Alesse

By P. Kalan. Florida Southern College.

Am J Psychiatry 1952;108: residents to rate seizure regularity? ECT technique: electrode placement best alesse 0.18 mg, stimulus type alesse 0.18mg otc, Convuls Ther 1994;10(2):153–164 alesse 0.18mg with mastercard. Cerebral blood flow and metabolic rate during sei­ of electroconvulsive therapy purchase alesse uk, vol. Effects of electroconvulsive sant medications and short-term clinical response to ECT [see therapy on EEG and cerebral blood flow in depression. The cerebral hemody­ intensity and electrode placement on the efficacy and cognitive namic response to electrically induced seizures in man. Brain effects of electroconvulsive therapy [see comments]. A prospective, raphy and autoradiographic studies of glucose utilization follow­ randomized, double-blind comparison of bilateral and right uni­ ing electroconvulsive seizures in humans and rats. Ann NY Acad lateral electroconvulsive therapy at different stimulus intensities Sci 1986;462:263–239. Treatment and clinical re­ erately suprathreshold vs fixed high-dose right unilateral electro­ sponse. Quantitative studies of slow wave activity age on quality of life in depressed inpatients. Relationship of electroencephalographic therapy is associated with superior symptomatic and functional delta activity to behavioral response in electroshock. Arch Neurol change in depressed patients after psychiatric hospitalization. Antidepressant effects of high- convulsive therapy on quantitative electroencephalograms. Rela- dose right unilateral electroconvulsive therapy. Arch Gen Psy­ tionship to clinical outcome [see comments]. Electroconvulsive therapy requires higher dosage lev­ 39. Effect of series of electro­ els: Food and Drug Administration action is required [com­ shock treatments on cerebral blood flow and metabolism. The anticonvulsant hypothesis of the mechanisms of selective serotonin reuptake inhibitors and tricyclics in the of action of ECT: current status. Delusional depression and electro­ ment, and number of treatments. Arch Gen Psychiatry 1987; convulsive therapy: one year later. Continuation therapy after and resistant depression: clinical implications of seizure thresh- ECT for delusional depression: a naturalistic study of prophylac­ old [see comments]. The impact of threshold, and the antidepressant efficacy of electroconvulsive medication resistance and continuation pharmacotherapy on therapy. American Psychiatric Association Task Force on 179–189. Relationship of sei­ apy: recommendations for treatment, training and privileging. Convuls Ther Washington, DC: American Psychiatric Press, 1978. Is postictal electrical in the private psychiatric hospital. J Clin Psychiatry 1985;46: silence a predictor of response to electroconvulsive therapy? The efficacy of apy for depression using outpatient electroconvulsive therapy. Endogenous anticonvulsant substance in Psychiatr Scand 1987;75(6):559–562. The use of maintenance Chapter 76: Electroconvulsive Therapy 1107 electroconvulsive therapy for relapsing depression. Jefferson J ECT in major depression and adverse cognitive effects: role of Psychiatry 1988;6:52–58. Comparison of bifrontal of electroconvulsive therapy. Asymmetric bilateral right frontotemporal left fron­ 73. Use of mainte­ tal stimulus electrode placement for electroconvulsive therapy. The efficacy and safety stimulation of human motor cortex [letter]. Lancet 1985; of maintenance ECT in geriatric patients. Pascual-Leone A, Valls-Sole J, Wassermann EM, et al. Maintenance sponses to rapid-rate transcranial magnetic stimulation of the ECT for treatment of recurrent mania [letter]. Cost reduction and stimulation: a neuropsychiatric tool for the 21st century. J Neu­ maintenance ECT in refractory bipolar disorder. J Ect 1998; ropsychiatr Clin Neurosci 1996;8(4):373–382. Continuation electroconvulsive therapy in a new repetitive transcranial magnetic stimulator. J Med Assoc Thailand 1997;80(5): alogr Clin Neurophysiol 1996;101(5):412–417. Lancet 1954;2: excitability by low-frequency transcranial magnetic stimulation. Does electroconvulsive therapy cause brain dam- cortex. Does ECT stimulation mimics the effects of ECS in upregulating astroglial alter brain structure? Am J Psychiatry 1994; gene expression in the murine CNS. A prospective magnetic resonance stimulation: applications in neuropsychiatry [comment]. Prefrontal cortex dysfunction induced memory disturbances. Naloxone in the tive transcranial magnetic stimulation (rTMS) improves mood prevention of the adverse cognitive effects of ECT: a within- in depression. Pascual-Leone A, Catala MD, Pascual-Leone Pascual A. Double-blind controlled electroconvulsive therapy: preliminary findings. Biol Psychiatry investigation of transcranial magnetic stimulation for the treat­ 1991;30(6):623–627. J Neuropsychiatr Clin Neurosci 1998;10(1): evaluation of vasopressin for ECT-induced memory impair­ 20–25. ACTH4-10 and memory in ECT- repetitive transcranial magnetic stimulation in treatment-resis­ treated and untreated patients. Dexamethasone magnetic stimulation in patients with depression: a placebo- in electroconvulsive therapy: efficacy for depression and post- controlled crossover trial [see comments]. A randomized effect on memory after electroconvulsive therapy. Neuropsycho­ clinical trial of repetitive transcranial magnetic stimulation in biology 1990;24(4):165–168. Substitution of rapid transcranial magnetic stimula­ 126. Combining SPECT tion treatments for electroconvulsive therapy treatments in a and repetitive transcranial magnetic stimulation (rTMS): left course of electroconvulsive therapy.

Lithium prophylaxis of randomized 0.18mg alesse with amex, controlled studies of acute bipolar mania and depression in bipolar I purchase alesse online now, bipolar II and unipolar patients purchase alesse 0.18 mg without prescription. A double-blind randomized purchase 0.18 mg alesse visa, controlled maintenance studies of patients with comparison of valproic acid and lithium in the treatment of bipolar disorder. Importance of psychiatric diagnosis in prediction of 29. A molecular mechanism for the effect mood disorders. Griel W, Kleindienst N, Erazo N, Muller-Oerlinghausen B. CBZ in the maintenance treatment of BDs: a randomized study. CBZ versus chlorpromazine prophylaxis in bipolar patients. Arch Gen Psychiatry 1991;48: in mania: a double-blind trial. Protein kinase C signaling in the brain: dam: Excerpta Medica, 1984:177–187. Biol in acutely manic and depressed bipolar I patients. Signaling: cellular insights into the path- ophysiology of bipolar disorder. Lithium at 50: have the neuro- chiatry 1990;47:665–671. Prophylactic lithium the pathophysiology and treatment of bipolar affective disorder. Lamotrigine compared with lithium tions: mechanisms of action. Washington, DC:American Psychi- in mania: a double-blind randomized controlled trial. Comparative effects dence for the neurotrophic and effects of mood-stabilizing of lithium and chlorpromazine in the treatment of acute manic agents: implications for the pathophysiology and treatment of states. Pharmacologic agents for the treat- imipramine in the prophylaxis of unipolar and bipolar II illness. Keck, PE, Jr, Ice K, and the Ziprasidone Study Group. Clinical and re- American Psychiatric Association Annual Meeting. Chicago, IL, search implications of the diagnosis of dysphoric or mixed mania May 13–15, 2000. Anticonvulsants in tial treatment of acute psychotic mania. Neuropsychobiology 1993;27: outcome of bipolar patients following hospitalization for a 146–149. Prophylactic lithium: a double-blind trial in recurrent 46. VPA as adjunct to neuro- choses by the administration of lithium salts. J Neurol Neurosurg leptic medication in the treatment of acute episodes of mania. Outcome of BD on lithium and haloperidol in mania: a double-blind randomized long-term treatment with lithium. A preliminary double- in mania: a controlled comparison of lithium carbonate, chlor- blind study on the efficacy of CBZ in prophylaxis of manic- promazine and haloperidol. CBZ compared with manic efficacy of CBZ and chlorpromazine: a double-blind con- lithium in the treatment of mania. A pilot study of disorder: a placebo-controlled trial of adjunctive therapy. Gaba- lithium carbonate plus divalproex sodium for the continuation and maintenance treatment of patients with bipolar I disorder. Bipolar Disord 2000;2: J Clin Psychiatry 1997;58:95–99. Lithium prophylaxis of lithium and chlorpromazine in the treatment of manic states. The comparative efficacy An assessment in a lithium-prophylaxis study. Lancet 1974;1: and safety of CBZ versus lithium: a randomized, double-blind 619–620. A comparison of lithium carbonate and chlorpro- in affective disorders, III: a double-blind study of prophylaxis mazine in mania. Efficacy of lithium ment of acute mania: a placebo-controlled study. Arch Gen Psy- as acute treatment of manic-depressive illness. Comparison of lithium car- patients with treatment-resistant illness and a history of mania. Differential effect ium carbonate in manic-depressive illness. Report of the Veter- of previous episodes of affective disorder on response to lithium ans Administration and National Institute of Mental Health or divalproex in acute mania. Lithium carbonate and imi- of lithium carbonate and chlorpromazine in mania: report of pramine in prevention of affective episodes. Arch Gen Psychiatry collaborative study group on treatment of mania in Japan. Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled Psychopharmacology Bull 1990;26:409–427. The effect of stabilizers in the treatment of manic phase of BD [abstract]. CBZ and lithium on remission from affective illness. Although forms of dementia arising late in life had been tions account for nearly half of the families with autosomal identified by Kraepelin and his colleagues in the 1800s, it dominant early-onset AD (2). In FAD, a single gene defect, was not until 1907 that Alois Alzheimer identified the pre- interacting with the brain aging process, causes the disease senile form of dementia with unique neuropathologic fea- (reviewed in Chapter 83). However, in the other 90% of tures that now bears his name. Alzheimer described a 51- cases, designated sporadic AD, the emergence of disease is year-old woman who presented with personality changes influenced by environmental factors as well as by multiple and soon developed progressively worsening memory loss, genes with either neuroprotective or disease-facilitating ef- disorientation to time, and language disturbances but who fects. Although all forms of AD, by definition, share com- had relatively normal neurologic function. Mental deterio- mon neuropathologic features, the metabolic antecedents ration progressed, and she died 41⁄ years later. On autopsy, of this pathology in sporadic forms of the disease are poorly 2 her brain showed clear evidence of cerebral atrophy. Much is known about the genetic forms of the microscope, Alzheimer discovered that many cortical AD, yet issues as fundamental as the anatomic and cellular neurons contained argyrophilic fibrous structures—neuro- substrate of cognitive decline, the toxic cascades mediating fibrillary tangles (NFTs)—now known to be mainly com- cell degeneration, and the roles of A , -amyloid, and tau posed of abnormal filamentous forms of the microtubule- in the neurodegenerative process are just now being re- associated protein, tau. In this chapter, a discussion of Alzheimer neuropath- regions were extracellular plaquelike lesions. These neuritic ology provides the starting point for understanding how the or 'senile' plaques were later discovered to contain -amy- diagnosis of AD is made and how clinical symptoms arise loid, a fibrillar form of the A peptide, as their signature and progress. Later sections address the neuroanatomic and constituent. In 1910, Kraepelin proposed that this neuro- cellular basis for dementia and the molecular events that pathologic picture was pathognomic of a new presenile de- lead to neuropathologic lesions and, ultimately, to the death menting disease and introduced the eponym Alzheimer dis- of neurons. A consideration of current hypotheses on the ease (AD).

Am J intellectual impairment and mood disorder in the first year after Psychiatry 2000;157:351–359 cheap alesse 0.18mg without a prescription. Dementia of depres- cally ill hospitalized older adults: prevalence order alesse no prescription, characteristics purchase 0.18mg alesse overnight delivery, and sion or depression of dementia in stroke? Acta Psychiatr Scand course of symptoms according to six diagnostic schemes order alesse 0.18mg on-line. RYAN This chapter discusses critical conceptual and practical is- events. Today, as detailed by Keller and Kovacs (3), clinical sues confronting clinicians who must distill the massive neu- depressions are now recognized as far more chronic, more roscientific, psychopathologic, and clinical research infor- often recurrent (typically with a waxing and waning course), mation about the basis for clinical depression and its and more disabling. Historically, symptom severity has been treatment and who must apply that knowledge to individual used to distinguish different forms of depression (e. This chapter does not provide an encyclopedic depressive disorder versus dysthymia). More recent evi- review of antidepressant treatments. A more chronic course and greater symptom severity ment, and on practical dilemmas encountered in daily prac- both contribute to greater levels of disability. The latter often calls for types of information not prevalence rates and the degree of disability found in non- usually provided by standard clinical research protocols de- major forms of depression provide a basis for regarding even signed to obtain regulatory approval of new antidepressant modest levels of nontransient depressive symptoms as a agents. Consequently, efficacy studies After highlighting recent revisions in our knowledge have been undertaken with more chronic forms of depres- about depressive disorders, we discuss the implications of sion (9–11) and with 'nonmajor' forms of depression (e. We conclude with suggestions for further re- such as with myocardial infarction (24,25), stroke (26), de- search. Only two decades ago, clinical depression was seen as a That is, a chronic course may entail the development of an transient, typically self-limited reaction to 'untoward' underlying neurobiology that renders treatments less effec- tive acutely or over the longer term. Such an inference is suggested by apparently longer times to develop responses A. John Rush: Department of Psychiatry, University of Texas Southwest- and remissions in studies of chronic (10,11) as opposed to ern Medical Center, Dallas, Texas. Ryan: Western Psychiatric Institute & Clinic, University of nonchronic forms of depression (32,33). This recent em- Pittsburgh Medical Center, Pittsburgh, Pennsylvania. In many such cases, patient remission and full functional restoration (not simply re- preference with careful clinical monitoring, once therapy is sponse) are the targets of treatment. This conceptual shift has profound implications for prac- tice and development and use of newer agents. It also pro- vides a rationale for combining treatments when a mono- TRANSLATING KNOWLEDGE TO PRACTICE therapy does not lead to remission. Only a few clinical clues that recommend nature of these conditions. Whether different levels of func- one treatment over another have been established scientifi- tional impairment in the context of equivalent levels of re- cally. For example, the greater acute phase efficacy of mono- sidual symptoms herald a worse prognosis has yet to be amine oxidase inhibitors (MAOIs) as compared to tricyclic demonstrated. Furthermore, recent studies (21–23) suggest antidepressants (TCAs) in depressions with atypical symp- psychotherapy that effectively removes residual symptoms tom features is well established in double-blind, placebo- also improves prognosis, which in turn may reduce the need controlled trials (44,45). Furthermore, the greater efficacy for long-term maintenance medication. The need to most On the other hand, many practical dilemmas are con- aggressively pursue full symptom remission (also called fronted in routine practice, yet knowledge is sparse to ad- complete response), rather than to accept a clinically signifi- dress these issues. This lack of practical knowledge grounded cant reduction in symptoms (a response) is now accepted in empirical evidence, can be attributed to several factors: (a) because of the worse prognosis and functional impairment insufficient investment in clinical research that goes beyond associated with residual symptoms noted in the preceding. Mainte- conducted for regulatory purposes and representative prac- nance aims at preventing a new depressive episode—a recur- tices. When continuation ends and maintenance begins for Patients with minimally treatment-resistant, or non- an individual is unclear, although classically recovery from chronic forms of depressions enter trials. These patients are: the episode is estimated by when the episode would have (a) rarely severely ill; (b) rarely inpatients; (c) never psy- spontaneously ended based on the duration of prior epi- chotic; (d) rarely encumbered by common concurrent Axis sodes, if such information is available. The need for more III (general medical) or other Axis I (psychiatric) disorders; prolonged (i. Perhaps as a consequence, placebo response rates exactly how long to provide antidepressant treatment re- are often substantial (e. Consensus strongly recommends providing a 50% to 60% response rate (34). These recommenda- proval and the procedures characteristic of current practice. Whether patients with two episodes of major fore, also to adjust dosages); (c) use more frequent treatment depression plus a risk factor for recurrence should also be visits; (d) limit acute phase trial durations (e. Furthermore, recent regulatory and mar- toms with normalization of function) to define a clinical ket forces have encouraged studies in depressed children, 'success,' contrary to clinical practice recommendations adolescents, and geriatric patients. The National Institute of Mental Health (NIMH) has Routine clinical diagnoses often sharply disagree with recently begun to address some of the knowledge gaps noted those established by structured interviews (51) (Kashner et in the preceding by emphasizing effectiveness trials of anti- al. In addition, global judg- depressant treatments in children/adolescents, adults, and ments of the severity of illness, even if codified by the Clini- geriatric patients. The emphasis (50) was based on the reali- cal Global Impression-Improvement Scale (CGI-I) (52), zation that efficacy trials for regulatory approval are only may relate only modestly to symptom severity ascertained by the first step in defining a treatment. That is, they establish itemized clinician ratings, such as the Montgomery-Asberg˚ the safety and efficacy of an agent in carefully conducted, Depression Rating Scale (MADRS) (53) or the Hamilton highly internally valid designs. Generalizability of tolerabil- Rating Scale for Depression (HRS-D) (54,55) or the Inven- ity and efficacy findings requires different study designs. These When to use one as opposed to another agent (alone or in differences in clinical procedures used in efficacy RCTs and combination) requires still different study designs. For example, there is a reasonably strong basis DEPRESSION to believe that medications differ in their spectrum of ac- tions (1). That is, some patients/depressions respond to one Clinicians routinely confront a host of practical questions agent, whereas others respond to a different agent (58,59), that are not addressed in efficacy RCTs designed for regula- especially if the medications differ regarding presumed tory approval. These questions include the following: mechanisms of action. What is the 'next best' treatment following either an 'fit' into a multistep treatment plan is often left to tenuous unsatisfactory clinical response or intolerance to the inferences based on presumed mechanisms of action, to 'ex- first agent? What is a sufficient trial duration beyond which re- How to treat depressions that respond minimally or partially sponse is not likely (minimal duration)? What is a sufficient trial duration for those benefiting Perhaps pharmaceutical companies are reluctant to from the treatment beyond which further treatment search for specific indicators of when an agent is preferred (unchanged) is unlikely to produce any more sympto- or to study agents used as second or third steps in treatment- matic or functional improvement (maximal duration)? When is it best to augment the first agent with a second tors. Without specific indications of when to use an agent, treatment? When is it best to switch from the first agent a 'broad' spectrum of action can be claimed. Do antidepressants differ in their ability to produce largely avoided by the pharmaceutical industry, perhaps in response or remission, and if so, for which depression fear of finding that their agent will not fare as well as a is each better? Do different medications differ in the time to onset of economic forces within the industry provide a strong impe- clinical benefit or time to remission? What treatments are recommended if there is a return vital—information (e. Selecting the Initial Treatment In spite of these knowledge gaps, the industry has devel- oped a large number of newer antidepressants that are sim- All antidepressant medications have established efficacy in pler to take, better tolerated, and safer in overdose. Some even have placebo-con- 1084 Neuropsychopharmacology: The Fifth Generation of Progress trolled evidence supporting efficacy in dysthymic disorder drug–drug interactions, or likelihood of remission play a (sertraline) (15) or other 'nonmajor' disorders, such as pre- major role in selecting the first agent. However, when to How to Select the 'Next Best' Treatment select one over another agent is not well defined. Clinicians following an Unsatisfactory Response (or use 'rules of thumb' to make these judgments, but such Intolerance) to the First Agent reasonable guesses are rarely supported by prospective RCT evidence.

The second part of this chapter examines the renal complications in patients with human immunodeficiency virus (H IV) infection buy alesse now. O ur knowledge about H IV has increased greatly purchase discount alesse line, and dram atic advances have occurred in the treatm ent of patients with acquired im m unodeficiency syndrom e (AIDS) generic alesse 0.18mg fast delivery. For the first tim e since the dis- C H A P T ER covery of the disease cheap alesse 0.18mg overnight delivery, deaths are decreasing. N evertheless, in the United States, as of June 30, 1997, there were over 600,000 cum ula- tive cases of H IV infection, with over 400,000 deaths. W orldwide, the H IV epidem ic continues to spread; an estim ated 20 m illion per- sons are infected with H IV. Recent advances in the clinical m anage- m ent of these patients result from better understanding of the repli- cation kinetics of H IV, assays to m easure viral load, availability of 7 7. The incidence of renal aggressive protocols com bining antiviral drugs substantially com plications in this population is expected to increase further reduce H IV replication. Thus, prolonged survival of patients as patients live longer. Hepatitis B and C Virus FIGURE 7-1 RENAL DISEASE ASSOCIATED W ITH Renal disease associated with hepatitis B. Infection with HEPATITIS B VIRUS INFECTION hepatitis B virus (H BV) m ay be associated with a variety of renal diseases [1,2]. M any patients are asym ptom atic, with plas- m a serology positive for hepatitis B surface antigen (H BsAg), hepatitis B core antibody (H BcAb), and hepatitis B antigen Lesion Clinical presentations Pathogenesis (H BeAg). The pathogenetic role of H BV in these processes has Membranous nephropathy Nephrotic syndrome Deposition of HBeAg been docum ented prim arily by dem onstration of hepatitis B anti- with anti-HBeAb gen-antibody com plexes in the renal lesions [1,3,4]. Three m ajor Polyarteritis nodosa Vasculitis, nephritic Deposition of circulating form s of renal disease have been described in H BV infection. In antigen-antibody m em branous nephropathy, it is proposed that deposition of complexes H BeAg and anti-H Be antibody form s the classic subepithelial Membranoproliferative Nephrotic, nephritic Deposition of complexes im m une deposits [1,3–5]. Polyarteritis nodosa is a m edium -sized glomerulonephritis containing HBsAg and vessel vasculitis in which antibody-antigen com plexes m ay be HBeAg deposited in vessel walls [1,2]. Finally, m em branoproliferative glom erulonephritis is characterized by deposits of circulating HBeAg— hepatitis B antigen; HBsAg— hepatitis B surface antigen. Furtherm ore, evidence exists suggesting direct involve- m ent of H CV-containing im m une com plexes in the pathogenesis of Disease Renal manifestations Serologic testing this renal disease. Sansono and colleagues dem onstrated Mixed cryoglobulinemia Hematuria, proteinuria Positive cryoglobulins; H CV-related proteins in the kidneys of eight of 12 patients with [6–11] (often nephrotic), rheumatoid factor cryoglobulinem ia and m em branoproliferative glom erulonephritis variable renal insufficiency often present (M PGN ) by indirect im m unohistochem istry. Convincing clinical Membranoproliferative Hematuria, proteinuria Hypocomplementemia; data exist suggesting that H CV is responsible for som e cases of glomerulonephritis (often nephrotic) rheumatoid factor and cryoglobulins may be M PGN and possibly m em branous nephropathy [13–15]. In one present report of eight patients with M PGN , purpura and arthralgias were Membranous Proteinuria Complement levels normal; uncom m on and cryoglobulinem ia was absent in three patients. Establishing the diagnosis of H CV infection in these diseases is im portant because of the potential therapeutic benefit of -interferon treatm ent. A num ber of reports exist FIGURE 7-2 that dem onstrate a beneficial response to chronic antiviral therapy Renal disease associated with hepatitis C. H epatitis C virus (H CV) with -interferon [6,13,16,17]. Even m ore com pelling evidence for infection is associated with parenchym al renal disease. Chronic a beneficial effect of -interferon in H CV-induced m ixed cryoglob- H CV infection has been associated with three different types of ulinem ia was dem onstrated in a random ized prospective trial of 53 renal disease. Type II or essential m ixed cryoglobulinem ia has been patients given either conventional therapy alone or in com bination strongly linked with H CV infection in alm ost all patients with this with -interferon. Because of the likely recurrence of virem ia disorder [6–11]. The clinical m anifestations of this renal disease and cryoglobulinem ia with cessation of -interferon therapy after include hem aturia, proteinuria that is often in the nephrotic range, conventional treatm ent (3 106 U three tim es weekly for 6 m o), and a variable degree of renal insufficiency. Essential m ixed cryo- extended courses of therapy (up to 18 m o) and higher dosing regi- globulinem ia had been considered an idiopathic disease; however, m ens are being studied [19–21]. Renal Disease in Patients Infected with Hepatitis and Human Immunodeficiency Virus 7. Electron m icroscopy of m em branoproliferative glom erulonephritis M icrograph of a biopsy showing membranoproliferative glomeru- from the biopsy specim en shown in Figure 7-3. M esangial cell lonephritis (M PGN) in a patient with hepatitis C virus (HCV) infec- interposition is noted with increased m esangial m atrix. A lobulated glomerulus with mesangial proliferation and an subendothelial im m unocom plex deposits are noted. Fusion of the increase in the mesangial matrix are seen. Although still an idiopath- epithelial cell foot processes also is seen. It has been suggested that the decline in the incidence of idiopathic type 1 M PGN may be partly a result of more careful screening by blood banks, leading to a decrease in the overall incidence of HCV infection and subsequent glomerulonephritis. Envelope Protein W ORLDW IDE PREVALENCE OF ANTI–HEPATITIS C Capsid glycoproteins helicase Replicase AM ONG PATIENTS ON DIALYSIS 341 Nucleotides Open-reading C E1 E2 NS2 NS3 NS4a NS4b NS5a NS5b frame 5-1-1 Continent ELISA-1 positive, % North America [25–29] 8–36 C200 Epitope South America 39 Europe [31–41] 1–54 Asia [42–49] 17–51 C22-3 C33c C100-3 New Zealand and Australia [50,51] 1. Patients receiving Diagnostic tests for HCV infection. In 1989, hepatitis C virus (HCV) dialysis clearly are at greater risk for acquiring hepatitis C virus was cloned and identified as the major cause of parenterally transmit- (H CV) infection than are healthy subjects, based on the seropreva- ted non-A, non-B hepatitis. The first serologic test for HCV lence of anti-H CV antibodies am ong patients with end-stage renal employed an enzyme-linked immunosorbent assay (ELISA-1) that disease. These results of ELISA-1 testing likely underestim ate true detected a nonneutralizing antibody (anti-HCV) to a single recombi- positivity because studies have dem onstrated a nearly twofold nant antigen. Limitations of the sensitivity and specificity of this test increase in seropositivity when screening dialysis patients with the led to development of second-generation tests, ELISA-2 and a recom- ELISA-2 assay. Additional studies have dem onstrated that binant immunoblot assay (RIBA-2). The standard for identifying m ost patients receiving dialysis who have anti-H CV seropositive active HCV infection remains the detection of HCV RNA by reverse test results have circulating H CV RN A by polym erase chain reac- transcriptase polymerase chain reaction. N um erous studies have dem onstrated a strong POPULATION W ITH END-STAGE association between the prevalence of hepatitis C virus (H CV) infection am ong patients RENAL DISEASE AND HEPATITIS receiving dialysis and both the num ber of transfusions received and duration of dialysis C VIRUS INFECTION [53,61]. Although these two variables are related, the prevalence of anti-H CV in these patients has been shown to be independently associated with both factors by regression analysis. In contrast to patients receiving hem odialysis, patients receiving peritoneal dialy- Transfusions [24,27,30,32,54–57] sis consistently have a lower prevalence of anti-H CV antibody [60–70]. M oreover, units Duration of end-stage renal disease with a low prevalence of anti-H CV have been shown to have a lower seroconversion rate [29,30,32,35,37,53–61]. The latter two observations coupled with the independent association of duration of Mode of dialysis [60–70] dialysis with seropositivity argue in favor of nosocom ial transm ission of H CV in hem o- Prevalence of hepatitis C virus infection dialysis units. This conclusion is further supported by data showing a decreased incidence in the dialysis unit [71,72] of H CV seroconversion in dialysis units em ploying isolation and dedicated equipm ent for patients who test positive for H CV infection. FIGURE 7-8 TRANSM ISSION OF HEPATITIS C Transm ission of H CV during dialysis. Convincing data are available that dem onstrate an VIRUS IN HEM ODIALYSIS UNITS increased risk of anti-H CV seroconversion associated with both a failure to strictly follow infection control procedures and the perform ance of dialysis at a station im m ediately adja- cent to that of a patient testing positive for anti-H CV [71–75]. Units using dedicated Breakdown in universal precautions [73,74] m achines have shown a decreased incidence of seroconversion. The literature provides Dialysis adjacent to an infected patient [71,75] conflicting data on the likelihood of passage of H CV RN A into dialysis ultrafiltrate and the risk of contam ination by reprocessing filters [71,72,76–78]. At this tim e the Centers Dialysis equipment [46,60] for Disease Control does not recom m end that patients who are H CV positive be isolated Type of dialyzer membrane [76–78] or dialyzed on dedicated m achines and has no official policy concerning reuse of m achines Reuse [71,72] in these patients. FIGURE 7-9 Liver disease am ong anti-H CV–positive dialysis patients. Serum alanine am inotransferase levels are elevated in only 24% to 67% Chronic active of dialysis patients who test positive for the anti-hepatitis C virus Cirrhosis hepatitis (H CV). Caram elo and colleagues evaluated liver biopsies Pericentral 9% 42% from 33 patients on hem odialysis who tested positive using ELISA-2 fibrosis and found a variety of histologic patterns; however, over 50% of 3% these patients had chronic hepatitis or cirrhosis. N o correlation has been found between m ean levels of serum am inotransferase and Other Hemosiderosis severity of liver disease. At this tim e, liver biopsy is the only 6% 15% Reactive reliable m ethod to determ ine the extent of hepatic injury in patients hepatitis Chronic with end-stage renal disease infected with H CV. Liver function tests 18% persistent hepatitis and H CV serology testing m ay help identify patients who are at risk 6% for liver disease. H owever, a liver biopsy should be obtained before initiating therapy or as part of the evaluation before transplanta- tion.