Collapsibility of the internal jugular veins in the lateral decubitus body position: A potential protective role of the cerebral venous outflow against neurodegeneration.

Recent research has revealed that patients with neurodegenerative disease sleep longer in the supine position, while healthy controls prefer sleeping in the lateral decubitus position. Thus, sleeping in the lateral position seems to be protective against neurodegeneration. It has also been suggested that a protective role of this body position could be associated with better cerebral venous drainage in this body position, which results in more active glymphatic system of the brain (the system responsible for clearance of the cerebral tissue from waste products, e.g. amyloid-ß). Since no published evidence exists regarding venous outflow from the cranial cavity in the lateral decubitus position, we performed a pilot sonographic study of the internal jugular veins in 3 young healthy volunteers and 2 patients presenting with abnormal jugular valves. In all healthy volunteers both internal jugular veins were opened in the supine position and collapsed in the sitting one. In the right lateral decubitus position the right internal jugular vein was opened, while the left one was partially collapsed; and-vice versa-in the left lateral decubitus position the right internal jugular vein was partially collapsed and the left one opened. In patients with abnormal jugular valves both internal jugular veins were opened in both lateral decubitus body positions. We hypothesize that in the lateral decubitus body position, because of decreased flow resistance in the extracranial veins, cerebral venous outflow is optimal, which in turn optimizes the activity of the glymphatic system. Therefore, people intuitively prefer this body position during sleep, while other positions are associated with a higher risk of neurodegenerative disorders. Yet, it should be emphasized that our results need to be interpreted with caution, since only a few individuals have been assessed and this discovery should be confirmed in more patients and healthy controls, and by precise quantitative measurements.

Diagnostic accuracy of current sonographic criteria for the detection of outflow abnormalities in the internal jugular veins.

OBJECTIVES: This study was aimed at evaluation of the diagnostic value of Doppler sonography for the assessment of abnormalities in the internal jugular veins (IJVs). METHOD: One hundred and sixteen IJVs were assessed in 58 patients with associated multiple sclerosis. Findings of Doppler sonography were compared with results of the reference test: catheter venography. RESULTS: At least one positive extracranial sonographic criterion suggesting venous abnormality was found in 92.2% of the assessed veins. Yet, sensitivity, specificity, positive and negative predictive values of sonography were low: 93.4%, 12.0%, 79.4% and 33.3% for at least one positive criterion, and for at least two positive criteria: 29.3%, 75.0%, 81.8% and 21.7%, respectively. CONCLUSIONS: Our research has shown that currently used extracranial sonographic criteria for the detection of obstructive venous abnormalities in the IJVs are of limited diagnostic value. For the time being, diagnosis of this vascular pathology should be given using catheter venography.

Prevalence of extracranial venous abnormalities: results from a sample of 586 multiple sclerosis patients.

The aim of this study was to assess the prevalence of chronic cerebrospinal venous insufficiency in an unselected cohort of multiple sclerosis (MS) patients. A total of 586 patients with clinically defined MS underwent catheter venography of the internal jugular veins, brachiocephalic veins and azygos vein. The following findings were regarded as pathologic: no outflow, slowed outflow, reversal of flow direction, prestenotic dilation accompanied by impaired outflow, outflow through collaterals, intraluminal structures obstructing the vein, hypoplasia, agenesia or significant narrowing of the vein. Venous abnormalities were found in 563 patients (96.1%). Lesions in one vein were found in 43.5%, in two veins in 49.5%, and in three veins in 3.1% of patients. Venous pathologies in the right internal jugular vein were found in 64.0% of patients, in the left internal jugular vein in 81.7%, in the left brachiocephalic vein in 1.0%, and in the azygos vein in 4.9%. Venous pathologies were found to be highly associated with MS, yet the clinical relevance of this phenomenon remains to be established.

Endovascular treatment for chronic cerebrospinal venous insufficiency: is the procedure safe?

OBJECTIVES: The aim of this report is to assess the safety of endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI). Although balloon angioplasty and stenting seem to be safe procedures, there are currently no data on the treatment of a large group of patients with this vascular pathology. METHODS: A total of 564 endovascular procedures (balloon angioplasty or, if this procedure failed, stenting) were performed during 344 interventions in 331 CCSVI patients with associated multiple sclerosis. RESULTS: Balloon angioplasty alone was performed in 192 cases (55.8%), whereas the stenting of at least one vein was required in the remaining 152 cases (44.2%). There were no major complications (severe bleeding, venous thrombosis, stent migration or injury to the nerves) related to the procedure, except for thrombotic occlusion of the stent in two cases (1.2% of stenting procedures) and surgical opening of femoral vein to remove angioplastic balloon in one case (0.3% of procedures). Minor complications included occasional technical problems (2.4% of procedures): difficulty removing the angioplastic balloon or problems with proper placement of stent, and other medical events (2.1% of procedures): local bleeding from the groin, minor gastrointestinal bleeding or cardiac arrhythmia. CONCLUSIONS: The procedures appeared to be safe and well tolerated by the patients, regardless of the actual impact of the endovascular treatments for venous pathology on the clinical course of multiple sclerosis, which warrants long-term follow-up.

Extracranial Doppler sonographic criteria of chronic cerebrospinal venous insufficiency in the patients with multiple sclerosis.

AIM: The aim of this open-label study was to assess extracranial Doppler criteria of chronic cerebrospinal venous insufficiency in multiple sclerosis patients. METHODS: Seventy patients were assessed: 49 with relapsing-remitting, 5 with primary progressive and 16 with secondary progressive multiple sclerosis. The patients were aged 15-58 years and they suffered from multiple sclerosis for 0.5-40 years. Sonographic signs of abnormal venous outflow were detected in 64 patients (91.4%). RESULTS: We found at least two of four extracranial criteria in 63 patients (90.0%), confirming that multiple sclerosis is stronghly associated with chronic cerebrospinal venous insufficiency. Additional transcranial investigations may increase the rate of patients found positive in our survey. Reflux in internal jugular and/or vertebral veins was present in 31 cases (42.8%), stenosis of internal jugular veins in 61 cases (87.1%), not detectable flow in internal jugular and/or vertebral veins in 37 cases (52.9%) and negative difference in cross-sectional area of the internal jugular vein assessed in the supine vs. sitting position in 28 cases (40.0%). Flow abnormalities in the vertebral veins were found in 8 patients (11.4%). Pathologic structures (membranaceous or netlike septa, or inverted valves) in the junction of internal jugular vein with brachiocephalic vein were found in 41 patients (58.6%), in 15 patients (21.4%) on one side only and in 26 patients (37.1%) bilaterally. CONCLUSION: Multiple sclerosis is highly correlated with chronic cerebrospinal venous insufficiency. These abnormalities in the extracranial veins draining the central nervous system can exist in various combinations. The most common pathology in our patients was the presence of an inverted valve or another pathologic structure (like membranaceous or netlike septum) in the area of junction of the IJV with the brachiocephalic vein.

Cellular and molecular mechanisms of venous leg ulcers development--the "puzzle" theory.

This review presents a hypothetical model of the development of a venous leg ulcer. The primary pathology is venous hypertension that leads to increased capillary permeability, resulting in extravasation of erythrocytes. Macrophages produce proinflammatory cytokines, which enhance the expression of adhesion molecules in the endothelium of postcapillary venules and increase the recruitment of leukocytes to the pericapillary interstitium. Extravasated T lymphocytes stimulated by cytokines, which are produced by activated macrophages, differentiate toward the Th1 phenotype. In the case of excessive extracapillary passage of erythrocytes or impaired transport of ferric ions by macrophages, the accumulation of iron in the dermis can occur. In tissues with a high concentration of iron, T lymphocytes proliferate instead of undergoing apoptosis. This is possible due to the internalization of the INF-gR2 chain of the interferon-g receptor, the downregulation of inducible nitric oxide synthase expression in macrophages and the inactivation of the active site of caspases. Stimulated by interferon-g skin keratinocytes produce chemokines: CXCL9, CXCL10 and CXCL11, which attract T lymphocytes. Finally, positive feedback loops develop resulting in the migration of T lymphocytes toward the epidermis and in high local concentrations of interferon-g and keratinocyte-derived chemokines. T lymphocytes invading epidermis produce interferon-g and Fas ligand. High concentrations of interferon-g result in the overexpression of Fas by keratinocytes. Matrix metalloproteinases shed Fas ligand from T lymphocytes. The combined effect of Fas ligand and interferon-g on Fas-overexpressing keratinocytes results in their abundant apoptosis and dermo-epidermal detachment, which is clinically manifested as blister-like lesions that progress to chronic ulcerations.

Seasonal variations in the onset and healing rates of venous leg ulcers.

OBJECTIVES: As many vascular pathologies exhibit circannual fluctuation, the aim of this study was to assess the chronobiological features of venous ulcers. METHODS: Based on a retrospective survey of the case histories of 391 venous ulcer patients, the rates of ulcer onset and healing in each month were analysed statistically; a time series was constructed to evaluate the seasonality. RESULTS: There was a significantly higher frequency of ulcer onset during the warmer part of the year (April-October), and onset showed strong seasonality. Healing rates were also unequally and statistically significantly distributed throughout the year: ulcers that appeared or that were treated with specialized treatment in the winter or summer healed slower in comparison to ulcers that began in the spring or autumn. CONCLUSIONS: Venous ulcers exhibit circannual fluctuations in their onset and healing rates. Hypothetically, in addition to exacerbation of chronic venous insufficiency, seasonal variations in immune system activity might potentially be responsible for this phenomenon.

Hypothetical molecular mechanisms by which local iron overload facilitates the development of venous leg ulcers and multiple sclerosis lesions.

This paper presents a hypothetical model of role for iron in the development of venous leg ulcers and multiple sclerosis. Elevated concentrations of iron were found in the skin affected by venous hypertension and also in the areas of brain with multiple sclerosis lesions. Individuals with hemochromatosis gene (HFE) mutations: C282Y and H63D, which result in a less efficient transport of iron by macrophages, are characterized by an increased risk for venous leg ulcer and multiple sclerosis. Multiple sclerosis is a T cell-mediated disease, and T cells probably participate in the development of venous ulcers. This deleterious role of ferric ions could be related to the regulation of T cell proliferation and apoptosis. Under normal conditions excessive accumulation of T cells cannot take place, because nitric oxide and interferon-gamma drive these cells toward apoptosis. However, in tissues with a high concentration of iron, T lymphocytes proliferate instead of undergoing apoptosis. This is possible due to the internalization of the INF-gammaR2 chain of the interferon-gamma receptor, the downregulation of inducible nitric oxide synthase expression in macrophages and the inactivation of the active site of caspases. Yet, it should be emphasized that this hypothesis does not claim for the increased concentration of iron as a direct causal factor for the development of venous ulcerations or multiple sclerosis, but rather, iron is a factor that modulates and exaggerates the autoimmune process. Iron chelators, administered systemically or locally, should potentially exhibit therapeutic and prophylactic activity against venous leg ulcers and multiple sclerosis.

Delayed healing of chronic leg ulcers can result from impaired trafficking of bone marrow-derived precursors of keratinocytes to the skin.

In this paper, it is hypothesized that in chronic wounds the process of homing of bone marrow-derived precursors of keratinocytes is disturbed, and that the interaction between cutaneous T-cell attracting chemokine (CTACK/CCL27) and soluble P-selectin glycoprotein ligand-1 (PSGL-1) can be the cause of this impairment. Several studies have revealed that bone marrow-derived cells (BMDC) trans-differentiate into various cellular lineages, and probably they participate also in healing of wounded skin. Recent studies have demonstrated that BMDC can engraft into the epidermis, and probably they do not engraft into epidermis as keratinocyte stem cells, but rather as transient amplifying cells. So, bone marrow-derived keratinocytes build provisional epidermal layer, and later they are replaced by keratinocytes migrating from surrounding skin. Probably after injury BMDC are recruited by pro-inflammatory cytokines, like granulocyte-macrophage colony stimulating factor. Further homing to the skin is mediated by CTACK/CCL27. This chemokine is exclusively secreted by keratinocytes. In chronic wounds the recruitment of BMDC seems to be impaired. Inhibition of CTACK/CCL27 by as yet not determined factor could be the cause of delayed healing. PSGL-1 appears to be a good candidate for such inhibiting factor. PSGL-1 is expressed by several populations of leukocytes, and can be released from surface of activated neutrophils. It was demonstrated that soluble PSGL-1 binds CTACK/CCL27, and inhibits chemotaxis mediated by this chemokine. Because there are many activated neutrophils in the wound, it should be expected that wound exudate contains large amount of soluble PSGL-1. Thus, CTACK/CCL27 in the wound would be inhibited, and homing of bone marrow-derived precursors of keratinocytes would be disturbed. If this interaction were found to be the main cause of wound chronicity, above-mentioned molecules could be the potential targets for pharmaceutical agents.

A potential role of interferon-gamma in the pathogenesis of venous leg ulcers.

Venous leg ulcer is the most severe expression of chronic venous insufficiency. Venous ulcerations are always associated with venous ambulatory hypertension, but the exact mechanism leading from pathological hemodynamics in venous circulation to the necrotic lesions in the skin still remains undiscovered. It has been shown that tissue injury in venous ulcer patients was induced by leukocytes. However, though infiltrating leukocytes have at their disposal a powerfully cytotoxic arsenal, it has not been discovered which molecular mechanisms may contribute to the skin damage. The search for this hypothetical factor responsible for the development of ulceration should be focused on mechanisms leading to apoptosis of keratinocytes, on pathogenesis of related dermatological pathologies, on other pathologies associated with epithelial lesions, and on mechanisms responsible for the expression of adhesion molecules. A thorough review of the literature, with special regard to cytokines, has revealed that proinflammatory cytokine--interferon-gamma (INFgamma)--could be a pivotal cytokine in the pathogenesis of venous ulceration. This cytokine, however, has not been investigated in venous leg ulcer patients before. INFgamma is a glycoprotein with numerous immunological and antiproliferative activities. The most important message from recent investigations is the fact that INFgamma seems to be the main mediator of keratinocyte apoptosis. INFgamma mediates also leukocyte chemotaxis, and enhances the expression of adhesion molecules involved in the pathophysiology of chronic venous insufficiency. Therapeutic injections of interferons can result in skin necrosis. If it were proven that INFgamma was responsible for the development of venous leg ulcers, this fact would have important clinical consequences. In such a case, anti-INFgamma agent could be used, either in the management of active ulceration, or in the prevention of recurrent ulcer.

[Repeated excision of abdominal aortic aneurysm--case report]. / Ponowne wyciecie tetniaka aorty brzusznej--opis przypadku.

A case of 69-year-old male patient with recurrent abdominal aortic aneurysm is described. The patient had been successfully operated on for infrarenal abdominal aortic aneurysm 4 years before, and 2 months postoperatively dilatation of juxtarenal part of abdominal aorta was diagnosed in ultrasonic examination. Due to progressive enlargement of juxtarenal aneurysm the patient was admitted to hospital again and operated on. Excision of aneurysm with implantation of both renal arteries to the prosthesis was done. The perioperative course was uneventful. Authors emphasize the importance of evaluation of abdominal aorta after operative treatment of aneurysm (ultrasonic, CT, MRI) to diagnose recurrent aneurysms.

Thrombocytosis after prophylactic administration of enoxaparin: unexpected findings in a Polish prospective multicenter trial on the efficacy and safety of enoxaparin in the prevention of postoperative thromboembolism.

BACKGROUND: Heparin-related thrombocytopenia is a common complication of heparin administration and therefore platelet count was monitored in our study. EXPERIMENTAL DESIGN: Prospective multicentre study. SETTING: 14 Departments of General, Thoracic or OrthopaedicSurgery, Poland. PATIENTS: 290 patients--150 general or thoracic surgery patients aged above 40 years, and 140 orthopaedic surgery patients aged between 18 and 60 years. INTERVENTIONS: All patients received 20 mg (general and thoracic surgery) or 40 mg of enoxaparin (orthopaedic surgery) once daily subcutaneously both before surgery and during postoperative immobilisation. MEASURES: Platelet count was evaluated prior to surgery and on the 5th, 7th, 11th and 15th day following the operation. RESULTS: There was neither thrombocytopenia nor heparin-induced thrombosis. Paradoxically, postoperative platelet count in most cases increased slightly but statistically significantly, but in some however, even above 600 G/l, nevertheless in these patients no thrombotic complications occurred. Postoperative thrombocytosis was greater in patients with neoplasms as well as those with excessive perioperative blood loss and transfusions. CONCLUSIONS: As platelet count was not the main topic of our study, the presented data should be regarded only as preliminary. Further investigations to resolve the cause of the observed phenomenon of thrombocytosis are therefore necessary.

[Neoplastic ulceration of the stomach penetrating to the spleen as a cause of sudden fatal gastrointestinal hemorrhage--case report]. / Nowotworowe owrzodzenie zoladka drazace do sledziony przyczyna naglego smiertelnego krwotoku do przewodu pokarmowego--opis przypadku.

History of 71-year-old woman with sudden upper digestive tract hemorrhage is presented. Endoscopic attempt to control the hemorrhage was unsuccessful-patient died during endoscopy. On autopsy it was found that hemorrhage was caused by neoplastic ulceration of the stomach penetrating to the spleen.

[Aneurysm of the abdominal aorta complicated with a fistula into the inferior caval vein]. / Tetniak aorty brzusznej powiklany przetoka do zyly glównej dolnej.

The results of treatment are presented in three patients with a fistula between the lumen of abdominal aorta aneurysm and the inferior caval vein. Surgical operation was successful in two patients, and one patient with large fistula, operated on as urgent case, died. The results of treatment of this rare complication are influenced by: fistular dimensions, volume of blood lost during operation and good cooperation between surgical and anaesthesiological teams.