Atherosclerosis regulation via media lipid-driven VSMC cholesterol efflux switch.

It is known, that initial events in atherosclerosis arise in the intima with a parallel influx of inflammatory cells. I propose the opposite - that the disease onset begins from the media vascular smooth muscle cell (VSMC) involvement and through its utilization of modified low-density lipoproteins (LDL), and free or esterified cholesterol. Other oxidized lipoprotein molecules remain in the media which are non-removed by high-density lipoproteins (HDL), owing to their structural damages after local vasa vasorum and adventitia lymphatic disorders. Mechanism by which VSMC ingulf and degrade them includes lipid-driven activation of VSMC reverse cholesterol transport pathways from the media to macrophages, and from the last - to plasma HDL (non-damaged) and apoA-1 or - directly to them. When some of the pathways are impaired, its demands a reprogramming of the existing cholesterol removal route to another, or selective gene involvements and transcriptional regulation of inflammatory signaling. Intima cell call-effects may be linked after their down-regulation with the expression of cytokines, chemokines by migrating VSMC to stem cells for dose-dependent proliferation, VSMC and macrophage maturation in non- and inflammatory phases of early or late atherosclerosis.

Ultrasonic endarterectomy for long superficial femoral artery atherosclerotic occlusive disease.

OBJECTIVE: To report the long term results of ultrasonic superficial femoral artery endarterectomy (USFAE). DESIGN: Retrospective study. PATIENTS AND METHODS: From January 1998 to June 2004 218 USFAE were performed in 202 selected patients (178 males, 192 procedures) with a median age of 65 years (46-87 years). Indications for operation were disabling intermittent claudication in 137 procedures (68%), rest pain in 24 procedures (12%), and limb salvage in 41 procedures (20%). The new medical technology of ultrasonic endarterectomy is based on the application of the mechanical vibrations in the range of low frequency ultrasound. The ultrasonic device consists of the ultrasonic generator, acoustic unit and the flexible wave concentrators with special working tips in the shape of a ring. Follow up consisted of clinical evaluation, ankle-brachial index measurements and duplex scanning. RESULTS: The mean follow-up time was 30.1 months. The mean length of the endarterectomised SFAs was 29 cm (range, 15-43 cm). The five year cumulative primary patency rate by means of life table analysis was 45.8 +/- 4.4% (SE). Percutaneous transluminal balloon angioplasty and surgical re-interventions were performed in thirty three and five patients respectively resulting in a primary assisted patency rate of 57.5 +/- 4.1%. The five year secondary patency rate was 65.6 +/- 3.8%. Limb salvage was achieved in 35 of the 41 patients with gangrene. CONCLUSIONS: The long term results of ultrasonic SFA endarterectomy suggest this is an effective technique.

[Functional assessment of the lymphatic bed of patients in the late clinical classes of chronic venous insufficiency according to the international GEAP classification].

The author revises the contents and limits of the anatomic CEAP classification. For this purpose 84 patients with different types of trophic disorders of the lower limbs were examined with the aid of the author's technique of functional lymphography and lymphoscintigraphy. Impairment of drainage and transport function of the lymphatic capillaries was established from the ulcer edge at the level of the outgoing (from skin to collector) and collecting (from foot to regional nodes) capillaries. A close relationship was discovered between secondary changes in the lymphatic bed and the severity of trophic disorders. In groups with dilated and stenosed vessels, there were subgroups of patients with preserved function of lympangions. The data obtained evidence that lymphovenous insufficiency beyond the area of trophic disorders is more pronounced than in the focus itself. This may play a decisive role in the choice of the treatment modality as dependent on the condition of the drainage pathways. To refine the diagnosis in patients showing disease progression, with failed treatment of trophic ulcers including ulcerous defects, the author suggests that A category may be divided into two subgroups: Av for characterization of different veins and Al for lymphatic vessels of varying levels: S (skin), (Tissue) and Lnd (lymph nodes). The use of additional criteria for the diagnosis substantially improves the characteristics of the international CAAP classification.

[Pathogenesis of atherosclerosis in patients with lipid metabolism disturbances: hypothesis on cholesterol utilization and atheromatous plaque formation]. / Patogenez ateroskleroza u bol'nykh bez narusheniia lipidnogo obmena: gipoteza utilizatsii kholesterina i obrazovaniia ateromatoznoi bliashki.

Cholesterol is known to participate in atheromatous plaque formation coming from blood stream and affecting vascular endothelium in environment of elevated low-density lipoproteins (LDL). Nevertheless, the occurrence of single atheromatous plaque evidences the possibility of local lipoprotein accumulation by vascular wall without systemic increase in serum LDLs. The author hypothesizes that in the absence of hypercholesterolemia atheroma can evolve through the utilization of modified LDL and free or etherified cholesterol, that remain in media non-removed by high density lipoproteins (HDL) owing to their structural damage after local vascular wall ischemia caused by vasa vasorum disorders. Disturbances in HDL acceptor function and transport of cholesterol and modified LDL to blood circulation and further into liver are followed by local accumulation of these products in smooth muscle cells. Overloaded by lipids smooth muscle cells move through internal fenestrated membrane thus activating receptor mechanism for transmission of modified lipoproteins to monocytes and capture of endothelial membrane and amorphous lipids by them in local lipid peroxidation area. A framework for hypothesis experimental and clinical testing is suggested.

[Pancreas as one of the targets of "auto-enzyme explosion" in pancreatitis]. / Podzheludochnaia zheleza kak odna is mishenei "autofermentnogo vzryva" pri pankreatite.

The authors consider pancreatitis not as a nosological unity but as a clinical manifestation of enzymatic or autoenzymatic aggression. Based on clinical, histopathomorphological examinations, the authors describe pancreatogenous enzymatic injury of organs and tissues (pancreas, heart, kidneys, liver, gastrointestinal tract, etc). For 4-8 days to 2-10 years the syndrome may damage not only pancreatic parenchyma, but also vascular structures with formation of general vasculitis, lymphangitis and subsequent thrombotic microangiopathy. The authors regard pancreas as one of the target organs--of general disease, in which serious injuries of other organs and tissues may prevail over changes in the primary zone of aggression.

[Lymphography in clinical variants of posttraumatic edema]. / Limfografiia pri klinicheskikh variantakh posttravmaticheskikh otekov.

Early experience with lymphography, used in 28 patients with edema of the legs, descending from the site of injury (13) or ascending to the damaged area (15), is summarized. Purposive identification of the location of lymph reflux to abducting lymphatic vessels of the skin and subcutaneous fat helped to detect anatomic zones of lymph stasis, identify the cause and site of origin of the edema and exclude impaired lymph passage through neighbouring lymphatic vessels and collectors. Local or generalized disorders of lymph flow were shown to be at different distances from the damaged lymphatic vessels. The emergence of different clinical variants of descending and ascending edema is caused by the movement of the lymph reflux area from the original site of edema.

[Clinical lymphographic diagnosis of posttraumatic edema in the substitution of bone defects]. / Kliniko-limfograficheskaia diagnostika posttravmaticheskogo oteka pri zameshchenii defektov kostei.

The method of direct "lower" lymphography of the medial superficial collector was used for the examination of 11 patients with a moderate chronic posttraumatic edema developed against the background of atrophy of muscle tissues before and in the process of substituting bone defects after Ilizarov. In substituting bone defects against the background of a previous posttraumatic blockade of lymph vessels and their alterations there appears a complete or partial decompensation of the lymph flow, resulting in the development of edema in the atrophied earlier segments of lower extremities. In part of the patients with substituted bone defects the edema increased with persistent previous alterations. In other ones there appeared new foci of the rearrangement of lymph vessels.

[Lymphatic vessels of the upper extremity and their relation to nodes in the axillary area in healthy subjects and lymph flow blockade]. / Limfonosnye sosudy verkhnei konechnosti i ikh otnoshenie k uzlam podmyshechnoi oblasti v norme i pri blokade toka limfy.

Large and small lymphatic vessels have been studied roentgenologically on the medial, lateral, posterior and anterior surfaces of the upper extremity in 113 patients at the age of 19-63 years at blockade of the lymphatic stream. On the medial and lateral surfaces the lymphatic vessels are filled with the contrast substance via anatomical approaches from the palmar and dorsal sides of the forearm. With isolated contrasting of various large lymphatic vessels, zones in the skin and in the subcutaneous fatty layers drained by them are revealed, as well as distribution of small vessels in the forearm and shoulder in each region. Variants of large lymphatic vessels and their tributaries are defined; an essential variability of their inflow into the axillary lymph nodes from various anatomical areas of the upper extremity is found. Into every 1-4 groups of the lymph nodes of the axillary area, 1-3 large vessels inflow, through them the contrast substance switches from the same anatomical zone repeatedly.

[Clinico-roentgenological evaluation of persistent edema of the foot and ankle joint]. / Kliniko-rentgenologichaskaia otsenka stoikikh otekov stopy i golenostopnogo sustava.

Persistent non-progressing edemas of distal parts of extremities developed after bone fractures in the lower part of the shin were studied in 12 patients. The clinicoroentgenological examination has established a substantial difference in the character of the injury and compensatory-reparative changes of the lymphatic bed in different clinical variants of the edemas.

[Clinico-lymphographic classification of post-traumatic edema]. / Kliniko-limfograficheskaia klassifikatsiia posttravmaticheskikh otekov.

The article generalizes the experience with diagnosis of disturbances of the lymph flow in 133 patients with edema after extremity traumas. On the basis of clinico-lymphographic examinations a classification of posttraumatic edemas is proposed facilitating the selection of the method for treatment of such patients.

[Diagnosis of acute and chronic disorders of lymph outflow following injury by lymphography]. / Diagnostika ostrykh i khronicheskikh narushenii limfootoka posle travmy metodom limfografii.

Direct "inferior" lymphography of the medial superficial collector was used for the examination of 54 patients. It was established that acute and chronic edemas of lower extremities were followed by different changes of small lymphatic vessels of the skin and subcutaneous fat.

[Radionuclide multicollector lymphography of the extremities]. / Radionuklidnaia mnogokollektornaia limfografiia konechnostei.

A study was made of the lymph flow rate and accumulation-absorption function of the inguinal and popliteal lymph nodes in healthy persons and in patients with leg and forearm bone fractures. The lymph flow rate in the leg of a healthy person is 9.1 = 10.8 cm/min, much more in the hip 13.7 = 16.1 cm/min, in the deep collector it was 2 = 3 times as less. The lymph flow rate in the forearm is equal 5.6 = 7.9 cm/min, in the shoulder 7.4 = 10.0 cm/min. After the fracture the lymph flow rate lessened for a short period of time (up to the 21 st day) in the vessels of the medial leg collector but increased in the lateral and deep collectors. In the upper limb the lymph flow rate decreased in the lateral and increased in the medial collectors.