Michele Bellantoni

Effects of single nightly injections of growth hormone—releasing hormone (GHRH 1–29) in healthy elderly men

Age-related reductions in growth hormone (GH) and insulin-like growth factor-I (IGF-I) may contribute to decreased muscle mass and strength in older persons. The relationship of this phenomenon to skeletal muscle bioenergetics has not been reported. We sought to determine whether administration of GH-releasing hormone (GHRH) would sustain increases in GH and IGF-I and improve skeletal muscle function and selected measures of body composition and metabolism. We measured GH secretion, muscle strength, muscle histology, and muscle energy metabolism by phosphorus nuclear magnetic resonance spectroscopy (31P-NMRS), body composition, and endocrine-metabolic functions before and after 6 weeks of treatment. Eleven healthy, ambulatory, non-obese men aged 64 to 76 years with low baseline IGF-I levels were treated at home as outpatients by nightly subcutaneous self-injections of 2 mg GHRH for 6 weeks. We measured GH levels in blood samples obtained every 20 minutes from 8:00 PM to 8:00 AM; AM serum levels of IGF-I, IGF binding protein-3 (IGFBP-3), and GH binding protein (GHBP); muscle strength; muscle histology; the normalized phosphocreatine abundance, PCr/[PCr + Pi], and intracellular pH in forearm muscle by NMRS during both sustained and ramped exercise; body composition by dual-energy x-ray absorptiometry (DEXA); lipid levels; and glucose, insulin, and GH levels during an oral glucose tolerance test (OGTT). GHRH treatment increased mean nocturnal GH release (P < .02), the area under the GH peak ([AUPGH] P < .006), and GH peak amplitude (P < .05), with no change in GH pulse frequency or in levels of IGF-I, IGFBP-3, or GHBP Two of six measures of muscle strength, upright row (P < .02) and shoulder press (P < .04), and a test of muscle endurance, abdominal crunch (P < .03), improved. GHRH treatment did not alter exercise-mediated changes in PCr/[PCr + Pi] or intracellular pH, but decreased or abolished significant relationships between changes in PCr/[PCr + Pi] or pH and indices of muscle strength. GHRH treatment did not change weight, body mass index, waist to hip ratio, DEXA measures of muscle and fat, muscle histology, glucose, insulin, or GH responses to OGTT, or lipids. No significant adverse effects were observed. These data suggest that single nightly doses of GHRH are less effective than multiple daily doses of GHRH in eliciting GH- and/or IGF-I-mediated effects. GHRH treatment may increase muscle strength, and it alters baseline relationships between muscle strength and muscle bioenergetics in a manner consistent with a reduced need for anaerobic metabolism during exercise. Thus, an optimized regimen of GHRH administration might attenuate some of the effects of aging on skeletal muscle function in older persons.

Air-Fluidized Bed Treatment of Nursing Home Patients with Pressure Sores

There are no large studies on long‐term treatment of nursing home patients with pressure sores. A 4‐year experience of treating 95 nursing home patients on air‐fluidized beds was reviewed. Treated patients were elderly (median age 73 years) and neurologically impaired (79% with dementia, cerebral vascular accident, or anoxic encephalopathy). The index pressure sores (deepest truncal sore for each patient) were large (median surface area 35.3 cm2) and commonly located on the sacrum (41%) and trochanters (38%). Only 13 of 95 (14%) index sores healed completely, and only two small sores healed in <30 days. No others treated <30 days had ≥ 50% reduction in sore surface area. Patients were grouped according to whether or not treatment was < 30 days, and for those treated ≥ 30 days, according to whether or not ≥ 50% reduction in sore surface area occurred. None of the easily measured patient characteristics examined were associated with longer or more successful treatment. These results indicate that although air‐fluidized beds can be used to treat pressure sores successfully, even in severely debilitated nursing home patients, no simple criteria can be used to predict which patients will benefit from this treatment. Because long periods of time are necessary for treatment [median trial length 79 days and 17 of 95 (18%) trials >180 days], substantial patient‐care expenditures result. Prospective studies comparing other medical and surgical interventions with air‐fluidized bed therapy are needed before these beds are used routinely for long‐term treatment of nursing home patients with severe pressure sores.

A Theory-Based Online Hip Fracture Resource Center for Caregivers: Effects on Dyads

Background:Hip fracture is a serious injury for older adults, usually requiring surgical repair and extensive therapy. Informal caregivers can help older adults make a successful recovery by encouraging them to adhere to the therapy plans and improve their health behaviors. Few resources, however, are available for these caregivers to learn about how to assist their care receivers and cope with their unique caregiving situations. Objective:The study aims were to develop a comprehensive theory-based online hip fracture resource center (OHRC) for caregivers, Caring for Caregivers, and conducted a feasibility trial. Methods:The OHRC included self-learning modules, discussion boards, Ask the Experts, and a virtual library. The feasibility of the intervention was assessed by usage and usability. The feasibility of the future trial was tested using a one-group pre–post design on 36 caregiver–care receiver dyads recruited from six hospitals. The caregivers used the OHRC for 8 weeks. The impact of the intervention was assessed on both caregivers (primary) and care receivers (secondary). The data were analyzed by descriptive statistics, paired t tests, and content analyses. Results:On average, caregivers reviewed five modules and used the discussion board 3.1 times. The mean perceived usability score for the OHRC was 74.04 ± 7.26 (range, 12–84). Exposure to the OHRC significantly improved caregivers’ knowledge about the care of hip fracture patients (t = 3.17, p = .004) and eHealth literacy (t = 2.43, p = .002). Changes in other caregiver outcomes (e.g., strain, coping, and social support) and care receiver outcomes (e.g., self-efficacy for exercise and osteoporosis medication adherence) were favorable but not significant. Discussion:The findings suggest that the OHRC was user-friendly and could be beneficial for caregivers. Additional larger-scale trials are needed to assess the effectiveness of the intervention on outcomes.

Interrelationship of spontaneous growth hormone axis activity, body fat, and serum lipids is healthy elderly women and men☆

Aging is associated with decreased growth hormone (GH) secretion and plasma insulin-like growth factor-I (IGF-I) levels, increased total and abdominal fat, total and low-density lipoprotein (LDL) cholesterol, and triglycerides, and reduced high-density lipoprotein (HDL) cholesterol. Similar changes in lipids and body composition occur in nonelderly GH-deficient adults and are reversed with GH administration. To examine whether GHIGF-1 axis function in the elderly is related to the lipid profile independently of body fat, we evaluated GH secretion, serum IGF-I and IGF binding protein-3 (IGFBP-3) levels, adiposity via the body mass index (BMI), waist to hip ratio (WHR), dual-energy x-ray absorptiometry (DEXA), and magnetic resonance imaging (MRI), and circulating lipids in 101 healthy subjects older than 65 years. Integrated nocturnal GH secretion (log IAUPGH) was inversely related (P < .005) to DEXA total and abdominal fat and MRI visceral fat in both genders. Log IAUPGH was inversely related to visceral fat in women (P < .005) and men (P < .0001), but was not significantly related to total fat in either gender. In women, log IAUPGH was related inversely to total and LDL cholesterol and positively to HDL choleterol (P < .008). In men, log IAUPGH was inversely to total cholesterol and triglycerides (P < .005). In women, HDL cholesterol was inversely related to the WHR (P < .005). In men, triglycerides were positively relaed (P < .001) to the WHR and DEXA abdominal and MRI visceral fat. Multivariate regression revealed log IAUPGH, but not DEXA total body fat, to be an Independent determinant of total (P < .001 for women and P = .01 for men) and LDL (P < .007 and P = .05) cholesterol in both sexes and of HDL cholesterol (P < .005) and triglycerides (P < .03) in women. Log IAUPGH, but not DEXA abdominal fat, related to total (P < .005 and P < .03) and LDL (P < .03 and P = .05) cholesterol in both genders and to HDL in women (P < .05). Log IAUPGH, but not MRI visceral fat, was related to total cholesterol (P < .03 and P = .05) in women and men. Age, IGF-I, and IGFBP-3 were not significantly related to any body fat or lipid measures, except for a positive corelation of IGF-I with triglycerides in men. Thus, endogenous nocturnal GH secretion predicts total, LDL, and HDL cholesterol levels independently of total or abdominal fat, suggesting that it is an independent cardiometabolic risk factor in healthy elderly people.

An International Model for Geriatrics Program Development in China: The Johns Hopkins–Peking Union Medical College Experience

China has the worlds largest and most rapidly growing older adult population. Recent dramatic socioeconomic changes, including a large number of migrating workers leaving their elderly parents and grandparents behind and the 4:2:1 family structure caused by the one‐child policy, have greatly compromised the traditional Chinese family support for older adults. These demographic and socioeconomic factors, the improved living standards, and the quest for higher quality of life are creating human economic pressures. The plight of senior citizens is leading to an unprecedented need for geriatrics expertise in China. To begin to address this need, the Johns Hopkins University School of Medicine (JHU) and Peking Union Medical College (PUMC) have developed a joint international project aimed at establishing a leadership program at the PUMC Hospital that will promote quality geriatrics care, education, and aging research for China. Important components of this initiative include geriatrics competency training for PUMC physicians and nurses in the Division of Geriatric Medicine and Gerontology at JHU, establishing a geriatrics demonstration ward at the PUMC Hospital, faculty exchange between JHU and PUMC, and on‐site consultation by JHU geriatrics faculty. This article describes the context and history of this ongoing collaboration and important components, progress, challenges, and future prospects, focusing on the JHU experience. Specific and practical recommendations are made for those who plan such international joint ventures. With such unique experiences, it is hoped that this will serve as a useful model for international geriatrics program development for colleagues in the United States and abroad.

Influence of Testosterone on the GH—IGF-I Axis in Healthy Elderly Men

Numerous in vivo and in vitro animal studies attest to the complex interplay between gonadal steroids and the GHRH—somatostatin-GH—IGF-I axis in the male and female, a topic that has been excellently and extensively reviewed (1–3). In male rats, consensus exists that the daily secretion of growth hormone (GH) is severalfold greater than that of females; that males release GH in high-amplitude, regular pulses, with low interpulse GH concentrations, whereas females secrete GH in low-amplitude, irregular pulses, with higher interpulse GH levels; and that there are many gender-distinct differences in the central nervous system and peripheral regulatory components of the GH axis, both in the absence and presence of endogenous or exogenous testosterone (1–3).

Dissemination of a theory-based online bone health program: Two intervention approaches

With the increasing nationwide emphasis on eHealth, there has been a rapid growth in the use of the Internet to deliver health promotion interventions. Although there has been a great deal of research in this field, little information is available regarding the methodologies to develop and implement effective online interventions. This article describes two social cognitive theory–based online health behavior interventions used in a large-scale dissemination study (N = 866), their implementation processes, and the lessons learned during the implementation processes. The two interventions were a short-term (8-week) intensive online Bone Power program and a longer term (12-month) Bone Power Plus program, including the Bone Power program followed by a 10-month online booster intervention (biweekly eHealth newsletters). This study used a small-group approach (32 intervention groups), and to effectively manage those groups, an eLearning management program was used as an upper layer of the Web intervention. Both interventions were implemented successfully with high retention rates (80.7% at 18 months). The theory-based approaches and the online infrastructure used in this study showed a promising potential as an effective platform for online behavior studies. Further replication studies with different samples and settings are needed to validate the utility of this intervention structure.

Effect of Short-Term estrogen with and without progesterone therapy on circulating markers of endothelial activation and injury in postmenopausal women with unstable angina pectoris☆

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Factors associated with hormone replacement therapy use in low-income urban women

Hormone replacement therapy (HRT) in the postmenopausal period results in significant long-term health benefits for aging women. Epidemiologic data suggest it may prevent age-related cardiovascular disease (CVD) and bone loss. Cardiovascular disease is the leading cause of mortality and disability in women.1 African-American women have a higher incidence of CVD and suffer the highest mortality compared to other races.2,3 Hormone replacement therapy use has been shown to decrease the risk of developing CVD by 20 –50%3,4 and overall mortality by 25%.4,5 Osteoporosis effects approximately 50% of women over 50 and 90% of women over 75. It is the major cause of nearly 1.5 million bone fractures in the U. S. annually.6 Postmenopausal bone loss can be decreased with HRT use resulting in a 50% reduction in fractures.7 Although the relationship is less clear, preliminary studies suggest that HRT may reduce the risk of developing Alzheimer’s disease as well.8,9 In spite of evidence supporting the benefits of HRT use, on average less than 40% of women use HRT and less than 50% of those stay on therapy for longer than one year.10 These rates vary significantly for different populations, with many studies reporting the highest use among white, younger, educated women,11–15 although one study found HRT use was more common in older

The Effects of an Online Theory-Based Bone Health Program for Older Adults:

An estimated 10 million Americans age 50 and older have osteoporosis, and many experience associated fractures. Although several interventions have been shown to be effective in preventing osteoporosis, their impact on bone health among older adults was limited. The aim of this study was, therefore, to examine the effects of a theory-based online bone health program (Bone Power program) for a large number of older adults. The 8-week program included learning modules, discussion boards, and other resources. Participants (N = 866; M age = 62.5 years) were recruited online and randomized into a Bone Power or control group. At the end of the intervention, the Bone Power group showed significantly greater improvement over the control group in osteoporosis knowledge, self-efficacy/outcome expectations for calcium intake and exercise, and calcium intake and exercise behaviors. This study’s findings suggest that online health programs can be effective in improving older adults’ knowledge, beliefs, and health behaviors.