LIST REFERENCES LIST REFERENCES A) EPSTEIN-BARR VIRUS 4785 D) INFECTIOUS MONONUCLEOS 3417 B) CHRONIC 76828 E) *ON B&D 46 C) *ON A&B 83 *** *** *****AMERICAN JOURNAL OF DISEASES OF CHILDREN***** 85145766 Herrod HG Wang WC Sullivan JL Chronic T-cell lymphocytosis with neutropenia. Its association with Epstein-Barr virus infection. AM J DIS CHILD 1985 Apr; 139(4):405-7 Chronic T-cell lymphocytosis with neutropenia has primarily been reported in adults. We have cared for a 14-year-old patient with this condition for over five years. This patient consistently had greater than 90% lymphocytes in his differential cell count. The majority of these cells had the OKT8 phenotype. Serologic studies demonstrated evidence for a chronic Epstein-Barr infection with elevated antibody titers to both early antigen and to the viral capsid antigen. Patients presenting with this condition should be carefully evaluated for possible viral infection. Department of Pediatrics University of Tennessee Center for the Health Sciences Memphis *****ANNALS OF ALLERGY***** 88021984 Steeper TA Horwitz CA Henle W Henle G Selected aspects of acute and chronic infectious mononucleosis and mononucleosis-like illnesses for the practicing allergist. ANN ALLERGY 1987 Oct; 59(4):243-9 The diagnosis of EBV-IM or a heterophil-negative mononucleosis-like syndrome is best approached by combining morphologic and serologic data. The minimal hematologic criteria should always be searched for before accepting a case as IM or an IM-like illness. If minimal morphologic data are not rigidly adhered to, the number of heterophil- negative cases included under the umbrella of IM or an IM-like illness will swell and include a variety of other illnesses where early diagnosis may be important for treatment purposes. When EBV studies are indicated, the entire profile (VCA-IgM, VCA-IgG, and anti- EBNA) should be performed. Anti-VCA-IgG titers alone, for example, are of very limited usefulness unless they are negative (less than 1:10), in which case the diagnosis of EBV-IM is excluded. The main problems connected with the diagnosis of the CMS center about the nonspecificity of both clinical and EBV serologic data. Thus, a significant effort must be made to rule out underlying disease, especially those chronic illnesses with immunosuppressive effects that are capable of reactivating the EBV latency state and producing EBV serology similar to that seen in CMS. Other dilemmas relate to diagnostic cut-off levels for particular EBV-related tests, including antibodies to EA and the relative unavailability of several tests for detection of subtle immunodeficiency or T-cell dysfunction in individual patients with suspected CMS. Future efforts will be directed to the diagnostic usefulness of antibody responses to well- defined recombinant fragments of the EBV genome (ie, anti-EBNA1 vs. - EBNA2 titers). Mount Sinai Hospital Minneapolis Minnesota. *****ANNALS OF INTERNAL MEDICINE***** 83072951 Ballow M Seeley J Purtilo DT St. Onge S Sakamoto K Rickles FR Familial chronic mononucleosis. ANN INTERN MED 1982 Dec; 97(6):821-5 A syndrome of chronic mononucleosis occurred in two members of a family. Symptoms were chronic malaise and fatigue; recurrent upper respiratory tract infections; and mild, variable immune abnormalities. Intermittently positive heterophil titers were present for more than 2 years after acute infectious mononucleosis. Epstein- Barr-virus-specific antibodies were persistently abnormal. In the proband, the R component of the early antigen complex was present for 3 years and she never developed normal antibodies to Epstein-Barr nuclear antigen. Her brother had low to absent Epstein-Barr nuclear antigen titers, and antibodies to both the R and D component of the early antigen complex. Primary and acquired immunodeficiency states can show abnormal Epstein-Barr-virus-specific serologic findings that may reflect an attempt by the host to limit virus spread in the presence of deficient immune responses. This action may result in alterations of the Epstein-Barr virus-latent state, and lead to a chronic active infection and a syndrome of chronic mononucleosis. 87182725 Dengler R Thomssen H Volkman M Emmerich B Chronic Epstein-Barr virus infection and human immunodeficiency virus infection [letter] ANN INTERN MED 1987 May; 106(5):775 86185031 Schooley RT Carey RW Miller G Henle W Eastman R Mark EJ Kenyon K Wheeler EO Rubin RH Chronic Epstein-Barr virus infection associated with fever and interstitial pneumonitis. Clinical and serologic features and response to antiviral chemotherapy. ANN INTERN MED 1986 May; 104(5):636-43 Two patients developed fever, interstitial pneumonitis, and pancytopenia associated with extremely high titers of antibody to replicative antigens of the Epstein-Barr virus. In contrast to most patients seropositive for Epstein-Barr virus, neither patient had an antibody response to the Epstein-Barr nuclear antigen K polypeptide. In addition, virus isolated from one patient had a deletion of the B95-8 type in the EcoRI C region of the genome. An etiologic relation between Epstein-Barr virus replication and the clinical manifestations of this syndrome is further shown by the response of each patient to acyclovir therapy. These patients have a new Epstein- Barr-virus-associated syndrome and provide additional evidence that acyclovir may play a role in therapy for selected patients with Epstein-Barr virus infection. Infectious Disease Unit Massachusetts General Hospital Boston 86048970 Tobi M Straus SE Chronic Epstein-Barr virus disease: a workshop held by the National Institute of Allergy and Infectious Diseases. ANN INTERN MED 1985 Dec; 103(6 ( Pt 1)):951-3 National Cancer Institute Bethesda, MD *****ANNUAL REVIEW OF MEDICINE***** 87211816 Jones JF Straus SE Chronic Epstein-Barr virus infection. ANNU REV MED 1987; 38:195-209 The Epstein-Barr virus (EBV) has been associated with classic infectious mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma, and B-cell lymphomas in primary and secondary immunodeficiency disease. The availability of specific serologic diagnosis of EBV, rather than dependence on heterophile antibody positivity, has broadened the scope of EBV-associated diseases. A chronic neuroasthenia syndrome accompanied by antibody titers to the viral capsid antigen and early antigen of EBV, which are higher than found in asymptomatic individuals, is one such additional EBV- associated syndrome. This paper describes the clinical and laboratory responses to EBV that are present in this chronic syndrome. It then discusses management of these patients and the difficulties in establishing a cause-and-effect relationship between EBV and chronic neuroasthenia along with recommendations for future studies. National Jewish Center for Immunology and Respiratory Medicine Denver Colorado 80206. *****ARCHIVES OF INTERNAL MEDICINE***** 87127149 Mirkin G Tests for mononucleosis and chronic daytime sleepiness [letter] ARCH INTERN MED 1987 Feb; 147(2):211 86241217 Guilleminault C Mondini S Mononucleosis and chronic daytime sleepiness. A long-term follow-up study. ARCH INTERN MED 1986 Jul; 146(7):1333-5 Twelve patients between 14 and 26 years of age, ten with infectious mononucleosis and two with Guillain-Barre syndrome, all of whom were suspected of having had Epstein-Barr viral infection, developed daytime sleepiness. The daytime somnolence was confirmed objectively by polygraphic monitoring seven weeks to 4 1/2 months after the onset of clinical symptoms. The patients have been followed up for three to 12 years. None has had any other neurologic sequelae, but all have disabling daytime sleepiness. Treatment brings only mild relief. A retrospective chart study of 35 patients with infectious mononucleosis did not identify, on the basis of initial clinical symptoms, those patients who developed chronic impairment. Sleep Disorders Clinic and Research Center Stanford University School of Medicine Calif *****ARCHIVES OF OPHTHALMOLOGY***** 87212744 Wong KW DAmico DJ Hedges TR 3d Soong HK Schooley RT Kenyon KR Ocular involvement associated with chronic Epstein-Barr virus disease. ARCH OPHTHALMOL 1987 Jun; 105(6):788-92 Ocular involvement with acute Epstein-Barr virus infection is usually limited to a transient follicular conjunctivitis, although other lesions have been reported. Chronic Epstein-Barr virus infection has recently gained attention, but ocular manifestations have not been emphasized. We describe three patients with chronic infection with prominent ocular involvement. Bilateral uveitis was noted in all patients, ranging from an anterior uveitis that was responsive to steroids to a severe panuveitis with vitritis, cataract, optic disc swelling, and macular edema. In one patient, topical acyclovir ointment resulted in a substantial decrease in the inflammatory reaction when added to systemic acyclovir therapy. Another patient displayed a keratitis that resolved with topical steroid therapy. Cataract and vitreous surgery were also beneficial in the management of these patients. Department of Ophthalmology Harvard Medical School Boston MA 02114. *****ARTHRITIS AND RHEUMATISM***** 88049838 Buchwald D Goldenberg DL Sullivan JL Komaroff AL The "chronic, active Epstein-Barr virus infection" syndrome and primary fibromyalgia. ARTHRITIS RHEUM 1987 Oct; 30(10):1132-6 Fifty patients with primary fibromyalgia who had been followed in an academic rheumatology practice frequently reported symptoms thought to be typical of "chronic Epstein-Barr virus infection," but not of fibromyalgia: recurrent sore throat (54%), recurrent rash (47%), chronic cough (40%), recurrent adenopathy (33%), and recurrent low- grade fevers (28%). In 55% of the patients, illness had begun suddenly, with what seemed to be a viral syndrome. Antibody titers to Epstein-Barr virus in the patients with fibromyalgia, however, were not significantly different from those in age- and sex-matched "healthy" and "unhealthy" control subjects. Department of Medicine Brigham and Women's Hospital Boston MA 02115. *****BLOOD***** 83179266 Herrod HG Dow LW Sullivan JL Persistent epstein-barr virus infection mimicking juvenile chronic myelogenous leukemia: immunologic and hematologic studies. BLOOD 1983 Jun; 61(6):1098-104 Epstein-Barr virus (EBV) infections may induce a diverse clinical picture, ranging from the well characterized infectious mononucleosis (IM) syndrome to the rare X-linked lymphoproliferative syndrome. We describe two unrelated children, a 21-mo-old white boy and a 15-mo- old black girl, who presented with the clinical and laboratory findings characteristically seen in juvenile chronic myelogenous leukemia (JCML). Results of periodic serodiagnostic tests indicated that they likely have persistent infection with EBV. Both had elevated IgG antibody to viral capsid antigen (greater than or equal to 1:320) and antibody to early antigen (1:20-1:40) that have persisted for 3 yr of more. Both patients had EBV-specific suppressor cell activity, decreased natural killer cell activity, and diminished antibody-dependent cell-mediated cytotoxicity (ADCC) activity. These changes suggest an underlying defect in the immunoregulatory network controlling EBV infection. The patients have shown clinical improvement without treatment. It appears that EBV infections are capable of inducing symptoms similar to those seen in JCML. Careful evaluation for evidence of EBV infection in patients presenting with symptoms compatible with JCML seems warranted. *****BRITISH MEDICAL JOURNAL [CLINICAL RESEARCH ED.]***** 83232255 Hamblin TJ Hussain J Akbar AN Tang YC Smith JL Jones DB Immunological reason for chronic ill health after infectious mononucleosis. BR MED J [CLIN RES] 1983 Jul 9; 287(6385):85-8 In a group of patients who suffered from chronic ill health after an attack of acute infectious mononucleosis a disorder of T cell regulation was found. By means of cytochemical reactions the staining pattern associated with T suppressor cells was found in a greater percentage and that associated with T helper cells in a smaller percentage than in normal subjects. In a few patients this finding was confirmed in a functional suppressor assay. The patients were unwell for at least a year but most later made a complete recovery, which was associated with return to normal of the lymphocyte subsets. *****CANADIAN MEDICAL ASSOCIATION JOURNAL***** 85048458 Alfieri C Ghibu F Joncas JH Lytic, nontransforming Epstein-Barr virus (EBV) from a patient with chronic active EBV infection. CAN MED ASSOC J 1984 Nov 15; 131(10):1249-52 A new wild-type isolate of Epstein-Barr virus (EBV) was identified in follow-up studies of a case of chronic active EBV infection in an 8- year-old girl who had high titres of antibody to viral capsid antigen and early antigen (EA) (greater than 20 480 and 2560 respectively), persistent splenomegaly and abnormal immunologic features. More than 10 throat washings from this patient failed to transform cord blood lymphocytes (CBL), but at least 7 were able to induce EA in Raji cells. Supernatants from cultures of the lymphoblastoid cell line obtained by in-vitro infection of this patient's leukocytes with the B95-8 strain of EBV revealed a herpesvirus particle when examined by electron microscopy. The same supernatants were unable to transform CBL but could induce EA in Raji cells upon superinfection. In 30 or more trials the patient's lymphocytes never transformed spontaneously but did become positive for EBV nuclear antigen and EA in the first week of culture at least twice. Parallel studies performed on the father of the patient yielded similar results. This, then, is the first report documenting lytic activity associated with a wild-type EBV isolate. Department of Microbiology and Immunology University of Montreal PQ 84106153 Joncas JH Ghibu F Blagdon M Montplaisir S Stefanescu I Menezes J A familial syndrome of susceptibility to chronic active Epstein-Barr virus infection. CAN MED ASSOC J 1984 Feb 1; 130(3):280-4 In two members of a family (daughter and father) active Epstein-Barr virus (EBV) infections persisted over periods of 4 and 3 years respectively (possibly 10 years in the father). Both had persistent splenomegaly and occasional bouts of unexplained fever but lived otherwise normal lives. The other members of the family (mother and son) were healthy. The titres of antibody to the EBV viral capsid antigen (VCA) and early antigen (EA) were extremely high in the daughter's blood, whereas the titres of antibody to the Epstein-Barr nuclear antigen were low in the daughter's blood and undetectable in the father's. Target cells of the EBV infection that were obtained from the daughter's blood were established in culture with great difficulty and showed increased expression of VCA and EA. Other immunologic investigations in the two patients revealed that the ratio of helper to suppressor T lymphocytes was inverted, natural killer-cell activity was abnormally low, lymphocyte responses to certain mitogens were depressed and there was a serum factor blocking mitogen-induced transformation. The possibility that the patients' unusual susceptibility to EBV infection represented an inherited syndrome (perhaps X-linked) is discussed. 87051147 Berris B Chronic viral diseases. CAN MED ASSOC J 1986 Dec 1; 135(11):1260-8 Until 20 years ago the only chronic viral diseases known were those considered to be confined to the nervous system. As a result of recent advances in epidemiology, molecular biology and immunology, new viral diseases have been recognized and their clinical features and pathogenesis elucidated. Chronic disease may result from infection with the hepatitis B and D viruses and whatever agent or agents cause hepatitis non-A, non-B, the herpesviruses, Epstein-Barr virus, cytomegalovirus and human T-lymphotropic virus type III. These diseases have common features, including long-term or even lifetime asymptomatic carriage, viremia, with virus free in the plasma or attached to circulating mononuclear cells, presence of virus in body secretions, irreversible tissue injury in target organs and oncogenic potential. New information on these diseases is reviewed. Other chronic diseases for which the cause is currently unknown may eventually prove to be due to viral infection. In addition, vaccines may be developed for prophylaxis of some chronic viral diseases and associated malignant diseases. Department of Medicine Mount Sinai Hospital Toronto Ont. *****CANCER RESEARCH***** 83129057 Levitt ML Barry WE Helfrich MK Hecht BK Henderson EE Characterization of Epstein-Barr virus-carrying cell lines established from chronic lymphocytic leukemia. CANCER RES 1983 Mar; 43(3):1195-203 Attempts were made to establish lymphoid cell lines from the cultured peripheral blood lymphocytes of six patients with chronic lymphocytic leukemia. In only one case was cell growth obtained following the addition of exogenous transforming Epstein-Barr virus, and those cell cultures proved not to have acquired the ability to proliferate permanently. In the same case, cell lines were established spontaneously from the peripheral blood without addition of Epstein- Barr virus. The cells which grew spontaneously were large, were occasionally weakly surface adherent, and grew in suspension as loose clumps or as single cells. They were negative for surface immunoglobulins and spontaneous rosette formation with sheep erythrocytes and positive for intracytoplasmic immunoglobulins (Fc and C3 receptors). At an early passage, the spontaneous lines had an aneuploid karyotype with some triploid and some tetraploid cells. Structural chromosomal aberrations include a 14q+. Electron microscopy of the chronic lymphocytic leukemia lines revealed relatively smooth surfaces with numerous mitochondria, widespread vacuolization, and numerous unusual "myelin" figures. Five to 10% of the cells were phagocytic as detected by internalization of latex particles; however, they were Epstein-Barr nuclear antigen positive. The nature of these cells and their possible relationship to the etiology of chronic lymphocytic leukemia are discussed. *****EUROPEAN JOURNAL OF HAEMATOLOGY***** 81152724 Pallesen G Hastrup J Thestrup-Pedersen K Madsen M Histological and immunopathological studies in a case of chronic Epstein-Barr virus infection terminating in a Burkitt-like lymphoma. SCAND J HAEMATOL 1980 Oct; 25(4):347-57 A 6-year-old boy suffered from a severe lymphadenopathy, characterized histologically by a fulminant polyclonal immunoblast proliferation simulating malignant lymphoma with many immunoblasts resembling Reed-Sternberg cells. He had no history of infectious mononucleosis but Epstein-Barr virus (EBV) infection was evident from serological findings, and EBV-associated nuclear antigen (EBNA) was demonstrated in a high percentage of lymphocytes of blood and lymph nodes. An adequate humoral response to EBV ruled out the possibility of an X-linked recessive lymphoproliferative syndrome as the underlying cause of chronic EBV infection. A chromosomal defect in a subpopulation of lymphocytes was induced by interferon and might somehow be associated with a subtle immunodeficiency of our patient. After exacerbation of the disease chemotherapy was included in the treatment but the patient died 9 months after the onset of the disease. At autopsy the lymphoblastic cell proliferation had changed from that of immunoblasts to cells resembling the Burkitt's lymphoma cells. A change of the proliferating cell type was supported by means of cytochemical and immunological cell markers. The presence of EBV in these cells was demonstrated with the EBNA technique. It is concluded that our case may well support the hypothesis, that EBV may induce lymphoma-like polyclonal immunoblast proliferation in immunodeficient individuals, and that occasionally a monoclonal proliferation of the Burkitt's lymphoma type may supervene. *****HOSPITAL PRACTICE (OFFICE EDITION)***** 87222720 Komaroff AL The 'chronic mononucleosis' syndromes. HOSP PRACT [OFF] 1987 May 30; 22(5A):71-5 Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston. *****HUMAN PATHOLOGY***** 86110143 Merlin TL Chronic mononucleosis: pitfalls in the laboratory diagnosis. HUM PATHOL 1986 Jan; 17(1):2-8 Department of Pathology University of New Mexico School of Medicine Albuquerque *****JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY***** 86279335 Olson GB Kanaan MN Kelley LM Jones JF Specific allergen-induced Epstein-Barr nuclear antigen-positive B cells from patients with chronic-active Epstein-Barr virus infections. J ALLERGY CLIN IMMUNOL 1986 Aug; 78(2):315-20 Enriched B cells and peripheral blood lymphocytes from patients with chronic-active Epstein-Barr virus (CA-EBV) infections and subjects with mild and moderate allergies were cultured in vitro with specific allergens known to cause allergic reactions. A significant increase in Epstein-Barr nuclear antigen+ cells occurred only in the B cells obtained from patients with CA-EBV when cells were stimulated with the specific antigen. Results indicate an association between EBV- transformed cells and B cells with idiotypic expressions and may help to explain the association between CA-EBV and allergy in these patients. Department of Microbiology and Immunology University of Arizona Tucson 85721 86279334 Olson GB Kanaan MN Gersuk GM Kelley LM Jones JF Correlation between allergy and persistent Epstein-Barr virus infections in chronic-active Epstein-Barr virus-infected patients. J ALLERGY CLIN IMMUNOL 1986 Aug; 78(2):308-14 Forty-six anti-Epstein Barr nuclear antigen-positive allergic patients, 11 of whom having clinical and laboratory evidence of chronic-active Epstein-Barr virus (CA-EBV) infections, were characterized by EBV serology, percentages of T cells, B cells, and IgE+ cells, serum levels of IgE, and allergen-induced responsiveness of lymphocytes. Results demonstrated patients with CA-EBV have significantly increased responsiveness toward specific allergens, responses toward greater numbers of allergens, numbers of IgE+ T and B cells, and levels of background DNA activity in nonstimulated lymphocytes than do subjects who suffer from allergies in the absence of the CA-EBV syndrome. Further comparison between subjects with laboratory-determined mild and moderate allergy and those with CA-EBV demonstrated a progressive increase in the serum levels of IgE as the degree of allergy increased, no difference in concentrations of T and B cells, and titers of anti-viral capsid antigen and anti-early antigen to be significantly greater in patients with CA-EBV. Statistical analysis demonstrated that patients with CA-EBV could be separated from subjects with allergies by metabolic and immunologic variables. The data suggested that allergen-induced responses may contribute to the CA-EBV syndrome. Department of Microbiology and Immunology University of Arizona Tucson 85721 86279329 Welliver RC Allergy and the syndrome of chronic Epstein-Barr virus infection. J ALLERGY CLIN IMMUNOL 1986 Aug; 78(2):278-81 Department of Pediatrics School of Medicine State University of New York at Buffalo *****JOURNAL OF CLINICAL PSYCHIATRY***** 87033541 Goldstein JA Treatment of chronic Epstein-Barr virus disease with H2 blockers [letter] J CLIN PSYCHIATRY 1986 Nov; 47(11):572 *****JOURNAL OF IMMUNOLOGY***** 85159019 Tosato G Straus S Henle W Pike SE Blaese RM Characteristic T cell dysfunction in patients with chronic active Epstein-Barr virus infection (chronic infectious mononucleosis). J IMMUNOL 1985 May; 134(5):3082-8 We evaluated immune functions in 16 patients with chronic active Epstein-Barr virus (EBV) infection (chronic infectious mononucleosis). Chronic infectious mononucleosis is an illness characterized primarily by chronic and occasionally disabling fatigue and other constitutional complaints, only sometimes beginning with an episode of acute infectious mononucleosis, and associated with an abnormal pattern of serum antibodies to EBV. In these patients, the frequency of circulating EBV-infected B cells that manifested spontaneous outgrowth in vitro was comparable to that found in EBV- seropositive normals, and the levels of EBV-specific suppressor activity were also normal. Upon stimulation with polyclonal activators, unseparated cells from these patients produced a relatively normal number of immunoglobulin-secreting cells. However, when purified T cells from these patients were mixed with normal mononuclear cells in co-culture, immunoglobulin production was strikingly suppressed. The degree of this T cell suppression correlated directly with the abnormally elevated titer of antibody to the early antigens of EBV. Interestingly, during normal convalescence from acute EBV-induced infectious mononucleosis a period is also seen during which T cells suppress the response of allogeneic but not autologous cells. Thus, from an immunologic viewpoint, patients with chronic active EBV infection appear "frozen" in a state typically found only briefly during the convalescence from acute EBV infection. Metabolism Branch National Cancer Institute Bethesda, MD 20205 *****JOURNAL OF INFECTIOUS DISEASES***** 87252414 Miller G Grogan E Rowe D Rooney C Heston L Eastman R Andiman W Niederman J Lenoir G Henle W et al Selective lack of antibody to a component of EB nuclear antigen in patients with chronic active Epstein-Barr virus infection. J INFECT DIS 1987 Jul; 156(1):26-35 The sera of 12 patients with presumed chronic active Epstein-Barr virus (EBV) infection lacked antibody to a component of the Epstein- Barr nuclear antigen (EBNA) complex encoded by the BamHI K fragment of viral DNA. This anomaly, detected in approximately 18% of sera obtained from patients with a diagnosis of "chronic mononucleosis," was more often found in patients with severe disease (approximately 32%) who had objective clinical findings and markedly elevated antibody titers to EBV replicative antigens than in those patients with the "fatigue syndrome" (10%). The lack of antibody to the K nuclear antigen is specific because most of those who did not have antibody to the K antigen made antibody to other latent nuclear (EBNA 2) antigens or nuclear early antigens. Such patients are thus able to lyse immortalized cells, release nuclear products, and present them to the immune system. Three hypotheses are suggested to explain the lack of antibody to the K antigen: a viral mutation, a failure of immune recognition, or lack of in vivo expression of the antigen due to extensive viral replication. Lack of antibody to one component of EBNA may serve as an objective serological marker for certain patients with chronic EBV infection. Department of Pediatrics Yale University School of Medicine New Haven Connecticut 06510-8064. 87252391 Minuk GY Sekla LH Nicolle LE Serological markers for Epstein-Barr virus infection in chronic carriers of hepatitis B surface antigen who live in northern Canada. J INFECT DIS 1987 Jul; 156(1):202-4 Department of Medicine University of Calgary Alberta Canada. 85132890 Chang RS Thompson H Pomerantz S Epstein-Barr virus infections in homosexual men with chronic, persistent generalized lymphadenopathy. J INFECT DIS 1985 Mar; 151(3):459-63 The status of infection by the Epstein-Barr virus (EBV) in 20 patients with chronic, persistent generalized lymphadenopathy was evaluated with use of three parameters: antibodies to EBV, EBV excretion, and EB virocytemia. Results were compared with those obtained from two groups of control subjects: patients with infectious mononucleosis and healthy EBV-seropositive adults. Profiles of antibody to EBV and the prevalence of EBV excretion were essentially similar for study subjects and healthy control subjects, but the level of EB virocytemia was significantly higher in study subjects than in healthy control subjects. Department of Medical Microbiology and Immunology University of California Davis *****JOURNAL OF PEDIATRICS***** 84010130 Hellmann D Cowan MJ Ammann AJ Wara DW Chudwin D Chang RS Chronic active Epstein-Barr virus infections in two immunodeficient patients. J PEDIATR 1983 Oct; 103(4):585-8 83215609 Palmer CG Provisor AJ Weaver DD Hodes ME Heerema N Juvenile chronic granulocytic leukemia in a patient with trisomy 8, neurofibromatosis, and prolonged Epstein-Barr virus infection. J PEDIATR 1983 Jun; 102(6):888-92 *****JAMA - JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION***** 87284260 Milbauer JJ 'Chronic active Epstein-Barr virus infection' [letter] JAMA 1987 Aug 21; 258(7):907 87199082 Buchwald D Sullivan JL Komaroff AL Frequency of 'chronic active Epstein-Barr virus infection' in a general medical practice. JAMA 1987 May 1; 257(17):2303-7 Twenty-one percent of 500 unselected patients, aged 17 to 50 years, seeking primary care for any reason were found to be suffering from a chronic fatigue syndrome consistent with "chronic active Epstein-Barr virus (EBV) infection," They had been experiencing "severe" fatigue, usually cyclic, for a median of 16 months (range, six to 458 months), associated with sore throat, myalgias, or headaches; 45% of the patients were periodically bedridden; and 25% to 73% reported recurrent cervical adenopathy, paresthesias, arthralgias, and difficulty in concentrating or sleeping. The patients had no recognized chronic "physical" illness and were not receiving psychiatric care. While antibody titers to several EBV-specific antigens were higher in patients than in age- and sex-matched controls subjects, the differences generally were not statistically significant. A chronic fatigue syndrome consistent with the chronic active EBV infection syndrome was prevalent in our primary care practice. However, our data offer no evidence that EBV is causally related to the syndrome. Indeed, we feel that among unselected patients seen in a general medical practice currently available EBV serologic test results must be interpreted with great caution. Department of Medicine Brigham and Women's Hospital Boston MA 02115. 87199081 Holmes GP Kaplan JE Stewart JA Hunt B Pinsky PF Schonberger LB A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause? JAMA 1987 May 1; 257(17):2297-302 A cluster of 134 patients who had undergone Epstein-Barr virus (EBV) serological testing because of suspected chronic EBV syndrome was investigated in Nevada. Fifteen case-patients were identified who had severe, persistent fatigue of undetermined etiology for more than two months. When compared with the remaining 119 patients who had less severe illnesses and with 30 age-, sex-, and race-matched control- persons, these 15 patients had significantly higher antibody titers against various components of EBV and against cytomegalovirus and herpes simplex and measles viruses. Epstein-Barr virus serology could not reliably differentiate individual case-patients from the others, and the reproducibility of the tests within and among laboratories was poor. As a group, the case-patients appear to have had a syndrome that is characterized by chronic fatigue, fever, sore throat, and lymphadenopathy. The relationship of this fatigue syndrome to EBV is unclear; further studies are needed to determine its etiology. Division of Viral Diseases Centers for Disease Control Atlanta GA 30333. *****LANCET***** 87114329 Kawa-Ha K Franco E Doi S Yumura K Ishihara S Tawa A Yabuuchi H Successful treatment of chronic active Epstein-Barr virus infection with recombinant interleukin-2 [letter] LANCET 1987 Jan 17; 1(8525):154 *****MMWR. MORBIDITY AND MORTALITY WEEKLY REPORT***** 86230444 Chronic fatigue possibly related to Epstein-Barr virus--Nevada. MMWR 1986 May 30; 35(21):350-2 *****NEW ENGLAND JOURNAL OF MEDICINE***** 88014088 Weinstein L Thyroiditis and "chronic infectious mononucleosis" [letter] N ENGL J MED 1987 Nov 5; 317(19):1225-6 *****PEDIATRIC INFECTIOUS DISEASE JOURNAL***** 84041934 Lederman HM Yolken R DSouza BJ Winkelstein JA Chronic disseminated Epstein-Barr virus infection and humoral immunodeficiency: detection of viral antigen by ELISA inhibition assay. PEDIATR INFECT DIS 1983 Sep-Oct; 2(5):388-90 87016499 Jones JF Chronic Epstein-Barr virus infection in children. PEDIATR INFECT DIS 1986 Sep-Oct; 5(5):503-4 National Jewish Center for Immunology and Respiratory Medicine Denver CO 80206. *****PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES O***** 87092450 Henle W Henle G Andersson J Ernberg I Klein G Horwitz CA Marklund G Rymo L Wellinder C Straus SE Antibody responses to Epstein-Barr virus-determined nuclear antigen (EBNA)-1 and EBNA-2 in acute and chronic Epstein-Barr virus infection. PROC NATL ACAD SCI USA 1987 Jan; 84(2):570-4 Five distinct Epstein-Barr virus (EBV)-determined nuclear antigens (EBNA-1 to EBNA-5) were recently identified. Antibody responses to these antigens could conceivably differ, and thus prove of serodiagnostic value, in EBV-associated disease processes. As a first step, murine or human cell lines transfected with appropriate EBV DNA fragments and stably expressing either EBNA-1 or EBNA-2 were used to determine the frequency and time of emergence of antibodies to these two antigens in the course of acute and chronic infectious mononucleosis (IM) and to assess their titers in so-called chronic active EBV infections. Following IM, antibodies to EBNA-2 arose first and, after reaching peak titers, declined again in time to lower persistent or even nondetectable levels. Antibodies to EBNA-1 emerged several weeks or months after anti-EBNA-2 and gradually attained the titers at which they persisted indefinitely. The ratios between the anti-EBNA-1 and anti-EBNA-2 titers therefore were generally well below 1.0 during the first 6-12 months after IM and turned to well above 1.0 during the second year. In clear cases of chronic IM, the inversion of this ratio was delayed or prevented. In the less well- defined chronic EBV infections, low ratios were observed in only some of the patients. Because many of these illnesses were not ushered in by a proven IM and often showed EBV-specific antibody profiles within the normally expected range, a causal role of the virus in these cases remains doubtful. Joseph Stokes Jr. Research Institute at the Children's Hospital of Philadelphia PA 19104. *****SOUTHERN MEDICAL JOURNAL***** 85040516 DuBois RE Seeley JK Brus I Sakamoto K Ballow M Harada S Bechtold TA Pearson G Purtilo DT Chronic mononucleosis syndrome. SOUTH MED J 1984 Nov; 77(11):1376-82 We present data on 14 patients with chronic symptoms of disabling fatigue in association with serologic evidence of active Epstein-Barr virus (EBV) infection. Two thirds were women, and the average age at onset was 29.6 years. Forty-three percent were known to have had previous infectious mononucleosis, but the usual criteria for that diagnosis were not helpful with the present syndrome. Eighty-six percent had serologic evidence of cytomegalovirus (CMV) infection. Profound immunodeficiency was not present, but 71% had partial hypogammaglobulinemia, and minor abnormalities of T cell subsets were noted in six of seven patients studied. Fifty-seven percent achieved temporary serologic and symptomatic remission after an average duration of 33 months. Only one patient has a sustained remission. Comparison is made with other reported chronic, recurrent, and persistent EBV syndromes, and tentative diagnostic criteria for chronic mononucleosis syndrome are presented. Recently available EBV serologic techniques allow for identification of patients who have reactivated EBV infection, and this reactivation may be related to symptoms. *** *** *****AIDS RESEARCH AND HUMAN RETROVIRUSES***** 86242445 Lipscomb H Tatsumi E Harada S Yetz J Davis J Bechtold T Volsky DJ Kuszynski C Purtilo DT Sonnabend J et al Epstein-Barr virus and chronic lymphadenomegaly in male homosexuals with acquired immunodeficiency syndrome (AIDS). AIDS RES 1983-84; 1(1):59-82 Male homosexuals at risk for developing AIDS frequently exhibit chronic lymphadenomegaly (LAD). They are at high risk for developing malignant B cell lymphomas. A study of Epstein-Barr virus (EBV) revealed marked abnormalities in these patients. One hundred percent of the patients were seropositive. The patients with most severe acquired immune deficiency disorders manifested a decreased number of circulating B cells with EBV receptors and decreased lymphocyte transformation. Patients often showed defective memory T cell cytotoxic responses to autologous EBV infection in vitro. Three of five lymph node specimens contain significant EBV genome copies to suggest a significant etiologic role. In addition, a Burkitt-like lymphoma carried EBV genome. Although all of the men were seropositive for EBV, reactivation patterns were not as common as anticipated. Given the presence of EBV genome in the lymph nodes of the patients who lack anti-early antigen (EA) antibodies indicative of reactivation, we suggest that reliance on serology to indicate EBV involvement is insufficient for assessing the patient. The detection of a t(8;14) transposition in the monoclonal mu kappa Burkitt-like lymphoma containing EBV genome supports the view that cytogenetic transposition is a mechanism in lymphomagenesis. Department of Pathology and Laboratory Medicine University of Nebraska Medical Center Omaha 68105 87156946 DuBois RE Gamma globulin therapy for chronic mononucleosis syndrome. AIDS RES 1986 Dec; 2 Suppl 1:S191-5 Antibodies against Epstein-Barr virus, associated with antibody dependent cytotoxic cell activity, were found to be present in diminished titer in 20 of 22 patients tested with chronic mononucleosis syndrome (CMS). Gamma globulin was shown to improve symptoms in 53% of the patients treated, compared with 32% of placebo injections. 89.5% of 57 patients treated with a gamma globulin treatment program remained in the treatment program because of relief of symptoms, and only four patients dropped out because there was no relief of symptoms or side effects. Four patients experienced complete relief of symptoms following a variable length treatment program. It would appear that intramuscular gamma globulin treatment is efficacious in the treatment of CMS and that the average interval between treatments is three weeks. Internal Medicine Group Atlanta Georgia 30308. 87156934 Okano M Sakiyama Y Matsumoto S Mizuno F Osato T Unusual lymphoproliferation associated with chronic active Epstein- Barr virus infection. AIDS RES 1986 Dec; 2 Suppl 1:S121-3 A chronic active Epstein-Barr virus (EBV) infection with no significant underlying diseases was evidenced in 7 Japanese children and adolescents. In these patients, massive EBV-positive polyclonal lymphoproliferation occurred with extremely high EBV antibody titers. Department of Pediatrics Hokkaido University School of Medicine Sapporo Japan. *****ARZNEIMITTEL-FORSCHUNG***** 85279645 Pernice W Schneider H Wais U Stier R Forster J [Improved immunocompetence in two children with chronic Epstein-Barr virus infection under treatment with a standardized thymus hormone preparation (thymostimulin)] ARZNEIMITTELFORSCHUNG 1985; 35(5):869-70 (Published in GERMAN) Two children with chronic Epstein-Barr virus infection were treated with a standardized thymic hormone preparation (thymostimulin, TP-1 Serono). The treatment was well tolerated. No adverse reactions, no side effects were observed. Results of immunological investigations showed a trend towards normalisation. Additional clinical evidence showed up, which pointed to a response to the therapy. Universitats-Kinderklinik Freiburg *****EXPERIENTIA***** 74290352 Gergely L Czegledy J Vaczi L Gergely P Epstein-Barr virus-binding receptor on the surface of chronic lymphocytic leukaemic lymphocytes. EXPERIENTIA 1974 Jul 15; 30(7):809-10 *****HEADACHE***** 87249744 Vanast WJ Diaz-Mitoma F Tyrrell DL Hypothesis: chronic benign daily headache is an immune disorder with a viral trigger. HEADACHE 1987 Mar; 27(3):138-42 *****INTERNATIONAL JOURNAL OF CANCER***** 72091944 Johansson B Klein G Henle W Henle G Epstein-Barr virus (EBV)-associated antibody patterns in malignant lymphoma and leukemia. II. Chronic lymphocytic leukemia and lymphocytic lymphoma. INT J CANCER 1971 Nov 15; 8(3):475-86 86249621 Dolken G Bross KJ Hecht T Brugger W Lohr GW Hirsch FW Increased incidence of IgA antibodies to the Epstein-Barr virus- associated viral capsid antigen and early antigens in patients with chronic lymphocytic leukemia. INT J CANCER 1986 Jul 15; 38(1):55-9 Antibody titers to Epstein-Barr virus (EBV)-associated early antigens (EA) and the viral capsid antigen (VCA) were determined by ELISA on 263 sera obtained from healthy donors, patients with Hodgkin's disease (HD), non-Hodgkin lymphomas (NHL), infectious mononucleosis (IM), Burkitt's lymphoma (BL), and nasopharyngeal carcinoma (NPC). As expected, most lymphoma patients showed markedly elevated anti-VCA IgG and anti-EA IgG antibody titers. Only one patient in the NHL group (n = 56) consisting of patients with lymphomas other than chronic lymphocytic leukemia (CLL) and hairy-cell leukemia (HCL), and 3 patients with HCL (n = 19) had high antibody titers of the IgA class to VCA and EA. Seventeen out of 48 patients (36%) with CLL had high IgA anti-VCA titers and 10 of these sera (21%) also contained IgA anti-EA. The geometric mean titer (GMT) of IgA anti-VCA was 2,510, the GMT of IgA anti-EA was 780. These antibody titers were about 10 times lower than the corresponding GMT of the NPC patients investigated in this study. The elevated IgG and IgA antibody titers to VCA and EA in CLL and HCL patients seem to reflect an immunodeficiency secondary to the malignant disease leading to reactivation of latent EBV infection. The possibility that at least some of these B-cell lymphomas are associated with EBV cannot be excluded. Abteilung fur Hamatologie und Onkologie Medizinische Universitatsklinik Freiburg, Fed. Rep. Germany *****JOURNAL OF CLINICAL IMMUNOLOGY***** 86304865 Merino F Henle W Ramirez-Duque P Chronic active Epstein-Barr virus infection in patients with Chediak- Higashi syndrome. J CLIN IMMUNOL 1986 Jul; 6(4):299-305 The results of clinical and Epstein-Barr virus (EBV) serological studies on nine Chediak-Higashi syndrome (CHS) patients are reported. Persistently elevated antibodies to the viral capsid antigen (VCA) and the restricted component of the early antigen complex (EA-R) developed in six patients who experienced primary EBV infection which either remained silent or were accompanied by clinical signs of infectious mononucleosis (IM). Hepatosplenomegaly and moderate lymphadenopathy, both clinical signs of the accelerated phase, remained detectable in the six patients for a long period of time after seroconversion. The clinical, serological, and histopathological observations are suggestive of a nonmalignant lymphoproliferative disease and consistent with an immunodeficiency to EBV. The abnormal serological responses to EBV in CHS are therefore considered manifestations of a chronic active EBV infection which may result in lethal lymphoproliferation. The three as yet seronegative CHS patients revealed no signs of the accelerated lymphoproliferative phase of the syndrome. Department of Experimental Medicine Instituto Venezolano de Investigaciones Cientificas (IVIC) Caracas, Venezuela 86112437 Kuis W Roord JJ Zegers BJ Rickinson AB Kapsenberg JG The H Stoop JW Heterogeneity of immune defects in three children with a chronic active Epstein-Barr virus infection. J CLIN IMMUNOL 1985 Nov; 5(6):377-85 Three children, all girls, showed long-lasting clinical and serologic evidence of chronic active Epstein-Barr virus (EBV) infection. Extremely high serum titers of IgG- and IgA-type VCA antibodies and EA antibodies were present, whereas EBNA antibody titers were in the range of those found in seropositive individuals. All three patients repeatedly showed the presence of nonspecific pokeweed mitogen (PWM)- activatable suppressor cells in the peripheral blood. The analysis of EBV-specific cytotoxic T cells showed that one patient exhibited normal cytotoxicity, whereas a second patient demonstrated no EBV- specific cytotoxicity together with unusually high levels of virus- infected B cells in the blood and lymph node. The third patient repeatedly showed refractoriness of the circulating B cells to EBV infection, probably on the basis of some developmental defect. It was concluded that each patient has his or her own peculiar defect in the virus-host balance, indicating that heterogeneity may underlie the syndrome of chronic active EBV infection in humans. University Children's Hospital Het Wilhelmina Kinderziekenhuis Utrecht The Netherlands 85158110 Kibler R Lucas DO Hicks MJ Poulos BT Jones JF Immune function in chronic active Epstein-Barr virus infection. J CLIN IMMUNOL 1985 Jan; 5(1):46-54 The spectrum of illness attributed to Epstein-Barr virus (EBV) includes patients with symptoms persisting for more than 1 year without any other obvious underlying disease. High titers of antibodies to EBV, either IgG antiviral capsid antigen or anti-early antigen, can be demonstrated. In this study, 13 patients diagnosed as having chronic active EBV infection were examined to determine aspects of their immunologic status. Morphological examination and fluorescent antibody analysis revealed no abnormalities in the phenotypes of peripheral blood white cells present in these patients. Compared to those from healthy control individuals, mononuclear cells from the patients showed a markedly depressed ability to produce both interleukin-2 and interferon after stimulation with mitogen and a phorbol ester. Studies of natural killer (NK) cell activity revealed that unfractionated mononuclear cells from patients with chronic active EBV infection were significantly lower in killing activity compared to the control group. Fractionation procedures to enrich for large granular lymphocytes resulted in an increase in NK activity for all individuals, but killing activity still remained slightly lower in the patients than in the control group. The dysfunctions which were found in patients with chronic active EBV infection may reflect a primary defect in natural immune functions of the patients predisposing them to a chronic or intermittent clinical disease rather than a self-limiting illness. Alternatively, the abnormalities detected in these experiments may be a result of the viral infection itself. Department of Microbiology and Immunology University of Arizona College of Medicine, Tucson 85724 *****MONATSSCHRIFT FUR KINDERHEILKUNDE***** 86091951 Schuchmann L Neumann-Haefelin D [Persistent (chronic active) Epstein-Barr virus infection and arthritis in childhood] MONATSSCHR KINDERHEILKD 1985 Nov; 133(11):845-7 (Published in GERMAN) Between 1981 und 1983 some 1300 patients with the primary diagnosis of juvenile chronic arthritis were admitted. In 9 of them a persistent EBV-infection was simultaneously evident. The course of disease was primarily systemic with the characteristic criteria: high septic intermittent fever, rheumatic exanthema, hepatosplenomegaly and lymphadenopathy. It is still unclear whether a replication of virus in the synovia or a precipiation of immune complexes is involved. A common cause for the persistent EBV-infection and arthritis via an immune-suppressive agent is possible. Kinderklinik und Rheumakinderklinik Universitat Freiburg i. Br *****PEDIATRIA MEDICA E CHIRURGICA***** 84070035 Cohen E Pietrogrande MC Corona F Varin E Delle Piane RM Bardare M [Chronic mononucleosis: a case of difficult diagnosis] PEDIATR MED CHIR 1983 May-Jun; 5(3):103-5 (Published in ITALIAN) Here is referred the case history of a boy - age 6 yrs - who was hospitalised for a persistent high temperature with generalised limphonodes hypertrophy. The limphonode biopsy together with decreased NK activity and increased antiEAD and antiVCA antibodies allowed the diagnosis of chronic mononucleosis. *****PEDIATRIC PATHOLOGY***** 85038294 Snover DC Filipovich AH Dehner LP Immunodeficiency-disease-associated atypical chronic hepatitis: a clinicopathologic study. PEDIATR PATHOL 1983 Apr-Jun; 1(2):229-41 Chronic hepatitis occurring in patients with primary immunodeficiency disease is an uncommonly reported phenomenon. This study describes our experience with 3 patients with various immunologic abnormalities who developed chronic atypical lymphocytic infiltrates in the liver. There was a temporal relationship to Epstein-Barr virus infection in 2 cases and hepatitis A in 1. In view of the increased incidence of malignant lymphoma in several of the primary immunodeficiency states, these cases present a difficult diagnostic challenge. The recognition of the association of infiltration of the liver with small cleaved lymphocytes and a viral infection in an immunodeficient patient should alert the pathologist to the possibility that the infiltrate does not represent malignant lymphoma. These cases may be analogous to similar virus-associated lymphoproliferative disorders described in the acquired immunodeficiency of renal transplantation. Department of Laboratory Medicine University of Minnesota Medical School Minneapolis Connect Time = 20.68 Minutes Connect Time Charge @ $16.00/HR 5.51 Communications Charge @ 6.00/HR 2.07 Search Element @ .10 .50 Reference Print @ .10 5.40 Title Scan @ .05 5.80 Abstract Print @ .10 3.50 Total Search Cost $ 22.78 Printing done. Please Deactivate, Then Press .