Increased DAPK1 but decreased CCL2 plasma levels of nucleic acids in patients with stable angina

Introduction: We hypothesized that patients with stable angina have increased plasma levels of mRNA from genes responsible for atherosclerotic plaque development and destabilisation, i.e. from death-associated protein kinase (DAPK1) and monocyte chemotactic protein-1 (CCL2). Materials and methods: Nucleic acids were isolated from plasma of patients with stabile angina and healthy subjects as controls. mRNAs were transcribed to cDNAs, quantified by real-time PCR and standardized to the amount of a reference gene. Reagents for PCR quantification are declared to be mRNA specific, but in our test conditions DNA was found to interfere in both assays. Results: Patients had 5.1-times higher plasma level of DAPK1 nucleic acids (mRNA and DNA) than controls (P < 0.001) and the highest levels were associated with the presence of diabetes. However, plasma levels of CCL2 tended to be lower than in controls, and in statin-treated patients the decre-ment reached significance (-66.3%; P = 0.041). Conclusion: The estimated levels are explicable in terms of current knowledge. Further studies with specific assays for mRNA PCR quantification are reasonable to access whether this approach offers non-invasive in vivo assessment and monitoring of gene expression profile in atherosclerotic vascular beds

Anatomy-Aware Inference of the 3D Standing Spine Posture from 2D Radiographs

An important factor for the development of spinal degeneration, pain and the outcome of spinal surgery is known to be the balance of the spine. It must be analyzed in an upright, standing position to ensure physiological loading conditions and visualize load-dependent deformations. Despite the complex 3D shape of the spine, this analysis is currently performed using 2D radiographs, as all frequently used 3D imaging techniques require the patient to be scanned in a prone position. To overcome this limitation, we propose a deep neural network to reconstruct the 3D spinal pose in an upright standing position, loaded naturally. Specifically, we propose a novel neural network architecture, which takes orthogonal 2D radiographs and infers the spine’s 3D posture using vertebral shape priors. In this work, we define vertebral shape priors using an atlas and a spine shape prior, incorporating both into our proposed network architecture. We validate our architecture on digitally reconstructed radiographs, achieving a 3D reconstruction Dice of 0.95, indicating an almost perfect 2D-to-3D domain translation. Validating the reconstruction accuracy of a 3D standing spine on real data is infeasible due to the lack of a valid ground truth. Hence, we design a novel experiment for this purpose, using an orientation invariant distance metric, to evaluate our model’s ability to synthesize full-3D, upright, and patient-specific spine models. We compare the synthesized spine shapes from clinical upright standing radiographs to the same patient’s 3D spinal posture in the prone position from CT

Low back pain as the presenting sign in a patient with primary extradural melanoma of the thoracic spine - A metastatic disease 17 Years after complete surgical resection

Primary spinal melanomas are extremely rare lesions. In 1906, Hirschberg reported the first primary spinal melanoma, and since then only 40 new cases have been reported. A 47-year-old man was admitted suffering from low back pain, fatigue and loss of body weight persisting for three months. He had a 17-year-old history of an operated primary spinal melanoma from T7-T9, which had remained stable for these 17 years. Routine laboratory findings and clinical symptoms aroused suspicion of a metastatic disease. Multislice computed tomography and magnetic resonance imaging revealed stage-IV melanoma with thoracic, abdominal and skeletal metastases without the recurrence of the primary process. Transiliac crest core bone biopsy confirmed the diagnosis of metastatic melanoma. It is important to know that in all cases of back ore skeletal pain and unexplained weight loss, malignancy must always be considered in the differential diagnosis, especially in the subjects with a positive medical history. Patients who have back, skeletal, or joint pain that is unresponsive to a few weeks of conservative treatment or have known risk factors with or without serious etiology, are candidates for imaging studies. The present case demonstrates that complete surgical resection alone may result in a favourable outcome, but regular medical follow-up for an extended period, with the purpose of an early detection of a metastatic disease, is highly recommended

Possible association of psoriasis and reduced bone mineral density due to increased TNF-alpha and IL-6 concentrations

Psoriasis is a chronic erythematosquamous disease affecting about 2–3% of the population. It is generally considered to be a T cell-mediated disorder. Psoriasis is characterized by Th1-type cytokine pattern with the predominant secretion of IL-2, IL-6, IFN-γ and TNF-α. Such cytokine pattern is sufficient in inducing keratinocyte hyperproliferation, a hallmark of psoriasis. It seems that development of psoriatic lesions is mediated by TNF-α and proliferation of local T cells is dependent on local TNF-α production. IL-6 enhances activation, proliferation and chemotaxis of T cells into psoriatic lesions. It is also a direct keratinocyte mitogen that could directly stimulate keratinocyte proliferation. Data of possible association between psoriasis and reduced bone mineral density (BMD) are limited and therefore, not fully conclusive. The major limitation of two studies reported so far was small sample size. Based on increased concentrations of TNF-α and IL-6 in psoriasis we hypothesized that these patients are more prone to osteoporosis than healthy subjects. TNF-α enhances bone resorption via stimulating osteoclast development and activity as well as bone formation. On the other hand, IL-6 is also a potent stimulator of bone resorption. Moreover, increased production of TNF-α and IL-6 has been found in postmenopausal women with osteoporosis. Several lines of evidence support our hypothesis; higher value of IL-6 was recorded in children with idiopathic osteoporosis than in healthy controls; TNF-α knock-out mice do not lose bone after ovariectomy; polymorphism of TNFRSF1B gene which encodes 75Kd TNF receptor is associated with BMD; treatment with anti-TNF-α antibody exert beneficial effect on bone metabolism in patients with rheumatoid arthritis and finally, raloxifene inhibit osteoclast activity by reducing TNF-α and IL-6 synthesis. However, our hypothesis raised number of questions. Are increased serum concentrations of TNF-α and IL-6 mirrored by increased concentrations of these cytokines on the local level? Furthermore, could other cytokines relevant in the pathogenesis of the psoriasis, first of all IFN-γ, modulate the risk of osteoporosis? Thus, a large prospective, case-control study with the data on BMD, biochemical parameters of bone turnover and fractures have to be done to test our hypothesis

Anatomy-Aware Inference of the 3D Standing Spine Posture from 2D Radiographs

An important factor for the development of spinal degeneration, pain and the outcome of spinal surgery is known to be the balance of the spine. It must be analyzed in an upright, standing position to ensure physiological loading conditions and visualize load-dependent deformations. Despite the complex 3D shape of the spine, this analysis is currently performed using 2D radiographs, as all frequently used 3D imaging techniques require the patient to be scanned in a prone position. To overcome this limitation, we propose a deep neural network to reconstruct the 3D spinal pose in an upright standing position, loaded naturally. Specifically, we propose a novel neural network architecture, which takes orthogonal 2D radiographs and infers the spine&rsquo;s 3D posture using vertebral shape priors. In this work, we define vertebral shape priors using an atlas and a spine shape prior, incorporating both into our proposed network architecture. We validate our architecture on digitally reconstructed radiographs, achieving a 3D reconstruction Dice of 0.95, indicating an almost perfect 2D-to-3D domain translation. Validating the reconstruction accuracy of a 3D standing spine on real data is infeasible due to the lack of a valid ground truth. Hence, we design a novel experiment for this purpose, using an orientation invariant distance metric, to evaluate our model&rsquo;s ability to synthesize full-3D, upright, and patient-specific spine models. We compare the synthesized spine shapes from clinical upright standing radiographs to the same patient&rsquo;s 3D spinal posture in the prone position from CT

Symptomatic cardiac metastases of breast cancer 27 years after mastectomy: a case report with literature review - pathophysiology of molecular mechanisms and metastatic pathways, clinical aspects, diagnostic procedures and treatment modalities.

Metastases to the heart and pericardium are rare but more common than primary cardiac tumours and are generally associated with a rather poor prognosis. Most cases are clinically silent and are undiagnosed in vivo until the autopsy. We present a female patient with a 27-year-old history of an operated primary breast cancer who was presented with dyspnoea, paroxysmal nocturnal dyspnoea and orthopnoea. The clinical signs and symptoms aroused suspicion of congestive heart failure. However, the cardiac metastases were detected during a routine cardiologic evaluation and confirmed with computed tomography imaging. Additionally, this paper outlines the pathophysiology of molecular and clinical mechanisms involved in the metastatic spreading, clinical presentation, diagnostic procedures and treatment of heart metastases. The present case demonstrates that a complete surgical resection and systemic chemotherapy may result in a favourable outcome for many years. However, a lifelong medical follow-up, with the purpose of a detection of metastases, is highly recommended. We strongly call the attention of clinicians to the fact that during the follow-up of all cancer patients, such heart failure may be a harbinger of the secondary heart involvement

Leptomeningeal and intramedullary metastases of glioblastoma multiforme in a patient reoperated during adjuvant radiochemotherapy

Despite huge advances in medicine, glioblastoma multiforme (GBM) remains a highly lethal, fast-growing tumour that cannot be cured by currently available therapies. However, extracranial and extraneural dissemination of GBM is extremely rare, but is being recognised in different imaging studies. To date, the cause of the GBM metastatic spread still remains under discussion. It probably develops at the time of intracranial progression following a surgical procedure. According to other hypothesis, the metastases are a consequence of spontaneous tumour transdural extension or haematogenous dissemination. We present a case of a 59-year-old woman with symptomatic leptomeningeal and intramedullary metastases of GBM who has been previously surgically treated with primary subtotal resection and underwent a repeated surgery during adjuvant radiotherapy and chemotherapy with temozolomide. Today, the main goal of surgery and chemoradiotherapy is to prevent neurologic deterioration and improve health-related quality of life. With this paper, we want to present this rare entity and emphasise the importance of a multidisciplinary approach, a key function in the management of brain tumour patients. The prognosis is still very poor although prolongation of survival can be obtained. Finally, although rare, our case strongly suggests that clinicians should be familiar with the possibility of the extracranial spread of GBM because as treatment improvements provide better control of the primary tumour and improving survival, metastatic disease will be increasingly encountered