Gene/Protein Disease Symptom Drug Enzyme Compound
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Rigorously developed clinical practice guidelines have the potential to improve patient outcomes. It is toward that end that the National Kidney Foundation (NKF) launched in March 1995 the Dialysis Outcome Quality Initiative (DOQI), an ambitious effort to develop evidence-based clinical practice guidelines for the care of patients with end-stage renal disease (ESRD). Independent, interdisciplinary work groups conducted a structured review of the content and methodologic rigor of all the published literature pertinent to four selected topics: hemodialysis adequacy, peritoneal dialysis adequacy, vascular access, and anemia. Following expert, organizational, and public review, the guidelines were issued in September and October 1997. An implementation plan that called for widespread dissemination of the guidelines and facilitation of adoption of them has resulted in their broad acceptance and Integration into quality improvement efforts. Additional guidelines on nutrition have recently been completed, while others on bone disease, hypertension, and hyperlipidemia are in various stages of planning or development. A major determinant of poor outcome of maintenance dialysis patients is the debilitated state of many individuals with ESRD at the time that they commence dialysis therapy. The recognition of this problem has stimulated an interest in extending the guidelines to management of patients with less severe renal insufficiency, well before they need renal replacement therapy; and to the early detection of renal insufficiency by a proteinuria and albuminuria risk assessment, detection, and elimination (PARADE) program. What started as an initiative to improve the quality of care of dialysis patients has evolved into a considerably expanded effort to making lives better for all individuals with any level of renal insufficiency.
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PMID:The dialysis outcomes quality initiative: history, impact, and prospects. 1076 3

For each individual, the genetic endowment at conception sets the limits on the capacity or metabolic function. The extent to which this capacity is achieved or constrained is determined by the environmental experience. The consequences of these experiences tend to be cumulative throughout life and express themselves phenotypically as achieved growth and body composition, hormonal status and the metabolic capacity for one or other function. At any time later in life the response to an environmental challenge, such as stress, infection or excess body weight is determined by an interaction amongst these factors. When the metabolic capacity to cope is exceeded, the limitation in function is exposed and expresses itself as overt disease. During early life and development the embryo, fetus and infant are relatively plastic in terms of metabolic function. The effect of any adverse environmental exposure is likely to be more marked than at later ages and the influence is more likely to exert a fundamental effect on the development of metabolic capacity. This has been characterised as "programming" and has come to be known as "the Barker hypothesis" or "the fetal origins hypothesis". Barker has shown that the size and shape of the infant at birth has considerable statistical power to predict the risk of chronic disease in later life. These relationships are graded and operate across a range of birth weight, which would generally be considered to be normal, and are not simply a feature of the extreme of growth retardation. The first evidence showed strong relations between birth weight and heart disease, the risk factors for heart disease, diabetes and hypertension, and the intermediary markers for heart disease, blood cholesterol and fibrinogen. Strong associations have also been found for bone disease, allergic disease and some aspects of brain function. In experimental studies in animals it is possible to reproduce all of the metabolic features predicted from this hypothesis by moderating the consumption of food, or its pattern during pregnancy, and determining metabolic behaviour in the offspring. It has been shown that aspects of maternal diet exert an influence on fetal growth, especially the dietary intake of carbohydrate, protein and some micronutrients. However, these relationships are less strong than might have been predicted, especially when compared with the associations which can be drawn with maternal shape, size and metabolic capacity. Maternal height, weight and body composition relate to the metabolic capacity of the mother and her ability to provide an environment in which the delivery of nutrients to the fetus is optimal. Current evidence suggests that the size of the mothers determines her ability to support protein synthesis, and that maternal protein synthesis, especially visceral protein synthesis, is very closely related to fetal growth and development. It is not clear the extent to which the effect of an adverse environment in utero can be reversed by improved conditions postnatally, but some care is needed in exploring this area, as the evidence suggests that "catch-up" growth imposes its own metabolic stress and may in itself exert a harmful effect.
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PMID:Nutrients, growth, and the development of programmed metabolic function. 1106 59

Many liver transplant recipients are now reaching survival beyond 5 years from the liver transplant procedure, and many others are alive more than a decade from acquiring their new liver. Orthotopic liver transplant recipients enjoy the benefits of normal liver function, but a variety of metabolic and other medical problems often develop that require diagnosis and adequate management. These problems include hyperlipidemia, obesity, diabetes mellitus, renal disfunction, arterial hypertension, bone disease and neuropsychiatric syndromes. The gastroenterologist, internist, or local family physician is frequently called on to identify and treat these postoperative complications in conjunction with physicians at the transplant center.
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PMID:Long-term care of the liver transplant recipient. 1123 68

Scurvy has been known since ancient times, but the discovery of the link between the dietary deficiency of ascorbic acid and scurvy has dramatically reduced its incidence over the past half-century. Sporadic reports of scurvy still occur, primarily in elderly, isolated individuals with alcoholism. The incidence of scurvy in the pediatric population is very uncommon, and it is usually seen in children with severely restricted diets attributable to psychiatric or developmental problems. The condition is characterized by perifollicular petechiae and bruising, gingival inflammation and bleeding, and, in children, bone disease. We describe a case of scurvy in a 9-year-old developmentally delayed girl who had a diet markedly deficient in vitamin C resulting from extremely limited food preferences. She presented with debilitating bone pain, inflammatory gingival disease, perifollicular hyperkeratosis, and purpura. Severe hypertension without another apparent secondary cause was also present, which has been previously undescribed. The signs of scurvy and hypertension resolved after treatment with vitamin C. The diagnosis of scurvy is made on clinical and radiographic grounds, and may be supported by finding reduced levels of vitamin C in serum or buffy-coat leukocytes. The response to vitamin C is dramatic. Clinicians should be aware of this potentially fatal but easily curable condition that is still occasionally encountered among children.
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PMID:An orange a day keeps the doctor away: scurvy in the year 2000. 1153 73

1. Forty percent of transplant centers expect the primary care physician to be the primary physician; 40% have both a primary care physician and a hepatologist manage the patient. 2. Transplant centers expect primary care physicians to provide general preventive medicine, physical examinations, vaccinations, and, rarely, management of hypertension, renal dysfunction, and diabetes. 3. A high percentage of primary care physicians feel comfortable caring and managing the overall health care of a long-term liver transplant patient. 4. Primary care physicians feel at most ease managing preventive care, annual physical examinations, hypertension, diabetes mellitus, hyperlipidemia, bone disease, and vaccinations. 5. Primary care physicians should be aware of the common medical conditions of the liver transplant patient of hypertension, diabetes, obesity, hyperlipidemia, and recurrent disease. 6. Common medical conditions for both the transplant centers and primary care physicians are hypertension, dyslipidemia, diabetes mellitus, malignancy, bone disease, pregnancy, vaccination, infectious prophylaxis, and headaches.
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PMID:Posttransplantation care: role of the primary care physician versus transplant center. 1168 71

The steady improvement in short-term success rates in renal transplant patients has translated into better long-term success rates and a large number of patients with long-functioning renal transplants. The necessity for the lifelong administration of immunosuppressive medications to prevent rejection, coupled with the presence in many patients of a variety of other medical problems dating from the period of renal insufficiency prior to the time of renal transplantation, has created a large group of patients with a unique and complex set of long-term medical care needs. Due to the constraints of managed care, considerations of geography, or patient preference, the long-term care of an increasing number of renal transplant recipients has shifted away from the transplant center to the community-based nephrologist or internist. For optimal care to be delivered, it is important that the physicians managing these patients be cognizant of the complex and interacting medical issues involved in their care. Appropriate management can significantly prolong the life of the allograft as well as that of the patient. Guidelines for understanding and managing some of the more important and common general medical problems facing the long-term renal transplant recipient (eg, infectious complications, cardiovascular disease, hypertension, diabetes, hyperlipidemia, malignancy, pregnancy, bone disease, dental care, preventive care) are addressed in this section.
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PMID:General health management and long-term care of the renal transplant recipient. 1172 2

It is estimated that there are greater than 100000 kidney transplant recipients with a functioning graft in the United States. Recent advances in immunosuppression have improved short-term graft survival rates and decreased early mortality by decreasing the incidence and therapy for acute rejection episodes. For those accepted on the waiting list, transplant prolongs patient survival compared with remaining on dialysis. During the 1990s, 3 new immunosuppressive drugs were introduced in clinical kidney transplantation. All were approved for use by the Food and Drug Administration after large, controlled, randomized trials. Mycophenolate mofetil (MMF), when combined with cyclosporine (CSA) and prednisone, lowered acute rejection rates by nearly 50% compared with control. Tacrolimus compared with CSA also significantly reduced acute rejection rates in kidney transplant recipients, but was associated with a significant increase in posttransplant diabetes mellitus (PTDM) in the early trials. When evaluated in combination with MMF, the incidence of PTDM was much lower. At the end of the decade, sirolimus was shown in several randomized trials to lower acute rejection rates and is believed to be less nephrotoxic compared with calcineurin inhibitors. All of the randomized trials were not statistically powered to assess long-term superiority. Registry analyses have been performed that appear to show some long-term benefit of immunosuppressive therapy with MMF. Other outcome assessments in kidney transplant recipients include risk factors for chronic allograft nephropathy, hypertension, hyperlipidemia, and bone disease. Although there are few randomized trials, understanding of the significance of these common complications has progressed and strategies for therapy and intervention have been developed. This article focuses on the randomized trials of immunosuppressive therapy and complications associated with use of these drugs. In addition, we review the current management and intervention for the comorbidities associated with the long-term clinical management of the kidney transplant recipient.
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PMID:Outcomes in kidney transplantation. 1283 99

The branch of medicine known as osteopathy was founded by Andrew Taylor Still in the mid to late 19th century. Osteopathy is a philosophy of medicine. Osteopathic physicians use techniques collectively referred to as osteopathic manipulative medicine (OMM). One of the most common diseases suffered by those residing in westernized nations is hypertension. Although osteopathic physicians are taught to incorporate OMM into the management of medical disorders, the usefulness of OMM in treating hypertension is less clear. This review reflects on the past 90 years of biomedical literature and attempts to address the utility of OMM used alone, or in combination with other treatments including antihypertensive medication, for the effective management of hypertension. Preliminary evidence may suggest a role for OMM in treating hypertension within the context of a multifaceted and long-lasting treatment regimen that may include traditional pharmacotherapeutics. To have universal acceptance, controlled and blinded outcome studies are needed to determine the effectiveness of OMM for the routine treatment of hypertension.
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PMID:Osteopathic manipulative medicine in the treatment of hypertension: an alternative, conventional approach. 1287 60

It is remarkable that phytoplankton and zooplankton have been producing vitamin D for more than 500 million years. The role of vitamin D in lower non-vertebrate life forms is not well understood. However, it is critically important that most vertebrates obtain an adequate source of vitamin D, either from exposure to sunlight or from their diet, in order to develop and maintain a healthy mineralized skeleton. Vitamin D deficiency is an unrecognized epidemic in most adults who are not exposed to adequate sunlight. This can precipitate and exacerbate osteoporosis and cause the painful bone disease osteomalacia. Once vitamin D is absorbed from the diet or made in the skin by the action of sunlight, it is metabolized in the liver to 25-hydroxyvitamin D [25(OH)D] and then in the kidney to 1,25-dihydroxyvitamin D [1,25(OH)2D]. 1,25(OH)2D interacts with its nuclear receptor (VDR) in the intestine and bone in order to maintain calcium homeostasis. The VDR is also present in a wide variety of other tissues. 1,25(OH)2D interacts with these receptors to have a multitude of important physiological effects. In addition, it is now recognized that many tissues, including colon, breast and prostate, have the enzymatic machinery to produce 1,25(OH)2D. The insights into the new biological functions of 1,25(OH)2D in regulating cell growth, modulating the immune system and modulating the renin-angiotensin system provides an explanation for why diminished sun exposure at higher latitudes is associated with increased risk of dying of many common cancers, developing type 1 diabetes and multiple sclerosis, and having a higher incidence of hypertension. Another calciotropic hormone that is also produced in the skin, parathyroid hormone-related peptide, is also a potent inhibitor of squamous cell proliferation. The use of agonists and antagonists for PTHrP has important clinical applications for the prevention and treatment of skin diseases and disorders of hair growth.
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PMID:Evolution and function of vitamin D. 1289 11

Liver transplantation is a standardized therapy for end-stage liver disease. With current immunosuppressive protocols and patient care, ten-year patient survival rate has reached 60%. Several medical complications may develop during this period, including renal dysfunction, hypertension, diabetes mellitus, hyperlipidemia, and metabolic bone disease. The aim of this article is to analyze long-term results of several clinical trials reporting common medical dysfunctions after liver transplantation and to discuss their management.
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PMID:Medical problems occurring during the long-term follow-up after liver transplantation. 1460 27


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