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- Volume 46, 1995
Annual Review of Medicine - Volume 46, 1995
Volume 46, 1995
- Review Articles
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REPETITIVE MOTION INJURIES
Vol. 46 (1995), pp. 1–16More Less▪ AbstractRepetitive motion injuries have presented clinicians with a significant challenge over the past two and a half decades. Acceptable treatment of inflammatory disorders is well established, but compressive neuropathies and nonspecific complaints of numbness, tingling, and discomfort in the upper extremity present vexing dilemmas. Current research and experience point to multilevel problems, including posturally induced muscular imbalance. Although surgical solutions to these problems are sometimes indicated, conservative approaches successfully treat many individuals and have narrowed the scope and indications for surgical intervention. These approaches include ergonomic changes at the workstation, postural changes, and muscle stretching and strengthening to correct imbalance.
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CLASS II ANTIGENS AND DISEASE SUSCEPTIBILITY
Vol. 46 (1995), pp. 17–25More Less▪ AbstractThe role for HLA typing in autoimmune disease is changing with the recognition that HLA markers can identify patients with poor prognosis in some autoimmune disease. Aggressive therapeutic intervention in patients with such HLA prognostic markers has the potential to improve or prevent progressive disease outcomes in a select group of patients.
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HYPERTENSION IN THE ELDERLY
Vol. 46 (1995), pp. 27–35More Less▪ AbstractElderly people have a very high prevalence of hypertension, which markedly increases their risk for cardiovascular morbidity and mortality. Convincing evidence demonstrates the effectiveness of antihypertensive therapy in reducing these risks significantly. With appropriate caution, most elderly hypertensives can be treated and thereby protected from many of the debilities of old age.
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BORDERLINE HYPOTHYROIDISM AND DEPRESSION
Vol. 46 (1995), pp. 37–46More Less▪ AbstractThis review defines subclinical hypothyroidism and examines its influence on the occurrence and course of major depression. Recommendations are presented for the identification and treatment of patients with coexisting mood disorders and borderline thyroid failure.
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THE CHANGING FACE OF TUBERCULOSIS1
Vol. 46 (1995), pp. 47–55More Less▪ AbstractTuberculosis (TB) remains an important public health problem worldwide, resulting in an estimated 8 to 10 million new cases and 2 to 3 million deaths each year. Between 1953 and 1985, the number of TB cases in the US declined by an average of 6% per year. However, since 1985, TB has been increasing in the US. Approximately 64,000 additional cases of the disease have been reported beyond the number expected had the rate of decline observed from 1980 to 1984 continued from 1985 through 1993. Increases in the number of TB cases have been significant in racial and ethnic minorities, in persons born outside the US, and in children less than 15 years of age. Infection with the human immunodeficiency virus (HIV) has also been recognized as a major risk factor for the development of active TB in persons with latent Mycobacterium tuberculosis infection. The unusual radiographic findings and the increased likelihood of extrapulmonary TB in HIV-infected persons make diagnosis of the disease problematic. Lastly, concomitant with the resurgence of TB has been the emergence of drug resistance. All of these factors make successful control of TB in the US difficult.
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THE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES1
Vol. 46 (1995), pp. 57–65More Less▪ AbstractThe human transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of rapidly progressive disorders characterized by a spectrum of clinical abnormalities that include cognitive impairment, ataxia, myoclonus, and visual, pyramidal, and extrapyramidal signs. They share a spongiform (vacuolar) degeneration and variable amyloid plaque formation. Examples of TSEs are kuru, an infectious disease; Creutzfeldt-Jakob disease (CJD), which may take an infectious, genetic, or sporadic form; and Gerstmann-Sträussler-Scheinker disease (GSS) and fatal familial insomnia (FFI), rare familial disorders. With the exception of FFI, all of these disorders have been experimentally transmitted to nonhuman primates and laboratory rodents. The pathogenic PrP protein accumulating in the brain of TSE patients is a protease-resistant and insoluble product of a precursor protein molecule of unknown function that is encoded by the PRNP gene on chromosome 20. Different mutations in this gene are responsible for various phenotypes of TSE in its familial form, and a polymorphism at codon 129 controls susceptibility to the infectious and perhaps sporadic forms of disease. TSEs are transmissible amyloidoses in which the host-encoded protein has the propensity to acquire a beta-sheet conformation and produce amyloid; the accumulation of amyloid eventually destroys the neurons and induces the deadly disease.
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FETAL SURGERY
Vol. 46 (1995), pp. 67–78More Less▪ AbstractFetal surgery, as defined for the purpose of this chapter, is the act of opening the gravid uterus, surgically correcting a fetal abnormality, and returning the fetus to the uterus for postoperative recovery and continued gestational development. By this definition, human fetal surgery has now been performed for more than a decade, primarily at a single center (1). Tremendous progress has been made in our understanding of the natural history and pathophysiology of fetal disease, in solving the technical challenges of fetal surgery, and in intra- and postoperative care and monitoring of the maternal-fetal unit. However, success and general application of fetal surgery continue to be limited by a number of unsolved and formidable problems. The most important of these is the control of preterm labor, which is the Achilles heel of fetal surgery. Preterm labor is to the infantile field of fetal surgery what rejection was to the field of transplantation. The discovery of effective tocolysis would be analogous to the development of effective immunosuppression and would allow fetal surgery to achieve its full potential. In addition, less invasive methods of operating on the fetus are emerging that will further reduce the maternal and fetal risk of this currently highly invasive treatment.
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MANAGEMENT OF EARLY NEPHROPATHY IN DIABETIC PATIENTS
Vol. 46 (1995), pp. 79–94More Less▪ AbstractDiabetic patients go through several stages of renal disease, moving from normo- to micro- to macroalbuminuria. Good metabolic control can prevent or postpone the development of microalbuminuria, the earliest sign of diabetic renal disease. Thus, efforts should focus on obtaining the best possible control before the onset of microalbuninuria. In patients with microalbuminuria, blood pressure starts to increase, and early antihypertensive treatment becomes important. Good glycemic control may be difficult to achieve. With overt nephropathy, defined as clinical proteinuria, a relentless decline in glomerular filtration rate (GFR) occurs unless patients are carefully treated with antihypertensive agents. Protein restriction may also be necessary, but a clear beneficial effect of optimized diabetes care is difficult to document. Early screening is recommended, with an emphasis on testing for albuminuria, including microalbuminuria, along with careful control of blood pressure.
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TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNTS
Vol. 46 (1995), pp. 95–102More Less▪ AbstractManagement of bleeding esophageal varices due to portal hypertension has traditionally relied on endoscopic sclerotherapy and operative intervention with placement of a portosystemic shunt. Although percutaneous decompression of portal hypertension was investigated 25 years ago, it was not clinically feasible until recently. With the advent of intravascular stents, the technique of creating a transjugular intrahepatic portosystemic shunt (TIPS) can now be effectively applied to treat the complications of portal hypertension, including variceal hemorrhage and refractory ascites. Since its introduction in 1989, TIPS has enjoyed widespread clinical application. The initial results with this procedure are encouraging and suggest that it is an effective means of reducing the frequency of variceal hemorrhage in patients with portal hypertension. The long-term patency rate and frequency of complications, however, have not been clearly defined. Similarly, the role of TIPS in the treatment of refractory ascites, Budd-Chiari syndrome, and hepatorenal syndrome remains unclear because sufficient data do not yet exist to support its general use in these settings.
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TISSUE FACTOR PATHWAY INHIBITOR AND THE REVISED THEORY OF COAGULATION
Vol. 46 (1995), pp. 103–112More Less▪ AbstractTissue factor pathway inhibitor (TFPI) is a multivalent, Kunitz-type plasma proteinase inhibitor that regulates tissue factor-induced coagulation. TFPI directly inhibits activated factor X and, in a factor Xa-dependent fashion, produces feedback inhibition of the factor VIIa/tissue factor catalytic complex. The properties of this rediscovered inhibitor appear, at least in part, to explain the clinical requirement for both the extrinsic and intrinsic pathways of the cascade and waterfall theories of blood clotting and have led to a reformulation of the coagulation mechanism. In the revised hypothesis, factor VIIa/tissue factor is responsible for the initiation of coagulation, but owing to TFPI-mediated inhibition, sustained hemostasis requires the persistent and amplified procoagulant action of intrinsic factors VIII, IX, and XI.
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BRAIN IMAGING IN SCHIZOPHRENIA1
Vol. 46 (1995), pp. 113–122More Less▪ AbstractNeuroimaging provides an unprecedented means by which to study psychiatric disorders. Structural imaging methods, i.e. computerized tomography (CT) and magnetic resonance imaging (MRI), have revealed subtle differences in the brains of schizophrenic patients that appear to be present before symptom onset. Radionuclide functional methods such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) have led to hypotheses about dysfunction in specific neuronal networks in schizophrenia. New advances in MRI allow functional data to be obtained noninvasively in a single individual using conventional MRI scanners. This chapter discusses the parallels between the historical technical developments in neuroimaging and the deepening understanding of the etiology and manifestations of schizophrenia.
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ALCOHOL IN THE ELDERLY1
Vol. 46 (1995), pp. 123–132More Less▪ AbstractAlthough older individuals drink less and report fewer alcohol-related problems than do younger individuals, alcohol use and abuse are significant health issues for older patients. The signs and symptoms of alcohol problems and dependence in the elderly may not only differ from those of young problem drinkers, but may also be present at lower levels of alcohol consumption. Older alcoholics do well in alcohol treatment. Therefore, discussion of alcohol consumption is a critical part of every history and physical examination for all patients, including older individuals.
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MOLECULAR APPROACHES TO AMYOTROPHIC LATERAL SCLEROSIS
Vol. 46 (1995), pp. 133–145More Less▪ AbstractNew discoveries are expanding our knowledge of mechanisms involved in amyotrophic lateral sclerosis (ALS) pathogenesis. Some recent advances in our understanding of motoneuron death in familial ALS (fALS) and sporadic ALS (sALS) are reviewed, with emphasis on molecular similarities that may further unite these phenotypically linked diseases.
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MINIMALLY INVASIVE SURGERY
Vol. 46 (1995), pp. 147–158More Less▪ AbstractWith the widespread introduction of laparoscopic cholecystectomy in late 1989, the practice and expectations of general surgery were changed forever. The techniques of laparoscopy were not new—they had been adopted by gynecologists and orthopedic surgeons at least a decade before—but it was laparoscopic cholecystectomy that captured the attention of the surgical profession and the public and spawned the tremendous growth in what has come to be called minimally invasive surgery. Although this surgery has tremendous appeal, offering quicker recovery, less pain, and possibly greater safety, it presents new challenges in the areas of training, credentialing, and quality assessment and raises serious questions about the real benefits of new technology at a time when the political and economic sensitivity of these issues is greater than ever.
In this chapter I limit myself to a discussion of laparoscopy in general surgery, with a focus on what we have learned from laparoscopic cholecystectomy and on what this knowledge suggests for the future of other laparoscopic general surgical procedures.
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THE ROLE OF CATHETER-DIRECTED THERAPIES IN THE TREATMENT OF CONGENITAL HEART DISEASE
Vol. 46 (1995), pp. 159–168More Less▪ AbstractOver the past decade, transcatheter interventions have become increasingly important in the treatment of patients with congenital heart defects. These procedures may be broadly grouped as dilations (valvuloplasty, angioplasty, and endovascular stenting) or as closures (vascular embolizations and device closure of defects). Balloon valvuloplasty has become the treatment of choice for simple valvar pulmonic stenosis in all age groups and, although not curative, appears at least comparable to surgery for noncalcific aortic stenosis in newborns through young adults. Balloon angioplasty is successfully applied to a wide range of aortic, pulmonry artery, and venous stenoses. Catheter-delivered coils are used to embolize a wide range of arterial, venous, and prosthetic vascular connections. Although still investigational, devices have been successfully used for closure of large numbers of atrial and ventricular septal defects.
In this review, the current role of each major catheter intervention is discussed and results are compared with alternative forms of therapy. Catheter-based therapeutics are then placed in context in a discussion of combined catheter-surgical treatment of patients with complex congenital heart defects.
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MARROW TRANSPLANTATION FROM UNRELATED VOLUNTEER DONORS
Vol. 46 (1995), pp. 169–179More Less▪ AbstractMarrow transplants from human leukocyte antigen (HLA)-compatible unrelated volunteer donors have become feasible for more than 30% of patients without a family match and have allowed long-term, disease-free survival in 15–65% of patients with a variety of hematological disorders. However, unrelated donor transplants have a higher incidence of graft failure and graft versus host disease (GVHD) than do HLA-matched sibling transplants. This increase may be due to disparities between donor and recipient for undetected HLA determinants or for non-HLA histocompatibility genes. Because of the large number of HLA loci and their high degree of polymorphism, fully compatible donors will not be found for most patients. Fortunately, a limited degree of HLA mismatch does not necessarily impair long-term survival in patients with hematologic malignancy. Current studies are defining the risk associated with mismatching for each histocompatibility locus and are developing methods for marrow transplantation that can decrease morbidity and improve survival despite genetic disparity between donor and recipient.
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FULMINANT HEPATIC FAILURE: Pathophysiology, Treatment, and Survival
Vol. 46 (1995), pp. 181–191More Less▪ AbstractFulminant hepatic failure is characterized by severe metabolic derangements, neurologic complications and, ultimately, multiorgan failure. In the past three decades, improved intensive care has increased mean survival from 15% to 50% in certain patient groups by providing metabolic support and management of specific, frequent, and potentially fatal complications. However, outcome remains highly dependent on etiology. While intensive care is sufficient therapy in some patients (Group I), those with irreparable hepatic damage (Group III) can only survive if transplanted. In intermediate cases (Group II), the liver retains the potential to regenerate if the patient receives hepatic functional support. Major areas of current research in this field include development of hepatic support devices, strategies to accelerate and maximize hepatic regeneration, and criteria for accurate prognostic classification of patients.
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THE MODERN VERSION OF ADULT RESPIRATORY DISTRESS SYNDROME
Vol. 46 (1995), pp. 193–202More Less▪ AbstractAdult respiratory distress syndrome (ARDS) remains a highly lethal complication of autodestructive inflammation. This syndrome originally referred to a single organ failure but is now considered a component, usually the first, of the multisystem organ failure syndrome (MOFS). Cytokines, neutrophils, and endothelial adherence molecules initiate the disease process, with cell injury caused by oxidants and proteases released from inflammatory cells. ARDS, if progressive, will result in pulmonary fibrosis. Improved ventilatory support techniques have not been shown to decrease mortality. Pharmacologic manipulation of the inflammatory response is a more promising method of controlling the disease process.
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RISKS OF HIV INFECTION IN THE HEALTH CARE SETTING
Vol. 46 (1995), pp. 203–211More Less▪ AbstractHealth care workers exposed to blood and body fluids have a low but measurable risk of occupational infection with human immunodeficiency virus (HIV). This risk is related to the prevalence of HIV among patients, the frequency of exposure to infected blood, and the method of exposure. The magnitude of risk is thus difficult to assess for any given situation, although the overall risk following percutaneous exposure is approximately 0.3%. Risk can be reduced by paying close attention to infection control procedures and by minimizing risky procedures. Exposure management should include preexposure education and immediate postexposure care and counseling. Chemoprophylaxis is widely used despite doubts as to its effectiveness, and much research is clearly needed to develop more effective prophylaxis. For patients, the risk of nosocomial acquisition of HIV remains extremely low and can be minimized by strict adherence to proper infection control procedures.
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MOLECULAR GENETICS OF HYPERTROPHIC CARDIOMYOPATHY
Vol. 46 (1995), pp. 213–222More Less▪ AbstractHypertrophic cardiomyopathy (HCM) is genetically and phenotypically a heterogeneous disease. Genes identified include the β myosin heavy chain gene (βMHC) on chromosome 14q1, the troponin T gene on chromosome 1q, and the α tropomyosin gene on chromosome 15q. In addition, a fourth locus is present on chromosome 11q11, but the gene remains to be identified. More than 35 missense mutations in the βMHC, 3 mutations in troponin T, and 2 mutations in α tropomyosin gene in HCM patients have been identified. Functional studies have shown that the mutant βMHC protein has impaired acto-myosin interaction and that expression of the mutant myosin disrupts the assembly of sarcomere in feline cardiocytes. Genotype-phenotype correlations of βMHC mutations have shown that mutations such as Arg403Gln, Arg453Cys, and Arg719Trp are associated with a high incidence of sudden cardiac death and a significantly decreased life expectancy, whereas mutations Gly256Glu and Leu908Val have a near-normal life span. Preclinical genetic diagnosis should help in genetic counseling and therapeutic stratification.
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ADVANCED PROTEIN GLYCOSYLATION IN DIABETES AND AGING
Vol. 46 (1995), pp. 223–234More Less▪ AbstractProducts of advanced protein glycosylation (advanced glycation end products, or AGEs) accumulate in tissues as a function of time and sugar concentration. AGEs induce permanent abnormalities in extracellular matrix component function, stimulate cytokine and reactive oxygen species production through AGE-specific receptors, and modify intracellular proteins. Pharmacologic inhibition of AGE formation in long-term diabetic animals prevents diabetic retinopathy, nephropathy, neuropathy, and arterial abnormalities in animal models. Clinical trials in humans are currently in progress.
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ORGAN PRESERVATION
Vol. 46 (1995), pp. 235–247More Less▪ AbstractOrgan preservation is the supply line for organ transplantation. Currently, the liver, pancreas, and kidney can be successfully preserved for up to two days by flushing the organs with the University of Wisconsin (UW) organ preservation solution and storing them at hypothermia (0–5° C). The UW solution is effective because it uses a number of cell impermeant agents (lactobionic acid, raffinose, hydroxyethyl starch) that prevent the cells from swelling during cold ischemic storage. Additionally, the UW solution contains glutathione and adenosine, agents that may stimulate recovery of normal metabolism upon reperfusion by augmenting the antioxidant capacity of the organs (glutathione) or by stimulating high-energy phosphate generation (adenosine) upon reperfusion.
Although this method of organ preservation is effective, some organs (5–15% of livers and 20–30% of kidneys) do not function well upon transplant. Injury may be preservation related but may also result from donor and recipient factors that render the organs more susceptible to preservation damage. Results with continuous perfusion of kidneys in the clinics show a reduction in preservation/reperfusion damage. This may be a more appropriate preservation method than cold storage. In this chapter we discuss the development and use of the UW solution and present clinical results. Although intraabdominal organs are well preserved at present, intrathoracic organs (lungs and heart) are less well preserved, and better methods for preservation of these organs are needed for increased use of lung and heart transplantation.
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TREATMENT OF OSTEOPOROSIS
Vol. 46 (1995), pp. 249–256More Less▪ AbstractOsteoporosis is a common disorder affecting the health of many adults. Strategies for fracture prevention include optimization of peak bone mass and prevention of bone loss at menopause and with aging. Genetic, nutritional, and life-style factors influence peak bone mass and may be used to focus preventive efforts. Once peak bone mass is reached, increased bone resorption may be the major pathogenetic factor. Calcium plus vitamin D, estrogen replacement therapy, calcitonin, and etidronate are agents currently available for treatment of osteoporosis; they act by inhibiting bone resorption. The failure of bone formation to keep pace with bone resorption also contributes to bone loss. Fluoride and intermittent parathyroid hormone therapy increase bone formation; however, more data are needed to determine efficacy. Insulin-like growth factors, transforming growth factor-β (TGF-β), and bone morphogenetic proteins may stimulate bone formation, but they have not yet been tested clinically. New approaches to treatment of osteoporosis will emerge as our understanding of the pathogenesis increases.
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NOVEL ANTITHROMBOTIC THERAPEUTICS TARGETED AGAINST PLATELET GLYCOPROTEIN IIb/IIIa
Vol. 46 (1995), pp. 257–265More Less▪ AbstractPlatelet aggregation is one of the best understood examples of adhesive cell-cell interactions. The platelet glycoprotein IIb/IIIa membrane receptor plays a pivotal role in platelet aggregation through its binding of fibrinogen. It is intimately involved in the pathogenesis of platelet-rich arterial thromboses. The IIb/IIIa receptor is an important target for recently described novel antiplatelet therapeutics. The development and clinical evaluation of this class of antiplatelet therapeutics are reviewed in this article.
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DIABETES CONTROL AND COMPLICATIONS
Vol. 46 (1995), pp. 267–279More Less▪ AbstractThe Diabetes Control and Complications Trial (DCCT) demonstrated that intensive treatment of patients with insulin-dependent diabetes mellitus (IDDM) can substantially reduce the onset and progression of diabetic retinopathy, nephropathy, and neuropathy. The major risk associated with intensive treatment is recurrent hypoglycemia. Implementation of intensive treatment recommendations is difficult but should be considered and probably recommended to most patients with IDDM. If intensive treatment is impractical, any improvement in glycemic control is probably beneficial. Improved glycemic control should be recommended to most patients with non-insulin-dependent diabetes mellitus (NIDDM). The use of insulin in patients with NIDDM is controversial, especially in patients who are overweight, overeating, and minimally symptomatic.
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PANCREAS TRANSPLANTATION FOR DIABETES MELLITUS
Vol. 46 (1995), pp. 281–298More Less▪ AbstractVascularized pancreas transplantation has assumed an increasing role in the treatment of diabetes mellitus. Through 1993, over 5500 pancreas transplants have been performed worldwide, with over 80% being combined pancreas-kidney transplants. Overall one-year patient survival exceeds 90% and graft survival (complete insulin independence) exceeds 70%. Although successful pancreas transplantation achieves euglycemia and complete insulin independence, this occurs at the expense of hyperinsulinemia and chronic immunosuppression. The net result of these changes on diabetic complications in the long term remains to be determined. In the short term, improvement in the quality of life and possible prevention of further morbidity associated with diabetes makes pancreas transplantation an important therapeutic option, particularly when combined with a kidney transplant, in appropriately selected diabetic patients.
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MARROW TRANSPLANTATION FOR MYELOMA
Vol. 46 (1995), pp. 299–307More Less▪ AbstractHigh-dose therapy with hemopoietic stem cell support in multiple myeloma (MM) has been used for 10 years. This approach is currently the most promising form of treatment for this disease. We review here its rationale and the results of clinical trials according to the source of hematopoietic stem cells [allogeneic or autologous, bone marrow or blood]. Finally, we discuss the ongoing uncertainties regarding the utility of this treatment and the future prospects for high-dose therapy in MM.
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HEPATITIS C: An Overview1
Vol. 46 (1995), pp. 309–317More Less▪ AbstractHepatitis C virus (HCV) has been associated with acute and chronic posttransfusion and with sporadic non-A non-B (NANB) hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Cloning of the sequence encoding an antigenic component of HCV in 1989 led to the development of tests to detect antibody to HCV in serum. Viral HCV RNA can be detected and estimated with polymerase chain reaction (PCR) and branched-chain DNA (bDNA) signal amplification tests. The entire viral genome has been sequenced. The HCV envelope region varies considerably, and infections with mutant HCV have been described. Approximately 0.5–1.5% of healthy blood donors test positive, and HCV infection can be acquired by blood transfusion or i.v. drug abuse. Vertical and sexual transmission of the virus is rare, and the transmission mode remains obscure in a large group of patients. Acute hepatitis C is mild and often asymptomatic. Chronic hepatitis C has an indolent course but may progress to cirrhosis and HCC. Recombinant alpha interferon (IF) is used to treat chronic HCV disease, but no consensus has been reached on patient selection, dose, and duration of treatment. Approximately 50% of treated patients respond, but 50–80% of responders relapse over time. Liver transplantation in patients with end-stage, HCV-related liver disease is often followed by allograft infection. Short-term survival with reinfection is good, but the long-term consequences remain to be defined.
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BONE MARROW TRANSPLANTATION IN THALASSEMIA
Vol. 46 (1995), pp. 319–330More Less▪ AbstractEarly trials of allogeneic bone marrow transplantation (BMT) for homozygous β-thalassemia and the analyses of results of transplantation in patients less than 16 years old have allowed us to identify three classes of risk based on the following criteria: (a) hepatomegaly, (b) presence of liver fibrosis at histological examination, and (c) quality of chelation treatment given before transplant. Patients with none of these adverse criteria were assigned to Class 1; patients with either one or two adverse criteria comprised Class 2; and patients for whom all three criteria were adverse constituted Class 3. Most patients older than 16 years have disease characteristics that place them in Class 3, with very few falling into Class 2. All patients with a histocompatibility leukocyte antigen (HLA)—identical donor are actually assigned to one of two conditioning regimens on the basis of the class they belong to at the time of BMT and independently of age. For Class 1, Class 2, and Class 3 patients, the probabilities of survival and event-free survival are 95 and 90%, 86 and 82%, and 87 and 63%, respectively. For those patients older than 16 years at the time of transplant, the probabilities of survival and of event-free survival are 78 and 74%, respectively. Allogeneic BMT is currently the only rational therapeutic modality for the eradication of β-thalassemia.
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MOLECULAR BIOLOGY OF DIABETES INSIPIDUS
Vol. 46 (1995), pp. 331–343More Less▪ AbstractThe identification, characterization, and mutational analysis of three different genes, namely the prepro-arginine-vasopressin-neurophysin II gene (prepro-AVP-NPII), the arginine-vasopressin receptor 2 gene (AVPR2), and the vasopressin-sensitive water channel gene (aquaporin-2, AQP2), provide the basis for our understanding of three different hereditary forms of diabetes insipidus: autosomal dominant neurogenic diabetes insipidus, X-linked nephrogenic diabetes insipidus, and autosomal recessive nephrogenic diabetes insipidus, respectively. These advances provide diagnostic tools for physicians caring for these patients.
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XENOTRANSPLANTATION
Vol. 46 (1995), pp. 345–360More Less▪ AbstractThe need for an alternative source of donor organs, together with the expansion of scientific data in this field, has focused attention on xenotransplantation as a possible alternative to allotransplantation in the treatment of patients with end-stage disease of vital organs. However, xenotransplantation is rarely successful. Not only are the immunological barriers to the acceptance of xenogeneic tissue more powerful than those seen in allotransplantation, but the potential for the transmission of xenograft-associated zoonoses to the human host at the time of transplantation is also present. In addition, data on the physiological performance of the xenograft in the human environment are lacking, although a few functioning xenografts have been shown to be capable of supporting human life.
Although progress has been made in clarifying some of the barriers to xenotransplantation and in defining appropriate therapeutic interventions, including interventions aimed at the removal of natural antibody and at the limitation of complement activation, xenotransplantation is not yet a viable alternative to allotransplantation in the clinical setting.
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THE CURRENT MANAGEMENT OF CARCINOMA OF THE HEAD OF THE PANCREAS
Vol. 46 (1995), pp. 361–370More Less▪ AbstractCarcinoma of the head of the pancreas can be diagnosed and staged effectively by computed tomography (CT) scan and by visceral angiography. If the tumor appears to be resectable, no further studies such as percutaneous biopsy are required. Pancreaticoduodenectomy is the only potentially curable treatment. This operation can be performed with a hospital mortality rate of approximately 2%. If the resection is curative, five-year survival in excess of 20% can be anticipated. Utilizing multivariate analysis, negative lymph node status, the absence of microscopic evidence of blood vessel involvement, and two or fewer blood transfusions during surgery are all independent predictors of long-term survival. Adjuvant therapy is effective and should be used routinely.
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GENETICS OF COLON CANCER: Impact of Inheritance on Colon Cancer Risk1
Vol. 46 (1995), pp. 371–379More Less▪ AbstractThe genes that are mutated in two of the rare syndromes of hereditary colon cancer were recently identified, and genetic diagnosis is already possible in some cases. Acquired mutations of these same genes also appear to be important in sporadic colon cancers. Familial clustering of sporadic cases is common and may likewise arise from inherited susceptibility. Screening strategies for both the rare syndromes and the common cases of colon cancer with familial risk have been suggested. Certain clinical features allow stratification of colon cancer risk among common cases. It is anticipated that continued genetic investigation will result in more precise screening and improved diagnostic and therapeutic options for colon cancer.
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CLASSIFICATION OF EPSTEIN-BARR VIRUS-ASSOCIATED POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASES: Implications for Understanding their Pathogenesis and Developing Rational Treatment Strategies
Vol. 46 (1995), pp. 381–394More Less▪ AbstractThe Epstein-Barr virus (EBV) is associated with a spectrum of B-cell lymphoproliferative diseases (LPD) that develop following organ transplantation. A classification scheme for these disorders has been developed based on the clinical, histologic, immunologic cell-typing, cytogenetic, immunoglobulin gene-rearrangement, and virologic characteristics of these LPD. Four disease groups have been identified: (a) uncomplicated posttransplant infectious mononucleosis, (b) benign polyclonal polymorphic B-cell hyperplasia, (c) early malignant transformation in polyclonal polymorphic B-cell lymphoma, and (d) monoclonal polymorphic B-cell lymphoma. This classification has furthered our understanding of the pathogenesis of these diverse LPD and has allowed the development of rational treatment protocols.
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MANAGEMENT OF PATIENTS WITH ZOLLINGER-ELLISON SYNDROME
Vol. 46 (1995), pp. 395–411More Less▪ AbstractZollinger-Ellison syndrome (ZES) is caused by gastrin-secreting tumors called gastrinomas. Patients commonly present with peptic ulcer disease and may have recurrent, multiple, and atypically located ulcers, e.g. in the jejunum. Alternatively, severe diarrhea may be the only presenting symptom. Patients with multiple endocrine neoplasia Type I (MEN-I) and ZES become symptomatic at an earlier age than patients with sporadic ZES. Patients with ZES have elevated fasting serum gastrin concentrations (>100 pg/ml) and basal gastric acid hypersecretion (>15 mEq/h). The secretin stimulation test is the best test to distinguish ZES from other conditions resulting in elevated gastrin levels. Gastric acid hypersecretion can be controlled in virtually all patients with H2-receptor antagonists or omeprazole, thus rendering total gastrectomy unnecessary. Computed tomography (CT), magnetic resonance imaging (MRI), radionuclide octreotide scanning, endoscopic ultrasound, and the selective arterial secretin injection test are the recommended imaging studies for localization of gastrinoma; nevertheless, 50% of gastrinomas are not evident on preoperative imaging studies. All patients with sporadic gastrinoma who do not have unresectable metastatic disease should undergo exploratory laparotomy for potential curative resection. With increased awareness of duodenal tumors, gastrinoma can be found in 80–90% of patients. Surgery may be the most effective treatment for metastatic gastrinoma if most or all of the tumor can be resected. The management of patients with MEN-I and ZES remains controversial. Some clinicians advocate an aggressive surgical approach, whereas others have had little success in rendering patients eugastrinemic.
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CATHETER ABLATION IN SUPRAVENTRICULAR TACHYCARDIA
Vol. 46 (1995), pp. 413–430More Less▪ AbstractThe evolution of catheter ablation for the treatment of supraventricular tachycardias represents a major advance in the management of cardiac arrhythmias. Excellent results in the majority of patients undergoing the procedure, together with a low rate of early complications and a brief hospitalization, make catheter ablation a highly cost-effective permanent cure. At present, however, its place in relation to alternate therapies in the management of supraventricular tachycardias has not been clearly established owing to unresolved risk-benefit issues. Continuing technical advances will likely enable catheter ablation to be successfully applied to a broader range of cardiac arrhythmias.
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VOLTAGE-GATED ION CHANNELOPATHIES: Inherited Disorders Caused by Abnormal Sodium, Chloride, and Calcium Regulation in Skeletal Muscle
Vol. 46 (1995), pp. 431–441More Less▪ AbstractThe pathological genetic defects in the inherited myotonias and periodic paralyses were recently elucidated using molecular genetic studies. These disorders are usually transmitted as a dominant trait from an affected parent to a child. The many clinical symptoms include cold-induced uncontrollable contraction of muscle, potassium-induced contraction and paralysis, myotonia with dramatic muscular hypertrophy, muscle stiffness, and insulin-induced paralysis (in males). Horses afflicted with the disorder can suddenly collapse, despite an impressive physique. In the past three years, these clinically defined disorders have been shown to share a common etiology: subtle defects of ion channels in the muscle-fiber membrane. Although the specific ion channel involved varies depending on the disease, most patients have single amino acid changes in the channel proteins, with both normal and mutant channels present in each muscle fiber. For each patient, we can now establish a precise molecular diagnosis in the face of overlapping clinical symptoms and begin specific pharmacological treatment based on the primary problem. These studies have also provided insight into basic muscle biology and emphasize the careful regulation of ions in muscle excitation.
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THE NUCLEAR HORMONE RECEPTOR GENE SUPERFAMILY
Vol. 46 (1995), pp. 443–453More Less▪ AbstractThe nuclear hormone receptor gene superfamily encodes structurally related proteins that regulate transcription of target genes. These macromolecules include receptors for steroid and thyroid hormones, vitamins, and other proteins for which no ligands have been found. These receptors have modular domains. The DNA-binding domain directs the receptors to bind specific DNA sequences as monomers, homodimers, or heterodimers. The ligand-binding domain responds to binding of the cognate hormone; this domain and the amino terminal domain interact with other transcription factors. Nuclear receptor-specific actions are derived from a combination of diverse elements, including availability of ligand, receptors, and nonreceptor factors; target-site structure; interactions with other proteins, such as the general transcription factors; and influences of other signaling pathways. These interactions result in ligand-regulated and ligand-independent effects on initiation of transcription of the target genes. Understanding the mechanisms of nuclear receptor action will enhance our knowledge of transcription and hormone influences on disease and facilitate the design of drugs with greater therapeutic value.
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LEFT VENTRICULAR REMODELING AFTER ACUTE MYOCARDIAL INFARCTION
Vol. 46 (1995), pp. 455–466More Less▪ AbstractThe loss of myocytes as a consequence of myocardial infarction results in a prompt reduction in regional wall motion and often leads to more protracted and progressive changes in ventricular architecture. The recognition that the process of ventricular enlargement following myocardial infarction is modifiable provided the initial rationale for the use of angiotensin-converting enzyme (ACE) inhibitors as therapy to prevent deterioration in ventricular size and function following infarction. Experimental and clinical studies have documented the effectiveness of this therapy in preventing this late enlargement following infarction. Increasing clinical evidence indicates that this new use of ACE inhibitor therapy in survivors of acute myocardial infarction will lead to an improvement in clinical outcome.
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PHARMACOLOGIC ENHANCEMENT OF WOUND HEALING
Vol. 46 (1995), pp. 467–481More Less▪ AbstractThe field of pharmacologic modulation of soft tissue repair is in its infancy. Although the soluble, cellular, and insoluble mediators that govern repair have not been elucidated, the application of pharmacologic concentrations of purified polypeptide growth factors, cytokines, and matrix molecules has nonetheless resulted in the acceleration of normal repair and the reversal of deficient repair in a wide variety of dermal wound models in animals. However, early clinical results using these factors have been less than encouraging, and their potential roles in the armamentarium of chronic wound therapies remain to be established.
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THE RELATIONSHIP OF PSYCHIATRIC ILLNESS WITH GASTROINTESTINAL DISEASE
Vol. 46 (1995), pp. 483–496More Less▪ AbstractHigher rates of psychiatric comorbidity as well as more impaired psychosocial adjustment occur with the functional bowel disorders and are particularly high in self-selected referral patients compared with community populations. Reciprocally, some studies show higher rates of functional bowel disturbances in patients with psychiatric diagnoses. Remaining alert for and addressing coexisting psychiatric illness will enhance treatment outcome (increased patient compliance, functioning, and satisfaction). Additionally, psychological factors affect the clinical expression of structural disease. Resetting treatment goals from cure to coping with chronic illness and setting personal limits are important.
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THE MANAGEMENT OF ULCERATIVE COLITIS
Vol. 46 (1995), pp. 497–505More Less▪ AbstractThe treatment of ulcerative colitis (UC) remains empiric because of undetermined etiology and pathogenesis and incomplete understanding of the underlying immunoinflammatory events. However, considerable progress has been made in the management of this disease with the availability and wider use of newer aminosalicylates and immunomodulating agents. The clinician confronted with a patient with chronic ulcerative colitis must weigh the advantages of continued medical therapy against the potential curability with improved surgical techniques. After a brief discussion of the current classes of medicines and their pathophysiological basis of action, we focus on standard approaches to the different clinical syndromes and their complications.
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REDUCED-SIZE HEPATIC ALLOGRAFTS
Vol. 46 (1995), pp. 507–512More Less▪ AbstractReduced-size hepatic transplantation (RSHT) was developed to alleviate the mortality resulting from the scarcity of suitable cadaveric grafts. RSHT consists of various techniques that reduce a full liver to a smaller size. These techniques include reduced-size cadaveric liver transplantation (RLT), split liver transplantation (SLT), and living-related liver transplantation (LRLT). RLT utilizes part of a liver, while the rest is discarded; in SLT, the whole liver is used for two recipients after bipartition; and in LRLT, a portion of the liver retrieved from a living donor is transplanted. Whereas RLT only redistributes the pool of organs to the advantage of pediatric recipients, both SLT and LRLT increase the availability of grafts for transplantation. RSHT yields results comparable to full-liver allografting and drastically reduces the mortality of patients waiting for transplantation. The procedures involved are technically demanding and should be restricted to experienced liver centers.
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Previous Volumes
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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)