Hypertension: Varga J

McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J, Anonymous00029, Anonymous00030, Anonymous00031, Anonymous00032, Anonymous00033. · No affiliation provided · J Am Coll Cardiol. · Pubmed #19389575 No free full text.

This publication has no abstract.

Varga J. · No affiliation provided · Curr Opin Rheumatol. · Pubmed #12410089 No free full text.

This publication has no abstract.

McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J, Harrington RA, Anderson JL, Bates ER, Bridges CR, Eisenberg MJ, Ferrari VA, Grines CL, Hlatky MA, Jacobs AK, Kaul S, Lichtenberg RC, Lindner JR, Moliterno DJ, Mukherjee D, Pohost GM, Rosenson RS, Schofield RS, Shubrooks SJ, Stein JH, Tracy CM, Weitz HH, Wesley DJ, Anonymous00037. · No affiliation provided · Circulation. · Pubmed #19332472 No free full text.

This publication has no abstract.

Varga J. · Northwest University, Feinberg School of Medicine, Chicago, Illinois, USA. · Bull NYU Hosp Jt Dis. · Pubmed #18937632 links to  free full text

Abstract: Systemic sclerosis (SSc) is a complex and heterogeneous chronic illness characterized by substantial patient to patient variability in clinical manifestations, internal organ involvement, and outcome. Genetic factors contribute to disease susceptibility, but environmental influences also play a significant role. The pathogenesis of SSc encompasses vascular, immunological, and fibrotic processes, which contribute to clinical manifestations and morbidity and must be addressed in the treatment plan. Although vascular interventions appear to reduce the frequency and severity of complications, such as scleroderma renal crisis and pulmonary hypertension, current therapies generally target the immune component of SSc in a non-selective fashion and have largely failed as diseases-modifying interventions. Newer insights into the mechanisms underlying autoimmunity, vascular injury and destruction, and particularly tissue fibrosis provide novel potential targets for therapy. Transforming growth factor-ss is a ubiquitous cytokine that appears to contribute to fibroblast activation, collagen overproduction, and pathological tissue fibrosis. Neutralizing antibodies and small molecules that block TGF-beta activation or function are effective in shutting down TGF-beta signaling and selectively inhibit the progression of fibrosis and may be entering clinical trials for the treatment of SSc.

Jain M, Varga J. · Division of Pulmonary and Critical Care, Feinberg School of Medicine, Northwestern University, 240 E. Huron Avenue, M-321, IL, USA. · Expert Opin Pharmacother. · Pubmed #16859432 No free full text.

Abstract: Systemic sclerosis (SSc) is a devastating multisytemic autoimmune disease associated with widespread vascular damage. Pulmonary arterial hypertension (PAH) occurs in a significant proportion of patients and contributes to the morbidity and mortality that occurs in this disease. The recent development of specific therapies for the treatment of PAH mandates the early recognition, appropriate evaluation and judicious management of PAH in patients with SSc. Because endothelin (ET)-1 plays an important role in the development of PAH in SSc, and may also contribute to the vascular damage and fibrosis that occur in multiple organs in patients with the disease, inhibiting the production and activity of ET-1 is an appealing strategy for the treatment of SSc. This article reviews the pathophysiology of SSc and its vascular complications, and critically evaluates the current knowledge regarding the potential role of the ET-1 receptor blocker bosentan in the management of patients with SSc.

Ramirez A, Varga J. · Andrew J. McKelvey Lung Transplantation Center, Emory University School of Medicine, Atlanta, Georgia, USA. · Treat Respir Med. · Pubmed #15658881 No free full text.

Abstract: It is increasingly recognized that significant pulmonary arterial hypertension (PAH) develops in more than 15% of patients with systemic sclerosis (SSc). As this complication of SSc may occur even in the absence of overt interstitial lung disease (isolated PAH), it has been likened to primary PAH and is attributable to intrinsic vascular pathology that is the hallmark of SSc. Deregulated activity of mediators controlling vasomotor tone has been implicated, and levels of endothelin-1 (ET-1) are elevated in the circulation and in the lungs. By causing enhanced vasoconstriction, vascular endothelial cell proliferation, smooth muscle hypertrophy, and irreversible vascular remodeling in the lungs, ET-1 appears to play a significant role in the pathogenesis of SSc-associated PAH.Although patients with the limited cutaneous form of SSc are more likely to develop PAH than those with the diffuse form, the true prevalence of PAH in SSc, and the risk factors for its development, are not yet known. Because the prognosis of patients with SSc-associated PAH is substantially worse than that of patients without this complication, intensive efforts are underway to develop sensitive screening strategies and effective treatments. Serial evaluation of SSc patients with Doppler echocardiography appears to be prudent. Antibodies against the centromere or fibrillarin proteins may be useful in identifying those patients with SSc at highest risk for developing PAH.The US FDA has approved a number of novel treatments, including long-acting oral ET-1 receptor antagonists such as bosentan and short-acting parenteral prostacyclin analogs, such as epoprostenol, for PAH. In particular, bosentan appear to be well tolerated, and short-term therapy results in improved exercise tolerance, improved hemodynamics, and possibly improved survival in patients with advanced PAH. These agents may be used alone, or possibly in combination with prostacyclin analogs. Therapeutic agents that modulate the synthesis of nitric oxide, and additional agents targeting the ET-1 signaling system are under preclinical development. Although the large-scale clinical trials that resulted in obtaining FDA approval for these agents were generally carried out in patients with primary PAH, it appears that patients with SSc-associated PAH respond similarly. Therefore, it is reasonable to conclude that ET-1 receptor antagonists and parenteral prostacyclin analogs should be used in SSc patients with moderate to severe PAH. The efficacy of these agents for treating patients with PAH who also experience significant interstitial lung disease, as occurs in many SSc patients, remains unknown. Additional important unresolved issues relate to the long-term efficacy of ET-1 receptor antagonists, and their effects on survival and progression of PAH. Additionally, it is not yet clear if early intervention for SSc patients with mild PAH is beneficial.

Ficzere A, Varga J, Csáti G, Csiba L. · Debreceni Egyetem, Orvos- és Egészségtudományi Centrum, Neurológiai Klinika. · Orv Hetil. · Pubmed #11478034 No free full text.

Abstract: To summarise the structural and functional changes of the brain, caused by chronic hypertension and overview the studies performed on hypertensive patients by computer tomography, magnetic resonance imaging, transcranial Doppler ultrasound, positron emission tomography and single photon emission tomography. The definitive lesions--global or local atrophy, lacunar infarcts--can be sensitively detected by different morphological methods, whereas the hemodynamical alterations can be observed by the functional techniques. Mild cognitive deficits could be diagnosed in the early stage of the disease with different neuropsychological testing. Positron emission tomographic and single photon emission tomographic investigations could not be used routinously on hypertensive patients. The authors--based on own experiences--suggest the combined use of transcranial Doppler and neuropsychological testing, because these techniques are sensitive enough to detect early, subclinical abnormalities.

Hinchcliff M, Varga J. · Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA. · Am Fam Physician. · Pubmed #18953973 No free full text.

Abstract: Systemic sclerosis (systemic scleroderma) is a chronic connective tissue disease of unknown etiology that causes widespread microvascular damage and excessive deposition of collagen in the skin and internal organs. Raynaud phenomenon and scleroderma (hardening of the skin) are hallmarks of the disease. The typical patient is a young or middle-age woman with a history of Raynaud phenomenon who presents with skin induration and internal organ dysfunction. Clinical evaluation and laboratory testing, along with pulmonary function testing, Doppler echocardiography, and high-resolution computed tomography of the chest, establish the diagnosis and detect visceral involvement. Patients with systemic sclerosis can be classified into two distinct clinical subsets with different patterns of skin and internal organ involvement, autoantibody production, and survival. Prognosis is determined by the degree of internal organ involvement. Although no disease-modifying therapy has been proven effective, complications of systemic sclerosis are treatable, and interventions for organ-specific manifestations have improved substantially. Medications (e.g., calcium channel blockers and angiotensin-II receptor blockers for Raynaud phenomenon, appropriate treatments for gastroesophageal reflux disease) and lifestyle modifications can help prevent complications, such as digital ulcers and Barrett esophagus. Endothelin-1 receptor blockers and phosphodiesterase-5 inhibitors improve pulmonary arterial hypertension. The risk of renal damage from scleroderma renal crisis can be lessened by early detection, prompt initiation of angiotensin-converting enzyme inhibitor therapy, and avoidance of high-dose corticosteroids. Optimal patient care includes an integrated, multidisciplinary approach to promptly and effectively recognize, evaluate, and manage complications and limit end-organ dysfunction.

Franken RA, Bellesso M, Cavazin AM, Polônio IB, Mattheucci E, Varga J. · Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, SP. · Rev Assoc Med Bras. · Pubmed #15253029 No free full text.

Abstract: OBJECTIVES: To evaluate angiotensin converting enzyme gene (ACE) polymorphism with transthoracic bidimensional echocardiogram of normotensive young medical students, siblings of hypertensive parents comparing them with those with normotensive parents. METHOD: We had studied 80 normotensive youngs divided in two groups. Hypertensive parents' normotensive young medical students 40 x Normotensive parents' and normotensive medical students. Exclusion criteria were hypertension, obesity, smoke, use of oral contraceptives, as well as those who use chronically drugs or the presence of any disease. The group has been enrolled between 1994 to 1996. 50 students made transthoracic bidimensional echocardiogram. The statistical analysis was done by "T-student" test. The evaluation of polymorphism ACE gene was studied in 80 people in each step: 1) 5 mL of blood in EDTA tube, 2) extraction of DNA, 3) evaluation of DNA concentration by electrophoresis analyses; 4) Polymerase chain reaction with primer of ACE gene, 5) Analysis of polymorphism ACE gene by electrophoresis 6) Statistical analysis by Chi-square test. RESULTS: The group of students with hypertensive parents presented thicker interventricular septum (7.82 mm +/- 0.69 against 7.38 mm +/- 0.8, p<0.05). On the other hand, we didn't find differences between the groups concerning ACE gene genotype: students with hypertensive parents DD: 42.5%, DI: 37.5%, II: 20% against Students with normotensive parents: DD: 37.5%, DI: 32.5%, II: 30%, (p=0.58), in addition we also did not find differences concerning the alleles Group of hypertensive parents: D: 61.25%, I: 38.75% versus normotensive parents: D: 53.75%, I: 46.25%, p=0.33. We divided these groups into two in relation to the mean thickness of interventricular septum and left ventricular mass and we did not find any difference: in students with hypertensive parents group septum > 7.82 mm: DD: 32%, DI: 24%, II: 20% x septum < 7.82 mm: DD: 8%, DI: 12%, II: 4%, p=0.7) in normotensive parents group septum septum > 7.38 mm: DD: 28%, DI: 12%, II: 12% x septum < 7.38 mm: DD: 16%, DI: 16%, II: 16%, p=0.59). The study of the left ventricular mass in hypertensive parents group mass > 131.52 g: DD: 20.69%, DI: 13.79%, II: 6.9% x mass < 131.52 g DD: 24.24%, DI: 17.24%, II: 17.24%, (p=0.72) in normotensive parents group mass > 117.11 g: DD: 30.43%, DI: 8.7%, II: 8.7% x mass < 117.11 g: DD: 13.04%, DI: 21.74%, II: 17.39%, (p=0.17). CONCLUSION: We found differences between the thickness of the interventricular septum of normotensive students sibling of hypertensive parents and normotensive parents. On the other hand we didn't find any difference between the two groups concerning the ACE gene polymorphism as well as any relation of ACE gene and thickness of interventricular septum and interventricular left ventricular mass.

Johnson BW, Davies WG, Hardy DW, Varga J, Gallagher KL, Ryan MT, Jones RM. · Alaska Native Medical Center, Anchorage, AK 99508, USA. · Mil Med. · Pubmed #12775183 No free full text.

Abstract: Because current methods of tracking hypertension are time-consuming and expensive, the prevalence of hypertension in retired military populations is often unknown. Tracking military retiree hypertension is important because it can help to conserve scarce resources and save lives by preventing strokes and other diseases. Intended as a case study, an alternative method of tracking hypertension using pharmacy records and ambulatory data system records to confirm diagnosis of hypertension was used to determine the prevalence of hypertension in a retired military population (ages 40-85 years). The results indicated that matching pharmacy data with ICD9 401 diagnosis data and medical records is a more efficient method of tracking hypertension.

Varga J. · No affiliation provided · Curr Rheumatol Rep. · Pubmed #12628045 No free full text.

This publication has no abstract.

Gussin HA, Ignat GP, Varga J, Teodorescu M. · University of Illinois College of Medicine, Chicago 60612, USA. · Arthritis Rheum. · Pubmed #11229469 links to  free full text

Abstract: OBJECTIVE: To investigate the presence and clinical significance of anti-Scl-70 antibodies in patients with systemic lupus erythematosus (SLE). METHODS: Levels of antibodies against Scl-70 were determined by a commercial clinical enzyme-linked immunosorbent assay (ELISA) during routine evaluation. Results were verified by an additional ELISA with a characterized bovine Scl-70, by ELISA with a recombinant human topoisomerase I, by Western blot, and by double diffusion in agar gel. Disease activity was estimated retrospectively by the Systemic Lupus Activity Measure (SLAM). RESULTS: Of 128 consecutive SLE patients, 25% were positive for anti-Scl-70 antibody; this antibody activity was cognate in nature. No SLE patient could be classified as also having systemic sclerosis. The levels of anti-Scl-70 were significantly correlated with the SLAM score for the entire cohort (r = 0.563, P < 0.001) and for 7 individual patients with multiple longitudinal measurements (r = 0.755-0.951, P < 0.001; n = 6) (r = 0.378, P < 0.05; n = 1). A significant correlation was also found between the levels of anti-Scl-70 and anti-double-stranded DNA antibodies (r = 0.558, P < 0.001). Patients with anti-Scl-70 had significantly higher risk of pulmonary hypertension (P < 0.01) and renal involvement (P < 0.001) than patients without this antibody. CONCLUSION: Anti-Scl-70 antibody is present in a significant subset of patients with SLE. For this subset, it offers a good correlate of disease activity and suggests increased risk for pulmonary hypertension and nephritis.