Angela Gentili

NEUROPHYSIOLOGICAL REGULATION AND TARGET-TISSUE IMPACT OF THE PULSATILE MODE OF GROWTH HORMONE SECRETION IN THE HUMAN

Neuroendocrine axes function as an ensemble of regulatory loci which communicate and maintain homeostasis via time-delayed blood-borne signals. The growth hormone (GH)-insulin-like growth factor I (IGF-I) feedback axis sustains a vividly pulsatile mode of interglandular signalling. Pulsatility is driven jointly by hypothalamic GH-releasing hormone (GHRH) and GH-releasing peptide (GHRP), and modulated by somatostatinergic restraint. Paradoxically, intermittent somatostatin inputs also facilitate somatotrope-cell responses to recurrent secretagogue stimuli, thereby amplifying pulsatile GH secretion. A concurrent low basal (8-12% of normal total) rate of GH release is controlled positively by GHRH and GHRP and negatively by somatostatin. Sex-steroid hormones (such as oestradiol and aromatizable androgen) and normal female and male puberty augment GH secretory-burst mass 1.8- to 3.5-fold, whereas ageing, relative obesity, physical inactivity, hypogonadism, and hypopituitarism mute the amplitude/mass of pulsatile GH output. An abrupt rise in circulating GH concentration stimulates rapid internalization of the GH receptor in peripheral target tissues, and evokes second-messenger nuclear signalling via the STAT 5b pathway. Discrete GH peaks stimulate linear (skeletal) growth and drive muscle IGF-I gene expression more effectually than basal (time-invariant) GH exposure. A brief pulse of GH can saturate the plasma GH-binding protein system and achieve prolonged plasma GH concentrations by convolution with peripheral distribution and clearance mechanisms. A single burst of GH secretion also feeds back after a short latency on central nervous system (CNS) regulatory centres via specific brain GH receptors to activate somatostatinergic and reciprocally subdue GHRH outflow. This autoregulatory loop probably contributes to the time-dependent physiologically pulsatile dynamics of the GH axis. More slowly varying systemic IGF-I concentrations may also damp GH secretory pulse amplitude by delayed negative-feedback actions. According to this simplified construct, GH pulsatility emerges due to time-ordered multivalent interfaces among GHRH/GHRP feedforward and somatostatin, GH and IGF-I feedback signals. Resultant GH pulses trigger tissue-specific gene expression, thereby promoting skeletal and muscular growth, metabolic and body compositional adaptations, and CNS reactions that jointly maintain health and homeostasis.

Deconstructing Chronic Low Back Pain in the Older Adult: Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment: Part IV: Depression.

OBJECTIVE To present the fourth in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of twelve important contributors to pain and disability in older adults with CLBP. This article focuses on depression. METHODS The evaluation and treatment algorithm, a table articulating the rationale for the individual algorithm components, and stepped-care drug recommendations were developed using a modified Delphi approach. The Principal Investigator, a three-member content expert panel, and a nine-member primary care panel were involved in the iterative development of these materials. The algorithm was developed keeping in mind medications and other resources available within Veterans Health Administration (VHA) facilities. As panelists were not exclusive to the VHA, the materials can be applied in both VHA and civilian settings. The illustrative clinical case was taken from one of the contributors clinical practice. RESULTS We present an algorithm and supportive materials to help guide the care of older adults with depression, an important contributor to CLBP. The case illustrates an example of a complex clinical presentation in which depression was an important contributor to symptoms and disability in an older adult with CLBP. CONCLUSIONS Depression is common and should be evaluated routinely in the older adult with CLBP so that appropriately targeted treatments can be planned and implemented.

Deconstructing chronic low back pain in the older adult--step by step evidence and expert-based recommendations for evaluation and treatment: part I: Hip osteoarthritis.

OBJECTIVE To present the first in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of twelve important contributors to pain and disability in older adults with CLBP. This article focuses on hip osteoarthritis (OA). METHODS The evaluation and treatment algorithm, a table articulating the rationale for the individual algorithm components, and stepped-care drug recommendations were developed using a modified Delphi approach. The Principal Investigator, a five-member content expert panel and a nine-member primary care panel were involved in the iterative development of these materials. The algorithm was developed keeping in mind medications and other resources available within Veterans Health Administration (VHA) facilities. As panelists were not exclusive to the VHA, the materials can be applied in both VHA and civilian settings. The illustrative clinical case was taken from one of the contributors clinical practice. RESULTS We present an algorithm and supportive materials to help guide the care of older adults with hip OA, an important contributor to CLBP. The case illustrates an example of complex hip-spine syndrome, in which hip OA was an important contributor to disability in an older adult with CLBP. CONCLUSIONS Hip OA is common and should be evaluated routinely in the older adult with CLBP so that appropriately targeted treatment can be designed.

Deconstructing Chronic Low Back Pain in the Older Adult—Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment: Part X: Sacroiliac Joint Syndrome

OBJECTIVE To present an algorithm of sequential treatment options for managing sacroiliac joint (SIJ) pain in the setting of chronic low back pain (CLBP) in the older adult. This is the tenth part in a series, and includes an illustrative clinical case. METHODS The stepped care drug table and evaluation and treatment algorithm were created following a thorough literature review of approaches and subsequent analysis through a modified Delphi process. The principal investigator developed the initial draft, which was refined for content by an interdisciplinary panel of five experts. The refined materials were then assessed for the feasibility of implementation and validity of recommendations for older adults in a primary care setting by a panel of nine primary care providers. While not exclusive to Veterans Health Administration (VHA) facilities, an emphasis was made to include resources and medications available to providers in the VHA. RESULTS The algorithm and drug table developed to systematically identify and address SIJ pain in the older adult is presented here. The process should begin with recognizing the presenting symptoms of CLBP stemming from the SI region, and supporting physical exam testing using the compression test and thigh thrust maneuver. Identification of the SIJ as a pain generator is followed by assessment and treatment of contributory factors. SIJ pain treatment should begin with education and self-management including exercise, and may escalate to include interventional procedures and/or referral to a pain rehabilitation program. CONCLUSIONS Pain originating from the SIJ is often under-recognized, but a structured and consistent approach can help identify older patients who would benefit from treatment of this contributor to CLBP. KEY WORDS Chronic Low Back Pain; Sacroiliac Joint Pain; Older Adults.

Deconstructing Chronic Low Back Pain in the Older Adult – Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment: Part III: Fibromyalgia Syndrome

OBJECTIVE To present the third in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of 12 important contributors to pain and disability in older adults with CLBP. This article focuses on fibromyalgia syndrome (FMS). METHODS A modified Delphi approach was used to create the evaluation and treatment algorithm, the table discussing the rationale behind each of the algorithm components, and the stepped-care drug recommendations. The team involved in the creation of these materials consisted of a principal investigator, a 5-member content expert panel, and a 9-member primary care panel. The evaluation and treatment recommendations were based on availability of medications and other resources within the Veterans Health Administration (VHA) facilities. However, non-VHA panelists were also involved in the development of these materials, which can be applied to both VA and civilian settings. The illustrative clinical case was taken from the clinical practice of the principal investigator. RESULTS Following expert consultations and a review of the literature, we developed an evaluation and treatment algorithm with supporting materials to aid in the care of older adults with CLBP who have concomitant FMS. A case is presented that demonstrates the complexity of pain evaluation and management in older patients with CLBP and concomitant FMS. CONCLUSIONS Recognition of FMS as a common contributor to CLBP in older adults and initiating treatment targeting both FMS and CLBP may lead to improved outcomes in pain and disability.

Deconstructing Chronic Low Back Pain in the Older Adult—Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment: Part VII: Insomnia

OBJECTIVE : To present the seventh in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. This article focuses on insomnia and presents a treatment algorithm for managing insomnia in older adults, along with a representative clinical case. METHODS : A modified Delphi process was used to develop the algorithm and supportive materials. A multidisciplinary expert panel representing expertise in health psychology and sleep medicine developed the algorithm and supporting documents that were subsequently refined through an iterative process of input from a primary care provider panel. RESULTS : We present an illustrative clinical case and an algorithm to help guide the care of older adults with insomnia, an important contributor to CLBP and disability. Multicomponent cognitive behavioral therapy for insomnia (CBTI) and similar treatments (e.g., brief behavioral treatment for insomnia [BBTI]) are the recommended first-line treatment. Medications should be considered only if BBTI/CBTI is suboptimal or not effective and should be prescribed at the lowest effective dose for short periods of time (< 90 days). CONCLUSIONS : Insomnia is commonly comorbid with CLBP in older adults and should be routinely evaluated and treated because it is an important contributor to pain and disability. The algorithm presented was structured to assist primary care providers in planning treatment for older adults with CLBP and insomnia.

Bypass Graft Stent Fracture Leading to Saphenous Vein Graft Pseudoaneurysm

An 83-year-old man, with a history of coronary artery bypass graft surgery 19 years before presentation and subsequent percutaneous coronary intervention to saphenous vein graft with placement of a paclitaxel drug-eluting stent 16 years later, presented with a 2-week history of fevers, productive cough, and pleuritic chest pain. He was found to have leukocytosis and chest x-ray evidence of pneumonia with a widened mediastinum. He was admitted for treatment of protracted pneumonia. He had a borderline elevated troponin I, which, in the absence of anginal pain, was thought to be secondary to demand ischemia. A chest radiograph obtained at admission showed bilateral pleural effusions, a right lower lobe infiltrate, and a widened …

The Importance of "High Valence" Events in a Successful Program for Teaching Geriatrics to Medical Students.

Abstract Virginia Commonwealth University developed an enhanced medical student geriattic curriculum that includes required home visits and nursing home visits for second year students (180 per year), an annual Forum on Aging for all first and second year students, and small group exercises. We added 30 hours of basic science material to pre-clinical courses and increased clinical exposure to geriatricians in third and fourth years. Student satisfaction with individual experiences was high. Persistent effects of “high valence” required activities, where emotion played a role, was shown by post-pre survey techniques and focus groups. Fourth year AAMC exit questionnaire items in areas addressed by this curriculum improved markedly between 2002 and 2006, while an internal control changed much less.

Deconstructing Chronic Low Back Pain in the Older Adult-Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment. Part VI: Lumbar Spinal Stenosis.

OBJECTIVE . To present the sixth in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. This article focuses on the evaluation and management of lumbar spinal stenosis (LSS), the most common condition for which older adults undergo spinal surgery. METHODS . The evaluation and treatment algorithm, a table articulating the rationale for the individual algorithm components, and stepped-care drug recommendations were developed using a modified Delphi approach. The Principal Investigator, a five-member content expert panel and a nine-member primary care panel were involved in the iterative development of these materials. The illustrative clinical case was taken from the clinical practice of a contributors colleague (SR). RESULTS . We present an algorithm and supportive materials to help guide the care of older adults with LSS, a condition that occurs not uncommonly in those with CLBP. The case illustrates the importance of function-focused management and a rational approach to conservative care. CONCLUSIONS . Lumbar spinal stenosis exists not uncommonly in older adults with CLBP and management often can be accomplished without surgery. Treatment should address all conditions in addition to LSS contributing to pain and disability.