Gene/Protein Disease Symptom Drug Enzyme Compound
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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical aspects of FK-506 or cyclosporine immunosuppression regimens were evaluated in 48 consecutive pediatric renal transplant recipients. Tapering and discontinuation of prednisone was employed only in children receiving FK-506 who experienced minor or no rejection episodes during the 1st posttransplant month. At 1 year follow-up, 17 of 22 (77%) of all children with functioning allografts were receiving no prednisone (n = 13) or a mean dosage of 0.07 mg/kg per day (n = 4). During the 1st month, acute cellular rejection was more common in the FK-506 group (0.58 vs. 0.21 rejections per patient, P < 0.05) but allograft survival (92%) and renal function at 1 year posttransplant were identical in both groups. Compared with the cyclosporine regimen, FK-506 immunosuppression may be associated with a higher incidence of cytomegalovirus or reversible Epstein-Barr virus-induced lymphoproliferative disease. However, the FK-506 group had less hirsutism and gingival hypertrophy and required fewer antihypertensive medications independent of steroid use. Height standard deviation scores and weight-for-height index improved only in pre-adolescents receiving FK-506 but no prednisone (P < 0.02 and P < 0.05, respectively), but did not differ between children on FK-506 plus prednisone and those in the cyclosporine group. We conclude that the major advantages of FK-506 over cyclosporine immunosuppression are a reduced severity of hypertension and an improved cosmetic appearance which may improve long-term medical compliance. When used as monotherapy, FK-506 also shows promise in relieving the growth retardation associated with cyclosporine regimens that include prednisone.
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PMID:Comparison of FK-506 and cyclosporine regimens in pediatric renal transplantation. 1199 67

The application of lung transplantation to the pediatric population was a natural extension of the success realized in our adult transplantation program, which began in 1982. Twenty pediatric patients (age range 3 to 18 years) have had heart-lung (n = 11), double lung (n = 8), and single lung (n = 1) transplantation procedures. The causes of end-stage lung disease were primary pulmonary hypertension (n = 7), congenital heart disease (n = 5), cystic fibrosis (n = 4), pulmonary arteriovenous malformation (n = 2), graft-versus-host disease (n = 1), and desquamative interstitial pneumonitis (n = 1). Four (20%) patients had thoracic surgical procedures before the transplantation operation. The survival was 80% at a mean follow-up of 2 years. Immunosuppressive drugs included cyclosporine (n = 9) or FK 506 (n = 11) based therapy with azathioprine and steroids. Children were followed up by means of spirometry, transbronchial biopsy, and primed lymphocyte testing of bronchoalveolar lavage fluid. The mean number of treated episodes of rejection was 1.4 at 30 days, 0.5 at 30 to 90 days, and 1.4 at more than 90 days, and the first treated rejection episode occurred on average 28 days after the operation. Obliterative bronchiolitis developed in four (25%) of 16 patients surviving more than 100 days. Results of pulmonary function tests have remained good in almost all recipients. The greatest infectious risk was that of cytomegalovirus: one death and one case of pneumonia. Posttransplantation lymphoproliferative disease was diagnosed in two (12.5%) patients; both recovered. The most common complications were hypertension (25%) and postoperative bleeding (15%). Early results indicate that lung transplantation is a most promising therapy for children with severe vascular and parenchymal lung disease.
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PMID:Pediatric lung transplantation. The years 1985 to 1992 and the clinical trial of FK 506. 767 72

Children with cystic fibrosis represent the largest group referred for, and undergoing, heart-lung transplantation at our institute. Between June 1988 and July 1993, 76 patients were accepted for transplantation, of whom 25 were transplanted, while a further 36 died waiting. Those transplanted ranged from 5-18 years of age and included 13 males and 12 females. Organs were used from donors matched by ABO blood group, size and cytomegalovirus (CMV) status. Post-transplant maintenance immunosuppression comprised cyclosporin A, azathioprine and prednisolone. Anti-thymocyte globulin and high dose methylprednisolone were given peri-operatively and for acute rejection episodes. Actuarial survival was 67% at 1 year, 61% at 2 years and 54% at 3 years. Obliterative bronchiolitis (OB) has occurred in 13 patients (52%) and was the major cause of mortality and morbidity. In three patients, OB was associated with the development of tracheal anastomotic stenosis. Other complications included diabetes mellitus (n = 9), pancreatitis (n = 1) and hypertension (n = 8). Despite these problems, those surviving the first year post-transplant showed a mean FEV1 of 71% (compared to 29% pre-transplant) and enjoyed an overall improved quality of life.
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PMID:Results of heart-lung transplantation in children with cystic fibrosis. 772 39

A 58 year old woman developed systemic symptoms, interstitial lung disease, splenomegaly, leukopenia and anti-histone and anti-nuclear antibodies (ANA), while treated with hydralazine for hypertension. Five months after presentation she was admitted with high fever, skin rash and atypical lymphocytosis due to acute cytomegalovirus (CMV) infection. Worsening leukopenia and increased ANA were found, and high titres of anti-DNA antibodies, anti-cardiolipin antibodies and rheumatoid factors appeared. Hydralazine was stopped and the patient gradually became asymptomatic. All autoantibodies spontaneously disappeared (over 16 weeks), and the white cell count and spleen size became normal. The patient was found to be a slow acetylator and to have both HLA-DR4 and selective IgA deficiency. Thus, a multifactorial genetic susceptibility to develop drug-induced lupus was brought out in stages first by hydralazine and then by CMV, yet all manifestations and autoantibodies resolved spontaneously, demonstrating the complex interplay of varied environmental factors with a genetic predisposition in the pathogenesis of autoimmunity.
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PMID:Effect of acute cytomegalovirus infection on drug-induced SLE. 783 Nov 73

The patient referred for liver transplantation typically has complications from a progressive, irreversible liver injury. Less traditional complications of end-stage liver disease, such as bone disease and some hepatobiliary malignancies, may also prompt referral. However, there are contraindications to liver transplantation, such as metastatic malignancy and persistent substance abuse. Each patient should be referred as early as possible. The evaluation process includes a complete physical examination and social and psychologic evaluations. If transplantation is agreed upon, the patient is listed by clinical status and enters a waiting period for a donor liver. Following transplantation, the patient is maintained on a regimen of immunosuppressive drugs to prevent allograft rejection. Each patient is also maintained on prophylactic medications, to decrease the risk of opportunistic infection. Many of the postoperative problems in liver transplantation are a result of immunosuppression, either as side effects of the medications used to prevent and control rejection or from the intensity of the resulting immunosuppression. These problems include headaches, systemic hypertension, acute and chronic allograft rejection, renal dysfunction, opportunistic infection with cytomegalovirus or Pneumocystis carinii, disease recurrence, and neoplasia. Routine, long-term care includes systematic clinical follow-up and repetitive blood tests. Communication among the transplant center, the patient, and the referring physician are essential to a successful outcome over the long term.
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PMID:Primary care management of the liver transplant patient. 810 82

This study was designed to evaluate whether myocardial risk factors other than those strictly related to human immunodeficiency virus infection contribute to histologic cardiomyopathic changes in acquired immunodeficiency syndrome patients. We analyzed 91 consecutive adult human immunodeficiency virus-positive autopsy cases (85% acquired immunodeficiency syndrome by Centers of Disease Control criteria) from 1987-1991 for histologic cardiomyopathic changes (e.g. myocyte hypertrophy and myocardial fibrosis). We correlated the presence of cardiomyopathy with the following common myocardial risk factors: hypertension, coronary artery disease, alcoholism, diabetes mellitus, and valve disease. Forty percent of all cases had cardiomyopathy. Hypertension and coronary artery disease were both more common in the cardiomyopathy group (P < 0.05), compared with those human immunodeficiency virus-positive cases without cardiomyopathy. The other myocardial risk factors did not differ significantly between the two groups when compared individually, but when these data were pooled, 67% of cardiomyopathic patients had one or more myocardial risk factors versus 45% in the noncardiomyopathic group (P < 0.05). Cardiomyopathic patients were also more likely to have multiple myocardial risk factors (P < 0.05). Nineteen percent of cardiomyopathic patients had myocarditis versus 11% in the noncardiomyopathic group (P = NS). Patient age, gender, risk factors for human immunodeficiency virus infection (71% intravenous drugs), and history or autopsy findings of viral infection (e.g. cytomegalovirus) did not differ significantly between the two groups. In our patient population, which is heavily weighted towards intravenous drug use, myocardial risk factors other than human immunodeficiency virus are common, and appear to be major contributors to histologic cardiomyopathic changes that might otherwise be attributed to human immunodeficiency virus infection alone.
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PMID:Myocardial risk factors other than human immunodeficiency virus infection may contribute to histologic cardiomyopathic changes in acquired immune deficiency syndrome. 824 12

From 1986 to February 1993, 40 children aged 2 months to 18 years (average age 10.4 +/- 5.8 years) underwent heart transplantation. Indications for transplantation were idiopathic cardiomyopathy (52%), congenital heart disease (35%) with and without prior repair (71% and 29%, respectively), hypertrophic cardiomyopathy (5%), valvular heart disease (3%), and doxorubicin cardiomyopathy (5%). Patients were managed with cyclosporine and azathioprine. No prophylaxis with antilymphocyte globulin was used. Steroids were given to 39% of patients for refractory rejection, but weaning was always attempted and generally successful (64%). Five patients (14%) received maintenance steroids. Four patients died in the perioperative period and one died 4 months later. There have been no deaths related to rejection or infection. Average follow-up was 36 +/- 19 months (range 1 to 65 months). Cumulative survival is 88% at 5 years. In patients less than 7 years of age, rejection was monitored noninvasively. In the first postoperative month, 89% of patients were treated for rejection. Freedom from serious infections was 83% at 1 month and 65% at 1 year. Cytomegalovirus infections were treated successfully with ganciclovir in 11 patients. No impairment of growth was observed in children who underwent transplantation compared with a control population. Twenty-one patients (60%) have undergone annual catheterizations and no sign of graft atherosclerosis has been observed. Seizures occurred in five patients (14%) and hypertension was treated in 10 patients (28%). No patient was disabled and no lymphoproliferative disorder was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pediatric heart transplantation without chronic maintenance steroids. 831 43

Liver transplantation poses enormous and complex medical problems. Of the infective complications, bacterial infections are the commonest overall, but the single commonest is cytomegalovirus and the most deadly are the fungal infections. Therapeutic options and possibilities for prophylaxis are improving. Rejection, both acute and chronic, is the other major cause of mortality, and the balance between immunosuppression and infection is difficult. Cyclosporin treatment contributes to renal impairment, hypertension, and multitudinous potential neurological problems. The risk of long-term neoplasia is unclear. Relatively more minor is the potential for osteoporosis and metabolic complications, such as diabetes and hyperlipidaemia. Hepatitis B disease has a sizable risk of recurrence, but the most recent prophylaxis regimes have improved relapse rates. Having survived the physical problems following transplantation, most of which occur in the first 6 months, there are considerable psychosocial adjustments to be made particularly in the case of children where growth and development may have been delayed. Despite all these difficulties, liver transplantation is an expanding and optimistic area with enormous potential.
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PMID:Medical complications of liver transplantation. 833 63

Cardiac transplantation has become an established therapy for cardiomyopathy and other irreversible cardiac diseases. Improvements in immunosuppression and management of infections has improved long-term survival following transplantation. The role of the primary care physician in the care of recipients will be expanding. Transplant recipients receive close outpatient follow-up after discharge, primarily to monitor immunosuppression through laboratory evaluation and drug levels, monitor for rejection through endomyocardial biopsy, and to assess for any signs of opportunistic infection. The foundation for long-term immunosuppression is administration of cyclosporin, azathioprine and corticosteroids. Antibiotic prophylaxis is used to decrease the chance of infection with cytomegalovirus, Pneumocystis, Candida, Toxoplasma, and other opportunistic organisms. The major long-term complications include rejection, infection, hypertension, renal dysfunction, lipid abnormalities, and accelerated coronary atherosclerosis. This review provides an overview of the short- and long-term follow-up of the cardiac transplant recipient, including routine care as well as detection and management of the common complications.
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PMID:Long-term follow-up and complications after cardiac transplantation. 834 Jun 85

There is an inverse correlation between systemic blood pressure and urinary kallikrein levels in humans and hypertensive animal models, suggesting that the tissue kallikrein-kinin system plays an important role in blood pressure regulation. In this study, we explored the potential of human kallikrein gene delivery on blood pressure reduction in spontaneously hypertensive rats (SHR). The human tissue kallikrein gene or cDNA was placed under the control of following promoters: the metallothionein gene metal response-element (MRE-pHK), albumin gene (ALB-pHK), Rous sarcoma virus 3' long terminal repeat (LTR) (RSV-cHK), and cytomegalovirus (CMV-cHK). A single injection of these kallikrein DNAs results in a significant reduction of blood pressure in SHR, which lasts for 5-6 weeks. Systemic delivery of CMV-cHK, RSV-cHK, and MRE-pHK has a greater effect on blood pressure reduction than ALB-pHK, whereas intraportal vein gene delivery of ALB-pHK is more effective than the other kallikrein DNA constructs. The degree of blood pressure reduction depends on the amount of administered DNA and the age of the animals. Reduction of blood pressure was observed in adult, but not young, SHR. The expression of human tissue kallikrein in rats was identified by an ELISA that is specific for human tissue kallikrein. No antibodies to either human tissue kallikrein or its DNA were detected in rat sera after somatic gene delivery. These results show that somatic gene delivery of human tissue kallikrein causes a lowering effect of systolic blood pressure in genetically hypertensive rats and provide valuable information for kallikrein gene therapy in the treatment of hypertension.
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PMID:Systemic and portal vein delivery of human kallikrein gene reduces blood pressure in hypertensive rats. 872 4


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