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)

Inflammatory processes induced by viral or bacterial infections are believed to be one of the major pathogenetic mechanisms in myocardial diseases. Although the reason for progression to myocardial failure is not fully understood, postulated mechanisms include persistent viral infection alone or in combination with autoimmune processes. A variety of cardiotropic viruses have been identified to elicit myocarditis, with enteroviruses and adenoviruses as the most frequent causative agents in children and adolescents. However, parvovirus B19 (PVB19) has recently emerged as another potential pathogen in adult patients associated with inflammatory heart disease. Many dimensions of inflammatory heart disease coexist while different phases of the disease progress simultaneously: phase 1 is dominated by viral infection, phase 2 by the onset of (probably) multiple autoimmune reactions, and phase 3 by the progression to cardiac dilatation without the role of an infectious agent and cardiac inflammation. Taking these mechanisms into account, screening for viral and bacterial genome by polymerase chain reaction (PCR) and detection of inflammatory infiltrates by immunohistochemistry are considered crucial for establishing an aetiological diagnosis, thereby allowing initiation of specific therapeutic strategies. In a large cohort of 3345 consecutive patients with left ventricular dysfunction evaluated over a period of 10 years, prevalence of PVB19, coxsackievirus (CVB), human cytomegalovirus (HCMV), influenza A virus and adenovirus (ADV) genome was assessed by PCR. Inflammatory infiltrates within the myocardium were detected by immunohistochemistry according to the WHF criteria and by histopathology according to the Dallas criteria of myocarditis. For control, endomyocardial samples of patients with arterial hypertension were studied. Parvovirus B19 was the most often detected virus in all patient subgroups, with positivity ranging from 17% to 33%. Except for PVB19, CVB RNA (3%), ADV (2%) and CMV (3.9%) were the most frequently detected viral genomes. Interestingly, detection of PVB19 genome was significantly correlated with inflammatory heart disease and reduced ejection fraction. Importantly, an aetiological diagnosis requires the immunohistochemical and molecular biological investigation of endomyocardial biopsies. Such an approach may change the management of these diseases in the future. One of the aims of the study was to reveal the underlying dominant pathophysiological mechanisms in a for deciding on the most approriate therapy.
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PMID:Pathophysiology and aetiological diagnosis of inflammatory myocardial diseases with a special focus on parvovirus B19. 1631 98

Calcineurin inhibitors (CNI) have played an important role in improving graft survival. However, the balance between preventing immunologic allograft losses and the management of CNI-related nephrotoxicity is still an issue in renal transplantation. There are three major CNI-sparing strategies. CNI MINIMIZATION: The advent of mycophenolate mofetil (MMF) allows cyclosporine (CsA) reduction to ameliorate renal function in patients with chronic renal allograft dysfunction, without increasing acute rejection rates. In combination with mTOR inhibitors, very low CNI levels may be sufficient to prevent acute rejection. However, in this association, CNI nephrotoxicity is magnified by pharmacokinetic interaction. CNI WITHDRAWAL: CNI withdrawal has been attempted in regimens containing MMF or sirolimus (SRL). Introduction of MMF in patients with chronic allograft nephropathy (CAN) followed by CNI withdrawal resulted in stabilization or improvement of renal function and hypertension profile, although there is some risk of acute rejection. In regimes based on SRL, CNI withdrawal is a safety strategy, achieving a sustained improvement of renal function, histology, and graft survival. There is not consensus at all whether MMF should be added or not in patients converted from CNI to mTOR inhibitor. CNI AVOIDANCE: Polyclonal-based regimens with MMF and steroids have shown acceptable acute rejection rates, but high rates of cytomegalovirus (CMV) and opportunistic infections. Conversely, anti-IL-2R in combination with MMF and steroids resulted in 50% incidence of acute rejection, thus suggesting that CNI avoidance is not feasible in a regimen based on MMF. Alternatively, a protocol based on anti-IL-2R induction therapy combined with SRL, MMF, and prednisone has shown an efficient prevention of acute rejection, higher creatinine clearance and lower rate of CAN in comparison with a group treated with CNI. New strategies using costimulation blockade may help in the development of safe CNI-free regimens. In summary, in renal transplantation the new immunosuppressive medications have made feasible old aspirations such as minimization, withdrawal, or even avoidance of CNI.
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PMID:Calcineurin-inhibitor-sparing immunosuppressive protocols. 1638 20

Cytomegalovirus (CMV) infection alone or in combination with other pathogens ("pathogen burden") has been postulated as a factor producing arteriosclerosis in some solid organ transplant recipients. The aim of this study was to assess whether the patients with CMV replication and/or "herpesvirus burden" experienced a greater incidence of cardiovascular events during the first year after kidney transplantation. One hundred twenty-one consecutive transplant recipients were prospectively studied for CMV replication using antigenemia and polymerase chain reaction (PCR) weekly during the 4 first months, and monthly thereafter for 1 year. Simultaneously, nested-PCR for human herpes virus (HHV)-6 and HHV-7 were performed to yield a herpesvirus burden (as determined by seropositivity), including CMV, herpes simplex virus (HSV), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV). The following additional parameters were analyzed: gender, age, smoking, duration of dialysis, preexistent diabetes, and preexistent cardiovascular events. After 1 year posttransplantation cardiovascular events, body mass index, arterial hypertension, number of antihypertensive drugs, use of ACE and/or ARBs inhibitors, diabetes, anemia, homocysteine, creatinine, cholesterol, HDLc, LDLc, PTH-i, proteinuria, and immunosuppression with cyclosporine or tacrolimus. CMV replication was present in 79 (65.3%) patients. Among 121 renal transplant recipients, 13 presented cardiovascular events, all associated with CMV replication (P = .004). Neither HHV-6 or HHV-7 replication influenced this complication. All patients with these events were seropositive for CMV, HSV, VZV, and EBV, as opposed to 64.8% without them (P = .009). Other factors that showed differences between patients with versus without events were as follows: preexistent events (76.9% vs 14.8%; P = .000), age (60 +/- 10 vs 49 +/- 14; P = .002), serum triglyceride value (191 +/- 82 vs 135 +/- 72; P = .02), and anemia (23.1% vs 5.6%; P = .05). Multiple logistic regression analysis for statistically significant variables only showed that preexistent events influenced the development of posttransplantation events (odds ratio, 27; 95% confidence interval, 4.7-154; P = .0005). In conclusion, cardiovascular events within 1 year after transplantation were more frequent among patients with CMV replication and seropositivity for other herpesviruses. An important risk factor was the presence of preexistent events.
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PMID:Cytomegalovirus replication and "herpesvirus burden" as risk factor of cardiovascular events in the first year after renal transplantation. 1638 30

We performed an outcome analysis of 28 pediatric renal transplant recipients whose mean age at transplantation was 15.2 +/- 2 years (range: 11 to 17 years) and the M/F ratio, 0.75. Four patients received cadaveric grafts. One patient needed retransplantation due to primary nonfunction. Mean HLA match was 3.6 (range: 3 to 5). Immunosuppression was cyclosporine (n = 13) or tacrolimus (n = 11) or sirolimus (n = 4), as well as steroids and azathioprine or mycophenolate mofetil. Delayed graft function occurred in four patients. The main complications were arterial hypertension (n = 11), anemia (n = 4), urinary tract infection (n = 10), hypercholesterolemia (n = 7), and cytomegalovirus infection (n = 1). An acute rejection episode (ARE) occurred in four patients. ARE and hypertension rates were similar between the immunosuppressive drug groups. All the patients with graft failure were on cyclosporine (P = .03). Hemodialysis and peritoneal dialysis (median duration: 6 months) were performed preoperatively in 25 and 3 patients, respectively. The length of pretransplant dialysis was longer among patients with graft failure (P > .05). Noncompliance (10.7%) resulted in an ARE in one patient and graft loss in two patients. One patient died with a functioning graft. Primary disease recurred in one patient. The median follow-up period was 44 months (range: 6 to 157 months). Mean serum creatinine level was 1.35 +/- 0.74 mg/dL at the last follow-up. One- and 3-year graft survival rates were 92% and 86%, respectively, and patient survival was 100%, each. Seventeen patients (60.7%) continued their education after the transplantation; six started working. Successful transplantation in the pediatric age group together with intensive rehabilitation posttransplantation are important to make these children productive individuals to the society.
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PMID:Pediatric renal transplantation: Clinical analysis of 28 cases. 1654 39

Our previous studies demonstrated that peripheral overexpression of angiotensin II (ANG II) type 2 receptors (AT(2)R) prevents hypertension-induced cardiac hypertrophy and remodeling without altering high blood pressure. This, coupled with the observations that AT(2)R play a role in the antihypertensive actions of ANG II type 1 receptor (AT(1)R) blockers (ARBs), led us to propose that peripheral overexpression of AT(2)R would improve the antihypertensive action of losartan (Los) in Sprague-Dawley (SD) rats made hypertensive via chronic infusion of ANG II. Here we utilized adenoviral vector-mediated AT(2)R gene transfer to test this hypothesis. A single intracardiac injection of adenoviral vector containing genomic AT(2)R (G-AT(2)R) DNA and enhanced green fluorescent protein (EGFP) gene controlled by cytomegalovirus (CMV) promoters (Ad-G-AT(2)R-EGFP; 5 x 10(9) infectious units) into adult SD rats produced robust AT(2)R overexpression in cardiovascular tissues (kidney, lung, heart, aorta, mesenteric artery, and renal artery) that persisted for 3-5 days postinjection. By 7 days post viral injection, the overexpressed AT(2)R are reduced toward basal values in certain tissues (lung, kidney, and heart) and are undetectable in others (kidney and blood vessels). In two separate protocols, we demonstrated that the hypotensive effect of Los (0.125, 0.5, and 1.0 mg/kg iv) was significantly greater in the AT(2)R-overexpressing animals (-40.7 +/- 4.3, -41.8 +/- 4.8, and -48.1 +/- 2.6 mmHg, respectively) compared with control vector (Ad-CMV-EGFP)-treated rats (-12.4 +/- 2.2, -20.2 +/- 3.4, and -27.3 +/- 3.4 mmHg, respectively). These results provide support for a depressor role of AT(2)R and the proposal that combined AT(2)R agonist and ARB treatment may be an improved therapeutic strategy for controlling hypertension.
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PMID:Potentiation of the antihypertensive action of losartan by peripheral overexpression of the ANG II type 2 receptor. 1708 38

Cardiovascular disease is the leading cause of death following renal transplantation, accounting for 40% to 55% of all deaths. An analysis in our center showed a 15% mortality in a cohort of renal transplant recipients followed for an average of 10 years. Various contributing risk factors of cardiovascular diseases in transplant recipients such as tobacco use, hypertension, hyperlipidemia, hereditary risk, diabetes, physical inactivity, obesity, dialysis duration, hyperuricemia, proteinuria, hyperhomocysteinemia, hyperparathyroidism, anemia; C-reactive protein level, and immunosuppressive regimen as well as some rare risk factors, such as cytomegalovirus infection, were evaluated in a population of 1200 kidney transplant recipients. Also we introduced methods for early detection, monitoring, and follow-up of proven risk factors of cardiovascular disease.
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PMID:How to decrease cardiovascular mortality in renal transplant recipients. 1711 56

Post-transplant clinical disease with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) is a known risk factor for graft dysfunction and lymphoproliferation. We postulate that subclinical, asymptomatic viremia also adversely impacts outcomes, and may warrant re-assessment of current monitoring and antiviral prophylaxis protocols. A single-center study was conducted on 102 pediatric (51 steroid-free and 51 matched steroid-based historical controls). Quantitative viral loads were serially monitored and correlated with outcome measures. Overall, the incidence of CMV and EBV clinical disease was 5% (1% CMV and 4% EBV); however, the incidence of subclinical viremia was 44% (12.7% CMV, 38.2% EBV, 6.9% CMV + EBV). Risk factors for subclinical viremia were EBV naivety (p = 0.07), age less than five yr (p = 0.04), lack of prophylaxis (p = 0.01), and steroid usage (p = 0.0007). Subclinical viremia was associated with lower three-yr graft function (p = 0.03), increased risk of acute rejection (odds ratio 2.07; p = 0.025), hypertension (p = 0.04), and graft loss (p = 0.03). Subclinical asymptomatic CMV and EBV viremia is a risk factor for graft injury and loss. These findings support the need for aggressive, serial viral monitoring to better determine the appropriate length of post-transplant antiviral prophylaxis, and to determine the effect of immunosuppression protocols on the development of viremia.
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PMID:Subclinical cytomegalovirus and Epstein-Barr virus viremia are associated with adverse outcomes in pediatric renal transplantation. 1730 Apr 99

Early steroid withdrawal after liver transplantation (LT) is desirable in order to reduce steroid side effects. Between February 2000 and August 2004, 110 patients after LT were included in this prospective, randomized, double-blind, placebo-controlled trial. Randomization was performed before LT. In all patients, tacrolimus was used without induction therapy. All patients received methylprednisolon for 14 days, thereafter a double-blinded medication containing either placebo (n = 56) or methylprednisolon (n = 54) for 6 months, which was completely stopped thereafter. End points were patient and graft survival, acute and chronic rejection, and incidence of steroid side effects during the first year after LT. One-year patient survival was 85.7% (placebo) and 88.8% (steroid) (p = 0.572). Twenty-seven (48.2%) and 19 (35.2%) patients experienced acute rejection (placebo versus steroid, respectively; p = 0.116). Two patients in the placebo group but none in the steroid group experienced chronic rejection (p = 0.257). The rates of side effects were (placebo versus steroid, respectively): CMV infection 25% versus 33% (p = 0.336), post-transplant diabetes 30% versus 53% (p = 0.024), hypertension 39% versus 52% (p = 0.248), hypercholesterolemia 10% versus 41% (p = 0.002) and hypertriglyceridemia 32% versus 54% (p = 0.046). In conclusion, early steroid withdrawal after LT is feasible under tacrolimus monotherapy without increased rejection rates and with a lower rate of side effects.
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PMID:Tacrolimus monotherapy without steroids after liver transplantation--a prospective randomized double-blinded placebo-controlled trial. 1751 85

Cytomegalovirus (CMV) infection is a risk factor for arteriosclerosis in renal transplant recipients. We sought to investigate the effects of CMV infection on atherosclerotic events (AE) in renal transplant recipients. This retrospective analysis included 200 patients: 52 women and 148 men of overall mean age of 36.18 +/- 10.23 years who were transplanted at our center between 1998 and 2001. We analyzed demographic features, dialysis duration, diabetes, blood pressure level, body mass index (BMI), medications, and lipid parameters. CMV infection was diagnosed in 23.5% of patients in the first 2 years after transplantation; these patients were followed for 4 years. All patients had been assessed for AE, including previous myocardial infarction, angina, revascularization procedures, intermittent claudication, stroke, or transient ischemic attack. AE occurred in 13% during the follow-up period. CMV infection was more frequent among these patients compared to those without AE, namely 42.3% versus 20.6%, respectively. Although the gender, dialysis duration, serum cholesterol level, presence of acute rejection, and BMI were not associated with AE, age, hypertension, and CMV infection did show a relation. A multivariate analysis by logistic regression revealed mean age and CMV infection to be independent risk factors for AE: odds ratio (OR)=5.6, 95% confidence interval (CI)=1.3 to 24.6 (P=0.02) and OR=4, 95% CI = 1.3 to 12.3 (P=.01). This study suggested that the presence of CMV infection may be a triggering factor for AE in renal transplant recipients.
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PMID:The association between cytomegalovirus infection and atherosclerotic events in renal transplant recipients. 1752 71

The use of the Internet is growing rapidly. Up to 70% of American Internet surfers use the Web for some kind of medical purpose. Only a few studies characterized the consulting population and their inquiries. The objective of this study was to define the content of queries and the characteristics of the consulting population in an open access 'Ask the family physician' non-commercial open forum. Data had been collected from the family medicine forum in www.doctors.co.il. This site has 10 - 15 new queries daily, and a physician reply is given on most occasions within 24 h. We analysed demographic characteristics and the content of the queries. In addition, we sent detailed questionnaires to 200 randomly selected consulters. We analysed 1,002 consecutive queries. The average age of the consulters was 31.8 years, 63.4% women. Women applied more often for someone else, compared to men (13.7 versus 8%p = 0.01). 82.2% applied to the forum for a first opinion on the subject matter. The most frequent subjects were: infectious diseases (7.3%), deciphering blood chemical analysis results (3.2%), vitamin B(12) (3.2%), deciphering blood count analysis results (2.9%), Epstein - Barr virus and Cytomegalovirus (2.8%), and hypertension (2.4%). Only 10% (20/200) replied to our e-mail questionnaire. We described the characteristics of inquiries to a Web-based question answering service. Its consumers are mainly younger females who consult the virtual physician prior to consulting their own family physician. They mainly seek medical knowledge especially in interpreting laboratory tests and information about various medical conditions.
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PMID:Web-based question-answering service of a family physician -- the characteristics of queries in a non-commercial open forum. 1754 62


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