- Home
- A-Z Publications
- Annual Review of Medicine
- Previous Issues
- Volume 48, 1997
Annual Review of Medicine - Volume 48, 1997
Volume 48, 1997
- Review Articles
-
-
-
THROMBOPOIETIN: UNDERSTANDING AND MANIPULATING PLATELET PRODUCTION
Vol. 48 (1997), pp. 1–11More Less▪ AbstractUntil recently, platelet production was the least understood aspect of blood cell development. This gap in our understanding resulted from the scarcity of megakaryocytes, the marrow precursor of blood platelets, and from confusion surrounding the cytokines and hormones that support their development. The recent cloning and characterization of thrombopoietin (TPO) has profoundly changed our udnerstanding of platelet production. Using in vitro assay systems, several groups have shown that TPO supports the proliferation of megakaryocytic progenitor cells and their differentiation into mature platelet-producing cells. Moreover, and somewhat surprisingly, TPO also acts in synergy with other pluripotent cytokines on the hematopoietic stem cell to augment development of erythroid and myeloid progenitors. These in vitro effects correlate well with the in vivo biology of the hormone. When administered to normal animals, TPO expands the numbers of hematopoietic progenitors of all lineages and greatly accelerates platelet production. Moreover, when TPO or its receptor is genetically eliminated, progenitor cell levels of all lineages are reduced, and platelet production is profoundly impaired. In animals administered cytoreductive therapy, the use of TPO is associated with accelerated hematopoietic recovery, not only of megakaryocytes and platelets, but also of erythrocytes and leukocytes. It, thus, is hoped that TPO may play an important role in reducing the myelosuppressive complications of naturally occurring and iatrogenic states of marrow failure.
-
-
-
-
BASIC DETERMINANTS OF MYOCARDIAL HYPERTROPHY: A Review of Molecular Mechanisms1
Vol. 48 (1997), pp. 13–23More Less▪ AbstractThe essential cardiac response to a fixed increase in hemodynamic load is an increase in cardiac mass. If the load increase is neither too severe initially nor indefinitely progressive, cardiac stress is renormalized, and compensated hypertrophy ensues. But hypertrophic compensation is often abrogated by progressively abnormal contractile performance per unit mass of myocardium, even when function at the organ level is maintained by the mass increase itself. That is, even when hypertrophy is appropriate to the load imposed, and in a manner analogous to dystrophic growth of skeletal muscle, specific phenotypic changes occurring during this growth response render compensation imperfect such that congestive heart failure ensues. This fact, and the fact that the presence of deleterious phenotypic changes in hypertrophied myocardium is critically dependent on the type of hemodynamic load imposed, mandates that cardiac hypertrophy be understood on the most basic level as a growth process if early, definitive interventions to prevent congestive heart failure following pathological hemodynamic overloads are to be realized.
-
-
-
INFECTIVE ENDOCARDITIS CAUSED BY HACEK MICROORGANISMS
Vol. 48 (1997), pp. 25–33More Less▪ AbstractThe HACEK group of fastidious gram-negative organisms is a recognized but unusual cause of infective endocarditis, responsible for approximately 3% of cases. We report our experience with 45 cases of endocarditis caused by HACEK organisms. In Olmsted County, Minnesota, the incidence of HACEK endocarditis was 0.14 per 100,000 person-years. In patients with native valves, 33 cases occurred, and in patients with prosthetic valves, 12 cases occurred. The most common presenting symptoms were fever, splenomegaly, new or changing murmur, and microvascular phenomena. Symptoms were present in the majority of patients anywhere from two weeks to six months prior to diagnosis. Blood cultures became positive in a mean of 3.375 days, and therapy with a beta-lactam alone or as part of a combination was given for anywhere between three and six weeks. Within the first month of diagnosis, surgery was performed for 13 regurgitant valves in 11 patients (24%). Echocardiography was an insensitive predictor of subsequent major arterial embolization (odds ratio, 1.33; 95% confidence interval, 0.31–5.67). The overall survival in our cohort of patients was 87%. These results confirm previous reports that HACEK endocarditis portends a favorable prognosis.
-
-
-
GENOMIC IMPRINTING: Nature and Clinical Relevance
Vol. 48 (1997), pp. 35–44More Less▪ AbstractMolecular genetic techniques allow investigators to trace chromosomes and genes from parent to child and, in a single individual, from tissue to tissue. These techniques have uncovered a new type of gene control in which the allele from one parent is expressed and the allele from the other parent is not. This differential expression is called genomic imprinting. It may lead to phenotypic differences when inheritance is from the mother versus the father. Genomic imprinting has been observed in a number of disorders having to do with growth, behavior, and abnormal cell growth. It is important to be aware that such a phenomenon exists and to consider it when making diagnoses and determining therapy.
-
-
-
ACTIVATED PROTEIN C RESISTANCE DUE TO A COMMON FACTOR V GENE MUTATION IS A MAJOR RISK FACTOR FOR VENOUS THROMBOSIS
Vol. 48 (1997), pp. 45–58More Less▪ AbstractInherited resistance to activated protein C (APC) was recently discovered to be a cause of familial thrombophilia and is now known to be the most common genetic risk factor for venous thrombosis. It is caused by a single point mutation in the gene for factor V, which predicts substitution of arginine (R) at position 506 with a glutamine (Q). Accordingly, the activated form of mutated factor V (FVa:Q506) is more slowly degraded by activated protein C than normal FVa (FVa:R506) is, resulting in hypercoagulability and a lifelong 5- to 10-fold increased risk of venous thrombosis. Previously known inherited hypercoagulable states, i.e. deficiencies of the anticoagulant proteins antithrombin III, protein S, and protein C, are found in fewer than 10–15% of thrombosis patients in western countries, whereas inherited APC resistance is present in 20–60% of such patients. The FV mutation is common in populations of Caucasian origin, with prevalences ranging from 1–15%, whereas it is not found in certain other ethnic groups such as Japanese and Chinese. The high prevalence of APC resistance, in combination with the availability of simple laboratory tests, will have a profound influence on the development of therapeutic and prophylactic regimens for thrombosis and will, it is hoped, result in a decreased incidence of thromboembolic events.
-
-
-
PARVOVIRUS B19 IN HUMAN DISEASE1
Vol. 48 (1997), pp. 59–67More Less▪ AbstractParvovirus B19, the only known human pathogenic parvovirus, is associated with a wide range of disease manifestations. In healthy individuals, the major presentation of B19 infection is erythema infectiosum. In patients with underlying hemolytic disorders, infection is the primary cause of transient aplastic crisis. In immunosuppressed patients, persistent infection may develop that presents as pure red cell aplasia and chronic anemia. In utero infection may result in hydrops fetalis or congenital anemia. Diagnosis is based on examination of bone marrow and virologic studies. Much is known of the pathophysiology of the virus, and studies are in progress to develop a vaccine to prevent this widespread infection.
-
-
-
CURRENT STATUS OF THE SURGICAL TREATMENT OF PATIENTS WITH CAROTID ARTERY DISEASE: The Surgical Management of Carotid Atherosclerosis
Vol. 48 (1997), pp. 69–77More Less▪ AbstractPatients with carotid atherosclerotic disease present with a history of a neurologic event or with the presence of a bruit on physical examination. Recently, large randomized prospective studies have examined this group of patients to determine the optimal course of medical and surgical management. The data from these studies, together with the natural history of carotid disease and factors associated with stroke risk, are reviewed.
-
-
-
LOW-MOLECULAR-WEIGHT HEPARIN: Prophylaxis and Treatment of Venous Thromboembolism
Vol. 48 (1997), pp. 79–91More Less▪ AbstractIntravenous heparin followed by warfarin has been the classical anticoagulant therapy of acute venous thromboembolism for the last 30 years. Furthermore, low-dose unfractionated heparin given two to three times daily has been the most popular form of prophylaxis for venous thrombosis. In recent years, a number of low-molecular-weight heparins have become available for clinical trials. These agents have many advantages over unfractionated heparin and are now being used widely internationally for the prevention and treatment of venous thromboembolism. Indeed, low-molecular-weight heparin will undoubtedly replace intravenous unfractionated heparin not only in the treatment of venous thromboembolism, but in other conditions where heparin therapy is indicated. Whether or not the low-molecular-weight heparins can decrease or eliminate some of the complications of unfractionated heparin will depend on the outcome of future clinical trials.
-
-
-
USE OF INTRAVENOUS IMMUNOGLOBULIN TO PREVENT OR TREAT INFECTIONS IN PERSONS WITH IMMUNE DEFICIENCY
Vol. 48 (1997), pp. 93–102More Less▪ AbstractIntravenous immunoglobulin (IVIG) concentrates were originally developed as replacement therapy for individuals with primary deficiencies of the immune system. However, in various well-designed, controlled clinical trials, the ability of IVIG to prevent and possibly treat infections in patients with secondary immune deficiencies has also been considered. In this review, we briefly consider these different applications and suggest whether the data are sufficient to employ IVIG in these clinical settings.
-
-
-
BETA-ADRENERGIC BLOCKING AGENTS IN THE TREATMENT OF CONGESTIVE HEART FAILURE: Mechanisms and Clinical Results
Vol. 48 (1997), pp. 103–114More Less▪ AbstractCongestive heart failure is a major public health problem in Western countries. Despite current treatment including angiotensin converting enzyme inhibitors, mortality and morbidity remain high. The sympathetic nervous system is markedly activated in heart failure, and inhibition of this system with the beta-adrenergic blocking agents may provide further benefit. Several clinical trials involving over 3000 patients have shown that beta-blocker therapy improves left ventricular function in patients with heart failure. However, the effects of such therapy on symptoms and exercise tolerance have been variable. Recent reports have suggested that survival is improved with the beta-blocker carvedilol. Large-scale, long-term clinical trials are required to confirm these findings and to clearly define the role of this promising therapy for patients with heart failure.
-
-
-
HYPERTENSION IN PREGNANCY: Current Concepts of Preeclampsia
Vol. 48 (1997), pp. 115–127More Less▪ AbstractHypertensive disorders (gestational hypertension, preeclampsia, chronic hypertension, superimposed preeclampsia) are the most common medical complications of pregnancy and constitute a major cause of maternal and perinatal morbidity and mortality. Prediction of those women destined to develop preeclampsia remains elusive. The benefits of calcium supplementation for prevention of preeclampsia are encouraging; however, the definitive study is not yet complete. Aspirin therapy for low-risk women has not been helpful; results of therapy for high-risk women are pending. More experience is being gained with antihypertensive therapy and expectant management in severe preeclampsia. Conservative management of severe preeclampsia, when performed in a tertiary care center, may benefit a select group of women and their fetuses.
-
-
-
RU486 (MIFEPRISTONE): Mechanisms of Action and Clinical Uses
Vol. 48 (1997), pp. 129–156More Less▪ AbstractRU486 (mifepristone) has proved to be a remarkably active antiprogesterone and antiglucocorticosteroid agent in human beings. The mechanism of action involves the intracellular receptors of the antagonized hormones (progesterone and glucocorticosteroids). At the molecular level, the most important features are high binding affinity to the receptor, interaction of the phenylaminodimethyl group in the 11β-position with a specific region of the receptor binding pocket, and RU486-induced transconformation differences in the ligand-binding domain. These particularities have consequences at different steps of the receptor function as compared with agonists. However, the reasoning cannot be limited to the RU486-receptor interaction, and, for instance, there is the possibility of a switch from antagonistic property to agonist activity, depending on the intervention of other signaling pathways. It would be desirable to have derivatives with only one of the two antagonistic properties (antiprogestin, antiglucocorticosteroid) in spite of similarities between steroid structures, receptors involved, and responsive machineries in target cells. Clinically, the RU486-plus-prostaglandin method is ready to be used on a large scale and is close to being as convenient and safe as any medical method of abortion may be. The early use of RU486 as a contragestive as soon as a woman fears a pregnancy she does not want will help to defuse the abortion issue. Research should now be conducted to define an efficient and convenient contraceptive method with RU486 or other antiprogestins. The usefulness of RU486 for obstetric indications, including facilitation of difficult delivery, has to be assessed rapidly. Gynecologic trials, particularly in leiomyomata, should also be systematically continued. The very preliminary results obtained with tumors, including breast cancers, indicate that further studies are necessary.
-
-
-
PARANEOPLASTIC SYNDROMES AFFECTING THE CENTRAL NERVOUS SYSTEM
Vol. 48 (1997), pp. 157–166More Less▪ AbstractParaneoplastic syndromes affecting the nervous system are rare neurologic syndromes caused by cancer but not ascribable to metastases. Any portion of the nervous system may be involved in a paraneoplastic syndrome. The pathogenesis of these disorders appears to be an immune reaction against antigens shared by the cancer and the nervous system. Some disorders, such as the Lambert-Eaton myasthenic syndrome, are effectively treated by removal of autoantibodies directed against the presynaptic cholinergic synapse. In other disorders, such as paraneoplastic cerebellar degeneration or paraneoplastic sensory neuronopathy, neither removal of the autoantibody nor treatment of the cancer is effective.
-
-
-
BONE DISEASE IN MODERATE RENAL FAILURE: Cause, Nature, and Prevention
Vol. 48 (1997), pp. 167–176More Less▪ AbstractThere are two primary types of bone disorders observed in patients with end-stage renal disease: a high-turnover osteodystrophy characterized by osteitis fibrosa, and a low-turnover osteodystrophy characterized initially by osteomalacia and, more recently, by adynamic or aplastic bone disease. This article reviews the clinical presentation, pathogenesis, and laboratory findings of patients with these two disorders. It discusses the important roles of phosphorus binding, vitamin D administration, and correction of acidosis in prevention and treatment of bone disease in patients with moderate renal insufficiency.
-
-
-
MANAGEMENT OF BENIGN PROSTATIC HYPERPLASIA
Vol. 48 (1997), pp. 177–189More Less▪ AbstractBenign prostatic hyperplasia (BPH) is a common cause of morbidity among older men. Primary care physicians need to develop expertise in its management. The causes of BPH are unknown; aging and the presence of male androgens are the dominant risk factors. Obtaining a medical history is a key step in assessing whether lower urinary tract symptoms are due to BPH or to some other process. A reliable and valid seven-item questionnaire has been developed to objectively assess symptom severity. A focused physical examination including a digital rectal exam should be performed, as well as a urinalysis and serum creatinine. Optional tests include uroflowmetry, post-void residual urine, and prostate-specific antigen measurements. BPH is treated primarily to improve the quality, rather than increase the quantity, of life. Optimal decisions about treatment are best made by a clinician and an informed patient working together.
-
-
-
ADJUVANT TREATMENT OF COLORECTAL CANCER
Vol. 48 (1997), pp. 191–202More Less▪ AbstractThe adjuvant therapy of colorectal cancer has seen many important advances in recent years. Chemotherapy improves long-term disease-free survival rates in high-risk patients with resected colon cancer. Combined modality therapy, using surgery, radiation therapy, and chemotherapy, improves both local control and survival in patients with stage II and III rectal cancer. We examine in detail the data on which current recommendations for adjuvant treatments are based. We also review some of the more promising experimental approaches currently under investigation.
-
-
-
TOWARD CYSTIC FIBROSIS GENE THERAPY
Vol. 48 (1997), pp. 203–216More Less▪ AbstractCystic fibrosis (CF) is a common genetic disorder characterized by defective epithelial chloride transport and progressive lung disease. Although great strides have been made in the treatment of CF, it remains lethal, often by early adulthood. CF is one of the most extensively researched genetic diseases as a target for gene therapy development. It may also serve as an important model for gene therapy of other diseases. Preclinical and clinical research has lead to the rapid development of a variety of vectors designed to correct the basic defect in CF, including adenovirus, adeno-associated virus, and liposomes. Clinical studies have identified the host immune response and low vector efficiency as key impediments to effective CF gene therapy. Further research promises to refine vector technology and bring CF gene therapy to the bedside.
-
-
-
NEUROPSYCHIATRIC CONSEQUENCES OF STROKE
Vol. 48 (1997), pp. 217–229More Less▪ AbstractNumerous emotional and behavioral disorders occur following cerebrovascular lesions. Depression is the most common of these, affecting up to 40% of patients. Clinical correlates of post-stroke depression include severity of physical and cognitive impairment as well as location of brain injury. Perhaps the most compelling reason to identify post-stroke depression, however, is its substantial impact on recovery in activities of daily living, cognitive function, and survival. Antidepressant medication has been shown to effectively treat depression, although its administration may require careful clinical monitoring. Other post-stroke emotional/behavioral disorders include mania, bipolar disorder, anxiety disorder, apathy, and pathological crying. Controlled studies have not documented the effect of these disorders on long-term recovery, but the potential impact of syndromes such as mania and apathy on rehabilitation efforts or pathological crying on social functioning are evident. With the exception of pathological crying, which has been shown to respond to antidepressant drug therapy, the other post-stroke emotional/behavioral disorders need to be evaluated in controlled treatment trials for response to therapy.
-
-
-
GLUCOCORTICOID AND MINERALOCORTICOID RECEPTORS: Biology and Clinical Relevance
Vol. 48 (1997), pp. 231–240More Less▪ AbstractMineralocorticoid and glucocorticoid receptors act as homodimers via canonical pentadecamer hormone response elements to regulate transcription. Glucocorticoid, but as yet not mineralocorticoid, receptors have been shown also to modulate AP-1- and NFκB-induced transcription by direct protein-protein interactions. The role of 11β-hydroxysteroid dehydrogenase in conferring aldosterone specificity on epithelial mineralocorticoid receptors has been proven by the demonstration of sequence mutations in all cases of apparent mineralocorticoid excess examined to date. The autosomal form of aldosterone resistance (pseudohypoaldosteronism) has been shown to reflect loss-of-function mutations in epithelial sodium channel subunit sequence. (Patho)physiological roles for aldosterone and glucocorticoid membrane receptors, and for the recently described nuclear receptors for 11–ketosteroids in 11β–hydroxysteroid dehydrogenase–protected epithelia, remain to be established.
-
-
-
PERIPHERAL BLOOD STEM CELLS FOR AUTOGRAFTING
Vol. 48 (1997), pp. 241–251More Less▪ AbstractHigh-dose therapy with autologous hematopoietic progenitor cell support is effective treatment for patients with a variety of high-risk malignancies. Accelerating of marrow recovery from near-lethal or lethal toxicity with hematopoietic cell support improves the safety and cost effectiveness of the high-dose regimens. Peripheral blood progenitor cells will soon replace marrow as the major source of hematopoietic support. This chapter reviews the techniques of peripheral blood progenitor cell collection, mobilization, purification (for tumor removal), and ex vivo expansion.
-
-
-
CIRCADIAN RHYTHMS: Basic Neurobiology and Clinical Applications
Vol. 48 (1997), pp. 253–266More Less▪ AbstractCircadian rhythms are major features of adaptation to our environment. In mammals, circadian rhythms are generated and regulated by a circadian timing system. This system consists of entrainment pathways, pacemakers, and pacemaker output to effector systems that are under circadian control. The primary entrainment pathway is the retinohypothalamic tract, which terminates in the circadian pacemakers, the suprachiasmatic nuclei of the hypothalamus. The output of the suprachiasmatic nuclei is principally to the hypothalamus, the midline thalamus, and the basal forebrain. This provides a temporal organization to the sleep-wake cycle, to many physiological and endocrine functions, and to psychomotor performance functions. Disorders of circadian timing primarily affect entrainment and pacemaker functions. The pineal hormone, melatonin, appears to be a promising agent for therapy of some circadian timing disorders.
-
-
-
APOPTOSIS AND DISEASE: Regulation and Clinical Relevance of Programmed Cell Death
Vol. 48 (1997), pp. 267–281More Less▪ AbstractRegulation of the homeostatic balance between cell proliferation and cell death is essential for development and maintenance of multicellular organisms. Physiologic, or programmed, cell death is dependent on a genetically encoded and evolutionarily conserved pathway that induces a form of cellular suicide known as apoptosis. In the past decade, it has become clear that the regulatory mechanisms controlling programmed cell death are as fundamental, and as complex, as those regulating cell proliferation. Perturbation of the signaling cascades regulating apoptosis, whether by extracellular triggers, acquired or germline genetic mutations, or viral mimicry of signaling molecules, can result in a wide variety of human diseases. Analysis of these regulatory pathways has led to a better understanding of the etiology and pathogenesis of many human diseases, notably cancers, infectious diseases including AIDS, autoimmune diseases, and neurodegenerative/neurodevelopmental diseases. Our understanding of the regulation of programmed cell death in health and disease is far from complete, and the challenge of converting that understanding into new therapeutic modalities has only begun to be approached.
-
-
-
MANAGEMENT OF ADULTS WITH CONGENITAL HEART DISEASE: An Increasing Problem
Vol. 48 (1997), pp. 283–293More Less▪ AbstractA small new population of patients in cardiology, the grown-up (adult) congenital hearts (GUCH), need superspecialist care and expertise, particularly those patients with complex defects previously operated on in childhood or who were not operated on. Arrhythmias are the most common cardiologic reason for admission to the hospital, and atrial flutter is the most frequent disorder of rhythm, usually related to hemodynamic disturbances. The GUCHs need solutions to problems of transition of care, ideally an adolescent area for the younger patients, knowledge of which and when to investigate each anomaly, expertise in cardiac catheterization and interventions, cardiac surgeons experienced in congenital as well as adult disease since one in five admissions are for cardiac surgery, at-risk pregnancy service, counseling on life's problems, and most of all a few dedicated centers with cardiologists and surgeons trained in this subspecialty. The profession needs to achieve optimal care for these precious patients, particularly those with complicated lesions and complex surgery, particularly with valve replacements. Although small in number and high in expense, GUCH patients should be centralized so expertise and experience can be concentrated despite the need to cross barriers of finance and bureaucracy. Currently, with the exception of a few expert centers, these patients receive suboptimal medical management.
-
-
-
NONREPLACEMENT OPERATIONS FOR MITRAL VALVE REGURGITATION
Vol. 48 (1997), pp. 295–306More Less▪ AbstractMitral valve reconstruction offers patients an important alternative to the traditional method for treating severe mitral regurgitation—mitral valve replacement. Over the last 15 years, surgical techniques have evolved for treating mitral regurgitation occurring from various anatomic mechanisms—annular dilatation, abnormal leaflet motion due to a variety of causes, or leaflet perforation. Currently, over 90% of regurgitant mitral valves of varying etiologies are amenable to nonreplacement therapy by reconstruction, with good intermediate- and long-term results. Reconstruction obviates the need for long-term anticoagulation, and thus, there has evolved a trend toward reconstruction earlier in the course of this disease, before fixed atrial fibrillation and ventricular dilatation occur.
-
-
-
BROWN ADIPOSE TISSUE, β3-ADRENERGIC RECEPTORS, AND OBESITY
Vol. 48 (1997), pp. 307–316More Less▪ AbstractBrown adipose tissue is distinguished by its unique capacity for uncoupled mitochondrial respiration, which is highly regulated by sympathetic nerve activity. Because of this, energy expenditure in brown fat is capable of ranging over many orders of magnitude. The fact that the function of brown adipose tissue is impaired in obese rodents and that transgenic mice with decreased brown fat develop obesity demonstrates the importance of brown fat in maintaining nutritional homeostasis. However, the role of brown fat in humans is less clear. β3-Adrenergic receptors are found on brown adipocytes, and treatment with β3-selective agonists markedly increases energy expenditure and decreases obesity in rodents. Whether β3-selective agonists will be effective anti-obesity agents in humans is presently under investigation.
-
-
-
TREATMENT OF TEMPORAL LOBE EPILEPSY
Vol. 48 (1997), pp. 317–328More Less▪ AbstractInitial management of patients with temporal lobe epilepsy is with antiepileptic drugs, but these control seizures in only half the patients. Patients refractory to drugs should be evaluated for resective surgery. That evaluation requires identification of a focus of onset of seizures, as well as establishing that the focus is in an area of the brain that can be removed with a low risk of new neurologic deficits. Techniques used in that evaluation, including electroencephalography, imaging, recording from intracranial electrodes, use of the intracarotid amobarbitol perfusion test, and the role of specialized studies such as positron emission tomography, are reviewed, along with the correlation of the findings on that evaluation to the control of seizures after surgery. The different surgical techniques for temporal lobe resections are also reviewed, along with the risks of surgery, particularly to recent memory, and the changes in quality of life following surgery.
-
-
-
PROTOZOAL AGENTS: What Are the Dangers for the Public Water Supply?
Vol. 48 (1997), pp. 329–340More Less▪ AbstractSafe and efficient treatment of drinking water has been one of the major public health advances of the twentieth century. People in developed countries generally take for granted that their water is safe to drink, a luxury the majority of the world's population does not have. The leading cause of infant mortality in the developing world is infectious diarrhea, and the prevalence of diarrheal pathogens is largely influenced by the quality and quantity of clean water available for drinking and washing. Until recently, modern water treatment had all but eliminated these concerns in developed nations. Over the past two decades, however, the safety of our water supply has been threatened by the emergence of Cryptosporidium parvum, a protozoal pathogen. The hearty oocysts of this organism survive chlorination and filtration to cause a diarrheal illness that, while unpleasant enough in healthy people, is devastating in immunocompromised individuals. The 1993 Milwaukee outbreak, in which 403,000 people developed diarrhea from drinking water that met all the updated federal safety standards, demonstrated the tremendous public health importance of this organism. While earlier attention had focused on Giardia and amebic infections, the other "emerging" protozoan besides Cryptosporidium is Cyclospora. This review discusses the protozoal pathogens, including Cryptosporidium parvum, Giardialamblia, Entamoebahistolytica, and Cyclospora cayetanensis, that cause waterborne diarrheal outbreaks and the threats they pose to the public.
-
-
-
ORAL TOLERANCE FOR THE TREATMENT OF AUTOIMMUNE DISEASES
Vol. 48 (1997), pp. 341–351More Less▪ AbstractOrally administered autoantigens suppress autoimmunity in animal models, including experimental allergic encephalomyelitis, collagen and adjuvant-induced arthritis, uveitis, and diabetes in the non-obese diabetic mouse. Low doses of oral antigen induce antigen-specific regulatory T-cells in the gut, which act by releasing inhibitory cytokines such as transforming growth factor-β, interleukin-4, and interleukin-10 at the target organ. Thus, one can suppress inflammation at a target organ by orally administering an antigen derived from the site of inflammation, even if it is not the target of the autoimmune response. Initial human trials of orally administered antigen have shown positive findings in patients with multiple sclerosis and rheumatoid arthritis. A double-blind, placebo-controlled, phase III multi-center trial of oral myelin in 515 relapsing-remitting multiple sclerosis patients is in progress, as are phase II clinical trials investigating the oral administration of type II collagen in rheumatoid arthritis, S-antigen in uveitis, and insulin in type I diabetes.
-
-
-
THE DEVELOPMENT AND CLINICAL UTILITY OF THE TAXANE CLASS OF ANTIMICROTUBULE CHEMOTHERAPY AGENTS
Vol. 48 (1997), pp. 353–374More Less▪ AbstractThe taxane class of antimicrotubule anticancer agents is perhaps the most important addition to the chemotherapeutic armamentarium against cancer over the past several decades. After only a brief period, the taxanes have not only demonstrated a unique ability to palliate the symptoms of many types of advanced cancers, including carcinoma of the ovary, lung, head and neck, bladder, and esophagus, they have also demonstrated effectiveness in the initial therapy of earlier stages of cancer, a setting in which any new therapy is likely to make its greatest impact. The challenge now facing investigators is to develop strategies to maximize therapeutic benefits with the taxanes in the early stages, as well as the advanced stages, of many cancers. This review describes the preclinical features and clinical results of the two major taxanes, paclitaxel (Taxol®, Bristol-Myers Squibb) and docetaxel (Taxotere®, Rhone-Poulenc Rhorer).
-
-
-
CHOLESTEROL EMBOLI: A Common Cause of Renal Failure
Vol. 48 (1997), pp. 375–385More Less▪ AbstractCholesterol embolization (CE), usually occurring in males in their sixth or seventh decade of life, can affect multiple organ systems, including the kidney. Interventive diagnostic procedures and aortic surgery greatly increase the risk of CE. Rapid or insidious progression of renal failure in association with surgical or diagnostic radiologic procedures should suggest this diagnosis. Progressive renal insufficiency in older patients with generalized arterial disease should suggest ischemic nephropathy secondary to bilateral renal artery stenosis, renal CE, or both. Recent worsening of hypertension is characteristic of either diagnosis. A number of clinical conditions can simulate renal CE, and final differentiation may be possible only by renal biopsy. Aggressive, supportive management of renal CE is warranted because renal function may stabilize and, in a limited number of cases, may even improve.
-
-
-
RECENT ADVANCES IN SURGERY FOR EMPHYSEMA
Vol. 48 (1997), pp. 387–398More Less▪ AbstractVolume reduction surgery is based on the removal of volume-occupying but nonfunctioning emphysematous lung, which is thought to improve pulmonary elastic recoil. The reduction in thoracic volume may also improve thoracic cage and inspiratory muscle function. In addition, dyspnea is lessened, exercise tolerance is increased, and measured pulmonary function is improved. Alveolar gas exchange may also be improved. Selection criteria include marked airway obstruction secondary to emphysema, marked hyperinflation of the chest wall, and regional heterogeneity in the distribution of the emphysema. The best results are obtained with a bilateral procedure utilizing stapling resection. The two surgical approaches are median sternotomy and video-assisted thoracic surgery.
-
-
-
CLINICAL TRIALS IN PULMONARY HYPERTENSION
Vol. 48 (1997), pp. 399–408More Less▪ AbstractProgress in treatment of pulmonary hypertension has been impaired by the lack of formal clinical trials. This is now beginning to change, and the impact on our approach to treating patients with pulmonary hypertension is substantial. As with other relatively uncommon medical disorders, randomized, controlled, multi-center trials are needed to assess the safety and efficacy of potential therapeutic modalities. Treatments showing promise at the level of small pilot studies within a single center should be studied more rigorously.
-
-
-
THE MOLECULAR GENETICS OF MULTIPLE ENDOCRINE NEOPLASIA TYPE 2A AND RELATED SYNDROMES
Vol. 48 (1997), pp. 409–420More Less▪ AbstractIdentification of RET gene mutations in patients at-risk for the development of the hereditary forms of medullary thyroid carcinoma has simplified management and expanded the scope of indications for surgical intervention. Patients who carry this mutation can be offered thyroidectomy at a very young age, hopefully at a point when the cancer has not yet developed or spread. Those who are found not to have inherited the mutation are spared further genetic and biochemical screening. This achievement marks a new paradigm in surgery—the recommendation that an operation be performed based on the result of a genetic test. Experience with management of patients with multiple endocrine neoplasia types 2A and 2B and with familial, non–multiple endocrine neoplasia medullary thyroid carcinoma will provide information that will aid in the future management of patients with other hereditary cancers.
-
-
-
BEREAVEMENT AND LATE-LIFE DEPRESSION: Grief and Its Complications in the Elderly
Vol. 48 (1997), pp. 421–428More Less▪ AbstractSpousal bereavement is a common event in later life and, not infrequently, an important cause of psychiatric and medical morbidity. Depression (along with suicide), anxiety, substance abuse, and symptoms of “complicated” grief are among the more important psychiatric sequelae of spousal bereavement. They may represent, in part, forms of abnormal reaction to the stress of loss and the challenges of adaption to becoming widowed. This paper summarizes current knowledge about the clinical phenomenology of the psychiatric sequelae to late-life attachment bereavment, some of the hypothesized antecedents of abnormal stress response to bereavement, psychobiologic correlates of bereavement-related depression, and the long-term course (including preliminary evidence on response to treatment with psychotherapy and antidepressant medication).
-
-
-
MARKERS FOR PREDICTING THE DEVELOPMENT OF ACUTE RESPIRATORY DISTRESS SYNDROME
Vol. 48 (1997), pp. 429–445More Less▪ AbstractThe acute respiratory distress syndrome (ARDS) is a relatively common, inflammatory lung disorder that is associated with major morbidity and high mortality. The pathogenesis of ARDS is complex, and unfortunately, the development of ARDS in an individual patient is difficult to anticipate. In this chapter, we outline the rationale for why accurately predicting the development of ARDS would be valuable. We also review the accumulated data on approaches for predicting ARDS and discuss the potential difficulties in establishing predictive markers.
-
-
-
PREMENSTRUAL SYNDROMES
Vol. 48 (1997), pp. 447–455More Less▪ AbstractThe recent inclusion of research criteria for premenstrual dysphoric disorder in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders should help physicians recognize women with symptoms of irritability, tension, dysphoria, and lability of mood that seriously interfere with their lifestyle. Premenstrual dysphoric disorder can be differentiated from premenstrual syndrome, which is primarily reserved for milder physical symptoms and minor mood changes. The use of criteria from the Diagnostic and Statistical Manualin conjunction with prospective daily charting for at least two menstrual cycles is now accepted as common practice in confirming the diagnosis. Treatment options range from the conservative (lifestyle and stress management) to treatment with psychotropic medications and hormonal or surgical interventions to eliminate ovulation for the more extreme cases. Results from several randomized, placebo-controlled trials have clearly demonstrated that selective serotonin reuptake inhibitors, as well as medical or surgical oophorectomy, are effective in treating premenstrual dysphoric disorder. Taken together, these data indicate that treatment may be accomplished by either eliminating the hormonal trigger or by reversing the sensitivity of the serotonergic system.
-
-
-
DYSTROPHIN-ASSOCIATED PROTEINS AND THE MUSCULAR DYSTROPHIES
Vol. 48 (1997), pp. 457–466More Less▪ AbstractDiscovery of the gene encoding the protein dystrophin delineated not only the cause of Duchenne dystrophy but also an expanding family of at least eight different dystrophin-associated muscle proteins. These include two that span the membrane (the dystroglycans), at least five within the membrane (the sarcoglycans), and a submembrane protein (utrophin). In recent years, defects in the genes for several of these proteins have been identified in several different muscular dystrophies. The spectrum of clinical deficits associated with these genetic lesions is broad, but typically it encompasses both milder proximal myopathies characteristic of limb-girdle dystrophy and more severe disorders reminiscent of Duchenne dystrophy. These discoveries will provide the basis both for improved understanding of physiology of this complex of proteins at the muscle membrane and for new strategies in the treatment of muscular dystrophy.
-
-
-
ACUTE RENAL FAILURE: Role of Dialysis Membrane Biocompatibility
Vol. 48 (1997), pp. 467–476More Less▪ AbstractRecent clinical studies of acute renal failure in adults have focused attention on the biocompatibility of the dialysis membrane as a possible factor influencing patient morbidity and mortality. In this article, we review the concept of dialysis membrane biocompatibility and highlight the difficulty of finding an ideal definition. We then expand on the possible roles of complement and neutrophil activation by dialysis membranes, which may prolong the recovery from acute renal failure. The results of several clinical studies analyzing the impact of dialysis membranes on the course and outcome of acute renal failure are discussed. Finally, the possible relevance of biocompatibility in continuous renal replacement therapies is emphasized.
-
-
-
NALTREXONE IN THE TREATMENT OF ALCOHOLISM
Vol. 48 (1997), pp. 477–487More Less▪ AbstractAlcoholism affects nearly 12.5 million Americans and is responsible for annual costs of over $130 billion from loss of job productivity, deleterious health effects, and direct treatment expenses. Research on treating alcoholism from the standpoint of relapse prevention using psychosocial interventions alone has produced only modest results. Studies on the efficacy of adjunctive medications using multiple medications in placebo-controlled and open trials combined with psychosocial interventions have shown mixed results. Recently, a safe and well-tolerated opiate antagonist, naltrexone, was approved by the Food and Drug Administration (FDA) for the adjunctive treatment of alcoholism. This review describes the pertinent preclinical and clinical research that led to the FDA's approval. Details are provided describing the subjects, methods, and results of the two pivotal human studies that led to the FDA review for this indication. Clinical therapeutic guidelines, appropriate patient selection, and future directions are also elucidated.
-
-
-
NITRIC OXIDE SYNTHASE: Role in the Genesis of Vascular Disease
Vol. 48 (1997), pp. 489–509More Less▪ AbstractThe product of nitric oxide (NO) synthase is the most potent endogenous vasodilator known. NO not only is a potent vasodilator, it also inhibits platelet adherence and aggregation, reduces adherence of leukocytes to the endothelium, and suppresses proliferation of vascular smooth muscle cells. A number of disorders are associated with reduced synthesis and/or increased degradation of vascular NO. These include hypercholesterolemia, diabetes mellitus, hypertension, and tobacco use. The endothelial dysfunction caused by these disorders contributes to the alterations in vascular function and structure observed in these conditions. A reduction in the activity of vascular NO likely plays a significant role in the development of atherosclerosis. Insights into the mechanisms by which NO production or activity is altered in these states will lead to new therapeutic strategies in the treatment of a number of vascular disorders, including hypertension, atherosclerosis, restenosis, and thrombosis.
-
-
-
THE SURGICAL MANAGEMENT OF ATRIAL FIBRILLATION
Vol. 48 (1997), pp. 511–523More Less▪ AbstractAtrial fibrillation is the most common dysrhythmia encountered in clinical practice. For some patients, satisfactory rate control is not possible by pharmacologic means. This led us to develop a surgical approach to its cure, which in turn has led to a deeper understanding of the electrophysiologic basis of atrial fibrillation and to the development of a surgical procedure that is highly effective in restoring sinus rhythm with an acceptable mortality and morbidity. We review these findings as well as the clinical results obtained with the Maze procedure.
-
-
-
VON WILLEBRAND'S DISEASE
Vol. 48 (1997), pp. 525–542More Less▪ Abstractvon Willebrand's disease (vWD) arises from abnormalities in von Willebrand factor (vWF), an adhesive glycoprotein uniquely involved in key aspects of both primary and secondary hemostasis. The current classification distinguishes disorders arising from partial (type 1) or complete (type 3) deficiencies and from qualitative defects (type 2). Type 2 vWD is further divided into four subtypes (A, B, N, and M), reflecting distinct classes of functional abnormalities. Missense mutations account for most of type 2 vWD, whereas major disruptions in the vWF gene produce type 3 variants. The molecular basis of type 1 vWD is largely undefined. The laboratory diagnosis of vWD and its several variants is made on the basis of immunologic and functional studies of vWF, factor VIII levels, and specialized electrophoretic analyses (multimer gels). The mainstay of therapy for most patients with vWD is desmopressin, a pharmacologic agent that stimulates the release of endogenous pools of vWF. Cryoprecipitate and selected factor VIII concentrates are useful sources of exogenous vWF for the treatment of patients unresponsive to this desmopressin.
-
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)