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)

A murine IgG1 antibody specific for the IL-2-binding site on the human lymphocyte IL-2 receptor beta chain (CD25) was evaluated in 11 patients who developed acute graft-versus-host disease following allogeneic marrow transplantation. All patients had received cyclosporine and methotrexate for prophylaxis of GVHD, either alone (4 cases), or in combination with antithymocyte globulin (4 cases) or with prednisone (3 cases). Patients had developed GVHD at 7-53 days (median 12) after transplantation and had failed treatment with corticosteroids for 3-44 days (median 19). Residual GVHD was of grade II severity in 4 patients, grade III in 5 patients, and grade IV in 2 patients. Sequential patients received monoclonal antibody in escalating doses from 0.1 mg/kg/day to 1.0 mg/kg/day for 7 days. Side effects were fever, respiratory distress, hypertension, hypotension, and chills occurring in 11 of 72 (14%) antibody infusions. Trough antibody levels greater than 6 micrograms/ml were achieved in patients treated with 0.5 or 1.0 mg/kg/day. Four of eight evaluable patients had an IgM antibody response, and one had an IgG response to the murine immunoglobulin. Clinical response of GVHD was evaluated in 10 patients who received the entire course of the antibody treatment. Among 7 patients treated within 40 days from transplantation, one patient had a complete response in the skin as the only involved organ, and 3 patients had a partial response, 2 in the skin and one in the gastrointestinal tract. No responses were achieved with liver disease at anytime or in any organ in patients treated beyond 40 days after transplantation. Since administration of this antibody was well tolerated and some efficacy was observed in patients with acute GVHD treated early after transplantation, there is a rationale for testing this antibody as an agent for prophylaxis of GVHD.
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PMID:A phase I-II study evaluating the murine anti-IL-2 receptor antibody 2A3 for treatment of acute graft-versus-host disease. 236 50

Patients with hypertension or ischemic heart disease are often treated with beta-adrenoceptor antagonists, yet the degree of beta-adrenoceptor blockade has rarely been studied in relation to anesthesia. We have constructed isoproterenol dose-response curves in four groups of patients under general anesthesia: group I, 27 elderly normotensive patients not receiving drugs; group II, 14 hypertensive patients treated with cardioselective beta-adrenoceptor antagonists; group III, 15 hypertensive patients receiving nonselective beta-adrenoceptor antagonists; group IV, 13 patients receiving an infusion of labetalol at 0.15 mg X kg-1 X hr-1. Geometric mean CD25, the dose of isoproterenol required to increase the heart rate by 25 beats/min was 4.4 micrograms (3.5-5.6, 95% confidence interval (CI) of the mean) in group I, and 27 micrograms (19-38, 95% CI), 39 micrograms (29-52, 95% CI), and 95 micrograms (62-147, 95% CI) in groups II, III, and IV, respectively. All differences were significant (P less than 0.01), except those between groups II and III (P less than 0.1). No signs of myocardial ischemia and only a few transient arrhythmias were observed. Isoproterenol dose-response curves are a safe means to assess the degree of beta-adrenoceptor blockade during anesthesia and the postoperative period.
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PMID:Assessment of beta-adrenoceptor blockade during anesthesia in humans: use of isoproterenol dose-response curves. 285 67

To investigate the impairment of beta-adrenoceptor responsiveness in human hypertension, we evaluated the effect of an oral salt load (400 mEq/day of NaCl for 7 days) on plasma catecholamine concentrations and beta-adrenoceptor-mediated effects in 11 young patients with mild essential hypertension. Responses of heart rate and plasma cAMP to isoproterenol administration were used as indices of beta-adrenoceptor responsiveness. Salt loading induced a significant reduction in the dose of isoproterenol required to raise the heart rate by 25 bpm (CD25) (from 7.6 +/- 1.5 to 5.3 +/- 0.9 micrograms, p less than 0.05) and an increase in the slopes of the regression lines for heart rate changes and isoproterenol doses (delta HR/IS) (from 3.3 +/- 0.6 to 4.7 +/- 0.7, p less than 0.05) and for plasma cyclic AMP (cAMP) level changes and isoproterenol doses (delta cAMP/IS) (from 0.3 +/- 0.06 to 1.4 +/- 0.3, p less than 0.05). After salt loading there was a significant reduction in plasma catecholamine concentrations with a significant relationship between changes in upright plasma epinephrine levels and changes in CD25 (r = 0.904, p less than 0.01) and in the slopes for delta HR/IS (r = 0.983, p less than 0.001) and delta cAMP/IS (r = 0.922, p less than 0.001). These results support the hypothesis that the impairment of beta-adrenoceptor sensitivity observed in human hypertension is associated with a beta-adrenoceptor overstimulation due to chronically elevated adrenergic tone.
Hypertension
PMID:Studies of the mechanisms underlying impairment of beta-adrenoceptor-mediated effects in human hypertension. 630 32

The relationships between left ventricular mass (LVM), assessed by echocardiography, and several biohumoral and hemodynamic parameters were studied in 63 mild or moderate hypertensive patients and in an age-matched group of 23 normotensive subjects. In hypertensive patients, but not in normotensives, LVM index was significantly correlated with beta-adrenoceptor responsiveness, as evaluated by the chronotropic response to isoproterenol ( CD25 ) (r = 0.525, p less than 0.001) and with the 24-hour catecholamine urinary output (r = 0.485, p less than 0.001). Both CD25 and the catecholamine urinary output were significantly higher in the hypertensives as compared with the normotensive subjects. Moreover, left ventricular wall thickness (septum + posterior wall) was significantly correlated with CD25 and urinary catecholamines only in hypertensive patients. No significant correlation was found between LVM or wall thickness and body surface area, age, blood pressure, heart rate, cardiac output, total peripheral resistance and left ventricular systolic wall stress, whereas CD25 was correlated with urinary catecholamines only in hypertensive patients (r = 0.606, p less than 0.001). These results seem to support the hypothesis that an elevated adrenergic tone may exert a permissive role in the development of left ventricular hypertrophy in human hypertension.
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PMID:Relationships between left ventricular mass and clinical, biohumoral and hemodynamic parameters in human hypertension. 632 39

To determine if alterations in adrenergic activity precede hypertension, we evaluated the pressor effect of an alpha agonist (phenylephrine) and the chronotropic effect of a beta agonist (isoproterenol) in prehypertensive young men. The subjects were selected from a 5-year follow-up of individuals in the upper ("high") and lower ("low") deciles of the blood pressure distribution in a high school population. At follow-up, the blood pressure differences between groups were maintained. The baroreflex slopes of the high (n = 13) and low (n = 10) blood pressure groups did not differ. The dose of phenylephrine required to increase systolic blood pressure by 20 mm Hg (PD20) was greater in the high blood pressure group than in the low blood pressure group (250 +/- 38 micrograms vs 167 +/- 35 micrograms, p less than 0.05). The dose of isoproterenol required to increase the heart rate by 25 beats/min (CD25) was also greater in the high than in the low blood pressure group (1.9 +/- 0.5 micrograms vs 0.9 +/- 0.2 micrograms, p less than 0.05). The increase in plasma renin activity in response to treadmill exercise was less in the high than in the low blood pressure group (1.8 +/- 0.6 ng/ml/hr vs 3.4 +/- 0.7 ng/ml/hr, p less than 0.03). Overall, systolic blood pressure correlated with PD20 (r = 0.52, p less than 0.01) and CD25 (r = 0.62, p less than 0.001). Plasma norepinephrine correlated with systolic blood pressure (r = 0.44, p less than 0.04) and with PD20 (r = 0.63, p less than 0.001). We conclude that baroreflex sensitivity is not altered in young men with relatively high blood pressure. Insensitivity to alpha and beta agonists may be related to the positive correlation of systolic blood pressure with plasma norepinephrine concentration.
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PMID:Adrenergic responsiveness in prehypertensive subjects. 703 47

Several studies have shown a significant reduction of acute cellular graft rejection in adult liver and kidney graft recipients treated with monoclonal anti-interleukin-2 (IL-2)-receptor antibodies. The mechanism was inhibition of activated T-helper cells by blocking the alpha-chain (CD25) of the IL-2 receptor. The pilot study described here evaluated the use of basiliximab in pediatric liver transplantation (LTx), which is the first report on its use in children. Fifty-two liver-transplanted children were analyzed in this study. A matched-pair historical control group (n = 26) received cyclosporin A (CsA) and prednisolone, and patients in the basiliximab group (n = 26) were treated with low-dose CsA and basiliximab (after reperfusion and on day 4 post-transplant). The incidences were compared of acute graft rejections, infectious complications, and the adverse effects of immunosuppressive medication within the first 6 months post-transplant. The incidence of acute rejection was significantly higher in the control group (61.5% vs. 11.5%, p = 0.0004). The frequency of infectious complications was similar (46.1% vs. 53.8%). Patients in the basiliximab group showed less arterial hypertension; however, the differences were not statistically significant (30.7% vs. 7.7%, p = 0.07). Nephrotoxicity, hepatotoxicity or neurotoxicity were only seen in the control group (7.7%; 3.8%; 3.8%, respectively). Hence, the use of basiliximab in combination with CsA and steroids in pediatric liver transplant recipients is safe and reduces the incidence of acute graft rejection. Further studies are needed to confirm our preliminary results and to analyze long-term effects on post-transplant lymphoproliferative disease, chronic rejection, and patient survival.
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PMID:First experience with basiliximab in pediatric liver graft recipients. 1173 61

There is a marked diurnal variation in blood pressure (BP), with BP dipping to its lowest levels during nighttime sleep. A day-night dip in systolic BP (SBP) of <10% has been used to characterize individuals as nondippers, and is associated with an increased risk for cardiovascular disease. The present study examined the contribution of the sympathetic nervous system (SNS) to BP dipping in a biracial sample of 172 men and women aged 25 to 45 years. Assessments included 24-h ambulatory BP monitoring and both waking and sleeping urinary catecholamines. In addition, cardiovascular alpha- and beta-adrenergic receptor (AR) responsiveness was determined by the doses of isoproterenol and phenylephrine required to attain an increase in heart rate of 25 points (CD25) and BP (PD25), respectively. Compared with dippers (n = 116), nondippers (n = 56) were more likely to be African American and to have a family history of hypertension as well as a higher body mass index (BMI). The nighttime fall in both norepinephrine (NE) and epinephrine (EPI) excretion rates was reduced in nondippers compared with dippers (NE dip 9.3 v 13.1 microg/mg; EPI dip 2.7 v 4.0 microg/mg; both P < .05). Nondippers also were characterized by heightened alpha1-AR responsiveness compared with dippers (PD25 = 252 v 321 microg, P < .05). These data suggest that the SNS may contribute to individual differences in nighttime BP dipping, and appears to account in part for blunted BP dipping in African Americans.
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PMID:Nighttime blood pressure dipping: the role of the sympathetic nervous system. 1186 45

The immune responsiveness of women is altered during pregnancy in order to retain protective properties against disease and at the same time allow tolerance of the fetus. Diseases such as pre-eclampsia (PE) have been suggested to arise as a result of maladaptations in these immune alterations. Here we evaluate the effect of PE on the composition of peripheral blood lymphocyte subpopulations using lymphocyte surface antigen expression. Fifty-four women of various parities with pregnancy-induced hypertension (PIH) (39 non-proteinuric and 14 proteinuric) and matched controls (30 normotensive pregnant women (NTP) and 15 healthy non-pregnant women (NP)) were investigated. Monoclonal antibodies specific for human T lymphocytes and subpopulations: CD2, CD3, CD4, CD8, CD19 and activation markers: CD25, CD45RA, CD45RO, CD54 AND HLA(-)DR were used and detected using a two-colour fluorescence analysis with an automated flow cytometer. The total number of T lymphocytes: CD2, CD3, CD4, CD8 and CD19 were significantly decreased in PIH particularly PE (P<0.05). T cells expressing NK surface markers (CD3/CD16(+)CD56) and CD4 cells expressing HLA(-)DR were higher in PE. CD8(+)HLA(-)DR(+) cells and T-helper cells expressing adhesion molecules) CD4(+)CD54(+)) were higher in NTP than in NP and PE (P<0.05, 0.05). PE is associated with elevated levels of CD4(+)HLA(-)DR(+), and CD3(+)NK cells but decreased total numbers of T lymphocytes, and the CD3(+)CD25(+) subpopulation. These findings indicate systemic alterations in maternal immunity associated with the PE state. This feature of the disease may contribute to abnormal adaptation to pregnancy resulting in PE and PIH, promoting adverse outcomes including pregnancy loss.
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PMID:Lymphocyte subpopulations in pregnancy complicated by hypertension. 1262 76

The 31st Annual Meeting of the American Society of Nephrology, held in Philadelphia, Pennsylvania, USA, October 25-28, 1998, presented the newest advances in basic and clinical nephrology science. Several presentations discussed the results of studies with the newer immunosuppressants such as tacrolimus, sirolimus, mycophenolate mofetil and the anti-CD25 monoclonal antibodies, with the conclusion that studies on long-term use of these agents are needed. A number of other issues on immunosuppression protocols in renal transplantation were addressed during the meeting, including the subjects of steroid withdrawal and the role of TGF-beta in the development of chronic allograft nephropathy. The use of NESP in the treatment of renal anemia, the use of sildenafil to treat erectile dysfunction in hemodialysis patients, and the use of ACE inhibitors in nondiabetic renal patients were other important issues discussed at this meeting. Newer approaches to the treatment of hypertension discussed at the meeting highlighted the potential role of angiotensin II receptor antagonists in renal disease patients. Researchers also presented the promising results of a trial of a new, hybrid cell vaccine approach to the treatment of renal cell carcinoma.
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PMID:Recent advances in nephrology. 1561 34

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


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