Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this 16-week trial was to determine the safety and efficacy of a step-care regimen of ramipril, an angiotensin converting enzyme inhibitor, from the minimal active dose (2.5 mg) in patients treated for mild to moderate hypertension. The trial was conducted by 102 general practitioners in 770 patients with mild to moderate hypertension. After a response rate to a 4-week placebo therapy of 9.1%, 57.0% of patients given active treatment with ramipril responded to daily doses of 2.5 mg. Ramipril 5 mg daily was effective in 55.6% of the remaining patients. There was no apparent statistically significant difference between the treatments with ramipril 10 mg or a combination of ramipril 5 mg + Lasix 20 mg daily (44.7% and 47.4% response respectively) in a 6-week double-blind arm of the study. In total, more than 90% of patients responded to treatment with ramipril by the end of the study. The incidence of adverse events was generally low, such as headache, cough, dizziness, asthenia, cramps and nausea. The incidence of cough appeared to be related both to the dosage of ramipril given and to outbreaks of influenza syndrome. Thirty-eight patients discontinued active treatment as a result of minor events such as cough, dizziness or diarrhoea, and one case each of myalgia and papular rash. There were no significant variations in laboratory parameters during the study, especially fasting blood glucose and apolipoprotein A1 and B. The results of this study provide evidence of the safety and efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The French multicentre study of ramipril in ambulatory patients with mild-to-moderate hypertension. 130 60

We report the case of a 61-year-old male who presented with a febrile illness accompanied by arthralgia and myalgia. Two months later he developed multiple subcutaneous nodules and enlarged parotid glands. Later two erythematous plaques, clinically compatible with erythema nodosum (EN), were observed. Laboratory investigations revealed abnormal levels of angiotensin converting enzyme and chest radiography showed bilateral hilar enlargement. The biopsy of the cutaneous lesions demonstrated multiple non-caseating granulomas in the subcutaneous tissue without any alterations in the epidermis and the dermis. The cultures for Mycobacteria and fungi were both negative. The clinical picture and histopathological findings were compatible with subcutaneous nodular sarcoidosis. The response to steroid treatment was satisfactory.
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PMID:Subcutaneous nodules as the first clinical manifestation of sarcoidosis. 145 Dec 99

The ideal antihypertensive drug should be effective in reducing blood pressure, but have a low incidence of adverse effects. Angiotensin II receptor blockers, such as eprosartan, are as effective as ACE inhibitors in reducing blood pressure, but lack the main adverse effect of ACE inhibitors, namely cough. Eprosartan has been shown to be well tolerated with a placebo-like adverse-effect profile. When given as monotherapy it is effective in reducing blood pressure; however, some patients require additional blood pressure control, which may be provided by combination therapy. Indeed, the combination of eprosartan and the thiazide diuretic hydrochlorothiazide has been shown to be effective in further reducing blood pressure in patients not optimally responding to eprosartan monotherapy. This article reviews the safety and tolerability of eprosartan in combination with hydrochlorothiazide from 17 studies of 1899 patients with hypertension and normotensive volunteers. Of these studies, four were controlled with patients receiving a fixed-dose combination, six were long-term, open-label, and another four were controlled studies with hydrochlorothiazide being given to eprosartan non-responders. The other three studies included healthy subjects receiving the combination of eprosartan and hydrochlorothiazide. There was a high completion rate in all studies evaluated. Most of the patients receiving eprosartan 600mg in combination with hydrochlorothiazide 12.5mg daily completed the studies, which supports acceptance of this combination therapy by patients. The most frequently reported adverse events in these combination studies were headache, dizziness, myalgia, and upper respiratory tract infection in patients with hypertension. The majority of adverse events were mild to moderate in intensity, and were not considered to be related to study treatment. The adverse event that was more common in patients receiving combination therapy compared with those receiving monotherapy was dizziness. This adverse event may be due to hydrochlorothiazide as it has previously been observed in patients taking thiazide diuretics. In healthy volunteers, the most frequently reported adverse events were headache, dizziness, and upper respiratory tract infection. However, none of these adverse events were considered related to study medication. In summary, the combination of eprosartan/hydrochlorothiazide is well tolerated, both as short- and long-term therapy, with most adverse events occurring early. The most frequent adverse events were headache, dizziness, and upper respiratory infection, which would be expected based on the safety profile of each of the components. Therefore, the combination of eprosartan with hydrochlorothiazide can be effectively and safely used in patients not adequately responding to eprosartan monotherapy.
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PMID:Safety and tolerability of eprosartan in combination with hydrochlorothiazide. 1211 44

From an association of nearly 50 years, the author had diagnosed biopsy proven 200 cases of sarcoidosis in Eastern India during the past three decades. It appears that most of these cases follow a distinct clinical pattern and presentation. The clinical course and prognosis differ considerably from that seen in Caucasians, Afro-Americans, South-African Bantus and Japanese. Males, above 40 years, coming largely from atopic and wealthier section of society (a particular business community with physicians, nurses with their families and other professionals). Patients present with constitutional symptoms (97%) like slow unrecognized fever with little malaise (fever-malaise dissociation in 70%), arthralgia (61%) or lone-myalgia (13%), appreciable loss of weight (33%), irritability, anorexia, respiratory symptoms (93%) like cough, dyspnea, etc., hepatomegaly (43.5%), splenomegaly (32.5%), lymphadenopathy (22%) with raised ESR (91%), hypergammaglobulinaemia (41.5%), hypercalciuria (40.5%), raised serum angiotensin converting enzyme (SACE) in 70.5% advance disease in chest radiograph (68%), positive 67-gallium scan and clinico-radiological dissociation in 81% (alarming looking chest radiograph with few physical signs). Course and prognosis also differ from the West. A different treatment schedule, avoiding oral prednisolone, has been found quite effective.
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PMID:Sarcoidosis: a journey through 50 years. 1243 38

Intermittent claudication (IC) is defined by leg muscle pain, cramping and fatigue brought on by ambulation/exercise; relieved on rest; and caused by inadequate blood supply and is the primary symptom of peripheral arterial disease (PAD). PAD has a detrimental effect on the quality of life. PAD is a debilitating atherosclerotic disease of the lower limbs and is associated with an increased risk of cardiovascular morbidity and mortality. IC is an extremely important marker of atheroma. Up to 60% patients with IC have significant underlying coronary and/or carotid disease and 40% of all patients suffering from IC die or suffer a stroke within 5 years of presentation. The therapeutic intervention of IC essentially aims at providing symptomatic relief and reducing the systemic cardiovascular complications. Although exercise therapy is one of the most efficacious conservative treatments for claudication, the pharmacotherapeutic goals can be best achieved through an increase in the walking capacity to improve quality of life and a decrease in rates of amputation. In the development of treatment for IC, an aggressive non-pharmacological intervention and pharmacological treatment of the risk factors associated with IC are considered. In the next 2 years, the results of major trials of drugs that stabilize and regress atherosclerosis such as statins and angiotensin converting enzyme inhibitors, and anti-platelet agents, recombinant growth factors and immune modulators will be available for IC. Levocarnitine (l-carnitine) and a derivative, propionyl levocarnitine, are emerging agents that increase the pain-free walking and improve the quality of life in IC patients by working at the metabolism and exercise performance of ischemic muscles. This article provides a comprehensive review of the pathophysiology involved, diagnosis of IC and existing and emerging pharmacotherapies with rationale for their use in its treatment.
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PMID:Intermittent claudication: an overview. 1638 60

A 75-year-old woman was admitted with a history of acute muscle weakness of her legs for two weeks. Physical examination showed no abnormal findings. Neurological examination revealed symmetrical proximal muscle weakness of legs with muscle pain on grasping. Laboratory data showed normal serum creatine kinase level and marked increases in the levels of serum ACE and soluble interleukin 2. Electromyography showed no myopathic changes. MRI T2 weighted imaging (T2WI) imaging for femoral skeletal muscle demonstrated scattered high and low intensity signals. Muscle biopsy from the right rectus femoris muscle showed granuloma with giant cells of Langhans. She was given a diagnosis of sarcoid myopathy, and motor weakness and abnormal intensity signals on T2WI in this patient were dramatically improved with oral administration of prednisolone (40 mg/day).
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PMID:[A case of elderly-onset sarcoid myopathy with features resembling polymyositis]. 1924 40

Since most lupus nephritis patients have an incomplete response to mycophenolate mofetil, combination regimens may improve outcomes. Tacrolimus (FK506) has shown some benefit in lupus nephritis in small trials, and combined with mycophenolate mofetil is standard immunosuppression in transplant patients. We investigate the addition of FK506 to mycophenolate mofetil, in patients who were mycophenolate mofetil failures. All patients were part of a prospective cohort, but evaluated retrospectively. Seven lupus nephritis patients (mean age 27.1, 100% female, 42% Caucasian and 42% African American) were evaluated. Three patients had combined ISN class III and V, two ISN class IV, one ISN class V and II and one ISN class IV and V. Six were taking an ACE-inhibitor or angiotensin receptor blocker, 6 hydroxychloroquine and 5 prednisone (mean dose 11.5 mg; range 0-30 mg). Mean mycophenolate mofetil dose at time of tacrolimus addition was 2.8 g (range 2-3 g). Mean tacrolimus dose was 3.4 mg (range 2-8 mg) titrated to a mean level of 4.67 ng/dl (range 2.2-11.8 ng/dl) for a mean of duration of 16 months (range 2-54 months). Two patients continued both therapies, while five discontinued therapy. One patient achieved a complete renal remission, while three achieved partial remission with 82.9%, 77.1%, 55.3% reductions in proteinuria. Toxicity limited the use of combination therapy: diabetic ketoacidosis (one patient), pneumonia (two) and muscle pain (two). These data suggest that adding tacrolimus in patients refractory to mycophenolate mofetil might have some benefit, although complete responses were rare. Unfortunately, tacrolimus toxicity appeared to be prevalent in these systemic lupus erythematosus patients, limiting its long term use.
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PMID:Combination therapy of mycophenolate mofetil and tacrolimus in lupus nephritis. 2038 22

The various types of glomerulonephritis, including many forms of vasculitis, are responsible for about 15% of cases of end-stage renal disease (ESRD). Arterial hypertension represents a frequent finding in patients suffering from glomerulonephritis or vasculitis and hypertension also serves as an indicator for these severe types of diseases. In addition, there are symptoms and signs like hematuria, proteinuria and renal failure. Especially, rapidly progressive glomerulonephritis (RPGN) constitutes a medical emergency and must not be missed by treating physicians. This disease can either occur limited to the kidneys or in the context of a systemic inflammatory disorder, like a vasculitis. If left untreated, RPGN can lead to a necrotizing destruction of glomeruli causing irreversible kidney damage within several months or even weeks. With respect to the immunologically caused vasculitis, there are - depending upon the severity and type of organ involved - many clinical warning signs to be recognized, such as arterial hypertension, hemoptysis, arthalgias, muscle pain, palpable purpura, hematuria, proteinuria and renal failure. In addition, constitutional signs, such as fever and loss of body weight may occur concurrently. Investigations of glomerulonephritis or vasculitis must contain a careful and complete examination of family history and medications used by the respective patient. Thereafter, a thorough clinical examination must follow, including skin, joints and measurement of arterial blood pressure. In addition, a spectrum of laboratory analyses is required in blood, such as full blood screen, erythrocyte sedimentation rate, CRP, creatinine, urea and glucose, and in urine, including urinalysis looking for hematuria, red cell casts and proteinuria. Importantly, proteinuria needs to be quantified by the utilization of a random urine sample. Proteinuria > 3g/d is diagnostic for a glomerular damage. These basic tests are usually followed by more specialized analyses, such as a screening for infections, including search for HIV, hepatitis B or C and various bacteria, and for systemic inflammatory diseases, including tests for antibodies, such as ANA, anti-dsDNA, ANCA, anti-GBM and anti-CCP. In cases of membranous nephropathy, antibodies against phospholipase-A2-receptor need to be looked for. Depending upon the given clinical circumstances and the type of disease, a reasonable tumor screening must be performed, especially in cases of membranous and minimal-change nephropathy. Finally, radiological examinations will complete the initial work-up. In most cases, at least an ultrasound of the kidney is mandatory. Thereafter, in most cases a renal biopsy is required to establish a firm diagnosis to define all treatment options and their chance of success. The elimination of a specific cause for a given glomerulonephritis or vasculitis, such as an infection, a malignancy or a drug-related side-effect, remains the key principle in the management of these diseases. ACE-inhibitors, angiotensin receptor-blockers, aldosteron antagonists and renin-inhibitors remain the mainstay in the therapy of arterial hypertension with proteinuria. Only in cases of persistently high proteinuria, ACE-inhibitors and angiotensin receptor blockers can be prescribed in combination. Certain types of glomerulonephritis and essentially all forms of vasculitis require some form of more specific anti-inflammatory therapy. Respective immunosuppressive drug regimens contain traditionally medications, such as glucocorticoids (e. g. prednisone), cyclosporine A, mycophenolate mofetil, cyclophosphamide, and azathioprine. With respect to more severe forms of glomerulonephritis and vasculitis, the antibody rituximab represents a new and less toxic alternative to cyclophosphamide. Finally, in certain special cases, like Goodpasture's syndrome or severe ANCA-positive vasculitis, a plasma exchange will be useful and even required.
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PMID:[Glomerulonephritis and vasculitis as causes of arterial hypertension]. 2254 60

This study was conducted to investigate the respiratory viruses and subtyping of influenza A virus when positive by multiplex PCR in patients with flu-like symptoms, after the pandemic caused by influenza A (H1N1)pdm09. Nasopharyngeal swab samples collected from 700 patients (313 female, 387 male; age range: 24 days-94 yrs, median age: 1 yr) between December 2010 - January 2013 with flu-like symptoms including fever, headache, sore throat, rhinitis, cough, myalgia as defined by the World Health Organization were included in the study. Nucleic acid extractions (Viral DNA/RNA Extraction Kit, iNtRON, South Korea) and cDNA synthesis (RevertAid First Strand cDNA Synthesis Kits, Fermentas, USA) were performed according to the manufacturer's protocol. Multiplex amplification of nucleic acids was performed using DPO (dual priming oligonucleotide) primers and RV5 ACE Screening Kit (Seegene, South Korea) in terms of the presence of influenza A (INF-A) virus, influenza B (INF-B) virus, respiratory syncytial virus (RSV), and the other respiratory viruses. PCR products were detected by automated polyacrylamide gel electrophoresis using Screen Tape multiple detection system. Specimens which were positive for viral nucleic acids have been further studied by using specific DPO primers, FluA ACE Subtyping and RV15 Screening (Seegene, South Korea) kits. Four INF-A virus subtypes [human H1 (hH1), human H3 (hH3), swine H1 (sH1), avian H5 (aH5)] and 11 other respiratory viruses [Adenovirus, parainfluenza virus (PIV) types 1-4, human bocavirus (HBoV), human metapneumovirus (HMPV), rhinovirus types A and B, human coronaviruses (HCoV) OC43, 229E/NL63] were investigated with those tests. In the study, 53.6% (375/700) of the patients were found to be infected with at least one virus and multiple respiratory virus infections were detected in 15.7% (59/375) of the positive cases, which were mostly (49/59, 83%) in pediatric patients. RSV and rhinovirus coinfections were the most prevalent (18/29, 62.7%) dual infections. The distribution of 436 respiratory viruses identified from 375 patients were as follows; 189 (43.3%) RSV, 93 (21.4%) rhinovirus, 86 (19.8%) INF-A, seven (1.6%) INF-B, 22 (5%) PIV types 1-3, 14 (3.2%) HMPV, 11 (2.5%) HCoV, nine (2%) HBoV, and five (1.2%) adenovirus. Fifty-five (64%) out of 86 INF-A viruses were subtyped as hH3, 24 (27.9%) were sH1 and seven (8.1%) were hH1. Avian H5 was not detected in any samples. The overall prevalence rates of INF-A, INF-B, RSV and other respiratory viruses were 12%, 1%, 27%, and 14.6%, respectively. RSV was the most prevalent respiratory agent in pediatric (161/313, 51%) cases, while INF-A virus in adult (24/62, 38.7%) patients. Influenza viruses were detected as responsible pathogens in 13.3% (93/700) of the patients with flu-like symptoms. Among the cases, a 1-month-old baby was infected with three virus strains (INF-A hH1+INF-A sH1+HCoV OC43) and a 82-year-old patient was infected with two INF-A virus subtypes (hH3 + sH1). INF-A viruses were mostly detected (79/86) in winter period, from December to March. INF-A virus sH1, was the most prevalent subtype in flu cases till February 2011 (22/86), after replaced by INF-A virus hH3. Beginning from February 2012, a significant increase observed in the cases infected with INF-A virus subtype hH3 (39/86). In conclusion, the identification and surveillance of influenza virus types and subtypes circulating in populations have importance both for epidemiological data and selection of vaccine strains.
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PMID:[Simultaneous detection of respiratory viruses and influenza A virus subtypes using multiplex PCR]. 2549 60

Due to the high prevalence of cardiovascular diseases and the corresponding prescription of cardiac drugs, side effects and interactions may occur in a substantial number of patients. They can be explained by either pharmacokinetic or pharmaco-dynamic drug interactions which may be desired, but may also be life-threatening. Despite the fact that the novel oral anticoagulants are well tolerated, several factors restricting the use of these drugs, such as renal failure, have to be considered. The use of antihypertensive drugs may be limited by concomitant use of drugs that either induce of inhibit enzymatic metabolism, respectively inhibit renal drug, electrolyte, and/or water excretion. In this respect, the interaction between beta-blockers, ACE inhibitors, angiotensin receptor blockers and thiazide diuretics with non-steroidal antiinflammatory drugs is especially important. Muscle disorders are frequent side effects in patients undergoing statin therapy and affect up to 5% of patients. They may manifest as mild myalgia, but also as life-threatening rhabdomyolysis.
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PMID:[Side effects and interactions of frequently used cardiovascular drugs]. 2665 14


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