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Biomedical subjects

A Szuba

Publications and source records attributed to A Szuba.

At least 19 recordsLinked to original sources
PubMed2005

The integrated and interdisciplinary treatment of chronic lymphedema.

Lymphedema is a chronic and incurable disease, deeply disturbing physical and psychical health of affected individuals. Lymphedema is a progressive, if left untreated. Affected patients are looking for help between physicians and therapists of different specialities. Chronic lymphedema leads to emotional disorders, depression, even to suicidal attempts--especially in young patients. In rare cases it may lead to lymphangiosarcoma--ominous neoplasm with poor prognosis. Complex interdisciplinary approach of the lymphedema team is the key to the success of lymphedema therapy. Optimal treatment of lymphedema requires close cooperation of all people involved in the therapeutic process including physicians, nurses, physiotherapists and psychologists. International Society of Lymphology (ISL) published its recommendations for lymphedema therapy, which are accepted in many countries around the world. Recommended by ISL physiotherapy consists of a manual lymphatic drainage, compressive bandaging, decongestive exercises and meticulous skin care. It is called a manual lymphedema treatment--complex physical therapy (MLT-CPT).

Chronic Disease↗
PubMed2005

LYVE-1 expression on high endothelial venules (HEVs) of lymph nodes.

LYVE-1 (lymphatic endothelium hyaluronan receptor) has been identified as a powerful marker for lymphatic endothelium. Apart from lymphatic endothelium, LYVE-1 is expressed in normal liver blood sinusoids, spleen endothelium and activated tissue macrophages. LYVE-1 has not been detected in blood vascular endothelium with the exception of blood vessels in the lung. High endothelial venules (HEVs) belong to the vascular compartment of lymph nodes. They are the major site of entry for circulating lymphocytes into the node. HEVs are characterized by cuboidal endothelial cells, the existence of discontinuous junctions between these endothelial cells, and the presence of large numbers of lymphocytes within their walls. 40 paraffin-embedded lymph node biopsy specimens from newly diagnosed patients with non-Hodgkin lymphoma were evaluated as well as 10 lymph node biopsy specimens from adult patients with reactive lymphadenitis, and 10 normal, non-metastatic lymph nodes obtained from adult patients during cancer surgery served as controls. Samples were fixed in 10% buffered formalin, paraffin embedded, and stained with hematoxylin and eosin for histopathological evaluation. Sections were also evaluated with mouse monoclonal antibodies against LYVE-1 and CD34, and expression of both LYVE-1 and CD34 was demonstrated in HEVs. LYVE-1 expression was also found on the endothelial cells of the lymphatic sinus and in reticular cells in the lymph nodes.

Antigens, CD34↗
PubMed2003

Platelets' glycoproteins and their ligands in patients with intermittent claudication.

BACKGROUND: Platelet thrombi play critical role in pathogenesis of cardiovascular complications in atherosclerotic peripheral arterial disease (PAOD). The aim of this study was to evaluate the concentration of platelets GP IIb/IIIa, GP I b/IX and plasma levels of their ligands (fibrinogen and vWF) and their relation to other atherosclerotic risk factors in the patients with intermittent claudication secondary to PAOD. METHODS: Consecutive patients of the University Vascular Clinic were studied: 64 claudicants and 38 controls were enrolled. The concentration of platelets GPII b/IIIa and GP Ib/IX was estimated by ELISA method using monoclonal antibody against GPII b/IIIa (CD41a) and GPI b/IX (CD42a Immunotech). Plasma levels of vWF, fibrinogen, and platelets were measured by routine METHODS RESULTS: Plasma vWF (145+/-41%), fibrinogen (3.8+/-1 g/l) and platelet concentration of GP Ib/IX (121.1+/-23.39), GPIIb/IIIa (117.9 6 +/-32.7%), as well as plasma lipids and uric acid were statistically higher in claudicants than in controls (vWF: 103+/-42%, fibrinogen: 2.9+/-0.5 g/l, GP Ib/IX: 100+/-16.9%, GP IIb/IIIa: 100+/-29.4%). We have observed statistically higher concentration of GP IIb/IIIa and GP Ib/IX in smoking patients than in non-smoking patients with PAOD and significant correlation between the concentration of GP Ib/IX and GP IIb/IIIa and plasma fibrinogen in patients with PAOD and controls. CONCLUSIONS: Our results demonstrate higher platelet concentration of GP Ib/IX,GP IIb/IIIa and elevated plasma levels of ligands for platelets receptors-fibrinogen and vWF in patients with PAOD. This prothrombotic conditions may explain increased cardiovascular morbidity and mortality in this patient's group.

Adult↗
PubMed2002

Quantitative radionuclide lymphoscintigraphy predicts outcome of manual lymphatic therapy in breast cancer-related lymphedema of the upper extremity.

Secondary lymphedema is a localized, acquired lymphatic microcirculatory disturbance that affects large numbers of patients after breast cancer therapy. There is a paucity of objective methods to quantitate lymphatic function and to anticipate the response to therapeutic interventions. We applied radionuclide lymphoscintigraphy to evaluate lymphatic transport and axillary lymph node visualization in women following breast cancer therapy to determine the utility of these data in these patients. Lymphoscintigraphy was performed after subcutaneous injection of 0.25 mCi of Tc-filtered sulfur colloid. Subcutaneous accumulation of radiotracer ('dermal backflow') and the visualization of axillary lymph nodes were graded using our own scoring system. The ratio of radioactivity within the affected to normal axillae (ARR) was also quantified. Nineteen patients with lymphedema after breast cancer therapy were evaluated. The disease severity was documented by serial measurements of the limb volume using the truncated cone formula. Responses to therapy were quantified after completion of the therapy. There was a correlation between the ARR and the percentage reduction in edema volume. The lymphoscintigraphic score correlated with the initial arm volume excess and with the durationof lymphedema. It can be concluded that quantitative and semi-quantitative assessment by radionuclide lymphoscintigraphy represents a potentially useful tool for the clinical assessment of upper extremity lymphedema.

Aged↗
PubMed2000

Photoangioplasty for human peripheral atherosclerosis: results of a phase I trial of photodynamic therapy with motexafin lutetium (Antrin).

BACKGROUND: In photoangioplasty, light activation of a photosensitive drug offers the potential for treatment of long segments of vascular disease. This is a brief description of a study designed to evaluate the safety and tolerability of a new photosensitizer, Antrin (motexafin lutetium), in the endovascular treatment of atherosclerosis. METHODS AND RESULTS: An open-label, single-dose, escalating drug- and light-dose study was performed in patients with atherosclerotic peripheral arterial insufficiency. Clinical evaluation, serial quantitative angiography, and intravascular ultrasonography were performed. Therapy was well tolerated, and only minor side effects were observed. Treatment produced no deleterious vascular effects. Although this study was not designed to examine clinical efficacy, several secondary end points suggested a favorable therapeutic effect. CONCLUSIONS: This phase I study demonstrates that photoangioplasty with motexafin lutetium is well tolerated and safe. Preliminary efficacy data suggest a future role for the treatment of flow-limiting atherosclerosis.

Humans↗
PubMed2000

Decongestive lymphatic therapy for patients with cancer-related or primary lymphedema.

PURPOSE: A prospective evaluation was undertaken to assess the efficacy of intensive, short-term decongestive lymphatic therapy coupled with focused patient instruction in long-term self-care for the management of lymphedema. METHODS: The therapeutic responses of 79 patients with lymphedema were analyzed prospectively. Each patient received intensive, short-term decongestive lymphatic therapy, with quantification of the extent and durability of the clinical response. Decongestive lymphatic therapy was performed by therapists trained in these techniques. The mean (+/-SD) duration of therapy was 8+/-3 days. Instruction in self-management techniques was incorporated into the therapeutic regimen by day 3 of the patient's treatment. The mean period of follow-up was 38+/-52 days. Changes in the volume of the affected limb were assessed with a geometric approximation derived from serial measurements of circumference along the axis of the limb. RESULTS: The mean short-term reduction in limb volume was 44%+/-62% of the excess volume in the upper extremities and 42%+/-40% in the lower extremities. At follow-up, these results were adequately sustained: mean long-term excess volume reductions of 38%+/-56% (upper extremities) and 41%+/-27% (lower extremities) were observed. CONCLUSION: Decongestive lymphatic therapy, combined with long-term self-management, is efficacious in treating patients with lymphedema of the extremity.

Bandages↗
PubMed2000

Nitric oxide induces the synthesis of vascular endothelial growth factor by rat vascular smooth muscle cells.

Vascular endothelial growth factor (VEGF) is known to induce the release of nitric oxide (NO) from endothelial cells. However, the effect of NO on VEGF synthesis is not clear. Accordingly, the effect of endogenous and exogenous NO on VEGF synthesis by rat vascular smooth muscle cells (VSMCs) was investigated. Two in vitro models were used: (1) VSMCs stimulated to produce NO by treatment with interleukin (IL)-1beta (10 ng/mL) and (2) VSMCs lipotransfected with pKecNOS plasmid, containing the endothelial constitutive NO synthase (ecNOS) cDNA. The synthesis of NO was inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME, 2 to 5 mmol/L) or diaminohydroxypyrimidine (DAHP, 2.5 to 5 mmol/L), inhibitors of NOS and GTP cyclohydrolase I, respectively. Some cells treated with L-NAME or DAHP were supplemented with L-arginine (10 mmol/L) or tetrahydrobiopterin (BH(4); 100 micromol/L), respectively. In addition, we studied the effect of sodium nitroprusside (SNP; 10 and 100 micromol/L) and chemically related compounds, potassium ferrocyanide and ferricyanide, on VEGF generation. IL-1beta induced iNOS expression and NO generation and significantly upregulated VEGF mRNA expression and protein synthesis. L-NAME and DAHP totally inhibited NO generation and decreased the IL-1beta-upregulated VEGF synthesis by 30% to 40%. Supplementation with L-arginine or BH(4) increased NO generation by L-NAME- or DAHP-treated cells, and VEGF synthesis was augmented by addition of BH(4). The cells generating NO after pKecNOS transfection released significantly higher amounts of VEGF than cells transfected with control plasmids. Inhibition of NO generation by L-NAME decreased VEGF synthesis. In contrast to the effect of endogenous NO, we observed the inhibition of VEGF synthesis in the presence of high (10 or 100 micromol/L) concentrations of SNP. This effect was mimicked by chemically related ferricyanide and ferrocyanide compounds, suggesting that the inhibitory effect of sodium nitroprusside may be mediated by an NO-independent mechanism. The results indicate that endogenous NO enhances VEGF synthesis. The positive interaction between endogenous NO and VEGF may have implications for endothelial regeneration after balloon angioplasty and for angiogenesis.

Animals↗
PubMed2000

Vascular endothelial growth factor is efficiently synthesized in spite of low transfection efficiency of pSG5VEGF plasmids in vascular smooth muscle cells.

The limitation of lipotransfection with plasmid vectors is its low efficiency and the short-term expression of introduced genes. This is particularly important when the synthesis of high amounts of therapeutic products is required. However, growth factors with paracrine action overcome this problem. The aim of our study was to check whether the amounts of vascular endothelial growth factor (VEGF) generated after plasmid lipotransfection into vascular smooth muscle cells (VSMC) can be sufficient to stimulate endothelial cell proliferation. Two plasmids, pSG5-VEGF121 and pSG5-VEGF165, harboring human VEGF121 and VEGF165 isoforms were constructed and lipotransfected into COS-7 cells or to rat VSMC. The transfection efficiency, estimated by the expression of control, beta-galactosidase gene, was about 50% in COS-7 but rarely exceeded 5% in VSMC. However, despite this, the smooth muscle cells generated high amounts of VEGF protein, up to 3 ng/ml medium. The biological activity of this VEGF was confirmed by enhanced proliferation of human umbilical vein and coronary artery endothelial cells, stimulated with conditioned media of pSG5-VEGF transfected cells. Thus, the low transfection efficiency does not preclude the generation of high amounts of VEGF by VSMC. After reaching the maximum at about 48 h after transfection, the generation of VEGF decreased in the following days. Such a situation may be sufficient for the gene therapy of restenosis when the long-term expression of therapeutic gene(s) is not necessary. Thus, we suggest that the pSG5-VEGF121, and pSG5-VEGF165 plasmids can be used for therapeutic application.

Animals↗
PubMed1999

Lymphoscintigraphic manifestations of Hennekam syndrome--a case report.

Hennekam syndrome is a rare, recently described genetic disorder in which facial anomalies and mental retardation accompany congenital lymphedema and intestinal lymphangiectasia. Several other somatic abnormalities have variously been described, as have milder degrees of lymphatic dysfunction. The authors herein describe a case of Hennekam syndrome in which the diagnostic difficulties were partially overcome by the judicious use of radionuclide scintigraphy to verify the lymphedematous component of the patient's presentation.

Adolescent↗
PubMed1999

Fibroblast growth factor as therapy for critical limb ischemia: a case report.

In an attempt to avert impending, primary amputation, an 85-year-old woman with chronic critical leg ischemia was enrolled in an experimental protocol to induce therapeutic angiogenesis. Treatment consisted of six consecutive, weekly intravenous infusions of recombinant basic fibroblast growth factor (bFGF). Angiographic evaluation was performed before and after therapy. The patient's clinical response was monitored through serial measurements of the ankle/brachial index and by repetitive assessment of limb flow by mercury strain-gauge plethysmography. A beneficial clinical response was detectable by week 4 of therapy, which was characterized by an improved walking distance, relief of ischemic pain, a marked reduction in analgesic consumption, and healing of persistent, unresponsive, painful inflammation of the hallux. The clinical improvement was sustained throughout the remaining weeks of therapy and follow-up evaluation. Plethysmography documented improved blood flow; specifically, the augmentation of digital flow was sustained and correlated with the marked improvement in the patient's clinical status.

Aged↗
PubMed1998

Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase. Because endothelial NO elaboration is impaired in hypercholesterolemia, we investigated whether plasma concentrations of ADMA are elevated in young, clinically asymptomatic hypercholesterolemic adults. We further studied whether such elevation of ADMA levels was correlated with impaired endothelium-dependent, NO-mediated vasodilation and urinary nitrate excretion. In a randomized, double-blind, placebo-controlled study, we investigated whether these changes could be reversed with exogenous L-arginine. METHODS AND RESULTS: We measured plasma levels of L-arginine, ADMA, and symmetrical dimethylarginine (SDMA) by high-performance liquid chromatography in 49 hypercholesterolemic (HC) and 31 normocholesterolemic (NC) humans. In 8 HC subjects, endothelium-dependent forearm vasodilation was assessed before and after an intravenous infusion of L-arginine or placebo and compared with 8 NC control subjects. ADMA levels were significantly elevated by >100% (2.17+/-0.15 versus 1.03+/-0.09 micromol/L; P<0.05) in HC subjects compared with NC adults. L-Arginine levels were similar, resulting in a significantly decreased L-arginine/ADMA ratio in HC subjects (27.7+/-2.4 versus 55. 7+/-5.4; P<0.05). In 8 HC subjects, intravenous infusion of L-arginine significantly increased the L-arginine/ADMA ratio and normalized endothelium-dependent vasodilation and urinary nitrate excretion. ADMA levels were inversely correlated with endothelium-mediated vasodilation (R=0.762, P<0.01) and urinary nitrate excretion rates (R=0.534, P<0.01). CONCLUSIONS: We find that ADMA is elevated in young HC individuals. Elevation of ADMA is associated with impaired endothelium-dependent vasodilation and reduced urinary nitrate excretion. This abnormality is reversed by administration of L-arginine. ADMA may be a novel risk factor for endothelial dysfunction in humans.

Arginine↗
PubMed1998

Lymphedema: classification, diagnosis and therapy.

This review presents the diagnostic features, the pathophysiology and the available therapies for lymphedema. This disease is often able to be diagnosed by its characteristic clinical presentation, yet, in some cases, ancillary tests might be necessary to establish the diagnosis, particularly in the early stages of the disease and in edemas of mixed etiology. These diagnostic modalities are also useful in clinical studies. Available modalities include isotopic lymphoscintigraphy, indirect and direct lymphography, magnetic resonance imaging, computed tomography and ultrasonography. Lymphedema may be primary or secondary to the presence of other disease and/or to the consequences of surgery. Primary lymphedema may occur at any phase of life but it most commonly appears at puberty. Secondary lymphedema is encountered more often. The most prevalent worldwide cause of lymphedema is filariasis, which is particularly common in south-east Asia. In the USA, postsurgical lymphedema of the extremity prevails. Complications of chronic limb lymphedema include recurrent cellulitis and lymphangiosarcoma. Most patients are treated conservatively, by means of various forms of compression therapy, including complex physical therapy, pneumatic pumps and compressive garments. Volume reducing surgery is performed rarely. Lymphatic microsurgery is still in an experimental stage, although a few centers consistently report favorable outcomes.

Combined Modality Therapy↗
PubMed1998

Thromboangiitis obliterans. An update on Buerger's disease.

Buerger's disease (thromboangiitis obliterans) is a nonnecrotizing vasculitis affecting small and medium-sized arteries, typically in young male smokers. The diagnosis can often be made on the basis of a careful history and physical examination, together with ancillary laboratory studies. Occasionally arteriography is warranted to confirm the diagnosis. The pathological findings are distinctive and distinguish this disorder from other arterial occlusive diseases. Successful therapy is possible only with absolute abstinence from tobacco.

Adult↗
PubMed1997

Three-dimensional flow-independent peripheral angiography.

A magnetization-prepared sequence, T2-Prep-IR, exploits T1, T2, and chemical shift differences to suppress background tissues relative to arterial blood. The resulting flow-independent angiograms depict vessels with any orientation and flow velocity. No extrinsic contrast agent is required. Muscle is the dominant source of background signal in normal volunteers. However, long-T2 deep venous blood and nonvascular fluids such as edema also contribute background signal in some patients. Three sets of imaging parameters are described to address patient-specific contrast requirements. A rapid, spiral-based, three-dimensional readout is utilized to generate high-resolution angiograms of the lower extremities. Comparisons with x-ray angiography and two-dimensional time-of-flight angiography indicate that this flow-independent technique has unique capabilities to accurately depict stenoses and to visualize slow flow and in-plane vessels.

Angiography↗
PubMed1997

Lymphedema: anatomy, physiology and pathogenesis.

The authors review the current understanding of lymphatic anatomy and physiology, and the pathophysiology of lymphedema. The skin lymphatic system consists of the initial lymphatics, which converge into lymphatic precollectors, collectors and lymphatic ducts; these in turn convey the lymph to the regional lymph nodes. Interstitial fluid and particles enter the initial lymphatics through interendothelial openings and by vesicular transport. Lymphatic uptake is enhanced by external compression. Lymphatic transport depends greatly on contraction of lymphangions, which generate the suction force that promotes absorption of interstitial fluid and expels lymph to collecting ducts. In lymphedema, various types of congenital and acquired abnormalities of lymphatic vessels and lymph nodes have been observed. These often lead to lymphatic hypertension, valvular insufficiency and lymphostasis. Accumulation of interstitial and lymphatic fluid within the skin and subcutaneous tissue stimulates fibroblasts, keratinocytes and adipocytes eventuating in the deposition of collagen and glycosaminoglycans within the skin and subcutaneous tissue together with skin hypertrophy and destruction of elastic fibers.

Collagen↗