Immune system disturbances in Clouston syndrome.

BACKGROUND: Clouston syndrome belongs to the family of ectodermal dysplasias. So far, a defective immune response has not been reported in Clouston syndrome. We report, for the first time, immunological particularities of a large multigenerational Polish family with Clouston syndrome. METHODS: Five members of the same family with Clouston syndrome, aged 6-76 years, and 20 healthy volunteers, aged 19-73 years, were enrolled in the study. In all participants, the ability of neutrophils to phagocytize opsonized Escherichia coli was assessed. Granulocyte oxidative burst was determined quantitatively, and an isolation of peripheral blood mononuclear cells and the detection of lymphocyte subsets were performed. All patients with Clouston syndrome underwent microscopic assessment of hair shafts, x-rays of the skull and hand bones, extra- and intraoral examination, and panoramic x-rays. RESULTS: Compared to the controls, all patients with Clouston syndrome presented with significantly reduced phagocytic activities of granulocytes and monocytes (P < 0.05). The percentages of granulocytes and monocytes being positive for oxidative burst were also significantly reduced in all patients with Clouston syndrome (P < 0.05). No disturbances in the percentages and absolute counts of T CD3+, T CD3+/CD4+, T CD3+/CD8+, natural killer, and B CD19+ cells were found. CONCLUSION: Although this study expands knowledge about Clouston syndrome, it also raises many questions. The results provide evidence of significantly reduced phagocytic activity and oxidative bursts of cells playing crucial roles in a nonspecific immune response. Further studies are required to understand the underlying mechanism of the hereby described abnormalities.

CIDE-A gene expression in patients with obesity qualified for endovascular treatment of abdominal aorta aneurysm.

UNLABELLED: CIDE-A gene and the genes of LRP group play a key role in the regulation of the body weight and lipid metabolism in mammals. CIDE-A is defined as a potential human obesity gene and the LRP1 gene is associated with the development of abdominal aortic aneurysm (AAA). The aim of the study was to define the role of CIDE-A gene in patients with dyslipidemia and asymptomatic AAA. MATERIAL AND METHODS: The study group consisted of 38 subjects, including 27 men and 11 women qualified for endovascular aneurysm repair (EVAR). The subjects with abdominal aortic aneurysm were enrolled in the study group, depending on the body mass index (BMI); in obese patients (BMI > 30). The control group (n = 16) included subjects without lipid disorders. One-step isolation of RNA from lymphocytes and adipose tissue cells was performed using the modified TRI method by Chomc-zynski and Sacchi, and then the gene expression was tested by real-time PCR. RESULTS: The highest mean relative of the gene expression for CIDE-A was reported in subjects with the normal body weight. The lowest mean relative of the gene expression for CIDE-A was observed in the group of obese patients with aortic aneurysm and lipid disorders. A high negative correlation (r = -0.7101) in the gene expression for CIDE-A was observed in the group of obese patients with aortic aneurysm, depending on the BMI. CONCLUSIONS: Due to the important role of the CIDE-A gene and Cide-A protein in the development of metabolic syndrome, obesity and the accompanying vascular lesions such as abdominal aortic an-eurysm, seen in this context, the tested gene and protein Cide-A represent a potential therapeutic target in these diseases.

Selected factors of fibrinolysis in the Buerger's disease.

UNLABELLED: Thrombangiitis obliterans (TAO marked by coexistence of thrombotic and inflammatory changes of neurovascular tract has evoked a considerable dispute concerning pathogenesis of this disease. The aim of the study was to define the level of activation of fibirinolitic system in course of TAO disease by means of determination its basic constituents as well as to examine the essence of level of fibrinolysis disorders in pathogenesis and development of this disease. MATERIAL AND METHODS: Fifty patients with thrombangiitis obliterans (TAO), 30 patients with peripheral occlusive disease - PAOD (ASO) and 20 healthy volunteers (K) have been subjected to the examination. We determined the activity some factors of fibrinolysis: t-PA, PAI-1, PAP, plasminogen, α2-antiplasminogen, D-dimmer as well as euglobulin lysis time. The analysis comprised 7 features and 8 factors of variability: a membership to a group of patients, sex, age, smoking, aggravation of the disease within last 3 months, occurrence of Raynaud's symptom, a degree of ischemia according to Fontaine, time the disease lasted. RESULTS: The significant differences between the average were checked by means of t-Student test or variance analysis (ANOVA) and co-relation rate r (Pearson). We concluded that the average value of PAI-1 in the group TAO was significantly higher than in comparison with ASO group. The increased values were revealed in case of 76 % of patients. The euglobulin lysis time was vitally extended in case of 60% of patients in ASO group. In all three groups higher levels of α2-antiplasmin were detected in case of elderly patients compared to the younger ones. CONCLUSIONS: The obtained results allow us to ascertain the state of potentially weakened fibrinolysis in case of patients with Buerger's disease as well as with PAOD.

The changes of plasma thrombin-antithrombin complex in the patients with peripheral arterial disease undergoing surgical revascularization.

UNLABELLED: In patients with severe lower limb ischemia the coagulation and fibrinolytic systems have been found to be activated preoperatively. The aim of the study was to evaluate the changes of TAT level as a selected coagulation factor, before, during and after surgical revascularization and the analysis of the impact of coexisting diseases on the coagulation during the procedure. MATERIAL AND METHODS: 50 patients with PAOD, in Fontaine stages IIb to IV (29 men and 21 women; median age 65.8 years, ASA II/III) undergoing elective surgical revascularization were studied. Two groups of patients were compared: 20 undergoing reconstruction on aorto-femoral and 30 on femoropopliteal level. Blood samples were collected 5 times: 24 hours before the operation; intraoperatively after artery exposure; after heparin administration and clamping; after reperfusion and -24 hours postoperatively. RESULTS: Elevated values of TAT (10.5 g/l ±7.1) were found before the operation. The elevated value of TAT increased intraoperatively (25.1 g/l ±44.58; p<0.001) (norm 1-4.1 g/l) and maintaining higher levels after the surgery. The significant correlations between plasma level of TAT and ischemia degree were found. Also the correlation between intraoperative increase of TAT and the duration of surgery was noticed. No significant differences between two analysed groups were observed. CONCLUSIONS: The results indicate the activation of coagulation and prothrombotic state in the patients with advanced arteriosclerosis. During the surgical revascularisation permanent increase of activation of blood coagulation was observed. This activation depends on duration of the procedure and maintains increased one-day after the operation. Our findings may explain the unexpected occurrence of early thrombotic complications after technically successful vascular reconstructions.

CIDE--A gene expression in patients with abdominal obesity and LDL hyperlipoproteinemia qualified for surgical revascularization in chronic limb ischemia.

UNLABELLED: According to the latest data, CIDE -A gene plays a key role in the regulation of body weight in both humans and mice, and therefore it is regarded a potential candidate gene for human obesity. The aim of the study was to define the role of CIDEA gene in patients with dyslipidemia and symptomatic limb ischemia. MATERIAL AND METHODS: The study group contained 28 patients, including 17 men and 11 women. Patients were enrolled in the study group, depending on the value of body mass index (BMI); there was BMI>30 for obese patients. The group included untreated patients (n=14) and patients (n=14) receiving atorvastatin 20 mg/day for at least three months prior to the initiation of the study. The control group (n=16) contained patients with no lipid disorders. A one-step isolation of RNA from lymphocytes and adipose tissue cells was carried out using the TRI method modified by Chomczynski and Sacchi. Next, gene expression was tested using real-time PCR. RESULTS: The highest mean relative expression of CIDE -A gene occurred in patients with normal body weight. The lowest mean relative expression of CIDE-A gene was observed in obese patients with lipid disorders. A high negative correlation (r=-0.7919) of CIDE -A gene expression, depending on BMI, was reported in the group of obese patients with lipid disorders. CONCLUSIONS: Due to an important role of Cide-A protein demonstrated in the development of metabolic diseases such as obesity, metabolic syndrome, type 2 diabetes and their vascular complications, CIDE -A gene and protein are potential therapeutic targets in the case of these diseases.

[Polish guidelines for the prevention and treatment of venous thromboembolism. 2012 update]. / Polskie wytyczne profilaktyki i leczenia zylnej choroby zakrzepowo-zatorowej. Aktualizacja 2012.

The overall objective of the Polish guidelines for the prevention and treatment of venous thromboembolism is to increase patient benefit and safety by appropriate prevention and treatment of deep vein thrombosis and pulmonary embolism as well as proper management of the complications associated with antithrombotic and thrombolytic therapy. These guidelines apply to adult trauma, cancer, surgical, and medical patients as well as those at increased risk of venous thromboembolism. Specific recommendations have been formulated for pregnant women, patients requiring surgery while receiving long-term oral anticoagulant treatment, and patients undergoing regional anesthesia and/or analgesia. We chose to update the existing Polish guidelines with the use of the most recent high-quality international guidelines that we identified and adjusted the final product to Polish cultural and organizational setting. We based our recommendations primarily on the 9th edition of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines on Antithrombotic Therapy and Prevention of Thrombosis, the European Society of Cardiology Guidelines on the Diagnosis and Management of Acute Pulmonary Embolism, the 3rd edition of the American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines on Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy, the ACOG practice bulletin on thromboembolism in pregnancy (Number 123), and Guidance from the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis on the Duration of Anticoagulant Therapy after a First Episode of Unprovoked Pulmonary Embolus or Deep Vein Thrombosis, as well as two other Polish practice guidelines on the prophylaxis and treatment of venous thromboembolism and the management of patients treated with oral direct inhibitors of factor X or factor II. To make recommendations regarding specific management issues that had not been addressed in other guidelines, or whenever the panel members felt they needed additional information to reach the decision, we also consulted the authors of guidelines developed by other professional societies and organizations as well as additional sources of evidence. For each adapted recommendation, we explicitly assessed its relevance and applicability in the context of the healthcare system in Poland. When necessary, we explicitly stated the rationale for modification of the previously published recommendations and judgements about the values and preferences we assumed. The information regarding reimbursement of drugs mentioned in the recommendations was added in chapters 6-9 and 13 and approved by the National Health Fund. The final version of the practice guidelines was officially approved by the scientific societies and institutions listed at the beginning of the document.  

Usefulness of 99mTc-ECD brain SPECT with voxel-based analysis in evaluation of perfusion changes early after carotid endarterectomy.

BACKGROUND: Association between preoperative perfusion pattern and reperfusion after carotid endarterectomy (CEA) is an important yet unexplored topic. Therefore, the aim of our study was to determine whether 99mTc-ECD single-photon emission computed tomography (SPECT) performed before carotid endarterectomy in patients with internal carotid artery (ICA) stenosis may be helpful in predicting early perfusion changes after revascularization. MATERIAL/METHODS: The examined group consisted of 30 patients (mean age 67.4±9.6 years) with ICA stenosis who underwent CEA. Infarction was demonstrated on computed tomography (CT) in 12 cases. Brain perfusion SPECT was performed 1-3 days before CEA and 3-5 days after the surgery. Voxel-based analysis was carried out with Brain SPECT Quantification software. For evaluation of preoperative interhemispheric asymmetry of perfusion, the percentage asymmetry index (AI) was calculated. For comparison of perfusion before and after CEA, the percentage relative difference (RD) was computed. RESULTS: Before CEA, cerebral hypoperfusion was seen in 26 cases, including 15 participants with normal CT. After CEA, the following changes of perfusion were observed: perfusion increase n=18 (ipsilateral and bilateral), deterioration n=1, mixed patterns n=2, no change n=9. In patients with preoperative ipsilateral hypoperfusion and perfusion increase after CEA, AI correlated significantly with RD (r=0.48, p=0.04). CONCLUSIONS: Our results suggest that perfusion increase 3-5 days after CEA is higher in patients with greater ipsilateral asymmetry index. Evaluation of preoperative AI may help to identify patients in whom rapid reperfusion is more likely.

[The role of matrix metalloproteinases and their tissue inhibitors in angiogenesis]. / Rola metaloproteaz macierzy i ich tkankowych inhibitorów w angiogenezie.

Cellular aspect of angiogenesis - the multilevel process involving the growth of new blood vessels from pre-existing vessels--includes migration and proliferation of the cells as well as remodelling of their environment--extracellular matrix (ECM). The key role in ECM remodelling is played by proteolytic enzymes classified as matrix metalloproteinases (MMPs). Recent research shows that performed by MMPs degradation of vascular ECM components is a significant event ocurring during angiogenesis. This process enables migration of endothelial cells that is crucial part in new vessel formation. MMPs also release sequestered angiogenic molecules, such as VEGF, bFGF and TGF-beta. Angiogenesis is a normal process in growth and development, as well as in wound healing, monthly reproductive cycle and during pregnancy. However, this is also a fundamental step in such conditions as malignancies, inflammation or ischaemia. The influence of MMPs on agiogenesis as terminal agents in many physio- and pathological events makes this group of enzymes very promissing aim of new therapeutic strategies based on modulation of angiogenesis.

[Etiological factors of vascular grafts infections and their resistance to antibiotics]. / Czynniki etiologiczne zakazen przeszczepów naczyniowych i ocena ich lekoopornosci.

THE AIM: of our study was the identification of microorganisms causing vascular graft infections and the evaluation of their antimicrobial susceptibility. MATERIAL AND METHODS: 25 patients with infected vascular graft, took part in our research. In 19 patients late type of infection was recognized, in 6 the infection was qualified as early. Purulent discharge obtained from the fistula was inoculated on the bacteriological media. Antimicrobial susceptibility was assessed by disc-diffusion method. RESULTS: Staphylococcus aureus and Pseudomonas aeruginosa proved to be the most frequently isolated microorganisms. Mixed infection, caused by two distinct bacteria, occurred in 5 patients; in all cases one species belonged to Gram-positive, and the second one to Gram-negative bacteria. In 50% of patients with early type infection different species of Gram-negative rods were present, in 37,5% of them S. aureus and S. epidermidis were isolated. In late type infection Gram-negative rods were isolated from 54,5% of patients and Gram-positive bacteria from 31,5% of patients. The most frequently isolated species appeared to be Pseudomonas aeruginosa. The isolated species of bacteria varied depending on the degree of infection (according to Shilagy and Samson). CONCLUSIONS: A diversity of isolated species, the presence of mixed infections and resistance patterns typical for hospital flora among bacteria infecting vascular grafts cause that antibiotic therapy should always be based on the results of microbiological examination.

[The role of matrix metalloproteinases in venous leg ulcers development]. / Rola metaloproteaz macierzy w powstawaniu owrzodzen zylnych goleni.

Venous leg ulcers are one of the most serious therapeutic and economic problems of current medicine. In spite of the rapid progress in the diagnostics of venous disorders, the pathogenesis of venous leg ulcers remains unclear. Current medicine describes many theories that try to explain the patophysiology of venous ulceration. Recent studies have revealed the role of extracellular matrix degradation processes in venous leg ulcers. The family of enzymes classified as matrix metalloproteinases (MMPs) play the leading role in these processes. The extensive knowledge of MMPs and the role played by them in venous leg ulcers and wound healing may result in development of the new methods of management with many vascular disorders.

[Acute cardiac failure secondary to brachiocephalic arteriovenous fistula in patient on chronic haemodialysis]. / Ostra niewydolnosc lewokomorowa po wytworzeniu wysokoprzeplywowego zespolenia tetniczo-zylnego u chorego przewlekle hemodializowanego.

Vascular access for hemodialysis is crucial for appropriate course of the treatment as well as for good prognosis for patients with chronic renal insufficiency. In this paper we present the case of chronically hemodialysed patient who developed high-output cardiac failure after several days before creation of the upper arm brachio-cephalic arteriovenous fistula. Ultrasonographic imaging of the fistula showed an over-functioning anastomosis with flow reaching 41/min. The surgical correction of the anastomosis length to 4 mm and reduction of the cephalic vein diameter to 5 mm, significantly improved general status of the patient, simultaneously maintaining an accurate function of the fistula, with the maximal flow up to 850 ml/min.