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 total of 22 patients with different solid tumours refractory to previous chemotherapy were treated between May 1985 and December 1986 (osteosarcoma, 7; Wilms' tumour, 6; rhabdomyosarcoma, 2; Ewing's sarcoma, 2; non-Hodgkin's lymphoma, 2; retinoblastoma, 1; cavum lymphoepithelioma, 1; dyktioma, 1). Patients were aged between 3 and 20 years (mean, 10.6 years). There was a 3.4:1 male-to-female ratio. The treatment consisted of ifosfamide given i.v. as a single agent at a dose of 3,000 mg/m2 over 1 h on days 1 and 2. Mesna was given as a uroprotector at 600 mg/m2 every 4 h, up to a total of 13 doses. The courses were repeated every 3 weeks. Every patient except those with osteosarcoma had previously received cyclophosphamide. There were 3 (13.6%) complete responses (CRs) in 2 osteosarcomas and 1 abdominal non-Hodgkin's lymphoma, lasting 12, 8 and 2 months, respectively; 4 (18.2%) partial responses (PRs) in 2 Wilms' tumours, 1 Ewing's sarcoma and 1 abdominal non-Hodgkin's lymphoma; 4 absences of remission (ARs); and 11 (50%) cases of progressive disease (PD). In all, 81 courses were given, and the toxicities found were leukopenia (less than 2,000 leukocytes) in 15 courses, thrombocytopenia in 3, microhaematuria in 7, neurotoxicity in 8, fever in 8 and hypertension in 2. The overall response rate (31.8%) was encouraging and the toxicity, acceptable and reversible. These results demonstrate that ifosfamide should be considered for introduction into phase III protocols for the treatment of solid malignancies in children.
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PMID:Phase II study of ifosfamide as a single drug for relapsed paediatric patients. 250 55

The pathophysiology of renal dysfunction in generalized sepsis remains unknown. In this study, 24 hours after surgical induction of peritonitis in 20 volume-loaded sheep, three patterns of renal function were seen. In group 1 (n = 8), glomerular filtration rate (GFR) decreased by 70%, urine volume by 85%, absolute sodium excretion by 95%, and fractional sodium excretion by 83%. Group 2 (n = 4) exhibited similar sodium retention but GFR did not fall. Group 3 (n = 8) showed no change in GFR or urine volume and only minimally reduced sodium excretion. Mean arterial pressure fell 17% in group 1 only; central venous pressure, pulmonary capillary wedge pressure, and plasma volume were maintained at or above presepsis values in all groups. Cardiac index was either increased or unchanged, and renal plasma flow was maintained in all groups; there was thus no hemodynamic evidence to suggest volume contraction. Histologic examination showed only minor changes with no consistent pattern. Renal functional changes correlated with other manifestations of severe sepsis--GFR and sodium retention correlated significantly with increased cardiac index, decreased systemic vascular resistance, pulmonary arterial hypertension, leukopenia, hypoproteinemia, and hypoglycemia. All of these changes were most marked in group 1. In groups 1 and 2, plasma renin activity (PRA) increased and urinary kallikrein excretion decreased. PRA correlated inversely with GFR, urine volume, and sodium excretion; urinary kallikrein excretion correlated positively with urine volume and sodium excretion. Urinary excretion of 6-keto-PGF1 alpha was increased in groups 1 and 2 and correlated inversely with mean arterial pressure in group 1 animals. During sepsis, urinary thromboxane B2 excretion continued at presepsis values in all groups. The results suggest that unusual reciprocal changes in activity of the renin-angiotensin and renal kallikrein-kinin systems may play a role in the renal response to sepsis. PGI2 synthesis is increased and may affect systemic hemodynamics and renal function; the role of thromboxane A2 in this context is unknown.
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PMID:Vasoactive hormones in the renal response to systemic sepsis. 327 70

An examination of the principal physiological actions of angiotensin II should make it clear why in vivo attempts to inhibit the rate of angiotensin II generation have been an attractive avenue in pursuing control of high blood pressure. The major physiological effect of angiotensin II relates to its direct pressor effect, but there are supplementary blood pressure regulating actions. Therefore, if we limit the rate of angiotensin II generation by inhibiting the angiotensin converting enzyme (ACE) we should expect to control high blood pressure in a number of clinical syndromes. This paper reviews the future of ACE inhibitors in the treatment of conditions such as hypertension associated with unilateral renal artery stenosis, essential hypertension and severe and previously unresponsive hypertension, with respect not only to efficacy but also to the side-effect profile and ancillary properties. Side effects seen with this class of drug are cough, rashes (both morbilliform and urticarial) and, rarely, angio-oedema. Proteinuria, nephrotic syndrome, leukopenia and taste disturbance were previously reported with captopril but only taste disturbance, and that less frequently, is apparent at the lower doses now employed. Several studies have examined the 'quality-of-life' aspects of ACE therapy and have usually but not always reported favourably. There are features of the ACE inhibitors which make them attractive drugs, and while we should be cautious because of limited experience, we should critically and creatively examine their properties over the next years.
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PMID:Angiotensin converting enzyme inhibition in hypertension. 331 25

The adverse effects of protamine sulfate, used to neutralize the anticoagulant action of heparin, include systemic hypotension, pulmonary artery hypertension, thrombocytopenia and leukopenia. For further evaluation of protamine's mechanism of action, a three-part investigation was performed. In part I platelet-rich plasma (PRP) was prepared from canine blood samples (n = 6) taken before and 2 minutes after injection of protamine. In part II human PRP (n = 5) was preincubated with protamine or distilled water. Adenosine diphosphate-induced aggregation of protamine-treated platelets was unchanged, but thrombin-induced aggregation was inhibited in both canine and human preparations (p less than 0.05). In part III thrombocytopenia was produced in splenectomized dogs (n = 5), using microporous filters, to 4.5-8.4% of the initial platelet count. Protamine reversal of the heparinization caused hypotension (maximally -29 mmHg 90 s after protamine), but not pulmonary arterial hypertension. Leukopenia developed before additional thrombocytopenia appeared. Protamine-platelet interaction inhibits thrombin-induced platelet aggregation. Platelets may play an important role in the pulmonary pressure rise during protamine reversal, but do not mediate the systemic hypotension.
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PMID:The effect of protamine sulfate on platelet function. 338 50

Renal transplantation is usually accompanied by an improvement in reproductive function. The possibility of conception in women of childbearing age emphasizes the need for counseling, and couples who want a child should be encouraged to discuss all implications, with the advice based on strict guidelines. If a recipient becomes pregnant, she must be monitored as a high-risk patient. Management requires particular attention to BP control, renal function, and all infection, as well as fetal surveillance. Just under 40% of conceptions do not go beyond the first trimester, but of those that do, greater than 90% end successfully. In most patients, renal hemodynamics improve during gestation, but permanent impairment occurs in 15% of pregnancies. Other patients may experience transient deterioration in late pregnancy (with or without proteinuria). Patients have a 30% chance of developing hypertension, preeclampsia, or both. Despite its pelvic location, the transplanted kidney rarely produces dystocia and experiences no apparent mechanical injury during vaginal delivery. Thus, cesarean section should be reserved for obstetric reasons only. Aseptic technique, bacterial prophylaxis even for trivial surgery, and steroid augmentation are necessary. Preterm deliveries occur in 45% to 60%, and intrauterine growth retardation in at least 20%, of gestations. Neonatal complications include respiratory distress syndrome, leukopenia, thrombocytopenia, adrenocortical insufficiency, and infection. No predominant or frequent developmental abnormalities have been described, and data on infancy and childhood are encouraging. Future goals should be to improve prepregnancy assessment criteria, to reassess the rationale and implications of immunosuppression during pregnancy, and to monitor the remote effects of pregnancy on both renal prognosis and the offspring.
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PMID:Renal transplantation and pregnancy. 355 13

We combined the angiotensin II (AT-II)-induced hypertension method with "two-route chemotherapy" (TRC), using cis-diamminedichloroplatinum(II) (CDDP) and its antidote, sodium thiosulfate (STS). The efficacy of the modified TRC was evaluated in rats bearing a limb tumor (transitional cell carcinoma). Immediately after infusing CDDP (15 mg/kg) and AT-II (15 micrograms/kg) via the femoral artery for 5 min, 1580 mg/kg STS (200-fold molar ratio to 15 mg/kg of CDDP) were administered i.v. for a further 5 min. Other treatments were as follows: 5 mg/kg of CDDP mixed or not mixed with 15 micrograms/kg of AT-II were given intraarterially (i.a.); 5 mg/kg of CDDP alone were injected i.v.; CDDP (15 mg/kg, i.a.) and STS (1580 mg/kg, i.v.) were simultaneously administered, without AT-II (conventional TRC). The antitumor effects of the modified TRC, evaluated by regression of tumor growth and extended life span, were superior to the other treatments. On the other hand, nephrotoxicity, loss of body weight, and leukopenia, seen in the rats given TRC with AT-II, occurred less than or at the same rate as in rats given other treatments. Thus, the TRC with AT-II was the most effective treatment given to rats bearing a regionally confined tumor. The feasibility of clinical application of modified TRC using i.a. CDDP plus AT-II and i.v. STS is discussed.
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PMID:Efficacy of two-route chemotherapy using cis-diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, in combination with angiotensin II in a rat limb tumor. 359 29

To further clarify the platelet dependence of acetyl glyceryl ether phosphorylcholine (AGEPC) physiologic activity and of IgE anaphylaxis in the rabbit, PGI2 was employed as an inhibitor of in vivo platelet function. Intravenous infusion of PGI2 (1 to 2 micrograms/kg/min) inhibited the AGEPC-induced decrease in dynamic compliance, increase in total pulmonary resistance, and transient decrease in tidal volume, but the right ventricular hypertension, bradycardia, and apnea were unaffected. Although PGI2 itself produced a marked systemic hypotension, AGEPC still induced a bimodal hypotensive response. Documentation that platelet function was inhibited by PGI2 included partial inhibition of AGEPC-induced thrombocytopenia, abrogation of platelet secretion (as assessed by plasma platelet factor 4 levels), and inhibition of ex vivo platelet aggregation. The AGEPC-induced leukopenia was not affected. In another group of rabbits, chlorpheniramine pretreatment inhibited the lung mechanical changes induced by AGEPC but did not affect the ventilatory or circulatory alterations, indicating that the lung mechanical alterations (but not any of the other alterations) are mediated by platelet-secreted histamine acting via H1 receptors. In IgE-producing rabbits intravenously challenged with antigen, PGI2 had no effect on any of the physiologic alterations, despite substantial inhibition of platelet secretion. From these results, together with previous platelet depletion studies, we conclude that AGEPC may be a significant mediator of the circulatory alterations and apnea of rabbit IgE anaphylaxis by platelet-independent mechanisms, but neither AGEPC nor platelets appear to be important in mediating the anaphylactic lung mechanical alterations.
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PMID:Participation of platelets in the physiologic alterations of the AGEPC response and of IgE anaphylaxis in the rabbit. Effects of PGI2 inhibition of platelet function. 388 Oct 60

The use of captopril in 19 patients with renal parenchymal disease and refractory hypertension was studied for a mean period of 12 months. There was a significant reduction in the systolic and diastolic blood pressures, with a reduction in the mean arterial pressure of 29 mmHg. The mean maintenance dose of captopril was 142 mg daily in three divided doses. All but one of the patients required a diuretic for satisfactory blood pressure control and 3 patients were also given a beta-blocker. In all patients a simplification of the previous therapeutic regimen was achieved. A significant rise in serum creatinine was noted in 2 patients, one of whom had to be withdrawn from the study. Despite the presence of renal functional impairment, proteinuria did not occur de novo nor did established proteinuria increase. Leukopenia was noted in any of the patients in this group.
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PMID:Captopril for refractory hypertension in patients with impaired renal function. 388 5

The safety and efficacy of captopril therapy in children with severe and refractory hypertension has been evaluated in a collaborative international study which enrolled a group of 73 patients, 15 years of age or younger. Most patients had hypertension associated with renal disease or vascular abnormalities. Captopril was administered for periods of less than 3 months to more than 1 year. A significant decrease in both systolic and diastolic blood pressures was produced by the administration of captopril, usually in conjunction with other antihypertensive agents (most commonly diuretics and/or beta-blockers). Systolic blood pressures were normalized in 62% and 53% and diastolic blood pressures in 56% and 45% of reported patients after the second and sixth months of captopril therapy, respectively. The response to captopril was sustained over a 12-month period. Adverse reactions were reported in 49% of the 73 patients; 48% of patients had experienced adverse reactions to other antihypertensive agents prior to entering the study. The reactions most frequently observed during captopril therapy were hypotension, vomiting, postural symptoms, anemia, rash, and anorexia. Leukopenia was reported in six patients, all of whom had renal impairment. Two of these patients had received concomitant therapy with immunosuppressants, and one had systemic lupus erythematosus. Captopril was discontinued in two of these six children. Statistically significant increases in mean serum urea nitrogen and potassium concentrations and decreases in mean serum CO2 levels were observed during the course of therapy. These effects could not be exclusively attributed to captopril administration as the study population received multidrug therapy and had significant intrinsic disease. Captopril was demonstrated to be an effective and safe drug for the treatment of children with severe hypertension.
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PMID:Efficacy and safety of captopril in the treatment of severe childhood hypertension: report of the International Collaborative Study Group. 388 18

Enalapril is the result of a targeted research programme to develop a non-mercapto converting enzyme inhibitor with a long duration of action and an improved safety profile for use in the therapy of hypertension and congestive heart failure. Over 3500 patients world-wide have received enalapril or enalaprilat. Long-term experience at present includes over 2500 patients. While enalapril and captopril produce similar efficacy, enalapril is better tolerated and appears not to be associated with occurrence of captopril-type side-effects, particularly the skin rash, taste loss, leukopenia and proteinuria. Enalapril and other converting enzyme inhibitors may be associated with renal insufficiency when given to patients with bilateral renovascular hypertension.
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PMID:Tolerance and safety of enalapril. 609 40


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