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- Volume 46, 1995
Annual Review of Medicine - Volume 46, 1995
Volume 46, 1995
- Review Articles
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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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Previous Volumes
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Volume 76 (2025)
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Volume 75 (2024)
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Volume 74 (2023)
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Volume 73 (2022)
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Volume 72 (2021)
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Volume 71 (2020)
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Volume 70 (2019)
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Volume 69 (2018)
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Volume 68 (2017)
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Volume 67 (2016)
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Volume 66 (2015)
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Volume 65 (2014)
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Volume 64 (2013)
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Volume 63 (2012)
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Volume 62 (2011)
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Volume 61 (2010)
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Volume 60 (2009)
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Volume 59 (2008)
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Volume 58 (2007)
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Volume 57 (2006)
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Volume 56 (2005)
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Volume 55 (2004)
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Volume 54 (2003)
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Volume 53 (2002)
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Volume 52 (2001)
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Volume 51 (2000)
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Volume 50 (1999)
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Volume 49 (1998)
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Volume 48 (1997)
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Volume 47 (1996)
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Volume 46 (1995)
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Volume 45 (1994)
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Volume 44 (1993)
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Volume 43 (1992)
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Volume 42 (1991)
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Volume 41 (1990)
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Volume 40 (1989)
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Volume 39 (1988)
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Volume 38 (1987)
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Volume 37 (1986)
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Volume 36 (1985)
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Volume 35 (1984)
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Volume 34 (1983)
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Volume 33 (1982)
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Volume 32 (1981)
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Volume 31 (1980)
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Volume 30 (1979)
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Volume 29 (1978)
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Volume 28 (1977)
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Volume 27 (1976)
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Volume 26 (1975)
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Volume 25 (1974)
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Volume 24 (1973)
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Volume 23 (1972)
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Volume 22 (1971)
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Volume 21 (1970)
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Volume 20 (1969)
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Volume 19 (1968)
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Volume 18 (1967)
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Volume 17 (1966)
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Volume 16 (1965)
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Volume 15 (1964)
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Volume 14 (1963)
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Volume 13 (1962)
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Volume 12 (1961)
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Volume 11 (1960)
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Volume 10 (1959)
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Volume 9 (1958)
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Volume 8 (1957)
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Volume 7 (1956)
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Volume 6 (1955)
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Volume 5 (1954)
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Volume 4 (1953)
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Volume 3 (1952)
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Volume 2 (1951)
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Volume 1 (1950)
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Volume 0 (1932)