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)

R24 is a mouse IgG3 monoclonal antibody that reacts with the ganglioside GD3 expressed by melanoma cells and other cells of neuroectodermal origin (e.g. adrenal medulla). Antitumour activity of R24 was demonstrated in initial phase I and pilot trials, but treatment was limited by urticaria at cumulative doses of 400 mg/m2. A trial exploring intensification of the dose of R24 was conducted in eight patients. Planned doses of R24 antibody were 800 and 1200 mg/m2 over 6-8 days by continuous i.v. infusion. All patients received concomitant therapy with hydroxyzine hydrochloride and cimetidine to minimize urticaria. One patient developed anaphylaxis, after which no further therapy was given. All patients developed peripheral blood lymphopenia and marked decreases in serum complement values during treatment, suggesting depletion of two possible effector mechanisms of the antitumour effects of R24. A vascular leak syndrome, manifested by weight gain, oedema and hypotension, was evident in seven patients during the initial 24-36 h of treatment. Serum sickness syndrome was observed in six of seven evaluable patients between days 5 and 8, coincident with the onset of the human anti-globulin response to R24. One patient given 1200 mg/m2 had a minor response (38% reduction in pelvic nodes) lasting 12 months. There was no detectable increase (by immunohistochemical staining) in deposition of R24 within tumour sites at doses used in this trial compared to that observed at doses of 240 and 400 mg/m2. The maximum tolerated dose was 800 mg/m2. Dose-limiting toxicity was manifest as reversible hypertension with end-organ symptoms (chest pain or visual field defects) in patients treated with a dose of 1200 mg/m2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment with high dose mouse monoclonal (anti-GD3) antibody R24 in patients with metastatic melanoma. 129 83

Treatment with the monoclonal antibody OKT3 specific for the CD3 complex associated with the T cell antigen receptor can reverse acute rejection of human renal allografts. However, efficacy of anti-CD3 antibodies for treatment of patients with acute graft-versus-host disease after marrow transplantation has not been established. The dose-limiting side effects resulting from T cell activation induced by some anti-CD3 antibodies in vivo have discouraged their use for this application. We now report a phase I-II study of GVHD treatment with the anti-CD3 antibody BC3, a monoclonal murine IgG2b that, unlike OKT3, does not activate T cells. Fourteen patients were treated with BC3 after progression of acute GVHD despite treatment with cyclosporine and corticosteroids, and three patients received BC3 as primary treatment for GVHD. BC3 was administered at a dose of 0.1 or 0.2 mg/kg/day for seven or eight days. Five patients achieved complete resolution of GVHD, eight patients had partial improvement, two patients had no change, and two patients had progression of GVHD on therapy. Responses were sustained in 8 of 13 patients. Mild chills, fever, hypertension, and chest discomfort occurred in various combinations following 6 of 17 (35%) initial infusions of BC3 and following 4 of 99 (4%) subsequent infusions. In each instance it was possible to continue BC3 therapy without adjusting the dose or treatment schedule. In each patient treated, the absolute count of peripheral blood lymphocytes decreased transiently but returned to baseline within 22 hr after the first infusion. Circulating T cells had surface CD3 molecules saturated by the infused antibody in all but one patient. Four patients survived longer than one year after treatment with antibody BC3, and 13 patients died of infection or organ failure. Administration of the nonmitogenic anti-CD3 antibody BC3 was associated with improvement in the clinical manifestations of GVHD with minimal acute toxicity. Efficacy of antibody treatment did not depend on depletion of circulating T cells. Therefore, antibody BC3 may be achieving therapeutic immunosuppression by modulating T cell function. Controlled studies in patients treated earlier in the course of GVHD should determine whether antibody BC3 can improve survival.
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PMID:Treatment of acute graft-versus-host disease with a nonmitogenic anti-CD3 monoclonal antibody. 144 Aug 52

15 patients aged between 24 and 66 years with 10 different malignant tumor diseases were treated with a recombinant human tumor necrosis factor preparation PAC-4D in a phase-I trial. The starting dose was 10(5) U PAC-4D as an intravenous short infusion. The maximally tolerable dose is around 18 X 10(5) U/m2. As the main clinical side effects were observed: fever, chills, hypertension with subsequent hypotension, lethargy, transient somnolence, headache, neurological deficiency symptoms, nausea and vomiting. Important laboratory-chemical parameters were the increase in transaminases and, in higher dose levels, leukocytosis with the left shift and lymphopenia in the differential blood picture. As dose-limiting toxicity are estimated hypotension, and neurological side effects and hepatotoxicity. In one female patient who received 27 X 10(5) U PAC-4D there appeared pronounced, histologically verified necroses in the metastases of a malignant fibrous histiocytoma.
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PMID:Human pharmacological investigation of a human recombinant tumor necrosis factor preparation (PAC-4D) a phase-I trial. 337 52

In 3 patients with low-grade astrocytomas clinical pharmacology of interferon-beta (10(7) U/mg protein) was investigated. Interferon-beta with escalating dosage (2.3, 6.9, 23, 69 X 10(6) U/patient) was given to each patient in 4 infusions at weekly time intervals. In these patients dose-dependent plasma-levels of interferon-beta of up to 5800 IU/ml were achieved. Plasma concentrations showed a biphasic decline (T1 1/2:0.095-0.49 hrs and T2 1/2: 5-14.5 hrs). Side effects were: mild fatigue, myalgia, tachycardia, hypertension, and fever; the latter was well controlled by pretreatment application of paracetamol. Hematological changes included lymphopenia (2-6 hrs after infusion) and granulocytosis (3-6 hrs after infusion). Natural Killer cell activity was also monitored: 6 hours after infusion a drop of activity - not clearly dose dependent - was observed to a minimum of 1% pretreatment activity; 24 hrs after infusion activity increased up to a maximum of 400%. In this phase I study high biological activity of interferon-beta could be detected in plasma of astrocytoma patients - clinical tolerance was good and only mild toxicity was observed.
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PMID:Interferon-beta in patients with low-grade astrocytomas--a phase I study. 403 71

Questions persist about the management of postoperative chylothorax in infants and children. Our experience with postoperative chylothorax over the most recent decade (1980 to 1990) has been reviewed. The type and amount of drainage, data from cardiac catheterization and echocardiography, operative decisions and details, and eventual outcomes have been cataloged. All patients were initially treated with total gut rest, with operation reserved for unabated drainage. Chylothorax developed postoperatively in 15 infants and 11 children (18 with a cardiac procedure and 8 with a noncardiac procedure). The average age was 3.1 years. Spontaneous cessation and cure occurred in 19 (73.1%) of these 26 patients, with an average drainage duration of 11.9 days (range, 4 to 30 days). Those for whom operation was chosen drained preoperatively for an average of 29.2 days (range, 25 to 40 days). There were no deaths in either group. Complications were lymphopenia (2 patients) and fungal sepsis (1 patient). The amount of drainage per day was not significantly different between patients treated operatively and those treated nonoperatively. Failure of nonoperative management was associated with venous hypertension from increased right-sided cardiac pressures or central venous thrombosis (p < 0.05, Fisher's exact test). Presumably this increased pressure is transmitted to the lymphatic system. These patients should be identified early and considered for thoracic duct suture or pleuroperitoneal shunting.
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PMID:Management of pediatric postoperative chylothorax. 837 18

It was shown that in patients with hypertension, duodenal and gastric ulcers and erosive gastritis leukopenia and lymphopenia are seen. At the same time contents of T- and B-lymphocytes are decreased and contents of C- lymphocytes are increased in circulation blood. Peroral daily intake of 20 mg of beta-carotene during 3-4 weeks caused increasing the contents of B- and T-cells and decreasing contents of C-lymphocytes in blood of patients.
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PMID:[Study of immunomodulating properties of beta-carotene in patients]. 856 Aug 70

The objective of the study was to assess the efficacy and the safety of pamidronate (APD) in recalcitrant reflex sympathetic dystrophy (RSD). Ten women and 13 men with a mean (+/-standard deviation, SD) age of 44 +/- 11 years were included. The involved sites were: the ankle (n = 10), the foot (n = 7), the hand (n = 3), the hip (n = 2), the knee (n = 2) and the shoulder (n = 1). Some patients had more than one site involved. Mean (+/-SD) duration of the disease was 15 +/- 13 months. RSD was in pseudo-inflammatory phase in 16 patients and in ischaemic phase in 7 patients. RSD was post-traumatic in 17 cases; 11 patients have been previously treated unsuccessfully by sympathetic blockades. APD was administered intravenously (perfusion) to a dose of 1 mg/kg/day during 3, 2 or one day. Fourteen patients received APD during 3 consecutive days whereas 7 patients have been treated during 2 consecutive days and 2 patients only during 1 day mainly due to adverse events. Efficacy was assessed by a decrease of pain = visual analogic scale (VAS, 0-100 mm) and verbal scale (PVS, range 0-3). Moreover, the patient and the observer have estimated the efficacy of the treatment on a verbal scale (EVS, range 0-3). Measurements of these parameters were performed immediately before the treatment and 7, 30, 60 and 90 days later. The maximum duration after treatment was 9 months. A significant decrease of VAS and PVS were observed between D0 and D30 (p = 0.0002 and p = 0.0002 respectively), D0 and D60 (p = 0.0004, p = 0.0004 respectively), and D0 and D90 (p = 0.00003, p = 0.0001 respectively). A significant increase of EVS was only observed between D0 and D90 (p = 0.03). Adverse events were noted in 14 patients: transient fever (n = 6), venous inflammation (n = 2), transient symptomless hypocalcaemia (n = 3), nausea (n = 1), lymphopenia (n = 1), transient hypertension (n = 1). These results suggest an efficacy of APD in recalcitrant RSD. Double-blind placebo controlled studies are required to back up these preliminary results.
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PMID:Treatment of severe, recalcitrant reflex sympathetic dystrophy: assessment of efficacy and safety of the second generation bisphosphonate pamidronate. 913 26

A Danish multicentre study was undertaken of the manifestations, infections, thrombotic events, survival and predictive factors of survival in 513 Danish patients with systemic lupus erythematosus (SLE) according to the 1982 classification criteria of the American College of Rheumatology. The mean duration of follow-up was 8.2 years from diagnosis and 12.8 years from first symptom. This paper describes the most common clinical and laboratory manifestations and their relationship to sex and age at the time of onset and diagnosis. Cluster analysis revealed three clinically defined clusters at the time of disease onset. Cluster 1 (57% of patients) consisted of relatively elderly patients without nephropathy or malar rash, but with a high prevalence of discoid lesions. Cluster 2 (18%) consisted of patients with nephropathy, a third of whom also developed serositis and lymphopenia. The patients of the third cluster (25%) all had malar rash and half were photosensitive. Follow-up showed that the patients of cluster 2 developed azotaemia, large proteinuria, arterial hypertension and myositis significantly more often than did the rest of the patients, but the mortality was not increased. The risk of developing renal end-stage disease was highest in men with early-onset disease.
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PMID:A multicentre study of 513 Danish patients with systemic lupus erythematosus. I. Disease manifestations and analyses of clinical subsets. 989 Jun 74

Anatomo-pathological correlation in a case of systemic talc granulomatosis affecting lungs, pleura, liver, spleen and mesenteric lymph nodes resulting in pulmonary arterial hypertension and cor pulmonale is described. The patient, a 26-year-old male HIV-negative intravenous drug addict had no lymphopenia or any histopathologic findings at necroscopy compatible with AIDS, despite of a chronic high-risk behavior favoring this illness.
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PMID:[Systemic talc granulomatosis in a HIV-negative intravenous drug addict]. 1051 62

Sphingosine 1-phosphate (S1P) is a bioactive lysolipid with pleiotropic functions mediated through a family of G protein-coupled receptors, S1P(1,2,3,4,5). Physiological effects of S1P receptor agonists include regulation of cardiovascular function and immunosuppression via redistribution of lymphocytes from blood to secondary lymphoid organs. The phosphorylated metabolite of the immunosuppressant agent FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol) and other phosphonate analogs with differential receptor selectivity were investigated. No significant species differences in compound potency or rank order of activity on receptors cloned from human, murine, and rat sources were observed. All synthetic analogs were high-affinity agonists on S1P(1), with IC(50) values for ligand binding between 0.3 and 14 nM. The correlation between S1P(1) receptor activation and the ED(50) for lymphocyte reduction was highly significant (p < 0.001) and lower for the other receptors. In contrast to S1P(1)-mediated effects on lymphocyte recirculation, three lines of evidence link S1P(3) receptor activity with acute toxicity and cardiovascular regulation: compound potency on S1P(3) correlated with toxicity and bradycardia; the shift in potency of phosphorylated-FTY720 for inducing lymphopenia versus bradycardia and hypertension was consistent with affinity for S1P(1) relative to S1P(3); and toxicity, bradycardia, and hypertension were absent in S1P(3)(-/-) mice. Blood pressure effects of agonists in anesthetized rats were complex, whereas hypertension was the predominant effect in conscious rats and mice. Immunolocalization of S1P(3) in rodent heart revealed abundant expression on myocytes and perivascular smooth muscle cells consistent with regulation of bradycardia and hypertension, whereas S1P(1) expression was restricted to the vascular endothelium.
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PMID:Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes. 1474 17


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