Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basiliximab is a chimeric anti-intcrleukin-2 receptor monoclonal antibody. Basiliximab is a glycoprotein produced by recombinant technology. It is used to prevent white blood cells from acute renal transplantation rejection. It specifically binds to and blocks the alpha chain of interleukin-2 receptors (IL-2R alpha), also known as CD25 antigen, on the surface of activated T-lymphocytes. Due to its monoclonal nature it provides safer and more predictable therapeutic, that is, immunosuppressive response of the polyclonal antibodies. The most common adverse effects in adult patients are constipation, infections, pain, nausea, peripheral oedema, hypertension, anaemia, headache, hyperkalacmia, hypercholesterolemia, increase in serum creatinine, and hypophosphataemia.
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PMID:Basiliximab, mechanism of action and pharmacological properties. 1564 37

Recurrence of hepatitis C (HepC) has been a most difficult dilemma in liver transplantation (OLT) because the effects of immunosuppression with steroid, mycophenolate mofetil (MMF) calcineurin antagonists, and anti-interleukin-2 antibody as well as the role of preemptive antiviral therapy are uncertain. In this study, we randomized OLT recipients with HepC into two treatment arms: tacrolimus+daclizumab+MMF (study arm) versus tacrolimus+steroids+MMF (control arm). The study arm only received steroids for the treatment of biopsy-proven rejection episodes. Both arms received preemptive anti-viral therapy with Pegasys and ribavirin. The 39 enrolled patients (among 50 to be enrolled) have median follow-up of 458 days with 23 patients (8 in study arm, 15 in control arm) having reached 1 year. The incidences of rejection episodes within 0 to 3 months, 3 to 6 months, and 6 to 12 months were (study vs control): 0% vs 28%; 0% vs 6%; and 13% vs 20%; respectively (P = NS). The 1-year protocol biopsies showed advanced fibrosis (stage 3 or greater) in 20% (3 of 15) of the control arm, but none (0 of 7) of the study arm (P = NS). We compared anticipated side effects of steroids in the first 3 months (study vs control): hypertension (36% vs 58%, P = NS), PTDM (7% vs 43%, P = .02), and wound infections (14% vs 37%, P = NS). In conclusion, liver transplant recipients with HepC tolerate a steroid-free protocol. There was a trend toward reduced steroid side effects and a lower incidence of advanced fibrosis in 1-year biopsy samples among patients receiving the steroid-free protocol.
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PMID:Steroid-free induction and preemptive antiviral therapy for liver transplant recipients with hepatitis C: a preliminary report from a prospective randomized study. 1584 74

Although heart failure is predominantly caused by cardiovascular conditions such as hypertension, coronary heart disease and valvular heart disease, it can also be an adverse reaction induced by drug therapy. In addition, some drugs have the propensity to adversely affect haemodynamic mechanisms in patients with an already existing heart condition. In this article, non-cardiac drugs known to be associated with the development or worsening of heart failure are reviewed. Moreover, drugs that may adversely affect the heart as a pump without causing symptoms or signs of heart failure are also included. The drugs discussed include anticancer agents such as anthracyclines, mitoxantrone, cyclophosphamide, fluorouracil, capecitabine and trastuzumab; immunomodulating drugs such as interferon-alpha-2, interleukin-2, infliximab and etanercept; antidiabetic drugs such as rosiglitazone, pioglitazone and troglitazone; antimigraine drugs such as ergotamine and methysergide; appetite suppressants such as fenfulramine, dexfenfluramine and phentermine; tricyclic antidepressants; antipsychotic drugs such as clozapine; antiparkinsonian drugs such as pergolide and cabergoline; glucocorticoids; and antifungal drugs such as itraconazole and amphotericin B. NSAIDs, including selective cyclo-oxygenase (COX)-2 inhibitors, are included as a result of their ability to cause heart disease, particularly in patients with an already existing cardiorenal dysfunction. Two drug groups are of particular concern. Anthracyclines and their derivatives may cause cardiomyopathy in a disturbingly high number of exposed individuals, who may develop symptoms of insidious onset several years after drug therapy. The risk seems to encompass all exposed individuals, but data suggest that children are particularly vulnerable. Thus, a high degree of awareness towards this particular problem is warranted in cancer survivors subjected to anthracycline-based chemotherapy. A second group of problematic drugs are the NSAIDs, including the selective COX-2 inhibitors. These drugs may cause renal dysfunction and elevated blood pressure, which in turn may precipitate heart failure in vulnerable individuals. Although NSAID-related cardiotoxicity is relatively rare and most commonly seen in elderly individuals with concomitant disease, the widespread long-term use of these drugs in risk groups is potentially hazardous. Pending comprehensive safety analyses, the use of NSAIDs in high-risk patients should be discouraged. In addition, there is an urgent need to resolve the safety issues related to the use of COX-2 inhibitors. As numerous drugs from various drug classes may precipitate or worsen heart failure, a detailed history of drug exposure in patients with signs or symptoms of heart failure is mandatory.
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PMID:Heart failure induced by non-cardiac drugs. 1680 50

In the era before cytokine therapy, controversy existed about the need for cytoreductive nephrectomy in treating patients with metastatic renal cell carcinoma. In 1978, Dekernion showed that nephrectomy alone had no effect on survival. During this period, removal of the malignant kidney was confined to palliative therapy in some settings of metastatic RCC, such as pain related to the kidney mass, intractable hematuria, erythrocytosis, uncontrolled hypertension, or poorly controlled hypercalcemia. When interleukin-2 was approved by the Food and Drug Administration in 1992, the role of nephrectomy was reexamined. After a decade of controversy, two randomized controlled studies established that cytoreductive surgery has a role in properly selected patients and offers a survival advantage when done before cytokine therapy. Unfortunately, the mechanisms underlying this benefit remain poorly understood. Immunotherapy may work best when there is a small volume of cancer present, and removing a large primary tumor may prevent the seeding of additional metastases. Data have also suggested that primary tumors were capable of producing immunosuppressive compounds that might decrease the efficacy of immunotherapy. Another hypothesis suggested that removing the kidney altered the acid/base status of the patient to such an extent that the growth of the tumor was hindered. With the emergence in 2006 of two targeted agents for advanced renal cell carcinoma, the role of cytoreductive nephrectomy has re-emerged as a source of controversy. Although evidence-based medical practice suggests a role for nephrectomy before the use of targeted agents, the arguments for and against this practice will be weighed.
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PMID:Cytoreductive nephrectomy for metastatic renal cell carcinoma: is it still imperative in the era of targeted therapy? 1725 95

We evaluated the hypothesis that a relationship exists between inflammation and the outcome of pharmaceutical cardioversion with amiodarone in recent onset atrial fibrillation. We studied 86 patients with symptomatic recent onset AF and coexisting hypertension and/or chronic stable coronary artery disease. All study participants underwent evaluation with a standardized protocol including echocardiography, cytokine level measurement [interleukin-2 (IL-2), interleukin-6 (IL-6) and high sensitivity C reactive protein (hsCRP)] on admission and at 48h, and administration of intravenous amiodarone. By 48h, 70 patients cardioverted to sinus rhythm. Median serum IL-2 levels on admission were higher in non-cardioverted compared to cardioverted patients (P=0.002). At 48h, non-cardioverted had significantly higher IL-6 (P=0.005) and hsCRP values (P=0.001) compared to cardioverted. Multivariate logistic regression analysis showed that lower IL-2 admission levels were a powerful independent predictor for successful cardioversion (OR: 0.154, 95% CI: 0.043-0.552, P=0.004). In patients with hypertension and/or chronic stable coronary artery disease and symptomatic recent onset AF, low serum IL-2 levels on admission are associated with successful cardioversion with amiodarone. This observation highlights the role of inflammation in AF and might have further prognostic and therapeutic implications.
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PMID:Interleukin-2 serum levels variations in recent onset atrial fibrillation are related with cardioversion outcome. 1792 14

Sunitinib is an orally administered multitargeted tyrosine kinase inhibitor that has demonstrated substantial antitumour activity in patients with metastatic renal cell carcinoma. The more common grade 3 or 4 adverse effects of sunitinib include hypertension, fatigue, hand-foot syndrome, elevated lipase and lymphopenia. We report the case of a 69-year-old patient with metastatic renal clear-cell carcinoma, treated with nephrectomy and three lines of therapy (interleukin-2 plus interferon-alpha2a, vinorelbine plus gemcitabine, and capecitabine), who started a fourth-line therapy with oral sunitinib because of disease progression. At the end of his fifth cycle of sunitinib therapy, the patient complained of the development of abnormally large mammary glands associated with pain and peri-areolar erythema. After 2 weeks' off therapy, a partial reduction in mammary gland enlargement, local pain and erythema was observed. However, re-initiation of sunitinib treatment was followed by bilateral breast enlargement again. The mechanism by which sunitinib induces gynaecomastia is thought to be associated with an unknown direct action on breast hormonal receptors. To the best of our knowledge, this is the first report of an association between sunitinib and gynaecomastia.
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PMID:Onset of male gynaecomastia in a patient treated with sunitinib for metastatic renal cell carcinoma. 1949 66

Pediatric liver transplantation is now so successful that we expect more than 80% of children to survive into adolescence and adulthood. As the focus of care shifts toward long-term patient management, immunosuppressive regimens should, in addition to preventing acute and chronic rejection, promote good quality of life and be free of significant long-term side effects. Historically, the most effective immunosuppressive regimens have been based on induction with a combination of calcineurin inhibitors (cyclosporin or tacrolimus) and steroids. Usually, maintenance is monotherapy with cyclosporin or tacrolimus or dual therapy with low-dose alternate-day steroids to encourage growth. A number of studies, including long-term follow-up, have shown significantly lower incidences of rejection, hypertension, hyperlipidemia and cosmetic side effects in patients treated initially with tacrolimus compared with cyclosporin. The use of anti-interleukin-2 inhibitors as induction therapy, with low-dose tacrolimus or in combination with mycophenolate mofetil, has a key role in preventing significant renal dysfunction and reducing infection and rejection. Steroid-free immunosuppression is also proving to be an effective option for the management of pediatric liver recipients. The main challenges now facing pediatricians include ensuring long-term quality of life, optimizing immunosuppression while preventing associated adverse events, and managing a smooth transition from childhood to adolescence and adulthood.
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PMID:Safety and efficacy of tacrolimus in pediatric liver recipients. 2117 18

A 58-year-old man with a history of hyperlipidemia and hypertension presented to the dermatology clinic with a 3-month history of a sudden onset, progressively worsening pruritic eruption involving the torso and extremities. Prior treatment included azithromycin and oral and intramuscular steroids, without improvement. Laboratory results demonstrated a serum eosinophil count of 7x10(3)/uL (normal 0-4). A 4-mm punch biopsy of the plaque on the patient's left thigh revealed a diffuse dermatitis with innumerable eosinophils with formation of "flame figures." Histologically, these findings are consistent with a diagnosis of Wells syndrome (WS). A work up for possible underlying malignancy found that the patient had underlying clear cell renal carcinoma. The eruption largely resolved following right laparoscopic nephrectomy with negative surgical margins, thus confirming the diagnosis of paraneoplastic WS. However, 2 years later the patient developed metastasis to his liver, lungs, and ribs. The patient's cancer has continued to progress despite treatment with high-dose interleukin-2, oral sunitinib, afinitor. avastin, azacytidine, and currently axitinib. Our case is the first to describe eosinophilic cellulitis arising in a patient with underlying renal cell carcinoma.
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PMID:Recurrent paraneoplastic wells syndrome in a patient with metastatic renal cell cancer. 2494 51

Adaptive immune function is implicated in the pathogenesis of vascular disease. Inhibition of T-lymphocyte function has been shown to reduce hypertension, target-organ damage, and vascular stiffness. To study the role of immune inhibitory cells, CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), on vascular stiffness, we stimulated the proliferation of Treg lymphocytes in vivo using a novel cytokine immune complex of Interleukin-2 (IL-2) and anti-IL-2 monoclonal antibody clone JES6-1 (mAbCD25). Three-month-old male C57BL/6J mice were treated with IL-2/mAbCD25 concomitantly with continuous infusion of angiotensin type 1 receptor agonist, [Val(5)]angiotensin II. Our results indicate that the IL-2/mAbCD25 complex effectively induced Treg phenotype expansion by 5-fold in the spleens with minimal effects on total CD4(+) and CD8(+) T-lymphocyte numbers. The IL-2/mAbCD25 complex inhibited angiotensin II-mediated aortic collagen remodeling and the resulting stiffening, analyzed with in vivo pulse wave velocity and effective Young's modulus. Furthermore, the IL-2/mAbCD25 complex suppressed angiotensin II-mediated Th17 responses in the lymphoid organs and reduced gene expression of IL-17 as well as T cell and macrophage infiltrates in the aortic tissue. This study provides data that support the protective roles of Tregs in vascular stiffening and highlights the use of the IL-2/mAbCD25 complex as a new potential therapy in angiotensin II-related vascular diseases.
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PMID:Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic Stiffening. 2525 81

Although regulatory T cells (Tregs) have been shown to play a protective role in abdominal aortic aneurysm (AAA) formation, it remains unclear whether expansion of endogenous Foxp3(+) Tregs prevents AAA. In the current study, we determined the effects of endogenous Foxp3(+) Treg expansion or depletion in an experimental model of AAA. We continuously infused 12-week-old apolipoprotein E-deficient mice fed a high-cholesterol diet with angiotensin II (n=60) or normal saline (n=12) by implanting osmotic mini-pumps and evaluated AAA formation at 16 weeks. The angiotensin II-infused mice received interleukin-2/anti-interleukin-2 monoclonal antibody complex (interleukin-2 complex; n=31) or PBS (n=29). Eighty-one percent of angiotensin II-infused mice developed AAA, with 42% mortality possibly because of aneurysm rupture. Interleukin-2 complex treatment systemically increased the number of Foxp3(+) Tregs and significantly decreased the incidence (52%) and mortality (17%) of AAA. Immunohistochemical analysis showed reduced accumulation of macrophages and increased numbers of Foxp3(+) Tregs in aneurysmal tissues, suggesting that expansion of Tregs may suppress local inflammation in the vessel wall and provide protection against AAA formation. Furthermore, genetic depletion of Foxp3(+) Tregs led to a significant increase in the mortality of AAA, suggesting the protective role of Foxp3(+) Tregs against AAA. Our findings suggest that Foxp3(+) Tregs may play a protective role in AAA formation and that promotion of an endogenous regulatory immune response may be a potentially valuable therapeutic approach for preventing AAA.
Hypertension 2015 Apr
PMID:Foxp3+ regulatory T cells play a protective role in angiotensin II-induced aortic aneurysm formation in mice. 2560 31


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