Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease.

Sonic hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh + MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. The goal of this study was to test the hypothesis that, in humans with peripheral artery disease (PAD), there is increased number of circulating Shh + MPs. This was done by assessing the number of Shh + MPs in plasma of patients with PAD and control subjects without PAD. We found significantly higher number of Shh + MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs\u2014produced either by endothelial cells, platelets, leukocytes, and erythrocytes\u2014was not different between PAD patients and controls. We also found a significant association between the number of Shh + MPs and the number of collateral vessels in the ischemic limbs of PAD patients. Interestingly, the concentration of Shh protein unbound to MPs\u2014which was measured in MP-depleted plasma\u2014was not different between subjects with PAD and the controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel information on Shh signaling during ischemia in humans, with potentially important biological and clinical implications

Consensus document on intermittent claudication from the Central European Vascular Forum 1st edition - Abano Terme (Italy) - May 2005 2nd revision - Portroz (Slovenia) September 2007.

The paper contains the document on intermittent claudication: diagnosis, mangement and rehabilitation in the different stages of peripheral artery disease. The consensus is international and involves some nations from central Europe. This Document presents suggestions for General Practitioners for more precise and appropriate management of PAD, particularly of Intermittent Claudication, and underlines the investigations that should be required by GP and what the GP should expect from the vascular specialist (angiologist, vascular surgeon)

[The quality of interdisciplinary communication]

Because of a continued increase of complex patients and the development of many areas of sub-specialities in medicine, the use and quality of interdisciplinary communication has been found to be lacking, especially between hospital and primary care physicians, causing a significant gap in the documentation, coverage and care of individual patients. The study focuses on state of the art interdisciplinary communication, with consideration given to current used tools and priorities. An ad hoc questionnaire surveyed 118 physicians about their profession, the types of patients, the frequency of complex cases, the tools used to communicate with each patient and how the physicians rated these tools. The rate of patients needing interdisciplinary communication is 17% of the entire patient sample, all of this percentage having complex health care needs (terminally ill, disabled, often without a personal support network). Physicians frequently used paper documents, despite their lack of quality, as well as the telephone to communicate with other colleagues. Computer devices were scarcely used. Many Doctors (71%) value the actual interdisciplinary communication of low quality, despite the fact that it is considered to have a significant influence on the quality of health care. New tools and methods are needed. For example, dedicated standards of multidisciplinary and multi-professional Continuing Medical Education (CME), as well as the use of computer tools allowing for shared clinical records

Unusual codon 69 insertions : influence on human immunodeficiency virus type 1 reverse transcriptase drug susceptibility

Introduction: Multiple amino acid changes in the reverse transcriptase (RT) enzyme of the human immunodeficiency virus 1 (HIV-1) confer simultaneous resistance to most nucleoside RT inhibitors (NRTI). It may take place through different pathways: one of these is the codon 69 insertion, which can involve several 2-amino acid patterns. Materials and methods: We are reporting the case of three patients treated with various antiretroviral compounds. For these subjects we have conducted both a genotypical and a phenotypical analysis in order to understand what kind of influence these insertions may have on HIV-1 RT drug susceptibility. Plasma samples from these patients have been extracted and the RT region has been amplified, cloned and sequenced; meanwhile their PBMCs have been separated, cultivated and then tested for drug susceptibility. Results: Data obtained from the cloning assay showed that the patients had different mutational patterns but constant multiple resistance to NRTI. In particular, they harbored mutations related to Zidovudine (ZDV), 3TC and various NRTIs. Moreover, all three samples had a T69S substitution followed by three different dual amino acid insertions: SG, TG and VG. Several phenotypic experiments revealed that the viruses were resistant to 3TC as well as to ZDV and ABC . Different results were obtained using d4T and ddI. Discussion: In our three patients, all mutation inserts impaired the use of NRTI, particularly ZDV and 3TC. Patient 001 presented a pattern that should not cause a high phenotypic resistance to 3TC per se, and so we can argue that the concomitant presence of the insertion T69S (SG) makes this isolate moderately resistant to this drug. We observed a similar phenomenon in subject 003. d4T was less involved in the resistance generation caused by the RT insertion (in one out of three cases). Moreover, we identified a new 2aa insertion (TG) that has, to the best of our knowledge, never been reported before. A careful survey of novel RT genotypic insertion is thus warranted