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

The effect of cyclosporin A in acute and chronically active inflammatory bowel disease was tested in 11 patients with Crohn's disease and two with ulcerative colitis who had exhibited a poor response to at least eight weeks of conventional therapy. Trough levels of the drug in the therapeutic range were obtained in 12 of 13 patients. Cyclosporin A, which was usually added to the continued previous medication, including corticosteroids (11 of 13) or metronidazol (1 of 13), prompted an apparent clinical improvement in all but one patient. In six of the nine Crohn's disease patients with an initial Best index of greater than 150, a definite fall by at least 100 points was observed after 2-10 weeks of treatment, but the van Hees index declined only in two patients. All four patients with chronic perineal fistulation experienced symptomatic relief. Both patients with ulcerative colitis had a clinical remission. Erythrocyte sedimentation rate or serum albumin improved in eight of 13 patients. However, two of the nine responders with Crohn's disease relapsed during cyclosporin A therapy and three immediately after the medication was discontinued. Common side effects included hypertrichosis, tremor, and hyperesthesia; hypertension and epigastric pain each occurred only in one patient.
 ...
PMID:Cyclosporin A treatment in inflammatory bowel disease. 276 6

The renal glomeruli are vulnerable to injury by a number of drugs and other toxic agents. These agents may lead to damage by one of two basic mechanisms: direct, dose-related toxic injury; indirect, immunologically mediated injury, largely dose-independent. Proteinuria is the simplest and most important functional indicator of glomerular injury. It occurs almost immediately in direct toxic injury, but there is a latent period of weeks to months with immunologically mediated processes. Of the two mechanisms, the second is by far the more common in clinical settings. The best studied experimental agent causing direct toxic injury is the aminonucleoside of puromycin. Clinically, perhaps the most important agent is Cyclosporine A. Although this agent is usually thought of primarily as a tubular toxin, it is capable of giving rise to a microangiopathic glomerular lesion similar to that in the hemolytic uremic syndrome. The classic model for immunologic glomerular lesion is Heymann nephritis, which produces a membranous glomerulopathy. Clinically, most drug mediated glomerulopathies also take the form of a membranous nephropathy, usually with a frank nephrotic syndrome. Among the more common offenders are penicillamine, gold salts used in rheumatoid arthritis, and captopril used in hypertension. The other common type of drug-related glomerulopathy occurs as part of a lupus-like syndrome induced by a variety of drugs, including hydralazine, procainamide, and penicillamine. All of these give rise to a variety of antibodies, most prominently antinuclear antibodies, and in the more severe cases there may be lupus-like glomerular lesions as well.
 ...
PMID:Drug-associated glomerulopathies. 294 Jun 67

We examined whether ultrastructural changes in renal mitochondria associated with Cyclosporine A treatment might reflect underlying alterations in mitochondrial molecular structure. A nonrejected renal transplant removed from a patient treated with Cyclosporine A showed a decreased level of beta subunit antigen of mitochondrial F1-ATPase compared to controls. This decrease was more marked in the medulla than in the cortex (56% vs. 70% of pooled controls). Spontaneously hypertensive rats treated with a high dose of Cyclosporine A showed a similar decrease of beta-subunit antigen in the renal medulla and decreased levels of two subunit antigens of cytochrome c oxidase, but had increased medullary levels of the alpha subunit antigen of the F1-ATPase. Such changes were not detected in a normotensive strain of rats. Our data indicate that Cyclosporine A administration is associated with structural alterations in renal mitochondria at the molecular level, predominantly in the medulla, and that additional renal damage due to ischemia or hypertension may predispose to this cyclosporine effect.
 ...
PMID:Alterations in molecular structure of renal mitochondria associated with cyclosporine A treatment. 301 38

Cyclosporine is an immunosuppressive agent used to prevent rejection of transplanted organs. Monitoring cyclosporine blood concentrations is important to ensure adequate levels to prevent graft rejection while minimizing the risk of toxicity. A 45-year-old man who received a kidney transplant seven months previously is described. He had been receiving cyclosporine along with azathioprine and prednisone for immunosuppression since the transplant. His cyclosporine blood concentrations and renal function were stable during this time. Due to uncontrolled hypertension, sustained-release (SR) verapamil 240 mg/d was added with no change in cyclosporine levels. However, after increasing the dose of verapamil SR to 360 mg/d a dramatic increase in cyclosporine concentrations occurred. His renal function remained stable during this time. The interaction between cyclosporine and the calcium-channel blocking agents along with a possible nephroprotective effect of the calcium-channel blocking agents when used with cyclosporine are discussed.
 ...
PMID:Increased cyclosporine blood concentrations due to verapamil administration. 306 81

Cyclosporin A (CyA) is an immunosuppressive agent which has been used in children following kidney transplantation since 1982. The paediatric experience made with CyA in a single centre is reported here. Forty-seven children, ranging in age from 2 to 16 years, were given transplants between September 1982 and May 1986 and received CyA with low-dose prednisolone for immunosuppression. The mean cold ischaemia time of the grafts was 20.9 h. Under routine volume expansion during and 24 h posttransplantation, 40 grafts (85%) functioned immediately. Acute rejection episodes occurred with the highest frequency during the 1st month (0.6 rejection/patient). The actuarial survival rate for patients was 98% after 3 years. Graft survival was 92% after 1 year, 87% after 2 years and 78% after 3 years. The side-effects observed with CyA were hypertrichosis (38%), neurological complications (21%), and infections (17%). One girl of 16 years developed benign mammary fibroadenomas. Hypertension was common (60%), but less so than seen with conventional therapy (83%). Graft function was reduced. The mean creatinine clearance at 6 weeks after transplantation was 60 ml/min per 1.73 m2, after 1 year was 46.4 ml/min per 1.73 m2 and after 2 years it was 42.5 ml/min per 1.73 m2. Twenty-nine children with functioning grafts of at least 1 year could be evaluated for growth performance and normal or even catch-up growth could be demonstrated for the whole group. The individual annual growth rates expressed by standard deviation score (SDS) remained stable or even improved 3 years after kidney transplantation. Longer periods of follow-up are necessary to confirm whether the advantages concerning survival rates and growth rates persist over time and will outweigh the side-effects of CyA treatment.
 ...
PMID:Cyclosporin A in paediatric kidney transplantation. 315 67

After liver transplantation for cancer, there is a high incidence of disease recurrence within 18 to 36 months for most tumors, although there are a small number of long-term survivors. An extended resection of the upper abdominal viscera with replacement by a liver-pancreas cluster is being tried in Pittsburgh for lesions which have not been successfully managed with liver transplantation alone. Despite a high incidence of graft reinfection after liver transplantation for hepatitis B virus (HBV) related disease, a significant proportion of patients achieve long-term survival. Hyperimmune globulin and interferon have been of little benefit in preventing reinfection. Clinical trials with a human monoclonal antibody to HBsAg are in progress. Transplantation for alcoholic liver disease has been considered controversial. However, survival after liver transplantation for Laennec's cirrhosis is comparable to survival after liver transplantation for other chronic, benign, and non-HBV related liver diseases. Sclerotherapy followed by liver transplantation is the treatment of choice for patients with acute hemorrhage from esophageal varices and end-stage liver disease. Sclerotherapy alone or followed by selective shunting is an appropriate alternative in patients with good hepatic reserve. Only 25% of infants with biliary atresia benefit from portoenterostomy. To meet the demand for small infants waiting for transplantation, several transplant programs have successfully expanded their efforts to use partial (reduced) liver grafts. Cyclosporine and low-dose prednisone remain the basis for immunosuppression after liver transplantation. However, nephrotoxicity and hypertension are frequent and troublesome side effects of cyclosporine. Triple and quadruple drug regimens have been increasingly popular in an effort to minimize cyclosporine toxicity. Phase 1 clinical trials with a new drug, FK506, recently began in Pittsburgh. Hyperacute rejection of the liver has been demonstrated in animal models and has been strongly suspected in recent clinical descriptions of acute hemorrhagic necrosis after liver transplantation. So far, only transplantation across an ABO incompatibility has been identified as a risk factor for hyperacute rejection. The new preservation solution developed by Belzer and associates at the University of Wisconsin has significantly extended the preservation time for liver grafts, and improved the quality of liver preservation.
 ...
PMID:Changing perspectives on liver transplantation in 1988. 315 94

The use of cyclosporine long term after orthotopic liver transplantation has been analyzed in 73 adults with particular reference to the dose of drug used, either alone or in combination with other immunosuppressive agents, and the side effects observed. The first 22 patients were given cyclosporine 10 mg/kg/day for up to 2 years, but thereafter in these, and in all the other patients, the drug dose was regulated by whole blood trough levels. The proportion of patients maintained on cyclosporine alone increased from 11% at 3 months to 54.9% and 55.6% at 3 and 4 years, respectively. The dose of prednisolone used in combination with cyclosporine was lower than that used with azathioprine (P less than 0.05) up to 12 months after transplantation, but thereafter no significant difference was found. Acute cellular rejection was seen in 5 patients and in all instances was related to cessation of cyclosporine, while 10 patients developed chronic graft rejection manifested by the vanishing bile duct syndrome. At 12 months and onward, 54.5-73.3% of patients had normal serum bilirubin levels, and 47.6-80.0% had aspartate aminotransferase levels in the normal range. Cyclosporine was discontinued in 12 patients, in 8 cases because of impairment of renal function or hypertension. A trend toward rising serum creatinine levels was seen, and after 4 years on cyclosporine none of 12 patients had normal levels, and these exceeded 200 mumol/L in 5. The rise in creatinine levels was probably in part related to the higher doses used early in the study period. The incidence of hypertension progressively increased from 15.3% at 3 months to 63.6% at 4 years in patients maintained on cyclosporine.
 ...
PMID:An analysis of cyclosporine efficacy and toxicity after liver transplantation. 327 83

The majority of late recipients of heart transplantation have returned to age-appropriate activities and are showing normal linear growth. The only child who has significant symptoms is an 11-year-old heart-lung transplant recipient who developed airway rejection with restrictive pulmonary function 14 months after transplantation. Rejection continues to be a major threat to these children more than a year removed from their transplantation procedure. Until a satisfactory noninvasive method is developed to monitor graft rejection, endomyocardial biopsies will continue to be performed at 6-month intervals. Cyclosporine nephrotoxicity and systemic hypertension remain important and unresolved problems that could limit the initial success of transplantation. We believe that heart transplantation is an acceptable option for children with end-stage heart and heart-lung disease who have a grim outlook. Future improvements in immune suppression, and the development of improved methods of assessing rejection, will allow for improved survival.
 ...
PMID:Late follow-up of children after heart transplantation. 327 65

Hypertension is a common complication after renal transplantation and is associated with increased mortality. Cyclosporine is known to be nephrotoxic and raises blood pressure in recipients of cardiac and bone marrow transplants, but there is conflicting data on the role of cyclosporine after renal transplantation. We have examined this question in patients entered into the second Oxford prospective randomized comparison of short-term cyclosporine treatment alone with conversion to azathioprine and prednisolone at 90 days (CsA group), and conventional therapy with azathioprine and prednisolone throughout (AP group). Blood pressure and antihypertensive medication were similar in the CsA and AP treatment groups during the first 90 days. Following conversion from cyclosporine, mean blood pressure fell from 155/94 to 142/81 within 7 days, and this fall correlated with the change in plasma creatinine over the same period (r = 0.44, P less than 0.05). Blood pressure was subsequently lower in the converted patients than in those treated with AP throughout. Six months after transplantation patients converted from cyclosporine not only had lower blood pressure but also required fewer antihypertensive drugs than AP patients. This study demonstrates that cyclosporine may elevate the blood pressure in recipients of renal transplants. This effect may either be direct or mediated through the effect of cyclosporine on renal function. Administration of corticosteroids during the first three months after transplantation is implicated as a possible cause of persisting high blood pressure.
 ...
PMID:Hypertension after renal transplantation. A comparison of cyclosporine and conventional immunosuppression. 329 53

Cyclosporine treatment is associated with hypertension and suppression of plasma renin activity, the causes of which are unclear. To determine whether suppressed plasma renin activity is due to extracellular fluid volume expansion, 10 cyclosporine-treated renal transplant recipients were compared with 10 azathioprine-treated renal transplant recipients and seven patients with renal insufficiency. Glomerular filtration rate and effective renal plasma flow were significantly lower in cyclosporine-treated patients than in azathioprine-treated patients. Upright plasma renin activity was suppressed in cyclosporine-treated patients (cyclosporine 2.9 +/- 0.9, azathioprine 4.7 +/- 0.9, renal insufficiency 5.2 +/- 1.9 ng/ml/hour) but could be stimulated by a four-day period of dietary sodium restriction and diuretic administration (cyclosporine 15.8 +/- 4.4 ng/ml/hour). Extracellular fluid volume tended to be higher in cyclosporine-treated patients (cyclosporine 30.7 +/- 2.3, azathioprine 26.7 +/- 2.5, renal insufficiency 25.5 +/- 1.4 percent lean body mass), although the difference between cyclosporine-treated and azathioprine-treated patients did not attain statistical significance. There were no differences in the urinary excretion of prostaglandin E2 or 6-keto prostaglandin F1 alpha between the two groups of renal transplant recipients. It is concluded that suppression of plasma renin activity by cyclosporine is physiologic and may reflect expansion of extracellular fluid volume, which can be reversed by sodium depletion.
 ...
PMID:Suppression of plasma renin activity by cyclosporine. 330 Mar 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>