George Angelidis

Ghrelin New Insights into Female Reproductive System–Associated Disorders and Pregnancy

Ghrelin is considered the endogenous ligand of growth hormone secretagogue receptor type 1a, and its modulatory actions have been demonstrated in a large array of endocrine and nonendocrine functions. According to recent studies, ghrelin seems to act at different levels of the reproductive system, exerting predominantly inhibitory effects on mammalian reproduction. It has been shown to influence the reproductive system by regulating hormone secretion from the brain and by acting directly on the gonads to affect tissue development and steroidogenesis. Thus, the endocrine network, which integrates energy balance and fertility, might involve ghrelin. Furthermore, ghrelin levels and actions have been assessed in various female reproductive system disorders. The findings could lead to a better understanding of the pathogenesis of these disorders and, possibly, to more beneficial therapeutic strategies.Ghrelin is considered the endogenous ligand of growth hormone secretagogue receptor type 1a, and its modulatory actions have been demonstrated in a large array of endocrine and nonendocrine functions. According to recent studies, ghrelin seems to act at different levels of the reproductive system, exerting predominantly inhibitory effects on mammalian reproduction. It has been shown to influence the reproductive system by regulating hormone secretion from the brain and by acting directly on the gonads to affect tissue development and steroidogenesis. Thus, the endocrine network, which integrates energy balance and fertility, might involve ghrelin. Furthermore, ghrelin levels and actions have been assessed in various female reproductive system disorders. The findings could lead to a better understanding of the pathogenesis of these disorders and, possibly, to more beneficial therapeutic strategies.

The Emerging Roles of Adiponectin in Female Reproductive System-Associated Disorders and Pregnancy

Adiponectin, the most abundant adipose-released cytokine, has an important role in metabolism, primarily through reducing insulin resistance. Reproductive functions are known to be influenced by energy balance and adiponectin may be involved in the underlying mechanisms connecting reproduction and metabolism. Interestingly, adiponectin has been shown to exert actions in the female reproductive system, including the hypothalamic–pituitary–ovarian axis and the endometrium. The peripheral effects of this adipocytokine are mediated mainly via 2 receptors, AdipoR1 and AdipoR2. The expression of these receptors has been reported in the brain, ovaries, endometrium, and the placenta. Thus, adiponectin may influence fertility and pregnancy. Furthermore, adiponectin concentrations and effects have been assessed in some pregnancy-associated disorders and gynecological conditions. The findings may lead to the use of adiponectin or its receptors as therapeutic targets in novel treatment strategies of these disorders.

Current and potential roles of ghrelin in clinical practice

Ghrelin is a novel GH-releasing peptide, which has been identified as an endogenous ligand for GH-secretagogue receptor. Ghrelin is mainly secreted by the stomach and plays a critical role in a variety of physiological processes including endocrine, metabolic, cardiovascular, immunological, and other actions. Ghrelin stimulates food intake via hypothalamic neurons and causes a positive energy balance and body weight gain by decreasing fat utilization and promoting adiposity. Given the multiple effects of ghrelin, its potential clinical applications have been evaluated in various conditions. Preliminary trials have shown that it may prove valuable in the management of diseaseinduced cachexia. Ghrelin may improve the wasting syndrome through GH-dependent or GH-independent effects. Moreover, ghrelin may play a role in the management of disorders of gut motility and obesity. Finally, other potential clinical applications of ghrelin include the treatment of patients with diabetes mellitus, infections, rheumatological diseases or GH deficiency and the diagnosis of this hormonal disorder.

SPECT and PET Imaging of Meningiomas

Meningiomas arise from the meningothelial cells of the arachnoid membranes. They are the most common primary intracranial neoplasms and represent about 20% of all intracranial tumors. They are usually diagnosed after the third decade of life and they are more frequent in women than in men. According to the World Health Organization (WHO) criteria, meningiomas can be classified into grade I meningiomas, which are benign, grade II (atypical) and grade III (anaplastic) meningiomas, which have a much more aggressive clinical behaviour. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are routinely used in the diagnostic workup of patients with meningiomas. Molecular Nuclear Medicine Imaging with Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) could provide complementary information to CT and MRI. Various SPECT and PET tracers may provide information about cellular processes and biological characteristics of meningiomas. Therefore, SPECT and PET imaging could be used for the preoperative noninvasive diagnosis and differential diagnosis of meningiomas, prediction of tumor grade and tumor recurrence, response to treatment, target volume delineation for radiation therapy planning, and distinction between residual or recurrent tumour from scar tissue.

Myocardial strain may predict exercise tolerance in patients with reduced and mid-range ejection fraction

BACKGROUND Conventional echocardiographic parameters, such as rest ejection fraction, perform poorly in the prediction of exercise tolerance in heart failure. The aim of the present study was to evaluate the contribution of hemodynamic instability in the observed lower functional capacity and investigate the role of left ventricular strain for the prediction of stress test duration in obese hypertensive patients with reduced ejection fraction. METHODS Sixty-one patients with reduced ejection fraction underwent treadmill exercise echocardiography. Systolic and diastolic echocardiographic parameters were recorded. Moreover, the presence of hemodynamic instability was assessed through N-terminal pro B-type natriuretic peptide (NT-proBNP) measurements at baseline and peak exercise. RESULTS Rest and peak NT-proBNP levels, and their difference, were significantly correlated with mean global strain at peak, which was the only parameter associated with changes in NT-proBNP levels. Rest and peak mean global strain were found to be predictive for the duration of treadmill stress test. In particular, mean global strain, but not left ventricular ejection fraction, was independently correlated with exercise ability. CONCLUSIONS Stress echocardiography may provide important information regarding exercise tolerance in obese hypertensive patients with reduced ejection fraction, mainly through the evaluation of left ventricular strain. The obtained evidence may also have prognostic value, particularly in the early stages of the syndrome.

18F-fluorothymidine PET imaging in gliomas: an update

Brain neoplasms constitute a group of tumors with discrete differentiation grades, and therefore, course of disease and prognosis. Magnetic resonance imaging (MRI) remains the gold standard method for the investigation of central nervous system tumors. However, MRI suffers certain limitations, especially if radiation therapy or chemotherapy has been previously applied. On the other hand, given the development of newer radiopharmaceuticals, positron emission tomography (PET) aims to a better investigation of brain tumors, assisting in the clinical management of the patients. In the present review, the potential contribution of radiolabeled fluorothymidine (FLT) imaging for the evaluation of brain tumors will be discussed. In particular, we will present the role of FLT-PET imaging in the depiction of well and poorly differentiated lesions, the assessment of patient prognosis and treatment response, and the recognition of disease recurrence. Moreover, related semi-quantitative and kinetic parameters will be discussed.

The Clinical Use of SPECT and PET Molecular Imaging in Alzheimer’s Disease

Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are functional nuclear medicine techniques which allow for accurate non-invasive in vivo measurements of a wide range of regional tissue functions in man. Brain functional imaging with SPECT and PET is based on the recording of the distribution of administered radionuclides in three dimensions, thus producing maps of brain biochemical and physiological processes. SPECT and PET techniques are able to image brain perfusion and metabolism, as well as various neurotransmission or other cellular processes using specific radioligands which mark in vivo receptors, transporters or enzymes. Brain SPECT and PET imaging or molecular imaging -, has been applied to the study of Alzheimer’s disease (AD) for over two decades. These functional neuroimaging approaches have the capability of identifying subtle pathophysiologic changes in the brain before structural changes are present (Xu et al., 2000). Therefore they possess greater potential for accurate and early diagnosis, monitoring disease progression, and better treatment followup. Furthermore, the application of SPECT and PET techniques to the study of AD has led to increased understanding of the underlying pathology and the disease processes and improved the differential diagnosis from other neurodegenerative causes of dementia.

Bone Single Photon Emission/Computed Tomography in the Detection of Sacroiliitis in Seronegative Spondyloarthritis: A Comparison with Magnetic Resonance Imaging

Objective: Seronegative spondyloarthritis (SpA) is characterized by chronic inflammation affecting the axial skeleton, entheses and occasionally peripheral joints. The involvement of the sacroiliac joints, sacroiliitis, is considered as a pathognomonic radiographic finding. Magnetic resonance imaging (MRI) is the method of choice for its early detection. Bone scintigraphy (BS) is characterized by high sensitivity in the diagnosis of bone and articular diseases. Limited value of BS in the diagnosis of sacroiliitis may be attributed to the use of planar imaging. In the present study, we aimed to investigate the role of SPECT in SpA, compared to MRI. Methods: Forty-three patients suffering from inflammatory back pain underwent MRI evaluation of the sacroiliac joints and BS, combined with SPECT in the same region, for the assessment of sacroiliitis. Results: Bone SPECT revealed no findings of sacroiliitis in 11 patients, with total agreement with MRI. Findings of chronic lesions were demonstrated from both modalities in 2 patients. Bone SPECT and MRI findings were in concordance regarding the investigation of active sacroiliitis, with the exception of one patient with mild SPECT findings and negative MRI examination; the diagnosis of AS however, was established one year later, after a positive follow-up MRI. The evaluation of the planar imaging of the whole skeleton and SPECT imaging, revealed additional lesions. Conclusion: Bone SPECT is a reliable imaging method in the diagnosis of active sacroiliitis. Its application on planar BS, an economic and widely available diagnostic technique, appears to be a valuable aid for the clinician.

Clinical Significance of Tetrofosm in Extracardiac Uptake During Myocardial Perfusion Imaging

Coronary artery disease (CAD) is a major cause of mortality and morbidity and its management consumes a large proportion of national healthcare budgets (Underwood et al., 2004). It has been estimated that approximately twenty diseases account for over 80% of all the deaths in the world (Satra et al., 2011). Specifically, atherosclerosis which occurs in the coronary arteries as the underlying defect responsible for CAD accounts for nearly half of these deaths. Although CAD treatment protocols are improving, its prevalence has increased. New imaging technologies have added to the immediate costs of investigation but they also have the potential to reduce overall costs, by virtue of their greater diagnostic and prognostic accuracy. This allows a more informed selection of therapy, which in turn can lead to a better clinical outcome (Underwood et al., 2004). Myocardial perfusion scintigraphy (MPS) was developed in the 1970s and has been used increasingly in clinical cardiology since the 1980s (Underwood et al., 2004). Technical developments that have fuelled this recent increase are single-photon emission tomographic computed imaging (SPECT), pharmacological stress and ECG-gated imaging (Underwood et al., 2004). Nowadays, MPS comprises the only widely available method of assessing myocardial perfusion directly and many previously published reports support its evidence in the diagnosis of myocardial ischaemia and necrosis (Satra et al., 2011). Moreover, the prognostic value of this method for patients’ risk stratification has already been extensively reported, with an incremental prognostic value after clinical assessment, exercise electrocardiography and even above coronary angiography (Satra et al., 2011). Thus, MPS is an established imaging technique that is already an integral part of the management of CAD (diagnosis, prognostication, selection for revascularization and assessment of acute coronary syndromes) and is included in a number of professional guidelines (Underwood et al., 2004).

Low-dose radiation cancer risk hypothesis may lead to ‘radiophobia’-driven imaging avoidance?

Dear Sir, We read with great interest the recent expert consensus document on the optimal use of ionizing radiation in cardiovascular imaging. Radiation-induced cancer is a stochastic event and its likelihood is assumed to increase approximately linearly with dose. However, the assessment of risk, associated with the performance of low-dose diagnostic cardiovascular procedures (significantly lower than 100 mSv), is based on data that refer to much higher doses, using mathematical extrapolation models. Interestingly, it should be noted that a proposed model (the hormesis model) implies lower subsequent cancer risk in individuals exposed to low doses. Despite the inconclusive evidence regarding the potential adverse effects in the low-dose burden of nuclear cardiology procedures, we often face strong concerns over the radiation safety during our clinical routine. Commonly, patients and their relatives are troubled for the radiation-induced health consequences, and in particular the possibility of induced cancer risk. Similarly, referring physicians have to deal with such concerns when ordering a diagnostic exam that employs ionizing radiation. Moreover, personnel working in departments other than nuclear medicine are often troubled due to possible radiation exposure during the patient care after a nuclear cardiology procedure. Radiation hazards are occasionally presented to the public through mass media, including social media, possibly leading to an overestimated radiation fear deeply ingrained in the public psyche. The truth, however, is that the health risk posed by diagnostic ionizing radiation is nowhere near as great as commonly assumed, mainly based on the invalidated linear nothreshold hypothesis (LNTH). We believe that cardiovascular specialists should be well aware of the nonexistent credible evidence of cancer risk from diagnostic imaging procedures, in order to accurately assess the risk–benefit relationship and provide the required objective information, not only to the patients and their relatives but also to other healthcare professionals. Otherwise, we believe that there is a potential risk of (a) under-usage of beneficial diagnostic procedures, (b) patient’s ‘radiophobia’-driven imaging avoidance, and (c) physician-recommended substitution of alternative procedures due to non-evidence-based fear of low-dose radiation.