Biomedical subjects

Linda J Woodhouse

Publications and source records attributed to Linda J Woodhouse.

12 recordsLinked to original sources

PubMed2006

The influence of growth hormone status on physical impairments, functional limitations, and health-related quality of life in adults.

The availability of recombinant human GH and somatostatin analogs has resulted in widespread treatment for adults with GH deficiency (GHD) and those with GH excess (acromegaly). Despite being at opposite ends of the spectrum in terms of their GH/IGF-I axis, both of these populations experience overlapping somatic impairments. Adults with untreated GHD have low circulating levels of IGF-I that manifest as altered body composition with increased fat and reduced lean body and skeletal muscle mass. At the other end of the spectrum, adults with GH excess, who have elevated levels of IGF-I, also have altered body composition. Impairments that result from disorders of either GHD or GH excess are both associated with increased functional limitations, such as reduced ability to walk quickly for prolonged periods, and poorer health-related quality of life (HR-QoL). Adults with untreated GHD and GH excess both commonly complain of excessive fatigue that seems to be associated more with impaired aerobic than muscular performance. Several studies have documented that administration of GH or somatostatin analogs to adults with GHD or GH excess, respectively, ameliorates abnormal biochemical profile and the associated somatic impairments. However, whether these improvements translate into improved physical function in adults with GHD or GH excess remains largely unknown, and their impact on HR-QoL controversial. Review of placebo-controlled trials to date suggests that GH and somatostatin analogs have greater effects on gas exchange and aerobic performance than as anabolic agents on skeletal muscle mass and function. Future investigations should include dose-response studies to establish the optimal combination of pharmacological agents plus exercise required to improve not only biochemical markers but also physical function and HR-QoL in adults with GHD or GH excess.

Acromegaly↗

PubMed2006

Effects of transdermal testosterone administration on insulin sensitivity, fat mass and distribution, and markers of inflammation and thrombolysis in human immunodeficiency virus-infected women with mild to moderate weight loss.

OBJECTIVE: To determine the effects of raising serum T levels into the high normal female range by transdermal T administration on insulin sensitivity, fat volume, and markers of inflammation and thrombolysis in HIV-infected women with recent weight loss. DESIGN: Placebo-controlled, randomized clinical trial. SETTING: Academic clinical research center. PATIENT(S): Fifty-two HIV-infected, menstruating women with >5% weight loss over the prior 6 months and current T<33 ng/dL. INTERVENTION(S): Placebo or T patches twice weekly for 24 weeks to achieve nominal delivery of 300 microg T daily. MAIN OUTCOME MEASURE(S): Testosterone by liquid chromatography-tandem mass spectrometry, insulin sensitivity by the frequently sampled intravenous glucose tolerance test (FSIVGT), abdominal and thigh fat volumes by magnetic resonance imaging (MRI), and C-reactive protein (CRP) as a measure of inflammation and plasminogen-activated inhibitor-1 (PAI-1) levels as a marker of thrombolysis. RESULT(S): Serum and free T levels significantly increased into the high normal female range in T-treated but not placebo-treated women. Insulin sensitivity by FSIVGT, whole body, thigh SC, and intra-abdominal fat volumes, and CRP and PAI-1 levels did not change significantly in either group and were not significantly different between the two groups. Fasting insulin increased in the placebo group and fell slightly in the T group, resulting in significant differences in change between groups. CONCLUSION(S): Twenty-four weeks of elevation of serum T levels into the high normal female range in HIV-infected women with mild to moderate weight loss by transdermal T patches did not adversely affect insulin sensitivity, whole-body fat mass or regional fat distribution, or markers of inflammation and thrombolysis. More prolonged and larger studies are needed to determine the effects of higher doses of T on body composition and insulin sensitivity in women.

Administration, Topical↗

PubMed2006

Performance measures provide assessments of pain and function in people with advanced osteoarthritis of the hip or knee.

BACKGROUND AND PURPOSE: Pain and physical function are core outcome measures for people with osteoarthritis, and self-report questionnaires have been the preferred assessment method. There is evidence suggesting that self-reports of physical function represent what people experience when performing activities rather than their ability to perform activities. The purpose of this study was to examine the factorial validity of performance-specific assessments of pain and function. SUBJECTS: The sample consisted of 177 participants who had osteoarthritis of the hip (n=81) or knee (n=96) and who were awaiting total joint arthroplasty. METHODS: Through a cross-sectional design, participants performed 4 performance activities (self-paced walk test, stair test, Timed "Up & Go" Test, and Six-Minute Walk Test). OUTCOMES: were time or distance (function) and pain ratings obtained immediately after each activity. The authors conceptualized 2 correlated factors, with pain items loading uniquely on 1 factor and functional items loading on the second factor, and uncorrelated error terms. Confirmatory factor analysis was applied. RESULTS: Initial analysis yielded results consistent with the conceptualized model in this study with the exception of a nonzero correlation between the stair pain and function error terms. Dropping the stair test provided results consistent with the conceptualized model. DISCUSSION AND CONCLUSION: Given the limitations of self-report alone as a method of obtaining reasonably distinct assessments of pain and function, the extent to which performance-specific assessments could accomplish this goal was examined in this study. It was found that collectively the walk test, Timed "Up & Go" Test, and Six-Minute Walk Test yielded 2 factors consistent with the health concepts of pain and function. The authors believe that the application of these tests may provide clinicians and clinical researchers with more distinct impressions of pain and function that complement information from self-report measures.

Aged↗

PubMed2005

A randomized, placebo-controlled trial of nandrolone decanoate in human immunodeficiency virus-infected men with mild to moderate weight loss with recombinant human growth hormone as active reference treatment.

OBJECTIVE: We compared the effectiveness of a biweekly regimen of 150 mg nandrolone with placebo in HIV-infected men with mild to moderate weight loss and contrasted its effects against a Food and Drug Administration-approved regimen of recombinant human (rh)GH. METHODS: In this placebo-controlled, randomized, 12-wk trial, placebo and nandrolone (150 mg im biweekly) were administered double blind, and rhGH (6 mg sc daily) was administered in an open-label manner. Participants were HIV-infected men with 5-15% weight loss over 6 months and on stable antiretroviral therapy for more than 12 wk. Lean body mass (LBM), muscle performance, physical function, endurance, hormone levels, insulin sensitivity, sexual function, quality of life, and appetite were assessed at baseline and after 12 wk. RESULTS: Nandrolone administration was associated with a greater increase in LBM (+1.6 +/- 0.3 kg) by dual-energy x-ray absorptiometry scan than placebo (+0.4 +/- 0.3 kg; P < 0.05); however, the change in LBMs with nandrolone was not significantly different from rhGH (+2.5 +/- 0.3 kg). Nandrolone administration was also associated with significantly greater gains in fat-free mass (+1.6 +/- 0.3 kg), body cell mass (+1.0 +/- 0.2 kg), and intracellular water (+0.9 +/- 0.2 kg) than placebo; these changes in the nandrolone group were not significantly different from the rhGH group. rhGH administration was associated with greater loss of whole body fat mass and higher frequency of drug-related adverse effects and treatment discontinuations than nandrolone and placebo and a greater increase in extracellular water than nandrolone. Nandrolone treatment was associated with greater improvements in perception of health than rhGH and sexual function than placebo. The cachexia/anorexia scores, health care resource use, and insulin sensitivity did not significantly change. CONCLUSION: We conclude that nandrolone is superior to placebo and not significantly different from a Food and Drug Administration-approved regimen of rhGH in improving lean body mass in HIV-infected men with mild to moderate weight loss.

Adipose Tissue↗

PubMed2005

Dose-dependent effects of testosterone on sexual function, mood, and visuospatial cognition in older men.

CONTEXT: The relationships between testosterone dose and its effects on sexual function, mood, and visuospatial cognition are poorly understood. OBJECTIVE: To elucidate testosterone dose-response relationships in older men, we examined the effects of graded testosterone doses on sexual function, mood, and visuospatial cognition in healthy, older men (age, 60-75 yr). SETTING: This study was performed at the General Clinical Research Center. INTERVENTION/METHODS: Subjects each received a long-acting GnRH agonist to suppress endogenous testosterone production and were randomized to receive one of five doses (25, 50, 125, 300, and 600 mg) of testosterone enanthate weekly for 20 wk. Questionnaires were used to evaluate sexual function. Scores for overall sexual function as well as subcomponents of sexual function (libido, sexual activity, and erectile function) were calculated. RESULTS: Changes in overall sexual function (P = 0.003) and waking erections (P = 0.024) differed by dose. An interaction between libido and being sexually active was observed, such that libido changed by testosterone dose only among men who reported being sexually active at the beginning of the study (P = 0.009). Men's log-transformed free testosterone levels during treatment were positively correlated with overall sexual function (P = 0.001), waking erections (P = 0.040), spontaneous erections (P = 0.047), and libido (P = 0.027), but not with intercourse frequency (P = 0.428) or masturbation frequency (P = 0.814). No effects of testosterone dose were observed on two measures of mood: Hamilton's Depression Inventory (P = 0.359) and Young's Mania Scale (P = 0.851). The number of trials completed on a computer-based test of visuospatial cognition differed by dose (P = 0.042), but the number of squares correctly completed on this task did not differ by dose (P = 0.159). CONCLUSIONS: Different aspects of male behavior respond differently to testosterone. When considered together with previous data from young men, these data indicate that testosterone dose-response relationships for sexual function and visuospatial cognition differ in older and young men.

Affect↗

PubMed2005

Circulating and synovial levels of IGF-I, cytokines, physical function and anthropometry differ in women awaiting total knee arthroplasty when compared to men.

PURPOSE: Determine if gender differences in osteoarthritis relate to cytokine and growth factor levels. METHODS: Cross-sectional comparison of serum and synovial concentrations of cytokines (IL-1alphabeta, TNF-alpha, IL-6), growth factors (IGF-I, TGF-beta, IRAP), physical performance and perceived function in total knee arthroplasty candidates (TKAC) (n=17) and healthy controls (n=21) was done. RESULTS: Serum IGF-I values were reduced in female (TKAC 137.6+/-7.2; Controls 160.2+/-26.2) but not male TKAC (TKAC 182.6+/-18.4; Controls 184.0+/-18.4) (p<0.05).). Serum and synovial levels of cytokines and growth factors did not differ significantly by group or gender. Physical performance testing (SPW, TUG) revealed significant group and gender differences (p=0.001) with women demonstrating greater functional impairment. DISCUSSION: A systemic, not local component to OA pathophysiology may exist for female TKAC. Male TKAC were less impaired, and their IGF-I levels differ little from Control values.

Aged↗

PubMed2004

Dose-dependent effects of testosterone on regional adipose tissue distribution in healthy young men.

Testosterone supplementation reduces total body adipose tissue (AT), but we do not know whether the effects are uniformly distributed throughout the body or are region specific, or whether they are dose related. We determined the effects of graded doses of testosterone on regional AT distribution in 54 healthy men (18-35 yr) in a 20-wk, randomized, double-blind study of combined treatment with GnRH agonist plus one of five doses (25, 50, 125, 300, or 600 mg/wk) of testosterone enanthate (TE). Total body, appendicular, and trunk AT and lean body mass were measured by dual-energy x-ray absorptiometry, and sc, intermuscular, and intraabdominal AT of the thigh and abdomen were measured by magnetic resonance imaging. Treatment regimens resulted in serum nadir testosterone concentrations ranging from subphysiological to supraphysiological levels. Dose-dependent changes in AT mass were negatively correlated with TE dose at all sites and were equally distributed between the trunk and appendices. The lowest dose was associated with gains in sc, intermuscular, and intraabdominal AT, with the greatest percent increase occurring in the sc stores. At the three highest TE doses, thigh intermuscular AT volume was significantly reduced, with a greater percent loss in intermuscular than sc depots, whereas intraabdominal AT stores remained unchanged. In conclusion, changes in testosterone concentrations in young men are associated with dose-dependent and region-specific changes in AT and lean body mass in the appendices and trunk. Lowering testosterone concentrations below baseline increases sc and deep AT stores in the appendices and abdomen, with a greater percent increase in sc depots. Conversely, elevating testosterone concentrations above baseline induces a greater loss of AT from the smaller, deeper intermuscular stores of the thigh.

Abdomen↗

PubMed2003

Development of models to predict anabolic response to testosterone administration in healthy young men.

Considerable heterogeneity exists in the anabolic response to androgen administration; however, the factors that contribute to variation in an individual's anabolic response to androgens remain unknown. We investigated whether testosterone dose and/or any combination of baseline variables, including concentrations of hormones, age, body composition, muscle function, and morphometry or polymorphisms in androgen receptor could explain the variability in anabolic response to testosterone. Fifty-four young men were treated with a long-acting gonadotropin-releasing hormone (GnRH) agonist and one of five doses (25, 50, 125, 300, or 600 mg/wk) of testosterone enanthate (TE) for 20 wk. Anabolic response was defined as a change in whole body fat-free mass (FFM) by dual-energy X-ray absorptiometry (DEXA), appendicular FFM (by DEXA), and thigh muscle volume (by magnetic resonance imaging) during TE treatment. We used univariate and multivariate analysis to identify the subset of baseline measures that best explained the variability in anabolic response to testosterone supplementation. The three-variable model of TE dose, age, and baseline prostate-specific antigen (PSA) level explained 67% of the variance in change in whole body FFM. Change in appendicular FFM was best explained (64% of the variance) by the linear combination of TE dose, baseline PSA, and leg press strength, whereas TE dose, log of the ratio of luteinizing hormone to testosterone concentration, and age explained 66% of the variation in change in thigh muscle volume. The models were further validated by using Ridge analysis and cross-validation in data subsets. Only the model using testosterone dose, age, and PSA was a consistent predictor of change in FFM in subset analyses. The length of CAG tract was only a weak predictor of change in thigh muscle volume and lean body mass. Hence, the anabolic response of healthy, young men to exogenous testosterone administration can largely be predicted by the testosterone dose.

Absorptiometry, Photon↗

PubMed2003

Women awaiting knee replacement have reduced function and growth hormone.

Women experience greater functional impairment and occurrence of osteoarthritis than men. We hypothesized that lower levels of serum insulin-like growth factor-I may contribute to gender differences in physical impairments. A cross-sectional comparison (n = 139) was done on candidates having total knee arthroplasty and healthy controls subjects of similar age (range, 55-75 years). Physical function, perceived function, and serum insulin-like growth factor levels were compared across group and gender using analysis of variance. Insulin-like growth factor-I values were markedly reduced in women overall and women having surgery had significantly reduced levels despite lean body mass correction. Values consistent with clinical hormone deficiency were observed in 21% of women and only 4% of men having arthroplasty. Physical function was markedly reduced in women, at times functioning only 33% when compared with healthy women, whereas men's limitations were not as profound. The current findings indicate that physical function is more impaired and serum insulin-like growth factor-I is markedly reduced in women awaiting arthroplasty than their male counterparts. The gender differences observed biochemically and with functional performance indicate that the pathophysiology of end stage osteoarthritis may differ between men and women.

Activities of Daily Living↗

PubMed2003

A treadmill ramp protocol using simultaneous changes in speed and grade.

INTRODUCTION: A treadmill exercise test requiring a low initial metabolic rate that then increments the work rate linearly to reach the subject's limit of tolerance in approximately 10 min would have significant advantages for exercise testing and rehabilitation of subjects with impaired exercise tolerance. METHODS: We developed such a treadmill protocol that uses a linear increase in walking speed coupled with a curvilinear increase in treadmill grade to yield a linear increase in work rate. RESULTS: Twenty-two healthy, sedentary subjects performed both this new treadmill protocol and a standard cycle ergometry ramp protocol eliciting similar work rate profiles. The low initial treadmill speed and grade resulted in a low initial metabolic rate, commensurate with unloaded pedaling on a cycle ergometer (average [OV0312]O2 = 0.54 +/- 0.16 vs 46 +/- 0.12 l x min(-1)). This combination of simultaneous increase in speed and grade yielded a linear work rate and its oxygen uptake response (R2 = 0.96 +/- 0.03) with a slope of 11.4 +/- 2.4 ml x min(-1) x W(-1)-slightly, but significantly, higher than on the cycle (9.6 +/- 2.0 ml x min(-1) x W(-1)). This difference was attributed to unmeasured work associated, for example, with additional limb movements and frictional losses. As previously demonstrated, both the peak oxygen uptake and the estimated lactate threshold were higher on the treadmill than for cycle ergometry (averaging 23% and 27%, respectively, in these subjects). CONCLUSION: This treadmill protocol provides a linear profile of work rate as is currently standard for cycle ergometry and is appropriate for testing of subjects with low exercise tolerance.

Adolescent↗

PubMed2002

Ventilation threshold as a measure of impaired physical performance in adults with growth hormone excess.

OBJECTIVE: Fatigue is a prominent symptom among patients with GH excess and acromegaly. Identifying the physiological basis of such complaints and obtaining objective measures to quantify their severity remains an ongoing challenge. We investigated whether submaximal measures of aerobic performance can be used to assess GH excess-associated fatigue objectively. DESIGN AND PATIENTS: To investigate this possibility we examined the relation between physical function and physical capacity in 12 patients with active acromegaly and persistent fatigue before and after 3 and 6 months of treatment with the long-acting somatostatin analogue octreotide (LAR(R)). MEASUREMENTS: Heart rate (HR) and rating of perceived exertion (RPE using Borg's 10-point scale) were measured during a 160-metre self-paced walk test (SPW). Maximum oxygen uptake (VO2max) and ventilation threshold (VeT: a measure of work rate when breathlessness develops) were measured during a progressive treadmill test to fatigue or symptom-limited maximum. The Profile Of Mood States questionnaire (POMS) was used to quantify subjective feelings of fatigue and vigour. Morning fasting levels of GH and IGF-I were measured using immunoassay of serum samples. RESULTS: SPW speed at a fast pace of 1.69 +/- 0.18 m/s was achieved with higher than normal HR (112 +/- 15/min; normal = 102) and RPE (2.4 +/- 1.2). Similar to GH-deficient adults, VO2max (22.6 +/- 6.4 ml.kg-1.min-1; normal approximately 30 ml.kg-1.min-1) and VeT (13.1 +/- 2.9 ml.kg-1.min-1; predicted normal approximately 16 ml.kg-1(min-1) were low. However, VeT occurred at a normal fraction of VO2max (VeT/VO2max = 0.58). VeT was significantly increased and plasma IGF-I levels reduced following 3 and 6 months of octreotide LAR(R) treatment. Reduction in circulating IGF-I levels was correlated with improvement in reported vigour (r = 0.85) and VeT (r = 0.65) (P < 0.05). CONCLUSIONS: Our findings demonstrate impairment in physical function and physical capacity consistent with the perception of increased fatigue among acromegalic patients. These objective measures of compromised physical function are similar to the changes that we have reported previously in adults with GH deficiency. Taken together, these data suggest that a narrow window for GH/IGF-I levels is required to maintain optimal physical function.

Acromegaly↗

PubMed2002

Comparison of gender and group differences in self-report and physical performance measures in total hip and knee arthroplasty candidates.

Functional measures (fast self-paced walk test, stair climb, and timed up and go) and a self-report measure of function (Lower Extremity Activity Profile) were assessed in 1,805 total hip (761) and knee (1044) arthroplasty candidates (1,063 women, 742 men) preoperatively. Women represented 59% of the study subjects and showed greater disability than men (P <or= .001) in the physical performance and self-report measures. Although the hip arthroplasty group perceived greater functional disability and less satisfaction, the impact of osteoarthritis on the hip and knee was similar in terms of walking and stair performance. Overall, there was low-to-moderate correlation between the self-report and physical performance measures (r = .21- .50).

Activities of Daily Living↗