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 female patient with a history of migraines and chorea developed polyarthralgia at age 24 and was diagnosed with rheumatoid arthritis. In 1991 she was hospitalized because of impaired renal function and hypertension. Examination revealed thrombocytopenia and the presence of lupus anticoagulant. Antinuclear antibody was weakly positive, but anti-DNA antibody was negative, and no decrease in leukocyte count or complement level was observed. Rheumatoid arthritis with antiphospholipid syndrome was diagnosed. Renal biopsy showed renal thrombotic microangiopathy. This renal lesion was considered to be associated with antiphospholipid syndrome. Cyclophosphamide pulse therapy and anticoagulation therapy decreased proteinuria and improved renal function.
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PMID:Renal thrombotic microangiopathy in a patient with rheumatoid arthritis and antiphospholipid syndrome: successful treatment with cyclophosphamide pulse therapy and anticoagulant. 780 16

The authors present a case report of a 62-year old woman, with hypertension for many years. She suffered from weakness, anorexia and weight loss in the last 6 months. On admission, anemia, elevated ESR, haematuria, proteinuria and renal failure were present. Renal biopsy was compatible with chronic glomerulonephritis. The clinical picture and positivity for P-ANCA suggested systemic vasculitis. Later evidence of maxillary sinusitis and nasal mucosae ulcers as well as pneumonitis, although biopsy did not reveal granulomas, suggested the diagnosis of Wegener Vasculitis. Medicated with Cyclophosphamide and Prednisolone, for a year, with improvement. The authors make a brief discussion of the clinical criteria for classification of ANCA-associated systemic vasculitis.
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PMID:[Vasculitis associated with ANCA]. 794 37

Advances in immunosuppressive therapy have resulted in significantly improved patient and graft survival after solid organ transplantation. However, increased use has brought attention to specific toxicities associated with the use of these agents. Corticosteroid therapy can result in a wide array of short and long term toxicities. Management of these effects has focused on alternate day and dosage reduction protocols. Myelosuppression, hepatotoxicity, alopecia and gastrointestinal adverse effects are associated with azathioprine and generally respond to a reduction in dosage or withdrawal. Cyclophosphamide myelosuppression is managed in a similar manner. Use of cyclosporin, while the mainstay of immunosuppressive therapy, is often complicated by several well documented adverse effects. Short and long term nephrotoxicity is often managed through pharmacokinetic dosing strategies as well as pharmacological intervention with calcium channel blockers, prostaglandin analogues, pentoxifylline and thromboxane antagonists. Cyclosporin-induced hypertension, hyperlipidaemia, hyperkalaemia and hyperuricaemia are generally responsive to appropriate dietary restrictions and pharmacological therapies. The adverse effects associated with polyclonal antilymphocyte agents (fever, chills, rash, arthralgias) occur in response to the administration of foreign protein substances but can be prevented by pretreatment with corticosteroids, diphenhydramine and paracetamol (acetaminophen). The administration of muromonab CD3 (OKT3) stimulates the release of cytokines resulting in potentially severe complications seen during the first 1 or 2 doses. Pretreatment with diphenhydramine, low dose corticosteroids and paracetamol as well as proper fluid management has reduced the incidence of this syndrome. However, agents such as high dose corticosteroids, indomethacin, pentoxifylline and anti-tumour necrosis factor monoclonal antibodies may further decrease the severity of cytokine-induced toxicity. Antimurine antibodies may also develop during muromonab CD3 therapy, potentially limiting the efficacy of this agent. However, continued concomitant immunosuppressive therapy has significantly reduced antibody formation. In summary, as newer agents are developed with narrow therapeutic windows, it will be critical to identify specific drug toxicity and to develop preventative and management therapeutic strategies.
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PMID:Prevention and management of the adverse effects associated with immunosuppressive therapy. 839 89

Abnormal growth of vascular smooth muscle cells (SMC) is frequently associated with hypertension and atherosclerosis, and homeostasis within a normal vessel is maintained by the balanced generation of both vasoconstrictors and vasodilators. Moreover, several endogenous vasoconstricting factors induce SMC growth, whereas several vasodilators inhibit SMC growth. Inasmuch as adenosine is a potent vasodilator, it is possible that it too could inhibit SMC growth. Hence, the effects of adenosine (10(-8) to 10(-3) mol/L), 2-chloroadenosine (a stable analogue of adenosine; 10(-8) to 10(-3) mol/L), and 8-bromo-cAMP (10(-8) to 10(-3) mol/L) on fetal calf serum (FCS; 2.5%)-induced growth of rat aortic SMC were evaluated. Growth was analyzed by assaying DNA synthesis (thymidine incorporation in SMC pulsed for 4 hours with 1 microCi/mL [3H]thymidine) and cell proliferation (change in cell number). Growth-arrested SMC were treated with 2.5% FCS in the presence and absence of adenosine, 2-chloroadenosine, or 8-bromo-cAMP for 24 hours for DNA synthesis or 4 days for cell proliferation. All three substances inhibited DNA synthesis and cell proliferation in a concentration-dependent manner. Compared with adenosine, 2-chloroadenosine was more potent in inhibiting growth. The inhibitory effects of 2-chloroadenosine were reversed by KF17837 (a specific A2 receptor antagonist) but not by DPCPX (a specific A1 receptor antagonist). Furthermore, the inhibitory effects of 2-chloroadenosine were not mimicked by CGS21680 (an A2a receptor agonist), and the effects of N6-cyclopentyladenosine (CPA; an A1 receptor agonist) were not markedly more potent than those of 2-chloroadenosine, suggesting that the inhibitory effects of adenosine are possibly mediated via A2b receptors. These studies provide evidence that adenosine inhibits SMC growth and suggest that a decrease in local levels of adenosine may initiate SMC growth and contribute to the vascular remodeling process observed in hypertension and atherosclerosis.
Hypertension 1996 Mar
PMID:Adenosine inhibits growth of rat aortic smooth muscle cells. Possible role of A2b receptor. 861 41

Increased incidence of cardiovascular disease in postmenopausal women (PMW) is accompanied by ovarian dysfunction; hormone replacement therapy (HRT) can have cardioprotective effects. Because hypertension and atherosclerosis are associated with impaired release of endothelium-derived nitric oxide (NO) and increased levels of low-density lipoproteins (LDL), we investigated whether HRT augments NO release, and whether these increases are accompanied by a decrease in LDL levels in PMW. We determined serum nitrite/ nitrate (NO2-/NO3-) and LDL levels at baseline (before initiation of HRT) and during the 6th and 12th months of the study. The PMW (n = 26) received continuous oral administration of estradiol valerate (Progynova, 2 mg daily) for 21 days supplemented with either oral cyproterone acetate (CPA; 1 mg; n = 11) or medroxyprogesterone acetate (MPA; 5 mg; n = 15) on days 12-21 of each treatment cycle. Blood samples in the PMW receiving HRT were collected at times while the subjects were taking estradiol valerate alone and estradiol valerate plus CPA or MPA. Compared with the samples collected at baseline, serum NO2-/NO3- levels increased significantly from 20.1 +/- 1.58 mumol/L at baseline to 30 +/- 3.7 mumol/L (P < 0.01) in samples collected after 12 months of HRT while the PMW were not taking progestins (CPA or MPA), and to 25.4 +/- 2 mumol/L (P < 0.05) when all the samples, regardless of the treatment with CPA or MPA, were included in the analysis. Moreover, > 30% increase in serum NO2-/NO3- levels were observed only in 13 (responders) out of 26 PMW substituted with estradiol valerate, suggesting that estradiol may improve endogenous NO synthesis in a differential fashion. Compared with baseline, no significant increases in serum NO2-/NO3- were observed in samples collected while the estradiol-treated responders were taking either CPA or MPA. In contrast to NO2-/NO3- serum LDL levels were significantly reduced in samples collected after 12 months of HRT (P < 0.05 vs. baseline). Furthermore, levels of NO2-/NO3 showed a significant negative correlation with the levels of LDL (r2 = 0.17; P < 0.05) in the responders but not in nonresponders. These results indicate that oral administration of estradiol valerate in PMW for HRT increases circulating NO levels, an effect that may contribute to the cardioprotective effects of HRT in PMW. In addition, our data suggests but does not prove that concomitant administration of a progestin may attenuate the beneficial effects of estrogen replacement therapy with regard to NO release. Finally, our data provides evidence for the existence of responders and nonresponders to postmenopausal estrogen treatment with respect to improvement of endogenous NO levels, suggesting that a significant number, but not all, of the hormonally substituted PMW profit fully from the beneficial properties of a HRT.
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PMID:Differential effects of hormone-replacement therapy on endogenous nitric oxide (nitrite/nitrate) levels in postmenopausal women substituted with 17 beta-estradiol valerate and cyproterone acetate or medroxyprogesterone acetate. 902 24

The main purpose of this investigation was to evaluate whether the cyclic AMP-adenosine pathway, ie, the conversion of cAMP to AMP and, hence, to adenosine, is involved in the regulation of nitric oxide (NO) synthesis by vascular smooth muscle cells (SMCs). Treatment of confluent monolayers of SMCs with adenosine, 2-chloroadenosine (stable analog of adenosine), and agents that elevate endogenous (SMC-derived) adenosine (EHNA and iodotubericidin) increased nitrite/nitrate (stable metabolites of NO) levels in the medium and enhanced the conversion of 3H-L-arginine to 3H-L-citrulline by cytosolic extracts obtained from the pretreated SMCs. The stimulatory effects of adenosine were not mimicked by low (1 to 100 nmol/L) concentrations of CGS21680, an A2A receptor agonist, or CPA, a selective A1 receptor agonist. The stimulatory effects of 2-chloroadenosine and EHNA plus iodotubericidin were significantly inhibited by KF17837, a selective A2 receptor antagonist, and by DPSPX, an A1/A2 receptor antagonist, but not by DPCPX, a selective A1 receptor antagonist. DDA (adenylyl cyclase inhibitor) and Rp-cyclic AMP (protein kinase A inhibitor) did not block the effects of adenosine on NO synthesis. Incubation of SMCs with exogenous cyclic AMP, at concentrations previously shown to elevate levels ofadenosine in the medium, also increased nitrite/nitrate levels and 3H-L-citrulline formation, and the effects of cyclic AMP on NO synthesis were blocked by DPSPX and KF17837, but not by DPCPX. These findings provide evidence that exogenous and SMC-derived adenosine induce NO synthesis via A2B receptors linked to a pathway not involving adenylyl cyclase/protein kinase A. Moreover, extracellular cyclic AMP induces NO synthesis via conversion to adenosine and activation of A2B adenosine receptors. The cyclic AMP-adenosine pathway may be importantly involved in the vascular production of NO.
Hypertension 1998 Jan
PMID:Cyclic AMP-adenosine pathway induces nitric oxide synthesis in aortic smooth muscle cells. 945 19

Membranous nephropathy is a frequent cause of nephrotic syndrome in adults, and in one third of these patients, it leads to end-stage renal disease. Based on an extensive critical review of the literature, the following recommendations are offered. Oral high-dose corticosteroids are ineffective in producing either a sustained remission of nephrotic syndrome or in preserving renal function in patients with membranous nephropathy, and should not be used as the sole therapy (grade A recommendation). The use of azathioprine is not associated with any significant benefits, so its use is not justified (grade C). The alkylating agents cyclophosphamide and chlorambucil are both effective in the management of membranous nephropathy. Because of growing concern about long-term toxicity, especially with cyclophosphamide, these drugs should be reserved for patients who exhibit clinical features, such as severe or prolonged nephrosis, renal insufficiency, or hypertension, that predict a high likelihood of progression to end-stage renal disease. Chlorambucil in conjunction with oral steroids is the drug of first choice (grade A). Cyclophosphamide and oral steroids are alternatives (grade B). Cyclosporine may, in the future, become the agent of choice for membranous nephropathy. Currently, it is recommended (grade B) that cyclosporine use be considered in patients at high risk for progression in membranous nephropathy or if alkylating agents are contraindicated or ineffective.
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PMID:Management of idiopathic membranous nephropathy: evidence-based recommendations. 1036 95

This study was conducted to analyze the trend of histopathologic subtypes in idiopathic nephrotic syndrome (INS) in a homogenous racial group in India population. A prospective analysis of 400 consecutive children with INS was performed. Kidney biopsies were performed according to standard indications. Steroids were administered following the Arbeitsgeminschaft fur Padiatrische Nephrologie protocol. Cyclophosphamide was administered to children in the frequent-relapser, steroid-dependent, and steroid-nonresponder categories. Of the various histopathologic subtypes, focal segmental glomerulosclerosis (FSGS) was the most common (87 of 222 subtypes; 39.1%). Children who underwent biopsy between July 1992 and December 1996 (group B, n = 157) were compared with our initial published data of biopsies performed between January 1990 and June 1992 (group A, n = 65), with similar indications for biopsy in both groups. The incidence of FSGS was significantly greater in biopsies performed in the recent period (group B, 47% versus group A, 20%; P = 0.0002). The different clinical and biochemical parameters were also analyzed to differentiate FSGS from the other 2 subtypes. Hypertension (P = 0. 005), renal insufficiency at presentation (P = 0.001), and steroid resistance (P = 0.0006) were significantly greater in children with FSGS. On follow-up (mean, 5.4 years), children with FSGS were at a significantly greater risk for developing renal insufficiency (P = 0. 0001). We conclude there is a shift toward an increasing prevalence of FSGS over the years in the Indian population. This trend has immense therapeutic and prognostic significance.
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PMID:Changing trends of histopathology in childhood nephrotic syndrome. 1051 44

A 72-year-old woman had been treated for hypertension and hyperthyroidism by a local doctor. In May 1998, she came to this institution with a chief complaint of leg edema. Based on the clinical findings, she was diagnosed as having nephrotic syndrome with massive proteinurea, hypoproteinemia and hyperlipidemia. Renal biopsy findings showed minimal change nephrotic syndrome (MCNS). No substantial improvement was obtained by steroid therapy. We therefore additionally administered angiotensin-converting enzyme inhibitor (enalapril maleate). The urinary protein concentration significantly decreased. On decreasing the dose of steroids, the urinary protein concentration increased. Cyclophosphamide helped us to decrease the steroid dosage. This treatment resulted in type II incomplete remission. The final diagnosis was refractory MCNS. During steroid therapy, she developed hyperglycemia. She had no histology of diabetes mellitus. There is therefore a possibility that steroids can induce hyperglycemia even in patients without a history of diabetes mellitus. These results suggest that careful monitoring of plasma glucose is necessary during steroid therapy and that the administration of an angiotensin-converting enzyme inhibitor is effective in elderly patients with refractory primary nephrotic syndrome.
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PMID:[A decrease in urinary proteins in an elderly patient with refractory minimal change nephrotic syndrome administration of an angiotensin converting enzyme inhibitor in combination with steroids]. 1057 51

The Goal of this study was prospective evaluation of the blood flow parameters-maximal systolic velocity (MSV), minimal diastolic velocity (MDV) and Pourcelot's resistivity index (RI) in patients with swollen optic dis. 63 patients (79 eyes) were examined with swollen optic disc-10 patients (17 eyes) with intracranial hypertension, 12 patients (14 eyes) with pseudoedema of disk of the optic nerve, 7 patients (7 eyes) with inflammation swollen optic disc, 3 patients (6 eyes) with pseudotumor cerebri, 8 patients (12 eyes) with arteritic anterior ischemic optic neuropathy (A-AION) and 23 patients (23 eyes) with nonarteritic anterior ischemic optic neuropathy (N-AION) and 23 patients (23 eyes) with nonarteritic anterior ischemic optic neuropathy (N-AION). All patients had ophthalmological examinations and Color Doppler ultrasonography in central retinal artery (CRA), posterior ciliary artery (PCA), ophthalmic artery (OA) and in central retinal vein (CRV). The blood flow parameters of the swollen optic disc and normal optic disc were not significant changed at intracranial hypertension, pseudooedema cerebri, inflammation swelling, and at pseudotumour od the optic disc. A-AION and N-AION acallocated significant changes of the blood velocities and resistivity index. A-AION: significant increasing resistivity index at CRA, CPA, significant decrease of MSV and MDV and difficult mapping of the CPA in Color doppler mapping. At the fellow eye (without swollen optic disc) was significant decreasing of the blood velocities of the CRA, CPA, but not so much as at the defective eye with swollen optic nerve disk. N-AION: defective eye with swollen optic disc--there were: nonsignificant decreasing of MSV, MDV, significant decreasing of MSV, MDV and increasing of resistivity index of the CRA, CPA at the fellow eye. AO was without significant changes. Color Doppler information allowed to specify diagnosis of A-AION and N-AION.
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PMID:[Diagnosis of swollen optic disks using color Doppler ultrasonography] . 1105 37


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