- Home
- A-Z Publications
- Annual Review of Medicine
- Previous Issues
- Volume 51, 2000
Annual Review of Medicine - Volume 51, 2000
Volume 51, 2000
- Review Articles
-
-
-
Inferior Vena Cava Interruption: How and When?
Vol. 51 (2000), pp. 1–15More LessInterruption of the inferior vena cava (IVC) to prevent pulmonary embolism arising from venous thrombi in the lower extremities has become widely used since IVC filters became available about 30 years ago. However, reliable data regarding efficacy and safety of IVC filters are still lacking. The first controlled clinical trial of IVC filters demonstrated their effectiveness, but filters had no detectable impact on mortality and were associated with an increased risk of recurrent deep venous thrombosis. On the basis of the literature, indications for IVC interruption can be classified as accepted, debated, and debatable. The relevance of debated indications, more accurate identification of patients who remain “very high-risk” despite preventive or curative anticoagulant treatment, and selection of the most appropriate filter should be looked at in prospective clinical studies.
-
-
-
-
Ductal Carcinoma In Situ of the Breast
Vol. 51 (2000), pp. 17–32More LessDuctal carcinoma in situ of the breast is a heterogeneous group of lesions with diverse malignant potential. It is the most rapidly growing subgroup in the breast cancer family; it is projected that more than 39,000 new cases will be diagnosed in the United States during 1999. Most new cases are nonpalpable and are discovered mammographically. Treatment is controversial and ranges from excision only, to excision with radiation therapy, to mastectomy. Genetic changes routinely precede morphologic evidence of malignant transformation. Medicine must learn how to recognize these genetic changes, exploit them, and in the future, prevent them.
-
-
-
Gene Therapy for Adenosine Deaminase Deficiency
Vol. 51 (2000), pp. 33–47More LessThe clinical gene therapy trials for adenosine deaminase (ADA) deficiency have defined both the potential benefits and the present limitations of gene therapy with hematopoietic stem cells (HSC). Current clinical results indicate that (a) both umbilical cord blood and neonatal bone marrow HSC can be transduced with murine retroviral-based vectors, (b) the transduced HSC can engraft in nonmyeloablated patients, (c) the frequency of HSC transduction/engraftment is low (1/10,000), (d) an in vivo selective advantage can exist for transduced T lymphoid progeny, and (e) the transduced ADA gene is not expressed in nondividing T lymphocytes. Improving the clinical results of gene therapy for ADA deficiency and other genetic diseases involving HSC will require (a) developing new vectors that express the transduced gene in nondividing cells and (b) increasing the frequency of stable HSC transduction.
-
-
-
Acupuncture: An Evidence-Based Review of the Clinical Literature
Vol. 51 (2000), pp. 49–63More LessThis chapter reviews the experimental literature on the effects of acupuncture treatment. The review covers the 14 medical conditions for which the National Institutes of Health Acupuncture Consensus Development Panel (NIHCDP) concluded that acupuncture either is effective (2 conditions) or may be useful (12 conditions). My conclusions partially support those of the NIHCDP. There is evidence that acupuncture is effective for the treatment of postoperative and chemotherapyinduced nausea and vomiting. Also, some data indicate that acupuncture may be useful for headache, low back pain, alcohol dependence, and paralysis resulting from stroke (4 of the 12 conditions for which the NIHCDP found that acupuncture may be useful). For most of the remaining conditions, there is little evidence that acupuncture is either effective or ineffective. It is recommended that workers in the field design double blind, sham controlled trials using adequate acupuncture treatment regimens, with specific hypotheses, and sample sizes sufficient to allow both positive and negative conclusions.
-
-
-
Role of Telomerase in Cell Senescence and Oncogenesis
Vol. 51 (2000), pp. 65–79More LessThe ends of linear chromosomes are capped by specialized nucleoprotein structures termed telomeres. Telomeres comprise tracts of noncoding hexanucleotide repeat sequences that, in combination with specific proteins, protect against degradation, rearrangement, and chromosomal fusion events. Due to the polarity of conventional DNA synthesis, a net loss of telomeric sequences occurs at each cell division. It has been proposed that this cumulative telomeric erosion is a limiting factor in replicative capacity and elicits a signal for the onset of cellular senescence. To proliferate beyond the senescent checkpoint, cells must restore telomere length. This can be achieved by telomerase, an enzyme with reverse-transcriptase activity. This enzyme is absent in differentiated somatic tissues, but telomerase reactivation has been detected in most tumors. Much investigative effort is focusing on telomere dynamics with a view to possible manipulation of cellular proliferative potential. In this article, we review the role of telomeres and telomerase in senescence and tumor progression, and we discuss the potential use of telomerase in diagnosis and treatment.
-
-
-
Coronary Artery Disease in the Transplanted Heart
M. Weis, and W. von ScheidtVol. 51 (2000), pp. 81–100More LessCoronary artery disease in the transplanted heart limits the long-term success of cardiac transplantation. Intravascular ultrasound studies reveal a dual morphology with donor-transmitted and de novo plaques. Coronary vasomotor dysfunction may occur independently of morphological alterations. The disease is characterized by the interaction of activated T lymphocytes with cytokines and donor epicardial and microvascular endothelium. Various noxious stimuli contribute to the continuing inflammatory response. Consequently, adhesion molecule expression is upregulated, leukocytes migrate into the allograft, thrombocytes accumulate, and growth factors are expressed, finally resulting in functional and morphological chronic allograft lesions. Blocking the activation of T cells, CD4+ cytokines, and adhesion molecules may prevent endothelial injury and subsequent intimal thickening. Strategies to decrease the formation of antiendothelial and anti-HLA-DR antibodies may also be protective, as may antiproliferative drugs, augmentation of endogenous nitric oxide bioactivity, and new immunosuppressive regimens. Revascularization procedures have a limited role in treating significant focal lesions. Retransplantation, the only definitive treatment, remains ethically controversial.
-
-
-
Measures of Success and Health-Related Quality of Life in Lower-Extremity Vascular Surgery
Vol. 51 (2000), pp. 101–113More Less▪ AbstractLower-extremity vascular surgery is most often indicated for patients with critical leg ischemia but has increasingly been used for patients with disabling intermittent claudication. This article reviews indications, follow-up protocols, and procedure-related outcomes including perioperative and late mortality, complications, and long-term patency rates, which vary with patient risk factors, vascular disease severity, and hospital volume. Population-based studies have yet to establish whether rates of limb-preserving bypass surgery are related to overall amputation rates, partly because of the continued high rate of primary amputation. The functional benefits of vascular surgery have been traditionally assessed by treadmill protocols and batteries of physical tests. Claudication treatment is increasingly being measured by both generic and disease-specific functional and health-related quality-of-life questionnaires. Patient self-reported measures of physical functioning and walking ability are reviewed. Finally, conclusions are presented about trends in lower-extremity bypass surgery rates.
-
-
-
New Horizons in the Treatment of Autoimmune Diseases: Immunoablation and Stem Cell Transplantation
Vol. 51 (2000), pp. 115–134More Less▪ AbstractThe prevalence of autoimmune diseases (ADs) in Western countries is estimated to be from 3–7%, and the treatment of severe, relapsing/refractory cases is still not satisfactory. The concept of utilizing intense immunosuppression followed by allogeneic or even autologous hemolymphopoietic stem cells (HSCs) to treat AD is based on encouraging results in experimental animals and from serendipitous cases of patients with both ADs and malignancies who were allotransplanted for the latter. However, rare unexpected relapses despite donor immune engraftment have been reported following HSC transplantation for AD. Autologous transplantation is a more feasible procedure with lower toxicity than allogeneic transplantation. This article analyzes the experimental basis for stem cell transplantation in AD and discusses the most important clinical results of both allogeneic and autologous HSC transplants.
-
-
-
The Surgical Treatment of Parkinson’s Disease
Vol. 51 (2000), pp. 135–147More Less▪ AbstractSurgical treatment of Parkinson’s disease (PD) can provide gratifying symptomatic improvements for many individuals who suffer from persistent disabling symptoms despite the best available medical management. Current surgical therapies include ablative techniques (thalamotomy and pallidotomy), augmentative techniques (nondestructive) (deep brain stimulation), and restorative techniques (tissue transplantation and gene therapy). Ablative procedures can provide substantial clinical benefit, but the current trend is toward deep brain stimulation, which can provide similar symptomatic improvement in a nondestructive manner. Restorative techniques, such as tissue transplantation and gene therapy, are exciting but have significant obstacles to overcome before their promise can be realized. Until the underlying pathological defect of PD can be identified and treated, surgical intervention is likely to remain important in the symptomatic treatment of this disabling disease.
-
-
-
Atherogenic Lipids and Endothelial Dysfunction: Mechanisms in the Genesis of Ischemic Syndromes
Vol. 51 (2000), pp. 149–167More Less▪ AbstractAtherogenic lipids, particularly oxidized low-density lipoprotein, are responsible for a wide range of cellular dysfunctions within the vessel wall. The effects on endothelial cells disrupt normal control of vasomotion, with a reduction of effective nitric oxide activity, the development of a procoagulant surface, chronic low-grade inflammation, and abnormal cell growth. These changes are central not only in the development of atherosclerosis but also in the evolution of both stable and unstable ischemic syndromes. There is growing evidence that these abnormal changes in cell function respond rapidly to changes in the atherogenic lipids. Certain cell functions can improve within hours or days of cholesterol lowering.
-
-
-
Management of Patients with Hereditary Hypercoagulable Disorders
C. Kearon, M. Crowther, and J. HirshVol. 51 (2000), pp. 169–185More Less▪ AbstractThe inherited hypercoagulable states can be divided into those that are common and associated with a modest risk of thrombosis (i.e. factor V Leiden and G20210A prothrombin gene) and those that are uncommon but asssociated with a high risk of thrombosis. There is no convincing evidence that, independent of other clinical factors, the presence of factor V Leiden or the prothrombin gene mutation should influence the use of primary prophylaxis or the duration of anticoagulant therapy following an episode of thrombosis. Indrect evidence sugests that the presence of antithrombin, protein C deficiency, or protein S deficiency justifies avoiding additional risk factors for thrombosis, such as estrogen therapy, and justifies use of more aggressive primary prophylaxis when additional risk factors cannot readily be avoided (e.g. pregnancy). The presence of one of these three abnormalities also favors more prolonged anticoagulant therapy following venous thrombosis. However, their presence or absence appears to have less influence on the risk of recurrent venous thromboembolism than whether thrombosis was provoked by a major reversible risk factor, such as surgery.
-
-
-
Neurocysticercosis: Updates on Epidemiology, Pathogenesis, Diagnosis, and Management
Vol. 51 (2000), pp. 187–206More Less▪ AbstractNeurocysticercosis is now recognized as a common cause of neurologic disease in developing countries and the United States. The pathogenesis and clinical manifestations vary with the site of infection and accompanying host response. Inactive infection should be treated symptomatically. Active parenchymal infection results from an inflammatory reaction to the degenerating cysticercus and will also respond to symptomatic treatment. Controlled trials have not demonstrated a clinical benefit for antiparasitic drugs. Ventricular neurocysticercosis often causes obstructive hydrocephalus. Surgical intervention, especially cerebrospinal fluid diversion, is the key to management of hydrocephalus. Shunt failure may be less frequent when patients are treated with prednisone and/or antiparasitic drugs. Subarachnoid cysticercosis is associated with arachnoiditis. The arachnoiditis may result in meningitis, vasculitis with stroke, or hydrocephalus. Patients should be treated with corticosteroids, antiparasitic drugs, and shunting if hydrocephalus is present.
-
-
-
Anti-Cytokine Therapy for Rheumatoid Arthritis
R. N. Maini, and P. C. TaylorVol. 51 (2000), pp. 207–229More Less▪ AbstractTumor necrosis factor α (TNFα) and interleukin-1 (IL-1) are important in mediating inflammation in rheumatoid arthritis (RA). Randomized phase II and III clinical trials of anti-TNF reagents (infliximab and etanercept) have demonstrated an acceptable safety profile and marked clinical efficacy in cases of RA that have not responded adequately to conventional therapy. Combination therapy with methotrexate (MTX) appears to be particularly effective in patients whose disease activity persists despite prior disease-modifying antirheumatic drugs (DMARDs) and ongoing MTX monotherapy. DMARD-recalcitrant disease may become the main indication for the use of anti-TNF drugs in patients with RA. Trials of IL-1 receptor antagonist show a relatively modest anti-inflammatory effect and a possible retardation of joint damage. Whether anti-TNF therapy protects joints from structural damage is under investigation. One anti-TNF reagent has already been approved in the United States for the treatment of RA, and other cytokine antagonists or agonists are under development.
-
-
-
Artificial Skin
Vol. 51 (2000), pp. 231–244More Less▪ AbstractThe skin is a complex organ that is difficult to replace when it is irreversibly damaged by burns, trauma, or disease. Although autologous skin transplantation remains the most common form of treatment in patients with significant skin loss, there are now a number of commercially available products that can be used to replace the skin temporarily or permanently. Here we describe several such products under the rubric “artificial skin,” focusing on two types of technology that have been applied to the problem of permanent skin replacement.
-
-
-
Age-Associated Increased Interleukin-6 Gene Expression, Late-Life Diseases, and Frailty
Vol. 51 (2000), pp. 245–270More LessInterleukin-6 (IL-6) is a proinflammatory cytokine that is normally tightly regulated and expressed at low levels, except during infection, trauma, or other stress. Among several factors that down-regulate IL-6 gene expression are estrogen and testosterone. After menopause or andropause, IL-6 levels are elevated, even in the absence of infection, trauma, or stress. IL-6 is a potent mediator of inflammatory processes, and it has been proposed that the age-associated increase in IL-6 accounts for certain of the phenotypic changes of advanced age, particularly those that resemble chronic inflammatory disease [decreased lean body mass, osteopenia, low-grade anemia, decreased serum albumin and cholesterol, and increased inflammatory proteins such as C-reactive protein (CRP) and serum amyloid A]. Furthermore, the age-associated rise in IL-6 has been linked to lymphoproliferative disorders, multiple myeloma, osteoporosis, and Alzheimer’s disease. This overview discusses the data relating IL-6 to age-associated diseases and to frailty. Like the syndrome of inappropriate antidiuretic hormone, it is possible that certain clinically important late-life changes are due to an inappropriate presence of IL-6.
-
-
-
Streptococcal Toxic Shock Syndrome Associated with Necrotizing Fasciitis
Vol. 51 (2000), pp. 271–288More LessStreptococcal toxic shock syndrome (strep TSS) with associated necrotizing fasciitis is a rapidly progressive process that kills 30–60% of patients in 72– 96 h. Violaceous bullae, hypotension, fever, and evidence of organ failure are late clinical manifestations. Thus, the challenge to clinicians is to make an early diagnosis and to intervene with aggressive fluid replacement, emergent surgical debridement, and general supportive measures. Superantigens such as pyrogenic exotoxin A interact with monocytes and T lymphocytes in unique ways, resulting in T-cell proliferation and watershed production of monokines (e.g. tumor necrosis factor α, interleukin 1, interleukin 6), and lymphokines (e.g. tumor necrosis factor β, interleukin 2, and gamma-interferon). Penicillin, though efficacious in mild Streptococcus pyogenes infection, is less effective in severe infections because of its short postantibiotic effect, inoculum effect, and reduced activity against stationary-phase organisms. Emerging treatments for strep TSS include clindamycin and intravenous gamma-globulin.
-
-
-
Role of Cytokines in the Pathogenesis of Inflammatory Bowel Disease
Vol. 51 (2000), pp. 289–298More LessRecent advances in the drug treatment of inflammatory bowel disease (IBD) have paralleled our understanding of the pathophysiology of ulcerative colitis and Crohn’s disease. Several proinflammatory and immune-regulatory cytokines are upregulated in the mucosa of patients with IBD, and differences and similarities in the cytokine profiles of ulcerative colitis and Crohn’s disease have been elucidated. Several clinical trials involving a chimeric anti-TNF-α (tumor necrosis factor-α) antibody have shown marked clinical benefit in the majority of patients with Crohn’s disease, verifying the importance of TNF-α in the pathogenesis of Crohn’s disease. In preliminary studies, treatment with recombinant human interleukin-10 has been beneficial in Crohn’s disease but not in ulcerative colitis. Future treatment of IBD may include combination or sequential cytokine and anticytokine administration in defined groups of patients based on their mucosal cytokine profiles.
-
-
-
Anorexia and Bulimia Nervosa
Vol. 51 (2000), pp. 299–313More Less▪ AbstractAnorexia nervosa (AN) and bulimia nervosa (BN) are disorders characterized by abnormal patterns of weight regulation and eating behavior and by disturbances in attitudes and perceptions toward weight and body shape. Etiologic research has indicated substantial genetic influence on these disorders, suggesting significant biological contributions to their development. Obsessional, perfectionistic, and anxious personality styles may be premorbid traits that contribute to this pathogenesis. Studies of neuroendocrine, neuropeptide, and neurotransmitter functioning in patients with AN and BN indicate that disturbances of these systems may contribute to the maintenance as well as the etiology of these sometimes fatal disorders. The efficacy of psychological treatments and pharmacotherapy has been more clearly established for BN than for AN.
-
-
-
The Role of Protein Traffic in the Progression of Renal Diseases
Vol. 51 (2000), pp. 315–327More LessProgression to irreversible renal parenchymal damage and end-stage renal disease is the final common pathway of chronic proteinuric nephropathies and is relatively independent of the type of initial insult. In animals, a reduction in nephron mass exposes the remaining nephrons to adaptive hemodynamic changes that are intended to sustain renal function but may be detrimental in the long term. High glomerular capillary pressure impairs glomerular permeability to proteins, which are then filtered in excessive quantities and reach the lumen of the proximal tubule. The secondary process of reabsorption of filtered proteins can contribute substantially to renal interstitial injury by activating intracellular events, including upregulation of vasoactive and inflammatory genes. The corresponding molecules formed in excessive amounts by the renal tubules cause an interstitial inflammatory reaction that normally precedes renal scarring and correlates with declining function. In several clinical studies, the increase in urinary protein excretion correlated with the tendency of the renal disease to progress more than it correlated with the underlying renal disease itself. Whenever urinary protein excretion is reduced, the decline in the glomerular filtration rate (GFR) slows or stops. Thus, to the extent that angiotensin-converting enzyme inhibitors lower the rate of urinary protein excretion, they effectively limit the progressive decline in GFR. If treatment is sufficiently prolonged, the GFR decline can be effectively halted or reversed, even in patients with remarkably severe disease, and remission is now achievable in some patients.
-
-
-
Carotid Artery Dissection
Vol. 51 (2000), pp. 329–347More LessAmong the large variety of cerebrovascular syndromes, carotid artery dissections remain often under-recognized. Many patients present with minor or transient symptoms, some with local pain only, and some are asymptomatic. A useful rule is that the coincidence of any local pain in neck or face with an ipsilateral Horner’s syndrome preceding transient or persistent retinal or cerebral ischemic symptoms should alert physicians—notably those treating emergencies—to rule out an underlying dissection of the ipsilateral carotid artery. In most cases the extracranial part of the carotid artery is affected; therefore, this review will focus on this main subgroup of patients. We review the pathological anatomy, as well as possible underlying causes, clinical features, diagnostic tools, differential diagnosis, treatment options, and outcome data.
-
-
-
Bacterial Vaginosis
Vol. 51 (2000), pp. 349–356More Less▪ AbstractBacterial vaginosis represents a unique upheaval of the complex vaginal bacterial flora with disappearance of lactobacilli and overgrowth of Gardnerella vaginalis and resident anaerobic vaginal bacteria. Little progress has occurred in identifying causal factors, although the pathophysiology of this syndrome is better understood. Although symptoms are easily recognizable, obstetric and gynecologic complications continue to increase in number. Bacterial vaginosis is far more than a nuisance infection. Problems with diagnosis continue to dominate clinical practice, although new tests have been introduced. Therapeutic options have increased, although recurrent disease remains common, and management of this common complication constitutes a major challenge.
-
-
-
Current Concepts in Cobalamin Deficiency
Vol. 51 (2000), pp. 357–375More LessThe application of sensitive metabolic tests, such as the deoxyuridine suppression test and measurement of homocysteine and methylmalonic acid, to cobalamin status has identified the entity of mild, preclinical cobalamin deficiency. This state, common in the elderly, responds to cobalamin therapy. Preclinical deficiency may exist within the nervous system as well, although this requires further study. Nevertheless, it is well to remember that not all low cobalamin levels and not all abnormal metabolite results reflect cobalamin deficiency. Interpretation of metabolic results still requires caution, as do proposals to raise the cut-off point for low cobalamin levels to capture some normal levels that are associated with metabolic abnormality. The recognition of mild, preclinical deficiency has opened up many important issues. These include identifying its causes, what should be done about it, and what the clinical impact of the hyperhomocysteinemia itself is. Although malabsorptive disorders, especially food-cobalamin malabsorption, underlie about half of all cases of preclinical deficiency, no cause can be found in the remainder of these cases; poor dietary intake appears to be uncommon. In addition, unusual states of neurologically symptomatic cobalamin deficiency are being recognized, such as nitrous oxide exposure in patients with unrecognized deficiency and severe deficiency in children of mildly deficient mothers. All of these have broadened and complicated the picture of cobalamin deficiency while providing greater opportunities for prevention.
-
-
-
Adjuvant Therapy for Breast Cancer
Vol. 51 (2000), pp. 377–392More LessSubstantial progress has been made in the diagnosis and management of primary breast cancer over the past three decades. As a result, mortality related to this disease has been decreasing gradually for several years, treatment has become more effective, and side effects and complications related to treatment have decreased. In this report, we review the state of adjuvant therapy for breast cancer.
-
-
-
Kidney Transplantation from Living Unrelated Donors
Vol. 51 (2000), pp. 393–406More LessKidney transplant candidates increasingly are looking to their relatives, spouses, and even friends for a better chance at transplantation. The wait for a cadaver kidney might be 2–5 years. Although kidneys from well-matched family members have been transplanted with excellent results for many years, accepting living donors who are genetically unrelated to the patient has not been encouraged until recently. Results show that, among 1700 patients who received kidney transplants from living unrelated donors in the United States from 1995 through 1998, the one- and projected ten-year graft survival rates were 92% and 67%, respectively. These results are superior to the 87% and 50% rates for more than 26,000 cadaver kidney transplants during the same period. Risks to the donor are low (<0.005% mortality and <0.3% serious complications) but not absent. Thus, motivated spouses, friends, and adopted or stepfamily members can play an important role in the rehabilitation of patients who need a kidney transplant.
-
-
-
Global Epidemiology of Influenza: Past and Present
N. J. Cox, and K. SubbaraoVol. 51 (2000), pp. 407–421More Less▪ AbstractPandemics are the most dramatic presentation of influenza. Three have occurred in the twentieth century: the 1918 H1N1 pandemic, the 1957 H2N2 pandemic, and the 1968 H3N2 pandemic. The tools of molecular epidemiology have been applied in an attempt to determine the origin of pandemic viruses and to understand what made them such successful pathogens. An excellent example of this avenue of research is the recent phylogenetic analysis of genes of the virus that caused the devastating 1918 pandemic. This analysis has been used to identify evolutionarily related influenza virus genes as a clue to the source of the pandemic of 1918. Molecular methods have been used to investigate the avian H5N1 and H9N2 influenza viruses that recently infected humans in Hong Kong. Antigenic, genetic, and epidemiologic analyses have also furthered our understanding of interpandemic influenza. Although many questions remain, advances of the past two decades have demonstrated that several widely held concepts concerning the global epidemiology of influenza were false.
-
-
-
The Spectrum of Human Herpesvirus 6 Infection: From Roseola Infantum to Adult Disease
Vol. 51 (2000), pp. 423–430More Less▪ AbstractHuman herpesvirus 6 is the causative agent of roseola infantum, a generally benign rash illness of infants. Most persons acquire HHV-6 infection by age 2 years, and HHV-6 infection is a common cause of fever and febrile seizures in infants. In adults, primary infection with HHV-6 can produce a mononucleosis-like illness and, more rarely, severe disease, including encephalitis. In addition to primary infections, HHV-6 can cause clinical illness during reactivation, particularly in immunocompromised persons.
-
-
-
Catheter Ablation for Atrial Fibrillation
Vol. 51 (2000), pp. 431–441More Less▪ AbstractAtrial fibrillation is frequently disabling and resistant to antiarrhythmic drugs. Curative treatment by catheter-based ablation has been shown to be feasible either by achieving long linear lesions, mainly in the left atrium, or by targeting the initiating focus, most frequently in the pulmonary veins. This paper reviews the different ablation approaches, their results, potential complications, and relative merits.
-
-
-
Genetic Disorders Affecting Proteins of Iron Metabolism: Clinical Implications
Vol. 51 (2000), pp. 443–464More Less▪ AbstractRemarkable progress is being made in understanding the molecular basis of disorders of human iron metabolism. Recent work has uncovered unanticipated relationships with the immune and nervous systems, intricate interconnections with copper metabolism, and striking homologies between yeast and human genes involved in the transport of transition metals. This review examines the clinical consequences of new insights into the pathophysiology of genetic abnormalities affecting iron metabolism. The proteins recently found to be involved in the absorption, transport, utilization, and storage of iron are briefly described, and the clinical manifestations of genetic disorders that affect these proteins are discussed. This chapter considers the most common inherited disorder in individuals of European ancestry (hereditary hemochromatosis), a widespread disease in sub-Saharan populations for which the genetic basis is still uncertain (African dietary iron overload), and several less frequent or rare disorders (juvenile hemochromatosis, atransferrinemia, aceruloplasminemia, hyperferritinemia with autosomal dominant congenital cataract, Friedreich’s ataxia, and X-linked sideroblastic anemia with ataxia).
-
-
-
Genetics of Psychiatric Disease
Vol. 51 (2000), pp. 465–479More Less▪ AbstractGenetic epidemiologic studies reveal that relatives of bipolar (BIP) probands are at increased risk for recurrent unipolar (RUP), BIP, and schizoaffective (SA) disorders, while relatives of schizophrenia (SZ) probands are at increased risk for SZ, SA, and RUP disorders. The overlap in familial risk may reflect shared genetic susceptibility. Recent genetic linkage studies have defined confirmed susceptibility loci for BIP disorder for multiple regions of the human genome, including 4p16, 12q24, 18p11.2, 18q22, 21q21, 22q11–13, and Xq26. Studies of SZ kindreds have yielded robust evidence for susceptibility at 18p11.2 and 22q11–13, both of which are implicated in susceptibility to BIP disorder. Similarly, confirmed SZ vulnerability loci have been mapped for 6p24, 8p and 13q32. Strong statistical evidence for a 13q32 BIP susceptibility locus has been reported. Thus, both family and molecular studies of these disorders suggest shared genetic susceptibility. These two group of disorders may not be so distinct as current nosology suggests.
-
-
-
The Marfan Syndrome
Vol. 51 (2000), pp. 481–510More Less▪ AbstractThe Marfan syndrome (MFS), initially described just over 100 years ago, was among the first conditions classified as a heritable disorder of connective tissue. MFS lies at one end of a phenotypic continuum, with people in the general population who have one or another of the features of MFS at the other end, and those with a variety of other conditions in between. Diagnosis of MFS and these other conditions remains based on clinical features. Mutations in FBN1, the gene that encodes fibrillin-1, are responsible for MFS and (in a few patients) other disorders in the continuum. In addition to skeletal, ocular, and cardiovascular features, patients with MFS have involvement of the skin, integument, lungs, and muscle tissue. Over the past 30 years, evolution of aggressive medical and surgical management of the cardiovascular problems, especially mitral valve prolapse, aortic dilatation, and aortic dissection, has resulted in considerable improvement in life expectancy.
-
-
-
Nonsteroidal Anti-Inflammatory Drugs and Cancer Prevention
Vol. 51 (2000), pp. 511–523More Less▪ AbstractNonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, appear to have clinically significant anticarcinogenic effects in the gastrointestinal tract. Epidemiological data indicate that use of these drugs is inversely associated with the risk of sporadic colorectal cancer, and clinical trials among patients with familial polyposis coli show that NSAIDs can lead to the regression of large bowel adenomas. Animal studies have reported a similar efficacy of NSAIDs against experimental carcinogenesis. A consistent pattern in this research is that continued long-term use of NSAIDs is required for an anticancer effect—up to 15 or 20 years before a reduced risk of colorectal cancer appears. Epidemiological data also suggest possible protective effects in the stomach and esophagus. The mechanisms underlying any chemopreventive effect of NSAIDs are not clear. Inhibition of cyclooxygenase is one possibility, but pathways independent of cyclooxygenase and prostaglandins are also possible.
-
-
-
Lymphatic Mapping and Sentinel Lymph Node Biopsy in Patients with Breast Cancer
Vol. 51 (2000), pp. 525–542More Less▪ AbstractThe standard of care for the evaluation of axillary nodal involvement remains complete lymph node dissection. Lymphatic mapping and sentinel lymph node (SLN) biopsy are changing this long-held paradigm; indeed, several leading institutions already reserve complete axillary dissection for patients with metastasis to the SLN. In addition to reviewing the literature, this chapter describes our lymphatic mapping experience at the H Lee Moffitt Cancer Center and Research Institute with 1147 breast cancer patients. Our results, in addition to a meta-analysis of data from 12 institutions comprising an additional 1842 patients undergoing complete axillary dissection, demonstrate that SLN biopsy is an accurate method of axillary staging. Although the results from small series may exaggerate the probability of false negative results, the risk of nodal disease based on tumor size and other risk factors should be evaluated when considering the results of SLN sampling.
-
-
-
The Genetics of the Amyloidoses
Vol. 51 (2000), pp. 543–569More Less▪ AbstractThe amyloidoses are diseases in which abnormalities in the secondary structure of precursor proteins result in decreased solubility under physiologic conditions, with subsequent organ compromise. A total of 18 proteins have been definitively identified as amyloid precursors associated with human disease. Mutations in the genes that encode some of these proteins produce autosomal dominant disease in mid to late adult life. Until recently, the late onset has obscured the familial nature of some of the disorders. This is especially true in the apparently sporadic diseaseproducing deposits found even later in life. In many instances, these deposits are derived from precursors encoded by wild-type genes (perhaps influenced by alleles that are polymorphic in the normal population); in other cases, they represent autosomal dominant disease with age-dependent penetrance. The genetic aspects of amyloid diseases produced by the deposition of four different proteins have been investigated in detail and provide insights into the particular diseases and amyloidogenesis in general.
-
Previous Volumes
-
Volume 75 (2024)
-
Volume 74 (2023)
-
Volume 73 (2022)
-
Volume 72 (2021)
-
Volume 71 (2020)
-
Volume 70 (2019)
-
Volume 69 (2018)
-
Volume 68 (2017)
-
Volume 67 (2016)
-
Volume 66 (2015)
-
Volume 65 (2014)
-
Volume 64 (2013)
-
Volume 63 (2012)
-
Volume 62 (2011)
-
Volume 61 (2010)
-
Volume 60 (2009)
-
Volume 59 (2008)
-
Volume 58 (2007)
-
Volume 57 (2006)
-
Volume 56 (2005)
-
Volume 55 (2004)
-
Volume 54 (2003)
-
Volume 53 (2002)
-
Volume 52 (2001)
-
Volume 51 (2000)
-
Volume 50 (1999)
-
Volume 49 (1998)
-
Volume 48 (1997)
-
Volume 47 (1996)
-
Volume 46 (1995)
-
Volume 45 (1994)
-
Volume 44 (1993)
-
Volume 43 (1992)
-
Volume 42 (1991)
-
Volume 41 (1990)
-
Volume 40 (1989)
-
Volume 39 (1988)
-
Volume 38 (1987)
-
Volume 37 (1986)
-
Volume 36 (1985)
-
Volume 35 (1984)
-
Volume 34 (1983)
-
Volume 33 (1982)
-
Volume 32 (1981)
-
Volume 31 (1980)
-
Volume 30 (1979)
-
Volume 29 (1978)
-
Volume 28 (1977)
-
Volume 27 (1976)
-
Volume 26 (1975)
-
Volume 25 (1974)
-
Volume 24 (1973)
-
Volume 23 (1972)
-
Volume 22 (1971)
-
Volume 21 (1970)
-
Volume 20 (1969)
-
Volume 19 (1968)
-
Volume 18 (1967)
-
Volume 17 (1966)
-
Volume 16 (1965)
-
Volume 15 (1964)
-
Volume 14 (1963)
-
Volume 13 (1962)
-
Volume 12 (1961)
-
Volume 11 (1960)
-
Volume 10 (1959)
-
Volume 9 (1958)
-
Volume 8 (1957)
-
Volume 7 (1956)
-
Volume 6 (1955)
-
Volume 5 (1954)
-
Volume 4 (1953)
-
Volume 3 (1952)
-
Volume 2 (1951)
-
Volume 1 (1950)
-
Volume 0 (1932)