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: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sirolimus was used as a single agent for maintenance immunosuppression in a pilot trial of 29 primary kidney transplant patients using lymphocyte depletion with Campath-1H as an induction strategy. This allowed sirolimus to be analyzed (dose, blood level, and side effect profile) in the absence of steroid and calcineurin inhibitors. A sirolimus dose of 4 mg/day resulted in blood levels in the 8 to 9 ng/mL range. Of the 29 patients, 8 patients (28%) had rejection. The sirolimus levels were not significantly different in patients with or without rejection. The cardiovascular risk profile in terms of lipid profile and hypertension control was favorable. Increase in cholesterol and triglyceride levels at one month (not statistically significant) necessitated treatment in 60% of patients with decline in levels by 6 and 12 months. Management of hypertension was also favorable with the majority of patients (55%) being on one hypertensive medication. Sirolimus monotherapy was well tolerated on the whole. Wound healing, leukopenia, and anemia were not significant problems. In conclusion, monotherapy has been well tolerated with a favorable side effect profile. However, a rejection rate of 28% was noted.
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PMID:Sirolimus monotherapy following Campath-1H induction. 1274 84

Sirolimus (rapamycin) is a macrocyclic lactone isolated from a strain of Streptomyces hygroscopicus that inhibits the mammalian target of rapamycin (mTOR)-mediated signal-transduction pathways, resulting in the arrest of cell cycle of various cell types, including T- and B-lymphocytes. Sirolimus has been demonstrated to prolong graft survival in various animal models of transplantation, ranging from rodents to primates for both heterotopic, as well as orthotopic organ grafting, bone marrow transplantation and islet cell grafting. In human clinical renal transplantation, sirolimus in combination with ciclosporin (cyclosporine) efficiently reduces the incidence of acute allograft rejection. Because of the synergistic effect of sirolimus on ciclosporin-induced nephrotoxicity, a prolonged combination of the two drugs inevitably leads to progressive irreversible renal allograft damage. Early elimination of calcineurin inhibitor therapy or complete avoidance of the latter by using sirolimus therapy is the optimal strategy for this drug. Prospective randomised phase II and III clinical studies have confirmed this approach, at least for recipients with a low to moderate immunological risk. For patients with a high immunological risk or recipients exposed to delayed graft function, sirolimus might not constitute the best therapeutic choice--despite its ability to enable calcineurin inhibitor sparing in the latter situation--because of its anti-proliferative effects on recovering renal tubular cells. Whether lower doses of sirolimus or a combination with a reduced dose of tacrolimus would be advantageous in these high risk situations remains to be determined. Clinically relevant adverse effects of sirolimus that require a specific therapeutic response or can potentially influence short- and long-term patient morbidity and mortality as well as graft survival include hypercholesterolaemia, hypertriglyceridaemia, infectious and non-infectious pneumonia, anaemia, lymphocele formation and impaired wound healing. These drug-related adverse effects are important determinants in the choice of a tailor-made immunosuppressive drug regimen that complies with the individual patient risk profile. Equally important in the latter decision is the lack of severe intrinsic nephrotoxicity associated with sirolimus and its advantageous effects on arterial hypertension, post-transplantation diabetes mellitus and esthetic changes induced by calcineurin inhibitors. Mild and transient thrombocytopenia, leukopenia, gastrointestinal adverse effects and mucosal ulcerations are all minor complications of sirolimus therapy that have less impact on the decision for choosing this drug as the basis for tailor-made immunosuppressive therapy. It is clear that sirolimus has gained a proper place in the present-day immunosuppressive armament used in renal transplantation and will contribute to the development of a tailor-made immunosuppressive therapy aimed at fulfilling the requirements outlined by the individual patient profile.
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PMID:Benefit-risk assessment of sirolimus in renal transplantation. 1569 Dec 25

Reversible leukoencephalopathy syndrome (RLS) is a rare brain disorder, characterized by diffuse attenuation of cerebral white matter, which has been most commonly observed in transplant patients receiving calcineurin inhibitors or in patients with severe hypertension. We report an episode of RLS in a 22-year-old male patient on chronic hemodialysis with well-controlled moderate hypertension who presented with de novo headache and generalized seizures. Cranial magnetic resonance image (MRI) revealed multiple areas of increased signal intensity in the white matter on T2-weighed images which resolved spontaneously at subsequent MRIs. White blood cell count showed leucopenia with normal CD4 count at flow cytometry. A viral etiology could not be demonstrated. Reversible leukoencephaolopathy syndrome symptoms remitted within 72 h but leukopenia persisted over 10 months. The patient received a kidney transplant 15 months after RLS onset and has received cyclosporine since the second post-transplant day. No recurrence of RLS symptoms has been observed. The etiology of the MRI changes in the present case seemed not to be either vasogenic or cytotoxic.
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PMID:Reversible leukoencephalopathy syndrome associated to leukopenia in a chronic hemodialysis patient. 1582 10

Sirolimus (SRL) is a new immunosuppressive drug approved for renal transplantation, but is being used increasingly in orthotopic liver transplantation (OLT). Compared with the calcineurin inhibitors, SRL has different mechanisms of action and side effects profile. Thus, this drug offers significant potential advantages over other immunosuppressive agents. SRL does not cause glucose intolerance, hypertension or renal failure, but it may cause dyslipidemia, hepatic artery thrombosis, thrombocytopenia, anemia, leukopenia, oral mucosa ulcers, edema, arthralgias and wound complications. SRL inhibits the signal of interleukin 2 at a post-receptor level, inhibiting lymphocyte proliferation and fibroblast proliferation. It also has antineoplastic and antifungal effects. We report a 10 years old girl who underwent OLT, experiencing a biopsy-proven recurrent acute rejection (AR) in spite of using three immunosuppressive agents (tacrolimus, mofetil micofenolate and steroids). She developed diabetes mellitus as a consequence of the immunosuppressive therapy. She was rescued with SRL, not experiencing AR again. Mofetil micofenolate, steroids and insulin could be discontinued and tacrolimus doses were reduced, without experiencing severe complications. SRL is a new and safe immunosuppressive agent for rescue in patients with OLT and recurrent AR.
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PMID:[Sirolimus for rescue of recurrent acute rejection and diabetes mellitus after liver transplantation: report of one case]. 1634 73

Streptococcus pneumoniae ( S. pneumoniae ) has been associated with hemolytic uremic syndrome (HUS), which is an unusual but serious disease in childhood. We conducted a retrospective review of children aged less than 18 years with S. pneumoniae -associated HUS in northern Taiwan from January 2000 to June 2005. The demographic characters, clinical courses, and outcomes were analyzed. Seven children (three girls, four boys) with S. pneumoniae -associated HUS were studied. The median age at onset of HUS was 40 months (range: 25-60 months). The median duration of hospital stay was 36 days (range: 15-50 days). The interval between the onset of illness attributable to S. pneumoniae and the development of HUS was around 1-2 weeks. The onset of oliguria developed within 2 weeks after illness. Six patients required dialysis with median duration of 16 days. Three patients had leukopenia as the initial presentation. All seven patients had pneumococcal pneumonia complicating with empyema, and two of them received decortication via video-assisted thoracoscopic surgery. Between patients who needed dialysis or not, there was no significant difference in age, sex, duration of thrombocytopenia, incidence of extra-renal complications, such as hepatitis, pancreatitis, and hypertension, and length of hospital stay. The seven patients survived with normal renal function. HUS is a potentially fatal complication of S. pneumoniae infection. Clinicians managing patients with pneumococcal pneumonia with empyema accompanied by leukopenia should beware of the development of HUS. The long-term prognosis for recovery of renal function appears to be good in these patients in northern Taiwan.
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PMID:Hemolytic uremic syndrome associated with pneumococcal pneumonia in Taiwan. 1650 93

The objective of this study is to evaluate the efficacy, toxicity, and long-term outcome of low-dose IV cyclophosphamid therapy with repeated frequent intervals in combination with oral and IV methylprednisolone in patients with SLE nephritis. In this study, 113 patients diagnosed as having SLE and glomerulonephritis were assessed in between 1993 and 2002, with a median follow-up of 44.1+/-41.2 months. The patients were treated with 500 mg IV cyclophosphamide and 1 g IV methylprednisolone together with 60 mg/alternate-day oral methylprednisolone in a given schedule. The clinical and laboratory data were evaluated. There were significant improvements in the clinical and the laboratory parameters. Six patients died shortly after being hospitalized due to the disease activity itself. Eight patients were excluded from the study because of low compliance. The renal functions of the patients remained stable throughout the therapy; only 16/99 patients needed one or two additional pulses. Temporary leukopenia developed in 18/99 patients and diminished with the suspension or prolongation of the IV cyclophosphamide administration. Gastrointestinal side effects, which needed extra medication, developed in 20 patients. Hematuria was observed in 6/99 patients. Menstrual abnormalities were seen in 7/99 patients. No serious infections due to immunosuppression were observed with the given regimen. Hypertension was observed in 13 patients (minimum of 140/90 mmHg, maximum of 190/110 mmHg) and controlled with angiotensine-converting enzyme inhibitors. Mild central obesity was observed in 15 of the patients. Leimyosarcoma was observed in one patient who died during the follow-up period. Therapy starting with the weekly low-dose IV cyclophosphamide to induce remission together with IV and oral steroids, followed by prolonged intervals with the same doses for 2 years, appears to be useful in preserving renal function without major side effects in patients with lupus nephritis, in comparison to other studies.
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PMID:Intensified, intermittent, low-dose intravenous cyclophosphamide together with oral alternate-day steroid therapy in lupus nephritis (long-term outcome). 1654 92

(1) The prognosis for metastatic colorectal cancer is grim. The best treatment results are obtained by adding irinotecan to first-line fluorouracil + folinic acid therapy and then oxaliplatin to second-line fluorouracil + folinic acid therapy (or the reverse sequence), but median survival time still fails to exceed 2 years. (2) Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor (VEGF), a mediator involved in angiogenesis. Bevacizumab is marketed in Europe for first-line treatment of metastatic colorectal cancer, in combination with fluorouracil + folinic acid (with or without irinotecan). (3) The clinical evaluation includes 3 comparative trials. A double-blind trial involving 813 patients compared the American IFL protocol (irinotecan + fluorouracil + folinic acid) + placebo with the IFL protocol + bevacizumab. Median survival time was shorter with IFL + placebo (15.6 versus 20.3 months), but the results are difficult to extrapolate to the situation in Europe, where the FOLFIRI protocol is used (irinotecan + fluorouracil + folinic acid). This protocol is more effective than the IFL protocol. (4) Another double-blind trial, involving 204 patients, compared another American protocol, fluorouracil + folinic acid + placebo, with fluorouracil + folinic acid + bevacizumab. Median survival time did not differ significantly between the groups (12.9 and 16.6 months). (5) A combined analysis of 3 comparative trials showed an increase in median survival time of 3.3 months (17.9 versus 14.6 months) when bevacizumab was added to a fluorouracil + folinic acid combination. An indirect comparison suggests that this is no better than adding irinotecan. (6) In second-line treatment, preliminary data from a trial of bevacizumab + FOLFOX 4 (oxaliplatin + fluorouracil + folinic acid) fail to show a tangible benefit for bevacizumab. (7) Bevacizumab adjunction to current chemotherapy protocols increased the frequency of some potentially serious reactions, such as cardiovascular disorders (hypertension, arterial thrombosis); tumour haemorrhage; intestinal perforation; wound healing; and haematological disorders (severe leukopenia, etc.). (8) In practice, there is no evidence that bevacizumab is any better than current European chemotherapy protocols for first-line treatment of metastatic colorectal cancer.
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PMID:Bevacizumab: new drug. Metastatic colorectal cancer: good in theory, not in practice. 1676 97

A retrospective study was performed in 68 patients diagnosed as having idiopathic nephrotic syndrome with steroid-dependent, steroid-resistant or frequent relapse subtypes at the Department of Pediatrics, Siriraj Hospital during Jan 1996-Dec 2004. Male to female ratio was 3.3:1 and mean age (+/- SD) was 8.4 +/- 3.5 years. Mean follow up time (+/- SD) was 47.4 +/- 30.5 months. Renal biopsy was done in 60 patients, showing IgM nephropathy in 73.3%. Fifty-four patients (79.4%) received cyclophosphamide at a dose (+/- SD) of 2.2 +/- 0.5 mg/kg/d for 11.6 +/- 3.4 weeks. Negative proteinuria at 1 year was found in 70% and prednisolone was discontinued in 52%. Leucopenia was found in 9.2%. At last follow up, 34% of the patients were still in remission. Enalapril was prescribed in 50 patients for 12.4 +/- 10.0 months. Thirty-six patients also received cyclophosphamide. Remission at 1 year was achieved in 66% and prednisolone discontinued in 28%. Twelve patients (24%) were still in remission at last follow up. The results of 3 regimens: cyclophosphamide, enalapril, and cyclophosphamide plus enalapril were compared using chi-square test. Remission was significantly better in cyclophosphamide group (p = 0.014). Dipyridamole was prescribed in 14 patients due to thrombocytosis. Only 2 of 14 patients achieved remission although 11 patients received cyclophosphamide plus enalapril, and another 2 patients received only cyclophosphamide. Complications included hypertension (44%), cataract (40%), glaucoma (15%), short stature (17.6%), and obesity (5.9%). Recurrent infection was found in 69%, including dental caries (16.29%), urinary tract infection (14.7%), intestinal parasitic infestration (10.3%), respiratory tract infection (8.8%), and skin infection (7.4%). Chronic renal failure was found in 3 patients and portal vein thrombosis was found in 1 patient. We suggest that cyclophosphamide should be used as first line drug in difficult-to-treat nephrotic syndrome patients. Enalapril may be beneficial in some patients. Thrombocytosis may be associated with poor response to both medications. Difficult-to-treat patients also need long-term follow up and surveillance for complications due to disease and/or treatment.
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PMID:Difficult-to-treat nephrotic syndrome: management and outcome. 1685 34

Systemic sclerosis (scleroderma) is a chronic debilitating disease that is caused by the occurrence of fibrotic changes and vascular abnormalities at various levels such as: skin, lungs, kidneys or heart. Lung involvement in scleroderma is represented by scleroderma interstitial lung disease and by pulmonary arterial hypertension, and is one of the leading causes of mortality in this disease. Pulmonary arterial hypertension can be successfully treated with specific therapies such as sildenafil, bosentan or epoprostenol, whereas only cyclophosphamide has been shown to be effective for interstitial lung disease. The discussed study has shown that cyclophosphamide improved lung function, functional status and health-related quality of life, and reduced dyspnea in scleroderma patients. Most of these patients had acute alveolitis although higher incidences of treatment-related leukopenia and neutropenia were also detected.
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PMID:Cyclophosphamide for scleroderma interstitial lung disease. Tashkin DP, Elashoff R, Clements PJ et al.: Cyclophosphamide versus placebo in scleroderma lung disease. N. Engl. J. Med. (2006) 354(25):2655-2666. 1679 Jun 98

Transfusion-related acute lung injury (TRALI) is defined as new acute lung injury (ALI) that occurs during or within six hours of transfusion, not explained by another ALl risk factor. Transfusion of part of one unit of any blood product can cause TRALI. The mechanism may include factors in unit(s) of blood, such as antibody and biologic response modifiers. In addition, yet to be described factors in a patient's illness may predispose to the condition. The current incidence is estimated to be 1 in 5000 units. Patients present with acute dyspnea, or froth in the endotracheal tube in intubated patients. Hypertension, hypotension, acute leukopenia have been described. Management is similar to that for ALI and is predominantly supportive. When TRALI is suspected, Blood banks should be notified to quarantine other components from the same donation. No special blood product is required for subsequent transfusion of a patient who has developed TRALI.
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PMID:TRALI--definition, mechanisms, incidence and clinical relevance. 1765 Jul 71


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