Current Pharmaceutical Design - Volume 12, Issue 10, 2006

Hereditary Hemorragic Teleangiectasia or Osler-Weber-Rendu disease represents a rare genetic disorder which is under intensive investigation in view of its multidisciplinary aspects. In the present hot topic issue entitled: "Molecular and Clinical Aspects of Hereditary Hemorragic Telangiectasia: A Rare Disease" the full spectrum of this disease has been emphasized starting from basic concepts to diagnostic criteria and innovative Read More

A disease is considered rare in the United States when it affects one individual per 1, 250 and one individual per 2, 000 in Europe. Most rare diseases (RD) are of genetic origin; their rarity involves a difficult and/or late diagnosis. The greatest barrier to prevention, diagnosis and treatment of RD is inadequate knowledge. Hereditary haemorrhagic telangiectasia (HHT) is a "rare" genetic disorder that is becoming more comm Read More

Hereditary Haemorrhagic Telangiectasia, or Rendu-Osler-Weber syndrome, is a rare autosomal dominant disorder involving the vascular system and is characterised by a highly variable expressivity and age-dependent penetrance. Diagnosis is based on the presence of at least three of four of the following symptoms: spontaneous epistaxis, cutaneous telangiectases, arteriovenous malformations in internal organs and familiarit Read More

Hereditary hemorrhagic telangiectasia (HHT) is characterized by vessel alterations such as dilatation of postcapillary venules and arterio-venous communications, which account for the major clinical manifestations of the disease. Two types of HHT have been characterized HHT-1 and HHT-2, respectively, depending the former on endoglin mutations and the latter on activin receptor-like kinase 1 (ALK-1) mutations. Both endogl Read More

Experimental evidences on the adaptive immune response in patients with hereditary hemorragic telagiectasia (HHT) are lacking. Here, we report in 9 patients with HHT a multiple deficit involving the intracellular expression of T helper (h)1-derived cytokines [Interferon (IFN)-γ, Interleukin (IL)-2 and Tumor Necrosis Factor (TNF)-α] and of monocyte- derived TNF-α. On the other hand, percentages of Th2-derived cytokines (IL-4, IL- Read More

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare genetic disease characterized by mutations occurring in the endoglin and ALK-1, two receptors of transforming growth factor-β1. From a pathogenic point of view, a possible involvement of the immune system in HHT has been suggested since a mononuclear cell infiltrate was found around the area of telangiectases. Up until now, no information has been availa Read More

HHT is an autosomal dominant disease characterised by diffuse muco-cutaneous and visceral telangiectases in potentially all organs. Mutations in two different genes identify HHT type 1 and HHT type 2: endoglin located on chromosome 9q33-q34 and ALK-1 or ACVRL1 on chromosome 12q13, respectively. The existence of a third locus has also been hypothesised. HHT-1 is considered a more severe form of the disease with an Read More

Hereditary hemorrhagic telangiectasia (HHT) or the Rendu-Osler-Weber disease is a systemic fibrovascular autosomal dominant dysplasia, recognised when three of the following four clinical manifestations are present, according to the proposal of Shovlin .: recurrent nosebleeds, lelangiectasias of the skin, visceral lesions, and positive family history. HHT is often difficult to diagnose on the basis of history and physic Read More

Hereditary Haemorrhagic Telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is an autosomaldominant vascular disease characterised by mucocutaneous or visceral angiodysplastic lesions (telangiectases and arteriovenous malformations), which may be widely distributed throughout the cardiovascular system. Its diagnosis is based on clinical criteria. Liver, lungs and brain, in order of prevalence, are the m Read More

No optimal treatment modality is currently available for the treatment of recurrent epistaxis in HHT. In this review, different therapeutic concepts are discussed together with their pathophysiologic background. Patients often profess a preventive effect for nasal ointments and use packings which can be self-administed in the case of bleeding. An effective first-line treatment for physicians is the endonasal laser coagulation or Read More

Hereditary Haemorrhagic Teleangiectasia (HHT) is a vascular disorder of angiogenesis transmitted in an autosomal dominant pattern, characterised by heterogeneity in clinical manifestations. One of the most important organ involved is lung, including pulmonary arteriovenous malformations (PAVM). PAVM occur in 20 to 30% of the HHT population and recently are considered a marker of disease. PAVM are direct artery-to-vein Read More

In the last years, the understanding of HHT has greatly progressed. The two genes for most on cromosomes 9 and 12 have been discovered and the existence of a third involved gene has been predicted. Recent progress in the field of genetics has allowed the identification of many gene mutation thus facilitating the characterisation of the at risk members of the same family. Complications from bleeding or shunting (pulm Read More

Atherothrombotic diseases and especially coronary and cerebrovascular diseases are the most important causes of death in industrialized countries. The use of platelet aggregation inhibitors in this context improves morbidity and mortality. The effect of acetylsalicylic acid (ASA) as an inhibitor of the cylooxygenase is well established as shown in numerous major trial. In recent years, the dual role of P2Y1 and P2Y12 rec Read More

Platelets possess two receptors for ADP, P2Y1 and P2Y12. ADP is released from platelet dense granules upon platelet activation by numerous agonists and thereby amplifies platelet responses regardless of the initial stimulus. The P2Y1 receptor is one of many platelet receptors coupled to Gq and initiates ADP-induced activation. The P2Y12 receptor on the other hand is linked to Gi and plays a special role in the amplification Read More

Clopidogrel, in combination wih aspirin, is currently the drug of choice to prevent thrombosis after coronary stent implantation. Currently, clopidogrel is administered to the vast majority of patients without any assessment of platelet inhibition. Response variability and resistance, however, definitely occur to clopidogrel treatment. Preliminary data support the hypothesis that patients with reactive or clopidogrel no Read More

Clopidogrel and statins are frequently administered in patients with ischemic heart disease or other atherothrombotic manifestations and are effective in the prevention of cardiovascular disease. The thienopyridine clopidogrel is a pro-drug metabolised in the liver via the cytochrome P450 (CYP) 3A4 system to the active compound which inhibits the P2Y12 ADP platelet receptor. The assumption exists that the effect of clopid Read More

Due to the significant clinical and economic consequences of subacute stent thrombosis and the use of more complex devices (brachytherapy, drug eluting stents) in a variety of clinical situations (i.e. acute coronary syndromes), initiation and duration of a combined antiplatelet therapy using aspirin and a thienopyridine drug has become an issue of ongoing discussion in interventional cardiology. This review will provide a Read More

Transcatheter closure of septal defects has become a widely used alternative to surgery or life-long anticoagulant therapy especially in patients with atrial septal defects (ASD) and patent foramen ovale (PFO). Post-procedural complications include thrombus formation on the occluder in about 0-10% of all cases. Therefore antithrombotic prophylaxis after device implantation is believed to be necessary, but still is variable Read More

Aspirin is not effective in the primary prevention of stroke. Patients with TIA or ischemic stroke carry a risk of recurrent stroke between 5 and 20% per year. In patients with TIA or ischemic stroke of noncardiac origin antiplatelet drugs are able to decrease the risk of stroke by 11-15% and the risk of stroke, MI and vascular death by 15-22%. Aspirin is the most widely used drug. It is affordable and effective. Low doses of 50-325 Read More