Mechanical back pain and the facet joint syndrome

Mechanical back pain is a common disability often associated with the facet joint syndrome. Treatment is based on early, adequate pain relief with simple techniques of regional analgesia. In a few cases this is not enough and more sophisticated methods, such as radiofrequency denervation, cryo-analgesia and possibly intrathecal midazolam, are necessary. However, the main thrust of our approach is to treat the underlying structural disorder with strengthening of the back muscles and correction of postural abnormalities responsible for the mechanical back pain. Our report is based on an analysis of 83 patients who failed to respond to long periods of rest, suitable analgesic and allied drugs and other non-invasive measures. There had been no overriding indication for major surgery. A large number of these patients have been improved by our methods, but further work is in progress to extend the proportion of satisfactory results.     

Fibrinogen concentrate – a potential universal hemostatic agent

Background: Human fibrinogen concentrates have been commercially available for decades for substitution therapy in hypofibrinogenemia, dysfibrinogenemia and afibrinogenemia. Accumulating new data suggest that fibrinogen plays a critical role in achieving and maintaining hemostasis, particularly in patients suffering from acquired fibrinogen deficiency during massive bleeding, where benefit from early intervention with fibrinogen concentrate appears to be important. Objective/methods: This work focuses on pasteurized fibrinogen concentrate, with special emphases on product characteristics, pharmacodynamics, pharmacokinetics, laboratory monitoring, dosing, clinical efficacy, safety and tolerability. Future clinical and laboratory perspectives on fibrinogen are discussed and outlined. Results/conclusion: Pasteurized fibrinogen concentrate is derived from human plasma. Its half life is 2.7 days in patients with congenital fibrinogen deficiency. For congenital and acquired deficiency in vivo recovery rates vary from 60% to 109%. Reportedly, administration of pasteurized fibrinogen in patients with congenital deficiency is efficacious. Acquired deficiency of fibrinogen appears to be an early event in seriously bleeding patients, preceding critical levels of platelets or other coagulation factors. Experimental animal studies, as well as clinical observations suggest a beneficial role of early substitution with fibrinogen in management of critical traumatic and surgical bleeds. Pasteurized fibrinogen concentrate is well tolerated and associated with a low incidence of adverse thrombo-embolic events.     

Umbilical cord stem cell transplantation for primary immunodeficiencies

Primary immunodeficiencies (PIDs) are a rare but important cause of mortality and morbidity in childhood: the most severe – known as severe combined immunodeficiency (SCID) – are fatal within the first year of life; other PIDs are less immediately life-threatening, but have a poor long-term outlook. Haematopoietic stem cell transplantation (HSCT) is the best treatment for SCID and is increasingly offered for other PIDs. The best results are achieved with an HLA-matched family donor. Umbilical cord stem cells (UCSCs) are an alternative stem cell source. Results using UCSCs in the treatment of haematological disorders and malignancy are as good as those for which marrow is the stem cell source. Although PIDs make up a small proportion of disorders amenable to treatment by HSCT, UCSCs are an ideal source of haematopoietic stem cells for many of these patients. Of the 52 patients with SCID or other PIDs for whom detailed information on outcome is available, results of engraftment, immune reconstitution, incidence of graft-versus-host disease and survival are comparable with other stem cell sources. Small stem cell dose and prolonged time to viral immunity limit the patients for whom UCSCs can be used. Newer methods of achieving better engraftment, ex vivo expansion of stem cells and generation of antigen-specific cytotoxic T cells are being developed at present, and will widen the application of UCSCs as a viable source for more patients.     

Thyroid hormone and heart failure: from myocardial protection to systemic regulation

Heart failure (HF) is an intriguing model of chronic disease. It starts as an organ disorder developing, in its progression, into a systemic disease in which the dysfunction of other organs plays a relevant clinical and prognostic impact. Furthermore, continuous activation of systemic pathways plays a role in disease progression, switching their effect from protective to harmful. In this combination of organ dysfunction and systemic derangement, thyroid hormone (TH) have an important regulative impact from cardiovascular to systemic level and from molecular/cellular processes to clinical setting. Whether it is accepted to include TH and thyroid stimulating hormone assessment in the clinical HF course, the next challenge will be to ascertain the benefit of TH replacement therapy in HF patients, taking into consideration the type of hormone to administer, dosage and treatment schedule.     

Clopidogrel in acute coronary syndrome: implications of recent study findings

The platelet ADP receptor antagonist clopidogrel is recommended for the treatment of patients with acute coronary syndrome and/or percutaneous coronary intervention. Patients who received a coronary stent in particular should be protected by sufficient antiplatelet therapy to prevent stent thrombosis. Clopidogrel is a prodrug and has to undergo extensive metabolization before the active metabolite can irreversibly bind to platelets. This makes clopidogrel treatment susceptible to genetic and drug interactions. Recent study findings suggest that initial treatment with a higher dose of clopidogrel may be superior to the currently approved dose. It is not clear whether this approach will be sufficient to entirely overcome clopidogrel hyporesponsiveness, which worsens outcomes in up to one-third of patients. Newer antiplatelet agents are emerging but clopidogrel remains the best established treatment option, with more than 120,000 patients treated in randomized trials and 12 years of clinical postmarketing experience.     

Adiponectin: linking the metabolic syndrome to its cardiovascular consequences

Obesity and its related disorders, glucose intolerance, hypertension and hyperlipidemia, collectively named the metabolic syndrome, result in substantial cardiovascular morbidity and mortality. Recent data point to several underlying regulatory mechanisms through which obesity links these various outcomes. Adipose tissue is now understood to function not merely as a passive energy storage depot but as an active endocrine organ, producing a variety of bioactive substances termed adipocytokines. Adiponectin, an adipocytokine first described as the most abundant protein produced by adipocytes, appears to serve as a central regulatory protein in many of the physiologic pathways controlling lipid and carbohydrate metabolism, and to mediate various vascular processes. Adiponectin displays both anti-inflammatory and antiatherogenic properties. Unlike other adipocytokines, its levels are paradoxically decreased in obesity and insulin-resistance states including metabolic syndrome and diabetes, as well as hypertension and coronary artery disease. This review will detail the relationship of adiponectin to various features of obesity and insulin-resistance syndromes, as well as its relationship to the cardiovascular complications of these disorders.     

Thromboembolism risk following recurrent miscarriage

Normal pregnancy is associated with extensive changes in hemostasis such that the procoagulant effect becomes dominant. The evolutionary advantage of this hypercoagulability may be to counteract the inherent instability associated with hemochorial placentation, which is unique to human beings. However, overall, there is a four- to 10-fold increased thrombotic risk throughout gestation and the postpartum period. Certain inherited or acquired thrombophilic factors may predispose to arterial and/or venous thrombosis and have a possible association with pregnancy complications, including recurrent miscarriage (RM), which affects up to 5% of couples with childbearing desire. A subgroup of women with RM has been demonstrated to be in a prothombotic state before and after pregnancy. The long-term health implications of this hypercoagulability may imply an increased risk of ischemic heart disease. Moreover, the presence of antiphospholipid antibodies rather than thrombophilic genetic defects (i.e., factor V Leiden or prothrombin G202010A mutation) in patients with RM is a determinant of thrombotic events later in life, especially among those patients having also cardiovascular risk factors. This article highlights the thromboembolic risk in nonpregnant RM patients in different thrombophilic settings and the need for thromboprophylaxis among these patients.     

Effective treatment of hypertension by AT1 receptor antagonism: the past and future of telmisartan

Lowering blood pressure is the most effective treatment method to ensure a reduction in the total risk for cardiovascular morbidity and mortality. The renin–angiotensin system plays an important role in volume homeostasis and blood pressure regulation and is a target for several groups of pharmaceutical agents. Angiotensin II receptor blockers represent the newest class of antihypertensive compounds. They prevent the binding of angiotensin II to the subtype 1 receptor (AT₁), which is believed to mediate most of the physiological actions relevant to the regulation of blood pressure. Telmisartan, a widely used AT₁ receptor antagonist, is a highly selective compound with high potency, a long duration of action and a tolerability profile similar to placebo. Numerous randomized clinical trials and community-based studies have demonstrated that oral telmisartan and combinations of telmisartan with hydrochlorothiazide are at least as effective in lowering blood pressure as all other hypertensive medications. This has been demonstrated in different populations of adult patients with mild-to-moderate essential hypertension, including patients with coexisting Type 2 diabetes, metabolic syndrome or renal impairment. Several large-scale, long-term, clinical endpoint studies are in progress to assess the beneficial effects of telmisartan on hypertension-related end-organ damage in patients at high risk of renal, cardiac and vascular damage whose blood pressure is well controlled. The most recent data from clinical trials and latest research regarding telmisartan will be reviewed in this article.     

Non-invasive measurement of coronary plaque from coronary CT angiography and its clinical implications

Coronary CT angiography (CTA) is increasingly used worldwide for direct, non-invasive evaluation of the coronary arteries. Advances in computed tomography (CT) technology over the last decade have enabled such reliable imaging of the coronary arteries. Beyond arterial stenosis, coronary CTA also permits assessment of atherosclerotic plaque (including plaque burden) and coronary artery remodeling, previously only achievable through invasive means. It has been shown that coronary plaque volumes for non-calcified and mixed plaques and the arterial remodeling index, correlate closely with invasive intravascular ultrasound. Several studies have also shown a strong relationship of adverse plaque features imaged by coronary CTA with acute coronary syndrome, all-cause death, major adverse cardiovascular events and myocardial ischemia. The aim of this review is to summarize current methods for quantitative measurement of atherosclerotic plaque features from coronary CTA and to discuss their clinical implications.     

Fibroblast growth factor 21: a promising therapeutic target in obesity-related diseases

Fibroblast growth factor 21 (FGF21) is a peptide hormone secreted by the liver, adipocytes, pancreas and skeletal muscle. It acts locally but is also a circulating hormone. Administration of FGF21 in animals and humans results in a decrease in body weight, blood triglycerides and LDL-cholesterol, with improvement in insulin sensitivity. FGF21 is known to play an important role during fasting and starvation by stimulating gluconeogenesis in the liver and inducing lipolysis in white adipose tissues. FGF21 expression is mediated by the peroxisome proliferator-activated receptor-α, while its biological actions are mediated through binding to a complex formed by its receptors and an essential coreceptor, β-Klotho. Serum FGF21 levels are paradoxically elevated in obesity, suggesting a decreased responsiveness. Recent data showed that serum FGF21 level is elevated in hypertension, atherosclerosis and coronary artery disease, raising the possibility that FGF21 plays a role in the pathophysiology of these diseases.