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)

Patients with clinically definite multiple sclerosis, mild to moderately severe neurological disability (entry score on the Expanded Disability Status Scale (EDSS) between 3.0 and 7.0), and a progressive course defined by an increase in the EDSS of between 1 and 3 grades in the year prior to entry were randomized to receive either cyclosporine (n = 273) or placebo (n = 274) in a 2-year, double-blinded, multicenter trial. Treatment groups at entry proved balanced for age, gender, duration of illness, and neurological disability. Cyclosporine dosage was adjusted for toxicity and a median trough whole-blood level was maintained between 310 and 430 ng/ml. The mean increase in EDSS score was 0.39 +/- 1.07 grades for cyclosporine-treated patients and 0.65 +/- 1.08 grades for placebo-treated patients from entry until the time of early withdrawal or completion of the study (p = 0.002). Of three primary efficacy criteria, cyclosporine delayed the time to becoming wheelchair bound (p = 0.038; relative risk, 0.765), but statistically significant effects were not observed for "time to sustained progression" or on a composite score of "activities of daily living." Active treatment did have a favorable effect on several secondary measures of disease outcome. A large and differential withdrawal rate (44% for cyclosporine-treated patients, 32% for placebo-treated patients) complicated the analysis but did not appear to explain the observed effect of cyclosporine in delaying disease progression. Multivariate analysis did not show institutional effects but did demonstrate substantial effects of baseline neurological disability on outcome. Nephrotoxicity and hypertension were common troublesome toxicities and accounted for most of the excess loss of patients in the cyclosporine arm of the study. Thus, chronic cyclosporine therapy was associated with a statistically significant but clinically modest delay of progression of disability in a group of patients with multiple sclerosis selected for moderately severe and progressive disease. Close supervision by physicians familiar with cyclosporine is mandatory to minimize known adverse effects, particularly nephrotoxicity, when considering the use of this immunosuppressant.
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PMID:Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. The Multiple Sclerosis Study Group. 201 93

Thirteen patients with chronic intraocular inflammation which had not been adequately controlled with oral prednisolone entered into an open study of low-dose Cyclosporin A (mean 4.1 mg/kg/day) combined when required with oral prednisolone (15 mg prednisolone per day or less). The mean duration of treatment was 26 months (range 8-44) over a mean follow-up period of 29 months (range 8-49). Visual acuity improved overall in ten patients, and remained stable in three. Six patients have completed a course of Cyclosporin A therapy, and four of these patients have retained their visual improvement. Two have returned to the pretreatment level of vision. Only one patient has required conversion to alternative immunosuppressive therapy. The mean serum creatinine concentration had increased significantly by 26% after six months (p less than 0.05) and 32% after one year (p less than 0.01) but remained stable during the subsequent 18 months. Four patients developed hypertension requiring hypotensive therapy. On cessation of CsA treatment, the mean serum creatinine concentration fell to the upper reference limit. The elevation of serum creatinine concentration was significantly higher in patients who either developed hypertension during Cyclosporin A therapy or who were previously known to be hypertensive. Patients with nephrotoxicity were significantly older than those in whom serum creatinine concentration remained within the reference range. Lithium clearance studies showed evidence of proximal renal tubular dysfunction which was partially reversible on dose reduction or withdrawal.
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PMID:Combination low dose cyclosporin A and steroid therapy in chronic intraocular inflammation. 220 19

We report the intensive care management of 23 children (age 3-15 years) following orthotopic heart (HT) and combined heart and lung transplantation (HLT) performed at our 2 institutes between February 1985 and August 1989. Cyclosporin A, azathioprine and steroids were given as routine immunosuppression, whilst anti-thymocyte globulin (ATG) was used for the first 3 post-operative days. Mean ventilation time was 24.6 h (range 4-74 h). Cardiovascular support comprised isoprenaline infusions in all patients (mean period 65.7 h) whilst dopamine and other inotropic agents were used less frequently. Sequential atrioventricular pacing was required more often in the HT patients (n = 9) than in the HLT patients (n = 4). Fluid input was restricted to maintain a plasma osmolality of 290-300 mosm/kg. There were 2 perioperative deaths both due to acute right heart failure. Other post-operative complications included: bleeding (n = 3); acute graft rejection (n = 4); infection (n = 3); systemic hypertension (n = 6); neurological abnormalities (n = 2); renal dysfunction (n = 6) and hyperglycaemia (n = 6).
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PMID:Intensive care management of children following heart and heart-lung transplantation. 226 10

Renal vasoconstriction and hypertension are major side effects of cyclosporine. We tested the acute effects of cyclosporine on renal and systemic vascular reactivity to norepinephrine, angiotensin II, and arginine vasopressin. Renal vascular reactivity was tested in anesthetized Sprague-Dawley rats with denervated kidneys. Renal blood flow was measured with an electromagnetic flow probe in response to graded intra-arterial infusions of vasoconstrictors before and after intravenous administration of cyclosporine. Cyclosporine augmented the decrease in renal blood flow and the increase in renal vascular resistance produced by intrarenal norepinephrine, angiotensin II, and arginine vasopressin. In these studies, systemic blood pressure did not change and cyclosporine caused no direct change in basal renal blood flow. In contrast, in conscious animals, cyclosporine did not increase the pressor response to intravenous norepinephrine or to angiotensin II. Rather, cyclosporine caused enhanced baroreflex slowing of heart rate and a decrease in the pressor response to both norepinephrine and angiotensin II. Even when the baroreceptor reflex was blocked by pentolinium, the pressor response to norepinephrine in cyclosporine-treated animals was diminished compared with vehicle-treated animals. Therefore, although cyclosporine augmented renal vasoconstriction in response to norepinephrine, angiotensin II, and arginine vasopressin, it did not acutely increase the systemic vascular response to these agents. Enhanced renal vascular responsiveness is an additional mechanism for cyclosporine-mediated renal vasoconstriction. Lack of enhanced peripheral vascular responsiveness suggests that hypertension is not likely to be due to direct effects on the systemic vasculature and is more likely to be a consequence of renal functional impairment.
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PMID:Cyclosporine augments renal but not systemic vascular reactivity. 230 92

The determinants of ciclosporin A-induced blood pressure changes were analyzed initially and after 3 months in 30 recent type I diabetics submitted to chronic treatment with ciclosporin as single immunosuppressive drug. Prevalence of hypertension was 17% and relatively low as compared to those reported in organ transplantation. Ciclosporin induced a slight decrease in glomerular filtration rate and renal plasma flow, with unchanged filtration fraction, a mild average increase in blood pressure and a more pronounced increase in renal vascular resistance. There was a trend toward decrease in absolute urinary sodium excretion whereas fractional excretion of sodium was unchanged. Presence of familial history of essential hypertension was characterized by a slightly insignificantly lower renal plasma flow and did not affect the renal effect of ciclosporin except that the renal plasma flow was significantly lower in the groups of patients genetically predisposed.
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PMID:Blood pressure changes induced by ciclosporin A in type I diabetes. 232 92

In a group of 18 patients after orthotopic transplantation of the heart (OTH) operated, 4-56 months previously and treated by combined immunosuppression (Cyclosporin A, corticoids, azathioprine), systemic hypertension was revealed in six and borderline hypertension in three patients. The mechanism of the development of hypertension, after OTH has not been elucidated. As to the circadian rhythm of the blood pressure, as compared with normotensive subjects and patients with essential hypertension, in patients after OTH usually the drop of systemic pressure values does not occur during the night; on the contrary the blood pressure rises during the night. This finding may be due to denervation of the heart after OTH and an abnormal response of baroreceptors to the rise of blood pressure; in this the effect of corticoids may also participate. After a one-year interval the abnormal reaction of the systolic pressure remains preserved, while the 24-hour profile of the diastolic pressure has trend towards normalization.
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PMID:[Incidence of systemic hypertension after orthotopic heart transplantation]. 233 11

From 1982 to 1987 sixty-three children were treated with cyclosporin A and low dose prednisolone after kidney transplantation. Patient survival rate at 4 years after transplantation was 98.3%, survival rate of living related grafts 100% (n = 10), and survival rate of cadaveric grafts 73% (n = 53). Adequate cyclosporin blood levels were achieved in all children with a dosage regimen related to body surface area. Major concerns during the observation period were the loss of glomerular filtration rate from 51.8 to 40.5 ml/min/1.73 m2, a hypertension rate of 77.8%, and hyperuricemia. Cyclosporin A-side effects were mild. Infections occurred in 11.1%. Growth retardation in prepubertal children improved by 0.74 standard deviations of normal height, and in pubertal children by 0.51. We conclude that cyclosporin A treatment in children enables excellent long term graft survival rates with improved growth rehabilitation, however, the prevention of the cyclosporin associated nephrotoxicity and hypertension remains the major problem.
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PMID:Four years' experience with cyclosporin A in pediatric kidney transplantation. 238 53

The immunosuppressive agent, Cyclosporin A, (CsA) has been associated with nephrotoxicity and hypertension. The mechanism for these effects are not known. We therefore determined the levels of the catecholamines; epinephrine (EPI), norepinephrine (NE) and dopamine (DA) and some of their metabolites; epinine, dihydroxyphenyl-acetic acid (DOPAC), homovanillic acid (HVA), metanephrine (ME) and 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the kidneys of rats treated intraperitoneally with either CsA (120 micrograms/kg/body wt/day) or control vehicle (1 ml olive oil/kg body wt/day). Six control or CsA treated rats were sacrificed at 1 hour or 24 hours after a single treatment or after 7 days of daily treatment. Renal catecholamine levels were determined using HPLC-amperometric detector. Treatment with CsA increased renal NE and EPI levels by 59% and 70% respectively within 1 hour. In the rats sacrificed 24 hours after treatment, renal NE, EPI and DA levels were similar to or less than the control levels. Treatment with CsA for 7 days resulted in marginal increases in renal NE (22%) and EPI (30%). These changes were associated with a significant decrease in the levels of catecholamine metabolites in the CsA treated kidneys as compared to the controls. The above findings suggest that increases in renal catecholamines may be involved in the CsA-induced hypertension and nephrotoxicity, perhaps by increasing renovascular resistance.
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PMID:Effect of cyclosporin A on rat kidney catecholamines. 238 29

Hypertension is a serious side-effect of the clinical use of Cyclosporin A (CsA). One notion is that alterations of vascular reactivity contribute to this hypertension. In this study we used the isolated rat mesenteric vascular bed to test the specific hypothesis that CsA modifies vascular calcium regulation to potentiate vascular contractility. Mesenteric vessels from CsA-treated rats (10 mg/kg/day i.m. for 7 days) exhibited significantly greater vasoconstrictor responses to exogenous norepinephrine (NE) and potassium-induced depolarization than those of vehicle-treated animals. Similarly, in vitro CsA (8.3 X 10(-8) to 8.3 X 10(-6) M) augmented in a concentration-dependent manner both the sensitivity and the maximum response to NE and potassium. This effect of CsA on vasoconstriction was critically dependent on the presence of external calcium [( Ca++]o). The degree of vasoconstriction potentiation correlated significantly with the [Ca++]o which was used during exposure of the mesenteric bed to CsA. Reapplication of external calcium in the presence of CsA to "calcium-depleted" preparations increased significantly the amplitude of subsequent NE responses in a calcium-free medium. Thus, CsA-potentiated NE responses, once established, were not reversed by removing external calcium; however, attenuation occurred with the intracellular calcium antagonist dantrolene. Verapamil and nifedipine blocked potassium-elicited responses, but failed to prevent the CsA effect on NE-induced vasoconstriction. We conclude that CsA potentiation of vasoconstriction depends on extracellular calcium, and results from an enhanced transmembrane calcium transport. We speculate that CsA also increases the filling of intracellular stores of releasable calcium. These effects lead to greater calcium influx and greater intracellular calcium release upon stimulation.
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PMID:Mechanism of cyclosporin potentiation of vasoconstriction of the isolated rat mesenteric arterial bed: role of extracellular calcium. 239 12

We were concerned that clinical manifestations of rejection (R) might be subtle in small children transplanted with adult kidneys. We retrospectively analyzed the first rejection episode (biopsy proven) in 22 children (R group) under age 4 years [mean age, 23.7 +/- 2.2 months (+/- SEM); mean weight, 9.4 +/- 0.4 kg] receiving an adult-related donor kidney. We matched these patients for age, date of transplant, donor source and immunosuppression with 36 children without R (control or C group). We compared both groups at similar intervals from transplantation, based on the time of R (5.38 +/- 1.2 months) in the R group and analyzed the immediate 8-week period prior to R and the corresponding interval in the C group. Hypertension occurred in 82% (18/22) of the R versus 8% (3/36) of the C group (P less than 0.01). Fever longer than 7 days occurred in 45% (10/22) of the R versus 0% (0/36) of the C group (P less than 0.01). Increased creatinine occurred in only 45% (10/22) of the R versus 3% (1/30) of the C group (P less than 0.01). Cyclosporine did not influence these manifestations of R. The clinical manifestations did not predict the R grades on biopsy, which were moderate to severe in 13 and mild in 9 of the R patients. Graft survival was higher at 3 years in the C (95%) than in the R patients (65%), (P less than 0.004). Thus, clinical manifestations of acute R can be subtle in small children with adult renal allografts. Renal biopsy should not be delayed until the creatinine is elevated in these patients.
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PMID:Manifestations of renal allograft rejection in small children receiving adult kidneys. 240 Jun 54


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