQCT Bone Scanner XCT-900, Stratec, Pforzheim, Germany). BSI values were calculated on the basis of the moment of resistance and cortical density using system integrated software. These parameters were correlated with grip strength measurements obtained using a grip dynamometer. There were age-dependent increases in BCSA (r = 0.68), CA (r = 0.78), BSI (r = 0.79). SBD and CBD, however, did not show an increase with age. Grip strength correlates strongly with the parameters of bone geometry BCSA (r = 0.8), CA (r = 0.86), and BSI (r = 0.9) at p < 0.01. SBD and CBD showed no significant correlation to grip strength. The results of this study suggest that an increase in cortical thickness and cross-sectional area represent the most important adaptation mechanisms of the growing bones in response to biomechanical usage. These parameters represent the most important factors of bone strength. Volumetric bone density (material characteristic) of spongiosa and cortical bone is an age-independent parameter which does not change significantly with increasing muscular strength in healthy subjects. These relationships must be considered when selecting parameters to be used as success criteria in studies on the influence of physical exercise on bone status.

Adolescent↗

Increased bone volume and bone mineral content in xylitol-fed aged rats.

BACKGROUND: Our previous studies have shown that dietary xylitol supplementation protects against the loss of bone mineral after ovariectomy. The ovariectomy-induced decrease in trabecular bone volume is significantly retarded by dietary xylitol. OBJECTIVE: To study whether dietary xylitol can protect against bone loss also during aging, a long-term experimental study was performed with rats. METHODS: Twenty-four male Sprague-Dawley rats were divided into two groups. The rats in the control group were fed a basal RM1 diet, while the rats in the experimental group were continuously fed the same diet supplemented with 10% (w/w) xylitol. The rats were killed after 20 months. Their tibiae were used for the analyses of bone density and trabecular bone volume, and their femurs were used for the scanning analyses with peripheral quantitative computed tomography (pQCT). RESULTS: The tibial density of the xylitol-fed aged group (1.73 +/- 0.14 g/mm(3)) was significantly greater than that of the aged group without xylitol (1.56 +/- 0.14 g/ mm(3)). The trabecular bone volume of the xylitol-fed rats was 21.2 +/- 4.0%. It was significantly greater than that of the rats not receiving xylitol (9.3 +/- 4.3%). The pQCT-measured cortical bone mineral density and the pQTC-measured cortical bone mineral content of the femoral diaphysis were significantly greater in the xylitol-fed group than in the control group. The trabecular bone mineral density and the trabecular bone mineral content of the femoral distal metaphysis were also significantly greater in the xylitol-fed group than in the non-xylitol group. The total bone mineral density and the total bone mineral content of the femoral neck in the xylitol-fed aged group significantly exceeded those in the aged group without xylitol supplementation. CONCLUSIONS: A continuous moderate dietary xylitol supplementation leads to increased bone volume and increased bone mineral content in the long bones of aged rats. This indicates a xylitol-induced protection against aging-related osteoporotic changes.

Aging↗

Osteoporosis in male hypogonadism: responses to androgen substitution differ among men with primary and secondary hypogonadism.

BACKGROUND: No randomized study exists comparing the effects of different modes of androgen substitution on bone mineral density (BMD). METHODS: We performed a prospective, randomized, trial assigning 53 hypogonadal men to the following treatment groups: mesterolone 100 mg p.o. daily, testosterone undecanoate 160 mg p.o. daily, testosterone enanthate 250 mg i.m. every 21 days, or a single subcutaneous implantation of 1,200 mg crystalline testosterone. The BMD was determined by peripheral quantitative computed tomography. RESULTS: At baseline, men with secondary hypogonadism (n = 33) had a lower BMD (-1.52 +/- 0.23 SDS; Z-scores) than men with primary hypogonadism (n = 20, -0.87 +/- 0.23 SDS, p < 0.01). In men with primary hypogonadism, the BMD increased dose dependently (crystalline testosterone +7.0 +/- 1.3%, testosterone enanthate +4.8 +/- 0.2%, testosterone undecanoate +3.4 +/- 2.5%, mesterolone +0.8 +/- 1.6%) after 6 months of therapy. Only secondary hypogonadal men treated with testosterone enanthate experienced an increase of the BMD. CONCLUSIONS: In primary hypogonadal men the BMD responds dose dependently to testosterone substitution, whereas in secondary hypogonadism only testosterone enanthate treatment significantly increased the BMD.

Adult↗

Adrenal steroid hormones and metaphyseal bone in children.

BACKGROUND/OBJECTIVES: The responses of metaphyseal bone tissue to physiological variations of endogenous adrenal steroid hormones during childhood are unclear. Therefore, we studied potential hormonal influences in children before the appearance of pubic hair (onset of pubarche). METHODS: Excretions of major glucocorticoid metabolites (C21), cortisol, sum of adrenarchal dehydroepiandrosterone and its immediate 16-hydroxylated metabolites (DHEA&M), and 5-androstene-3beta,17beta-diol (hermaphrodiol) were analyzed in a cross-sectional study in 24-hour urine samples of 109 healthy boys and girls, aged 6-13 years, using steroid profiling by gas chromatography-mass spectrometry. Total and trabecular volumetric bone mineral densities, bone mineral content (BMC) and bone strength strain index were determined with peripheral quantitative computed tomography at the distal forearm. RESULTS: In multiple regression analyses significant associations with the metaphyseal radius were seen for grip force, age, or BMI depending on gender and bone variable analyzed. DHEA&M did not contribute to the explanation of the variance of any bone variable. However, hermaphrodiol positively explained a significant part of variation of bone mineral densities, and BMC (p < 0.01) in girls. Significantly negative associations with all bone variables were seen in boys for cortisol. CONCLUSIONS: The steroid hormones, cortisol and hermaphrodiol, in their physiological ranges, but not the adrenarche marker DHEA&M, appear to associate with metaphyseal bone in a sex-dependent manner during childhood.

Adolescent↗

Measuring bone mass in children: can we really do it?

Bone densitometry is used to assess skeletal health in clinical and research settings, with the goal of achieving reproducible measurements of bone mass that help to identify individuals predisposed to fracture. The search is now on for better methods of capturing additional factors that contribute to bone strength, including bone size, geometry, microarchitecture, and turnover rates. This has proved particularly challenging in growing children, whose bones continually change in size, shape, and mass. Dual energy X-ray absorptiometry is the preferred method for measuring bone mass in children, but the technique has several limitations, and interpreting the findings can be problematic. Peripheral quantitative computed tomography is a promising method for assessing bone mass and other indices correlating with bone strength, but a lack of precision and paediatric norms currently restricts its clinical utility. Although bone mineral density is predictive of future fracture risk in adults, the evidence in children is less conclusive, and a diagnosis of osteoporosis in a child should not be made on densitometric findings alone. Developing a clearer understanding of how measures of bone mass and strength correlate with bone fracture in children will help target preventive strategies for those in greatest need.

Bone Density↗

Using the Pathfinder system to reduce missed abnormal cervical cytologic smear cases in a rescreening program.

OBJECTIVE: To evaluate the effect of Pathfinder (CompuCyte Corp., Cambridge, Massachusetts, U.S.A.), a process control instrument for microscopes used by cytotechnologists to monitor the mechanical aspects of their screening process, on the false negative cervical cytologic smear rate as detected in daily quality assurance rescreening. STUDY DESIGN: Pathfinder was put into routine use in a large cytology laboratory. After cytotechnologists were trained in its use, they monitored their time spent screening each slide, the area (percent) of the slide screened and the average percentage of overlap of fields of view. The number of abnormal cases missed in screening before and after the introduction of Pathfinder was determined by rescreening a random 10% of the "negative" cases. The evaluation took place over a nine-month period. RESULTS: A decrease in the number of missed abnormal cases was identified. The false negative rate for atypical cells of undetermined significance (ASCUS) fell from 37/2,336 (1.6%) to 12/1,772 (0.7%), for a 56% decrease. The change in the number of squamous intraepithelial lesion cases, even over a nine-month period, was too small for comment. CONCLUSION: The effect of the continuous feedback and process standardization provided by the Pathfinder system was a decrease in the number of abnormal cases missed. This was due primarily to a marked decrease in the number of ASCUS cases missed. The Pathfinder provides a number of innovative management tools to ensure consistent high quality screening.

Cervix Uteri↗

Assistive technology and handwriting problems: what do occupational therapists recommend?

BACKGROUND: Handwriting difficulties for students are a common reason for referral to occupational therapy. Little research evidence is available concerning the factors guiding technology recommendations for these children. PURPOSE: The objective of this survey research was to describe the technology-related recommendations and factors involved in the decisions made by Canadian occupational therapists for these students. RESULTS: More therapists recommended the use of keyboard-based strategies (93%) than dictation-based strategies (72%). Experienced therapists were more likely to prescribe technology tools. Dictation to a scribe (93%) and desktop computers (89%) were the strategies most frequently recommended. Equipment cost and availability of funding, and the availability of support in the school for the student were the most influential factors, respectively, on the keyboard and dictation strategy type prescribed. PRACTICE IMPLICATIONS: The results confirmed that occupational therapists prescribe a range of technology solutions. Factors influencing these recommendations differ depending on the nature of the technology, the person, environment or occupation. Knowing the factors guiding occupational therapist technology recommendations will help provide valuable information about the practical implications of the available technologies.

Child↗

A method for evaluating head-controlled computer input devices using Fitts' law.

The discrete movement task employed in this study consisted of moving a cursor from the center of a computer display screen to circular targets located 24.4 and 110.9 mm in eight radial directions. The target diameters were 2.7, 8.1, and 24.2 mm. Performance measures included movement time, cursor path distance, and root-mean-square cursor deviation. Ten subjects with no movement disabilities were studied using a conventional mouse and a lightweight ultrasonic head-controlled computer input pointing device. Average movement time was 306 ms greater (63%) for the head-controlled pointer than for the mouse. The effect of direction on movement time for the mouse was relatively small compared with the head-controlled pointer, which was lowest at 90 and 270 deg, corresponding to head extension and head flexion, respectively. Average path distance and root mean square displacement was lowest at off-diagonal directions (0, 90, 180, and 270 deg). This methodology was also shown to be useful for evaluating performance using an alternative head-controlled input device for two subjects having cerebral palsy, and measured subtle performance improvements after providing a disabled subject with lateral torso support.

Adult↗