Evidence Of Cytomegalovirus Infection Research Articles

Pathology of the pituitary gland in patients with the acquired immune deficiency syndrome (AIDS)

The pituitary gland was examined at autopsy in 88 patients who died with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC). Pathologic findings included focal to widespread necrosis and/or fibrosis of the anterior pituitary gland in 10 cases, evidence of cytomegalovirus infection without an apparent inflammatory component in the anterior pituitary in 3 cases, and microglial nodules in the pars nervosa in 5 cases. In one instance, a multinucleated giant cell identical to those associated with direct human immunodeficiency virus infection of brain was identified in the pars nervosa. One patient showed focal anterior pituitary infection by Cryptococcus neoformans in the context of widespread and severe cryptococcosis. These findings are discussed in relation to the possible clinical manifestations and the neuropathologic and systemic pathologic findings in AIDS patients.

Lymphocyte abnormalities in infants born to drug-abusing mothers

To evaluate the possible effects of maternal intravenous drug use on infant immunity, we measured the in vitro peripheral blood mononuclear cell proliferative responses to phytohemagglutinin (PHA) and pokeweed mitogen, T cell subset numbers, immunoglobulin levels, and titers of antibodies to cytomegalovirus (CMV) and human immunodeficiency virus (HIV) in a group of drug-abusing mothers and their infants. Infants of drug abusers had a lower proliferative response to mitogen, associated with altered kinetics of the maximum response to PHA. The OKT4/OKT8 ratio decreased with age in the drug-exposed infants compared with control infants (P less than 0.005). There was no evidence of CMV infection in either group. One mother and her infant had antibody to HIV. Our data demonstrate that infants of intravenous drug-using mothers have distinct immunologic differences at birth compared with non-drug-exposed infants and that these persist throughout the first year of life. The cause appears unrelated to intrauterine viral infection, suggesting a direct toxic effect of the drugs on fetal immunologic development.

Treatment of cytomegalovirus pneumonitis with foscarnet (trisodium phosphonoformate) in patients with AIDS.

Foscarnet was administered to eight AIDS patients for suspected cytomegalovirus (CMV) pneumonitis as a continuous intravenous infusion for a minimum of 8 days. All the patients improved, three showing complete resolution of symptoms. Evidence of CMV infection from bronchoalveolar lavage samples was lacking in two patients. Adverse drug experiences consisted of thrombophlebitis, transient decreases in haemoglobin concentration, and reversible rises in serum creatinine levels.

Neonatal Hepatitis

SummaryFifty‐six patients with moderate to severe neonatal hepatitis were followed for 12 to 78 months. Two died from causes other than hepatitis itself and were free from liver disease at the time of death. Of the remaining 54 patients, seven died of hepatitis, two are living with chronic liver disease and psychomotor retardation, and 45 are living without liver disease. High peak bilirubin levels and liver histologic findings of periportal fibrosis, moderate to severe portal inflammation, and/or diffuse giant cell transformation appear to be major factors predictive for poor outcome. Cytomegalovirus (CMV) infection was a common associated infection. Evidence of CMV infection was found in 22 (49%) of the 45 patients studied. Three of them died, and one is still living with cirrhosis of the liver. Metabolic disorders such as alpha‐1‐antitrypsin deficiency, galaclosemia, and aminoaciduria and/or aminoacidemia were carefully screened but were not found in these cases. A fatal case had a sibling who had died of a similar disease course. Chinese infants may have metabolic and familial cholestasis diseases requiring further investigation.

Neonatal hepatitis: a follow-up study.

Fifty-six patients with moderate to severe neonatal hepatitis were followed for 12 to 78 months. Two died from causes other than hepatitis itself and were free from liver disease at the time of death. Of the remaining 54 patients, seven died of hepatitis, two are living with chronic liver disease and psychomotor retardation, and 45 are living without liver disease. High peak bilirubin levels and liver histologic findings of periportal fibrosis, moderate to severe portal inflammation, and/or diffuse giant cell transformation appear to be major factors predictive for poor outcome. Cytomegalovirus (CMV) infection was a common associated infection. Evidence of CMV infection was found in 22 (49%) of the 45 patients studied. Three of them died, and one is still living with cirrhosis of the liver. Metabolic disorders such as alpha-1-antitrypsin deficiency, galactosemia, and aminoaciduria and/or aminoacidemia were carefully screened but were not found in these cases. A fatal case had a sibling who had died of a similar disease course. Chinese infants may have metabolic and familial cholestasis diseases requiring further investigation.

Evaluation of Cytomegelisa™ Immunoglobulin M Assay and Comparison with Indirect Fluorescent Antibody Testing of QAE-Sephadex® A50-Treated Sera

The Cytomegelisa IgM assay (M. A. Bioproducts, Walkersville, MD) was evaluated as an alternative to indirect fluorescent antibody (IFA) testing of QAE-Sephadex A50-treated sera for detection of cytomegalovirus (CMV)-specific IgM. The Cytomegelisa assay was consistently more sensitive than IFA testing for detection of CMV-specific IgM. Of 101 rheumatoid factor-negative sera that were IFA positive before column separation, only 47 (46%) remained positive after column separation, while 72 (71%) were positive using Cytomegelisa. Nine transplant patients who had primary CMV infection develop were also evaluated. Two of the nine did not form sufficient IgM to remain IFA positive after column separation, however, all had IgM detected by Cytomegelisa. In all cases, Cytomegelisa provided laboratory evidence of CMV infection earlier or at the same time as IgG seroconversion or IgM testing by column/IFA. Comparison of both methods with 100 consecutive sera received for CMV testing yielded five sera positive for CMV-IgM with the column/IFA method and 20 using Cytomegelisa. The specificity of Cytomegelisa was evaluated with 56 RF-positive/CMV IgG-positive sera. Four of 56 (7%) appeared positive after column separation; however, of concern, 22 of 56 (39%) remained positive in the Cytomegelisa.

Acquired immune deficiency syndrome, leading to opportunistic infections, Kaposi's sarcoma, and other malignancies.

In early 1981 several cases of Pneumocystis carinii pneumonia in young male homosexuals were recognized. Between then and the end of 1982 almost 800 cases of serious opportunistic infections and malignancies have occurred in this group and now in other groups as well. The most common malignant disease to be seen is the otherwise uncommon endothelial cell sarcoma, Kaposi's sarcoma. The underlying abnormality, both to the opportunistic infections and the malignancies, is one of acquired immune deficiency of the cell mediated variety. Other common factors in affected persons are evidence of cytomegalovirus infection, a previous history of various sexually transmitted diseases and lifestyle characteristics. Recent evidence of the abnormality amongst Haitian immigrants, haemophiliacs, heterosexuals and neonates has enormously complicated what is already a perplexing problem, the understanding of which will shed light on the relationship between immunity, infectious diseases and malignancy.

Kaposi's sarcoma: immunoperoxidase staining for cytomegalovirus.

An immunoperoxidase technique was used to test for cytomegalovirus (CMV) proteins in lesions of Kaposi's sarcoma from 19 patients with acquired immune deficiency syndrome (AIDS) and 3 patients without AIDS. CMV proteins could not be detected in any of the cases of Kaposi's sarcoma. Thus, while CMV genetic material may be present in these cells, the virus is not actively directing the synthesis of proteins. This eliminates reactivation of latent CMV in tumor tissue, or late infection of Kaposi's sarcoma cells as explanations for the elevated antibody titers to CMV and other evidence of CMV infection in patients with Kaposi's sarcoma. However, the possibility remains that exposure to CMV occurs as a primary event in the development of Kaposi's sarcoma. These findings indicate that, as in Kaposi's sarcoma of the elderly, the virus is inactive in Kaposi's sarcoma cells of patients with AIDS, and there is no difference between the two lesions in immunoperoxidase staining for CMV proteins.

Impact of hepatitis on renal transplantation.

In order to delineate the incidence, etiology, and impact of liver disease in renal transplant patients, we reviewed 405 consecutive transplants performed between 1970 and 1980. Hepatic dysfunction of at least 2 weeks' duration was diagnosed in 42 patients (10.4%). Of 28 patients acquiring hepatitis in the first post-transplant year, 26 (92.8%) developed chronic hepatitis; of 14 acquiring hepatitis after the first year, 9 (64.2%) developed chronic hepatitis. Of the 42 patients, 19 (45.2%) died, as compared with 16% of the nonhepatitis patients (P less than 0.001). Only one of these patients died of liver failure, with 15 of the 19 (78.9%) dying of extrahepatic infection. In addition, 12 of the 23 survivors (52.1%) suffered life-threatening infections from which they recovered, as compared with 20% of the nonhepatitis patients (P less than 0.01). Conversely, graft survival was significantly increased among the hepatitis patients (73% 1-year cadaveric allograft survival as compared with 50% for the nonhepatitis patients (P less than 0.01)). The etiology of the liver disease was identified in the minority of patients: 5 (11.9%) with hepatitis B, with none occurring since 1973; 10 (23.8%) with evidence of cytomegalovirus infection; and 1 (2.3%) with azathioprine toxicity. We conclude that the major cause of liver disease in renal transplant patients is non-A, non-B hepatitis, and furthermore, that this disease has a marked immunosuppressing effect resulting in increased allograft survival and a marked increase of life-threatening extrahepatic infection.

Transient Protein-Losing Enteropathy and Enlarged Gastric Rugae-Reply

In Reply .—I appreciate Dr Bloom's comments on our article in theJournal. However, several annotations to those comments are appropriate. My colleagues and I believe, as does Dr Bloom, that the coincidence of hypertrophic gastric folds and protein-losing enteropathy in children does not necessarily signify Menetrier's disease, which is a condition with a course that differs from that of the children whom we described in our article. We sought to identify a subgroup of such children on historical and epidemiologic criteria and found that available evidence suggested a similar origin or pathogenesis in several instances. Using our standards, I can accept the cases reported by Floret et al 1 (this patient also had evidence of cytomegalovirus infection) and by Gwinn and Lee 2 as similar to our cases. However, the case reported by Colon and Sandberg 3 is identical to the case reported by Sandberg 4 alone and was

CYTOMEGALOVIRUS OOPHORITIS

Three of eight female patients with cytomegalovirus disease had evidence of ovarian infection at autopsy. All three patients with ovarian lesions were postmenopausal; the remaining five were premenopausal. The lesions, which may be bilateral and may occur without evidence of cytomegalovirus infection elsewhere, are distinctive macroscopically, pathognomonic microscopically, and characterized by acute focal ovarian cortical necrosis with numerous cytomegalic cells and a variable but usually severe inflammatory reaction. It is suggested that reduced ovarian cortical vascular perfusion reactivates a latent infection in cortical stromal cells. This elicits inflammatory necrosis and the characteristic morphological lesions. This previously unreported lesion is not likely to have clinical importance.

Primary Epstein-Barr Virus Infection in a Renal Transplant Recipient

A young girl with familial nephronophthisis and chronic renal failure contracted a primary Epstein-Barr virus infection after renal transplantation. During the illness she developed a clinical picture of fever and pneumonitis which closely resembled the posttransplantation syndrome usually associated with cytomegalovirus, although she had no evidence of cytomegalovirus infection. A younger sibling with the same renal disease was found retrospectively to have apparently had an earlier subclinical Epstein-Barr virus infection.

Cytomegalovirus oophoritis: Ovarian cortical necrosis

Three of eight female patients with cytomegalovirus disease had evidence of ovarian infection at autopsy. All three patients with ovarian lesions were postmenopausal; the remaining five were premenopausal. The lesions, which may be bilateral and may occur without evidence of cytomegalovirus infection elsewhere, are distinctive macroscopically, pathognomonic microscopically, and characterized by acute focal ovarian cortical necrosis with numerous cytomegalic cells and a variable but usually severe inflammatory reaction. It is suggested that reduced ovarian cortical vascular perfusion reactivates a latent infection in cortical stromal cells. This elicits inflammatory necrosis and the characteristic morphological lesions. This previously unreported lesion is not likely to have clinical importance.

Cytomegalovirus Infection in Patients Receiving Immunosuppressive Therapy for Rheumatologic Disorders

Evidence of cytomegalovirus infection was sought in 131 patients attending a rheumatology clinic, 211 blood donors, and 14 patients before and after the initiation of cytotoxic immunosuppressive therapy for a rheumatologic condition. The titer of complement-fixing antibody to cytomegalovirus was significantly related to age and sex, but not to rheumatologic disease. After adjustment for age and sex differences, the proportion of patients treated with corticosteroids who had measurable antibody was lower than that of controls (P less than 0.025). Immunosuppressive therapy with azathioprine or cyclophosphamide did not affect the proportion of patients with antibody, but there was a significantly increased titer of antibody in those who were seropositive (P = 0.04). Cytomegalovirus was isolated from the urine of 20% of patients receiving cytotoxic immunosuppressive drugs, but not from any of the patients receiving corticosteroids or neither form of therapy (P = 0.001). Eight of 14 patients followed prospectively after the initiation of therapy with immunosuppressive drugs became infected with cytomegalovirus as demonstrated by a fourfold or greater rise in complement-fixing titer, viruria, or both. Seven of the eight patients were seropositive before therapy, a finding suggesting that immunosuppression acts largely by reactivating latent infection. It is postulated that immunosuppressive agents alone may account for a large proportion of cytomegalovirus infections seen after allograft transplantation.

The value of isolation procedures for cytomegalovirus infections in children with leukemia

Standard contagious isolation procedures were used for 83 patients with acute lymphocytic leukemia and serologic and/or cultural evidence of cytomegalovirus infection. The infection rate, as determined serologically, for 9 months before and 13 months during isolation procedures was not decreased. Since the techniques employed were not helpful in preventing infection with cytomegalovirus in the immunosuppressed host, they have been discontinued at this hospital.

Transient Monoclonal Gammopathy Associated With Cytomegalovirus Infection

Abstract A transient monoclonal gammopathy, IgA-lambda light chain, associated with a cytomegalovirus (CMV) infection occurred in a patient with acute leukemia in remission. Evidence of CMV infection was confirmed by indirect hemagglutination titers, initially being 1:4096 and gradually falling to 1:64. During the infection, serum and salivary IgA levels rose to 2450 mg/100 ml and 72 mg/100 ml, respectively. Bence Jones proteinuria, lambda type, (0.1 g/24 hr) occurred during the period of excessive immunoglobulin synthesis. Antibody activity against CMV was detected in serum IgA and IgG. Also unusual were the histologic changes indistinguishable from malignant lymphoma seen in a cervical lymph node. After withholding for 1 wk the immunosuppressive drug (methotrexate) she had been receiving, symptoms and signs of the CMV infection and of the monoclonal gammopathy disappeared without recurrence after maintenance methotrexate was resumed.

Hypermacroglobulinemia associated with heroin use in adolescents

Increases of serum 19S IgM globulin were detected in adolescent patients admitted for narcotic detoxification. The mean IgM level was 294 ± 130 mg. per cent compared to 164 ± 63 mg. per cent in a control group. Twenty-six of the 64 adolescent narcotic users (40.6 per cent) had IgM levels above 290 mg. per cent, the upper limit of normal. There was no evidence of cytomegalovirus infection, infectious mononucleosis, primary biliary cirrhosis, mixed cryoglobulinemia, or cold agglutinins. The presence of Australia antigen in 2 patients and elevated serum glutamic oxaloacetic transaminase (SGOT) levels in 19 suggests that the increased IgM levels may be related to the presence of chronic persistent hepatitis. Heroin use should be considered as an important cause of elevated serum IgM, especially in association with relatively normal levels of IgG and IgA.

Cytomegalovirus Infection Associated With Cardiopulmonary Bypass

Five of six patients with the post-perfusion syndrome (PPS) following cardiopulmonary bypass had evidence of cytomegalovirus (CMV) infection. An additional patient who died in the immediate postoperative period had asymptomatic viruria preoperatively. One patient in whom postoperative lymphocytosis, hepatomegaly, and viruria developed had preoperative cytologic evidence of infection. In this study of 25 patients, the existence of latent infection prior to operation was suggested in this single patient. Nineteen other patients studied prospectively had no evidence of CMV infection or PPS.