Gene/Protein Disease Symptom Drug Enzyme Compound
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The complications of drug abuse encompass a spectrum of glomerular, interstitial, and vascular diseases. They comprise the heroin-associated nephropathy seen in African-American intravenous drug addicts, which, however, has given way in the 1990s to HIV-associated nephropathy. Infections with methicillin-resistant Staphylococcus aureus may cause acute glomerulonephritis by releasing bacterial superantigens. Hepatitis C has supplanted hepatitis B and may give rise to membranoproliferative glomerulonephritis and cryoglobulinemia. Addicts who inject drugs subcutaneously ('skin popping') may develop amyloidosis. Cocaine causes rhabdomyolysis, severe hypertension, occasionally renal failure in the absence of rhabdomyolysis, and may hasten progression to uremia in patients with underlying renal insufficiency. 'Ecstasy', an amphetamine-like recreational drug, has caused acute renal failure, electrolyte disturbances, and malignant hypertension. In Belgium and some other European countries, women taking Chinese herbs in a slimming regimen have developed a severe and irreversible interstitial fibrosis that is assuming epidemic proportions.
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PMID:Drugs of abuse and renal disease. 874 32

The introduction of tacrolimus has shown decreased rates of acute and steroid-resistant rejection after liver transplantation (LTx). The aim of the present study is to examine the long-term efficacy and safety of tacrolimus in primary liver transplant recipients. The first 121 consecutive adults (aged >16 years) who underwent primary LTx at a single center from August 1989 to February 1990 were followed up until August 1997. The mean follow-up was 93.2 +/- 1.2 months (range, 90.5 to 96.5 months). Patient survival, graft survival, rate of rejection, and adverse events were examined. The actual 7-year patient survival rate was 67.8%, and the graft survival rate was 63.6%. Infections, recurrence of disease, de novo malignancies, and cardiovascular events constituted the main causes of graft loss and death in the long term. Graft loss related to acute or chronic rejection was rare. The rate of acute rejection beyond 2 years was approximately 3% per year, and most rejections were steroid responsive. Approximately 70% of the patients received only tacrolimus after 1 year. Four patients developed end-stage renal disease, and 2 patients underwent kidney transplantation. Hyperkalemia and hypertension were observed in one third of the patients. New-onset insulin-dependent diabetes mellitus was observed in 9% and 13% of the patients at the 1-year and 7-year follow-up, respectively. Seven patients developed de novo malignancies, including two skin malignancies. Six patients developed posttransplantation lymphoproliferative disorder during the entire follow-up period. Actual patient and graft survival at 7 years was excellent, and few adverse events developed after the first year. Graft loss from acute or chronic rejection was rare under tacrolimus, and approximately 70% of the patients were steroid free on tacrolimus monotherapy after the first year after LTx.
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PMID:Primary adult liver transplantation under tacrolimus: more than 90 months actual follow-up survival and adverse events. 1007 54

We retrospectively analyzed the results of 75 living-related pediatric renal transplants performed at our center between January 1986 and December 1999. The major causes of end-stage renal disease (ESRD) were glomerulonephritis (26%) and nephrolithiasis (16%), while the etiology was unknown in 50%. The mean age of the recipients was 12 yr (range 6-17 yr) and that of the donors was 39 yr (range 20-65 yr). The majority (73%) of donors were parents. Eighty five per cent of donors were one-haplotype matched and the rest identical. Immunosuppression was based on a triple drug regimen. Thirty per cent of recipients were rapid metabolizers of cyclosporin A (CsA) (area under the curve [AUC]: < 6,000 ng/mL/h), while 16% were slow metabolizers (AUC: > 8,000 ng/mL/h). Forty three (57%) children encountered 59 rejection episodes, the majority of which (59%) were recorded in the first month post-transplant. Seventy-four per cent of the rejection episodes were steroid sensitive and the rest, except two, were resolved by therapy with antithymocyte globulin (ATG) or orthoclone thymocyte 3 (OKT3). After a mean follow-up of 37 months, 17 (22%) grafts had chronic rejection and 76% of these recipients had previously experienced acute rejection episodes. The overall infection rate was high, necessitating two hospital admissions/patient/year. The majority (53%) of the infections were bacterial. Urinary tract infections (UTIs) were seen in 17 (23%) recipients. Twelve of these had ESRD as a result of stone disease and eight grafts were lost because of UTIs. Eight per cent of recipients developed tuberculosis (TB), and extra-pulmonary lesions were seen in 50%. Surgical complications were encountered in eight patients. Free medication to all recipients and parental support ensured a compliance rate of 93%. Baseline growth deficit was seen in children of the two groups studied (the 6-12 yr and 13-17 yr age-groups), with Z-scores of - 2.39 and - 2.12, respectively. No growth catch-up was observed at 12 and 24 months in either group. Post-donation complications were seen most commonly in donors > 50 yr of age and included: proteinuria (> 300 mg/24 h, four patients), hypertension (three patients), and diabetes (one patient). Twenty-four grafts were lost, 54% as a result of immunological and the rest as a result of non-immunological causes, and 17 recipients died during the follow-up period. Infections were the main cause of patient and graft loss. Overall 1- and 5-yr graft and patient survival rates were 88% and 65%, and 90% and 75%, respectively.
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PMID:Living-related pediatric renal transplants: a single-center experience from a developing country. 1200 Apr 64

An enormous proportion of the worlds elderly live in rural areas and show wide variations in health status. Many, particularly those in the developing countries, are vulnerable to greater socioeconomic and health marginalization mainly due to inadequate provision of services and economic deprivation. As with the urban elderly, locomotor, visual and hearing disabilities, as well as life-threatening conditions of coronary heart disease, diabetes and hypertension are common among rural elders also. Infections continue to take a heavy toll in many parts of the world. Higher prevalence of health and functioning impairments and of risk factors like sedentarism and current smoking have been reported for the rural elderly in developed countries like the United States, where less frequent use of certain preventive services also has been observed among the rural elderly. The positive association of well-being and health with variables such as living with family, having children, and community involvement, which has been reported from developing countries like Ghana and India, supports the usefulness of the time-honored value of joint family systems and lifelong social and physical activity--all known to foster healthy aging. Such traditional virtues therefore need to be preserved and strengthened. Effective geriatric health care services need to stress a community approach to primary health care, with provision of support and training for both family caregivers and professionals. In addition, emphasis on health promotion, cost-effective indigenous systems of medicine and gender-sensitive programs is needed.
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PMID:Health status of the rural elderly. 1207 55

Kidney transplant recipients require careful follow-up in both the early (< 6 months) and late posttransplant periods. Monitoring should focus on graft function and the most common complications of immunosuppression therapy. Infections, especially CMV infection, require particular attention in the first few months after transplantation, when immunosuppression is most intense. In both the early and the late posttransplant periods, an emphasis should be placed on intensive management of CVD risk factors (e.g., hypertension, hyperlipidemia, cigarette smoking). Screening for malignancies known to occur with a high incidence after transplantation is also important. With the improved short-term survival rates brought about by new, potent immunosuppressive agents, emphasis has now shifted to the prevention and treatment of posttransplant complications in kidney transplant recipients. A heightened awareness of these complications, along with a cooperative effort between primary care physicians and transplant programs, offers the best hope for further improvement in outcomes after kidney transplantation.
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PMID:Care of the kidney transplant recipient. Vigilant monitoring creates the best outcome. 1236 Jun 61

The purpose of this study is to determine risk factors associated with mortality in surgical patients with vancomycin-resistant enterococcus (VRE) infections. The hospitalizations of surgical patients with VRE infections from January 1998 to December 2001 were reviewed. Statistical analysis was performed using the Student's t test, chi square, and Fisher's exact test. Thirty-one surgical patients (male:female, 14:17) with a mean age of 51.9 years (range, 21-83 years) developed VRE infection. Infections included bacteremia (12), urinary tract (11), surgical site (seven), and soft tissue (five) infections and intra-abdominal abscess (one). Nine (29.0 per cent) patients received recent outpatient antibiotics and 20 (64.5 per cent) were on steroids. Fifteen (48.4 per cent) patients were treated with intravenous vancomycin before infection. Twelve (38.1 per cent) patients died with a trend toward advanced age (60.7 vs 46.5 years; P = 0.06). The incidence of VRE infection in kidney transplant patients was 1.8 per cent. Six transplant patients (five kidney and one kidney/ pancreas) developed VRE infections with four deaths. Hypertension (P = 0.04), coronary artery disease (P = 0.02), and the need for intra-arterial pressure monitoring (P = 0.04) were associated with mortality. Isolate location, gender, diabetes, renal dysfunction, respiratory disease, liver disease, and serum albumin were not associated with mortality. Kidney transplant patients have a high incidence of VRE infection. Surgical patients with VRE infections have a high mortality rate. Hypertension and coronary artery disease are risk factors for mortality.
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PMID:Clinical characteristics and outcomes of surgical patients with vancomycin-resistant enterococcal infections. 1285 10

By the turn of the last century, flying in the face of over a hundred years of research and clinical observation to the contrary, medicine abandoned the link between infection and atherogenesis; not because it was ever proven wrong, but because it did not fit in with the trends of a medical establishment convinced that chronic disease such as heart disease must be multifactorial, degenerative and non-infectious. Yet it was the very inability of 'established' risk factors such as hypercholesterolemia, hypertension and smoking to completely explain the incidence and trends in cardiovascular disease that resulted in historically repeated calls to search out an infectious cause, a search that began more than a century ago. Today, half of US heart attack victims have acceptable cholesterol levels and 25% or more have none of the "risk factors" associated with heart disease, including smoking, high blood pressure or obesity, most of which are not inconsistent with being caused by infection. Even the case of the traditionalist's latest 2003 JAMA assault to 'debunk' what they call the "50% risk factor myth" falls woefully short under scrutiny. In one group 30% died of heart disease with a cholesterol of at least 240 mg/dl, a condition which also existed in 21% who did not die during the same period. And the overlap was obvious throughout the so-called risk categories. Under such scrutiny, lead author Greenland conceded that if obesity, inactivity and elevated cholesteriol in the elderly are included, just about everyone has a risk factor and he likened the dilemma of people who do or do not wind up with heart disease akin to the susceptibility of people who are exposed to tuberculosis but do not get the disease. In Infections and Atherosclerosis: New Clues from an old Hypothesis? Nieto stressed the need to extend the possible role of infectious agents beyond the three infections which have in recent years been the focus of research: Cytomegalovirus (CMV) Chlamydia pneumoniae and Helicobactor pylori. Mycobacterial disease shares interesting connections to heart disease. Not only is tuberculosis the only microorganism to depend on cholesterol for its pathogenesis but CDC maps for cardiovascular disease bear a striking similarity to those of State and regional TB case rates. Ellis, Hektoen, Osler, McCallum, Swartz, Livingston and Alexander-Jackson all saw clinical and laboratory evidence of a causative relationship between the mycobacteria and heart disease. And Xu showed that proteins of mycobacterial origin actually led to experimental atherosclerosis in laboratory animals Furthermore present day markers suggested as indicators for heart disease susceptibility such as C-Reactive Protein (CRP), interleukin-6 and homocysteine are all similarly elevated in tuberculosis. It therefore behooves us to explore the link between heart disease and typical and atypical tuberculosis.
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PMID:Heart disease: the greatest 'risk' factor of them all. 1508 5

Hemospermia refers to the presence of blood in the seminal fluid and is not very common urologic symptom. Its prevalence remains unknown. Historically, hemospermia was linked to excessive sexual overindulgence, prolonged sexual abstinence, interrupted coitus. Newer imaging modalities have altered the diagnosis and etiological factors of hemospermia are now more frequently identified. Hemospermia can result from many causes. Infections or inflammatory disorders account from 39% to 55% of cases, malignancies and trauma account just 4-13%. The remaining 11% of cases were caused by a variety of other pathologic conditions. Predisposing diseases are prostatitis, epididymitis, urinary stones, tuberculosis, cirrhosis of the liver, arterial hypertension, hematologic diseases. In 30-70% of the cases there is no association with any significant pathology. Cases of primary and solitary hemospermia can be adequately assessed by urinanalysis, blood pressure measurement, genital and rectal examination, PSA-test, and reassurance of the patient. Persistent and recurrent cases of hemospermia are best clarified by transrectal ultrasound examination, cystoscopy, computer tomography and magnetic resonance imaging. Treatment depends on the diagnostic findings but often simply involves reassurance.
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PMID:[Hemospermia]. 1586 11

Steroid-free immunosuppressive regimens reduce corticosteroid-related side effects in liver transplant recipients although their efficacy is very variable. We evaluated the efficacy and safety of a steroid-free regimen in a 6-month, open-label, multicenter, pilot study, which involved 102 liver transplant patients treated with daclizumab (2 mg/kg within 6 h following transplant and 1 mg/kg on day 7), mycophenolate mofetil (MMF, 1 g b.i.d) and tacrolimus (trough levels of 5-15 ng/ml in the first month and 5-10 ng/ml thereafter). One intra-operative dose of methylprednisolone was administered. At 6 months, the acute rejection rate was 9.8%, and patient and graft survival rates were 96% and 95%, respectively. Acute rejection rates were similar for hepatitis C-positive patients (8.6%) and hepatitis C-negative patients (10.4%). Infections occurred in 22% of patients; most cases were considered mild or moderate. Post-transplantation hypertension and diabetes mellitus developed in 37% and 14% of patients, respectively, during the study period, but were markedly less frequent (8% and 6%, respectively) at 6 months. Hypercholesterolemia was observed in only 2% of patients. In conclusion, the steroid-free immunosuppressive regimen of daclizumab, MMF, and tacrolimus effectively prevents acute rejection after liver transplantation without decreasing safety.
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PMID:Daclizumab induction and maintenance steroid-free immunosuppression with mycophenolate mofetil and tacrolimus to prevent acute rejection of hepatic allografts. 1682 81

Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is a genetic disorder with autosomal dominance and variable penetrance, characterized by epistaxis, telangiectasia and visceral manifestations of the disease. The estimated minimal prevalence is 1/10,000 inhabitants. The diagnosis is established on clinical criteria, and may be further confirmed by the identification of causative mutations in either the ENG or the ACVRL1 gene coding for endoglin and ALK1, respectively. Pulmonary vascular manifestations of HHT include pulmonary arteriovenous malformations (PAVMs; especially in patients with ENG mutations) and less frequently pulmonary hypertension (especially in patients with ACVRL1 mutations). In 15-33% of patients with HHT, PAVMs consist of abnormal communications between pulmonary arteries and pulmonary veins, causing right-to-left shunting, and thus, frequently hypoxemia and dyspnea on exertion, although PAVMs may remain asymptomatic and frequently undiagnosed unless complications occur. PAVMs result in severe and frequent complications often at a young age, which may reveal the diagnosis, e.g. transient ischemic attack and cerebral stroke (10-19% of patients), systemic severe infections and abscesses (including cerebral abscess in 5-19% of patients), and rarely massive hemoptysis or hemothorax. Infections in HHT are related to the right-to-left shunting that bypasses the pulmonary capillaries and facilitates the passage of septic or aseptic emboli into the systemic and especially cerebral circulation, and potentially to minor defects in innate immunity. Treatment of PAVMs based on transcatheter coil vaso-occlusion of the feeding artery significantly decreases right-to-left shunting, hypoxemia and dyspnea on exertion, and reduces the risk of systemic complications. Long-term follow-up is warranted after transcatheter vaso-occlusion of PAVMs due to frequent recanalization of treated PAVMs and development or growth of untreated PAVMs. Patients with HHT should be informed of the risk of PAVM and potentially severe complications occurring in heretofore asymptomatic subjects. All adult patients with HHT should be proposed systematic screening for PAVM, by contrast echocardiography (preceded by anteroposterior chest radiograph) or computed tomography of the chest. Pulmonary hypertension is rare in HHT, and may be due either to systemic arteriovenous shunting in the liver increasing cardiac output or be clinically and histologically indistinguishable from idiopathic pulmonary arterial hypertension. Pulmonary hypertension is detected by systematic examination of right cardiac cavities and tricuspid regurgitation flow at echocardiography, and the diagnosis is established by right heart catheterization.
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PMID:Pulmonary vascular manifestations of hereditary hemorrhagic telangiectasia (rendu-osler disease). 1764 82


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