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- Volume 52, 2001
Annual Review of Medicine - Volume 52, 2001
Volume 52, 2001
- Review Articles
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Mixed Chimerism and Transplantation Tolerance
Vol. 52 (2001), pp. 353–370More Less▪ AbstractAchieving transplanatation tolerance is an important goal in the effort to reduce long-term morbidity and mortality in organ transplant recipients. Robust, lifelong, donor-specific tolerance can be reliably achieved by induction of mixed chimerism in various animal models. To date, the clinical application of these proto-cols has been impeded partly by the potential toxicity of the required host conditioning regimens and the lack of successful studies in large animals. This article reviews the progress achieved in recent years in developing considerably milder conditioning protocols in rodents, and in extending some of these models to achieve permanent mixed chimerism and tolerance in large animals. Advances in the induction of xenogeneic tolerance through mixed chimerism are also discussed.
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Genetic Testing for Cancer Predisposition
Vol. 52 (2001), pp. 371–400More Less▪ AbstractClinical cancer genetics is becoming an integral part of the care of cancer patients. This review describes the clinical aspects, genetics, and clinical genetic management of most of the major hereditary cancer susceptibility syndromes. Multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and familial adenomatous polyposis are examples of syndromes for which genetic testing to identify at-risk family members is considered the standard of care. Genetic testing for these syndromes is sensitive and affordable, and it will change medical management. Cancer genetic counseling and testing is probably beneficial in other syndromes, such as the hereditary breast cancer syndromes, hereditary nonpolyposis colorectal cancer syndrome, Peutz-Jeghers syndrome, and juvenile polyposis. There are also hereditary cancer syndromes for which testing is not yet available and/or is unlikely to change medical management, including Li-Fraumeni syndrome and hereditary malignant melanoma. Thorough medical care requires the identification of families likely to have a hereditary cancer susceptibility syndrome for referral to cancer genetics professionals.
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Current Concepts in the Polycystic Ovary Syndrome
Vol. 52 (2001), pp. 401–419More Less▪ AbstractOver the past 20 years, it has been clearly documented that the polycystic ovary syndrome (PCOS) has major metabolic sequelae related to insulin resistance and that insulin resistance plays an important role in the pathogenesis of the reproductive disturbances of the disorder. Family studies have indicated a genetic susceptibility to PCOS. Polycystic ovaries and hyperandrogenemia are present in ∼50% of sisters of affected women. Increased androgen secretion and insulin resistance persist in cultured theca cells and skin fibroblasts, respectively, from women with PCOS; this finding suggests that these are intrinsic, presumably genetic, defects. Insulin resistance and elevated low-density lipoprotein (LDL) levels also cluster in the sisters of women with PCOS, consistent with genetic traits. Moreover, the brothers of women with PCOS have insulin resistance and elevated dehydroepiandrosterone sulfate (DHEAS) levels, which supports a genetic basis for these findings. Family-based studies of linkage and association have implicated several genes in the pathogenesis of PCOS. The strongest evidence to date points to a gene in the region of the insulin receptor. Insulin-sensitizing therapy mitigates the reproductive disturbances of PCOS.
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Renal Artery Stenosis: A Common, Treatable Cause of Renal Failure?
Vol. 52 (2001), pp. 421–442More Less▪ AbstractChronic azotemic renovascular disease is common in patients with atherosclerosis. Its prevalence appears to be increasing in the aging population. How often it is the primary cause of end-stage renal disease (ESRD) is not yet certain. Some studies suggest that 10%–40% of elderly hypertensive patients with newly documented ESRD and no demonstrable primary renal disease have significant renal artery stenosis (RAS). Atherosclerotic vascular occlusive disease of the renal arteries does progress, but current rates of progression and occlusion are lower than those reported a decade ago. Methods of identifying patients whose renal function is at true risk from vascular occlusive disease and determining who will benefit from intervention remain elusive. The presence of RAS in an azotemic patient can be assessed with noninvasive and risk-free radiologic techniques, including Duplex doppler velicometry and magnetic resonance angiography. Functional tests that predict the change in renal function after revascularization are not yet available. However, a renal length of greater than 7.5 cm in the absence of renal cysts and a short history of renal functional deterioration indicate a good prognosis. Patients with recent deterioration in renal function, those with bilateral renal artery stenosis or stenosis to a single functioning kidney, those with flash pulmonary edema, advanced chronic renal failure, or ESRD (who have much to gain), those with reversible azotemia during angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor antagonist (ARB) therapy, and those whose conditions cannot be managed medically should be considered for revascularization. Results from recent controlled clinical trials of the response to percutaneous transluminal renal artery angioplasty (PTRA) and stenting indicate that improvement in blood pressure control or renal function is not a predictable outcome of renal revascularization. In azotemic groups, 25%–30% of patients achieve important recovery of renal function. Thus, significant progress has been made recently in determining whether RAS is a frequent, treatable cause of renal failure. The decision to recommend revascularization remains a difficult balance between the risks and expense of the procedure and the undoubted benefits that accrue if renal function is successfully stabilized.
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Tissue Engineering: Current State and Prospects
Vol. 52 (2001), pp. 443–451More Less▪ AbstractOrgan shortage and suboptimal prosthetic or biological materials for repair or replacement of diseased or destroyed human organs and tissues are the main motivation for increasing research in the emerging field of tissue engineering. No organ or tissue is excluded from this multidisciplinary research field, which aims to provide vital tissues with the abilities to function, grow, repair, and remodel. There are several approaches to tissue engineering, including the use of cells, scaffolds, and the combination of the two. The most common approach is biodegradable or resorbable scaffolds configured to the shape of the new tissue (e.g. a heart valve). This scaffold is seeded with cells, potentially derived from either biopsies or stem cells. The seeded cells proliferate, organize, and produce cellular and extracellular matrix. During this matrix formation, the starter matrix is degraded, resorbed, or metabolized. First clinical trials using skin or cartilage substitutes are currently under way. Both the current state of the field and future prospects are discussed.
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Kaposi's Sarcoma–Associated Herpesvirus: A New DNA Tumor Virus
C. Boshoff, and Y. ChangVol. 52 (2001), pp. 453–470More Less▪ AbstractKaposi's sarcoma–associated herpesvirus (KSHV) is a newly identified gammaherpesvirus associated with all clinical forms of Kaposi's sarcoma (KS), body-cavity–based, primary effusion lymphomas (PELs), and a subset of Castleman's disease (CD). Sequence analysis of the KSHV genome demonstrates an extensive array of genes with homology to cellular genes involved in cell cycle regulation, cell proliferation, apoptosis, and immune modulation. Functional studies indicate that these genes may modify the host cell environment, contributing to the pathogenesis of KSHV-associated disorders. Several KSHV genes have been found to cause dysregulated cell proliferation or to interfere with established tumor suppressor pathways. The epidemiologic association of KSHV with malignancies and the coding features of its genome suggest that it is a new DNA tumor virus.
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Hereditary Distal Renal Tubular Acidosis: New Understandings
Vol. 52 (2001), pp. 471–484More Less▪ AbstractThe primary or hereditary form of distal renal tubular acidosis (dRTA), although rare, has received increased attention recently because of dramatic advances in the understanding of its genetic basis. The final regulation of renal acid excretion is effected by various acid/base transporters localized in specialized cells in the cortical collecting and outer medullary collecting tubules. Inherited defects in two of the key acid/base transporters involved in distal acidification, as well as mutations in the cytosolic carbonic anhydrase gene, can cause dRTA. The syndrome is inherited in both autosomal dominant and recessive patterns; patients with recessive dRTA present with either acute illness or growth failure at a young age, sometimes accompanied by deafness, whereas dominant dRTA is usually a milder disease and involves no hearing loss.
The AE1 gene encodes two Cl−/HCO3− exchangers that are expressed in the erythrocyte and in the acid-secreting intercalated cells of the kidney. AE1 contributes to urinary acidification by providing the major exit route for HCO3− across the basolateral membrane. Several mutations in the AE1 gene cosegregate with dominant dRTA. The modest degree of hypofunction exhibited in vitro by these mutations, however, does not explain the abnormal distal acidification phenotype. Other AE1 mutations have been linked to a recessive syndrome of dRTA and hemolytic anemia in which hypofunction can be discerned by in vitro studies. Several mutations in the carbonic anyhdrase II gene are associated with the autosomal recessive syndrome of osteopetrosis, renal tubular acidosis, and cerebral calcification. Some of these individuals present with deafness of the conductive type. By contrast, more recent studies have shown that mutations in ATP6B1, encoding the B-subtype unit of the apical H+ ATPase, are responsible for a group of patients with autosomal recessive dRTA associated with sensorineural deafness. Thus, the presence of deafness and the type provide an important clue to the genetic lesion underlying hereditary dRTA.
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Gene Transfer for Angiogenesis in Coronary Artery Disease
Vol. 52 (2001), pp. 485–502More Less▪ AbstractAngiogenesis is a promising novel therapeutic strategy to provide new venues for blood flow in patients with severe ischemic heart and peripheral vascular disease, who are not candidates for standard revascularization strategies. We describe the underlying mechanisms involved in physiologic and therapeutic angiogenesis, underscoring the relative importance of vasculogenesis, angiogenesis, and arteriogenesis. We then present the various gene transfer vectors including plasmid, viral, and cell-based vectors, and various delivery modalities. The available preclinical data are presented, followed by a description of preliminary clinical experience, with an emphasis on the preliminary nature of these results, which address safety and not efficacy. Finally, we discuss the promises and pitfalls of clinical angiogenesis and gene transfer studies, stressing the importance of proper design of clinical trials and adequate protection of research subjects.
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Atypical Antipsychotics: New Directions and New Challenges in the Treatment of Schizophrenia
Vol. 52 (2001), pp. 503–517More Less▪ Abstract“Atypical” antipsychotics represent a new generation of antipsychotics with a significantly lower incidence of extrapyramidal side effects (EPS), as well as little or no effect on prolactin elevation. These advantages constitute a major improvement in the treatment of patients with schizophrenia. The exact mechanisms that make these drugs atypical is not clear. However, a preferential action on serotonin 5-HT2 or D4 receptors, or a more rapid dissociation from the dopamine D2 receptor, may account for atypicality. Although the atypical antipsychotics have overcome EPS, other side effects such as weight gain and impaired glucose tolerance/lipid abnormalities have come to the fore. Thus, the challenges are far from over. The current atypicals are much more effective against the psychosis of schizophrenia than against the other, more enduring aspects of this disorder, e.g. negative symptoms and cognitive dysfunction. At present, the atypicals use a “pharmacological shotgun” strategy to treat aspects of the disease in all patients. A more sophisticated and perhaps effective approach to schizophrenia may lie in independently targeting the pathophysiological mechanisms of each clinical dimension (i.e. positive, negative, cognitive, and affective) with more selective drugs that can be combined and individually titrated to the needs of each patient.
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Previous Volumes
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Volume 76 (2025)
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Volume 75 (2024)
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Volume 74 (2023)
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Volume 73 (2022)
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Volume 72 (2021)
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Volume 71 (2020)
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Volume 70 (2019)
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Volume 69 (2018)
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Volume 68 (2017)
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Volume 67 (2016)
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Volume 66 (2015)
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Volume 65 (2014)
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Volume 64 (2013)
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Volume 63 (2012)
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Volume 62 (2011)
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Volume 61 (2010)
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Volume 60 (2009)
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Volume 59 (2008)
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Volume 58 (2007)
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Volume 57 (2006)
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Volume 56 (2005)
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Volume 55 (2004)
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Volume 54 (2003)
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Volume 53 (2002)
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Volume 52 (2001)
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Volume 51 (2000)
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Volume 50 (1999)
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Volume 49 (1998)
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Volume 48 (1997)
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Volume 47 (1996)
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Volume 46 (1995)
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Volume 45 (1994)
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Volume 44 (1993)
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Volume 43 (1992)
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Volume 42 (1991)
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Volume 41 (1990)
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Volume 40 (1989)
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Volume 39 (1988)
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Volume 38 (1987)
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Volume 37 (1986)
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Volume 36 (1985)
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Volume 35 (1984)
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Volume 34 (1983)
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Volume 33 (1982)
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Volume 32 (1981)
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Volume 31 (1980)
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Volume 30 (1979)
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Volume 29 (1978)
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Volume 28 (1977)
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Volume 27 (1976)
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Volume 26 (1975)
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Volume 25 (1974)
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Volume 24 (1973)
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Volume 23 (1972)
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Volume 22 (1971)
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Volume 21 (1970)
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Volume 20 (1969)
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Volume 19 (1968)
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Volume 18 (1967)
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Volume 17 (1966)
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Volume 16 (1965)
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Volume 15 (1964)
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Volume 14 (1963)
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Volume 13 (1962)
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Volume 12 (1961)
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Volume 11 (1960)
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Volume 10 (1959)
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Volume 9 (1958)
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Volume 8 (1957)
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Volume 7 (1956)
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Volume 6 (1955)
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Volume 5 (1954)
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Volume 4 (1953)
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Volume 3 (1952)
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Volume 2 (1951)
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Volume 1 (1950)
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Volume 0 (1932)