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An illness lasting for two years, with recurrent fever, rash, abdominal pain, and arthralgia, developed in a four year old boy. He was found to have a combined Epstein-Barr virus and cytomegalovirus (CMV) infection. His symptoms, CMV in his urine, and an absent in vitro lymphocyte response to CMV antigen persisted for two years. After treatment with orally administered bovine transfer factor clinical symptoms and viruria disappeared and specific immunity to CMV developed. Evaluation of this treatment in chronic virus infections is warranted.

Two Navajo Indian children with severe combined immunodeficiency disease (SCID) lost reconstituted immune function after virus infections. A serum factor which inhibited normal lymphocyte response to mitogens was found in one of them and led to the examination of sera from five other Navajos with SCID. Mean inhibition by six Navajo sera was 67%; no inhibitor was found in sera from normal adults and children. The inhibitor activity was nondialyzable and heat stable, yet partially sensitive to pH 2.0, suggesting that interferon(s) was present. Interferon (IFN) activity in patient sera ranged from 10 to 300 U/ml. Normal children had peak serum IFN levels of 100 and 30 U/ml in the acute and convalescent periods, respectively, of virus infections. IFN alpha, IFN beta, and IFN gamma were identified in SCID sera by specific antisera. Both inhibitor and IFN activities in three Navajo sera were 88-95 and 89-100%, respectively, removed with anti-IFN antisera. Similar patterns of inhibition of lymphoblastogenesis were seen with IFN standards. IFN levels in the SCID patients did not correlate with documented infections; elevated levels were present when no infections could be documented. The immunologic imbalances in some forms of SCID may be related to circulating inhibitors, possibly interferon.

Serum varicella-zoster (VZ) antibody titers were determined by a simple, indirect immunofluorescent antibody technique in 50 children with leukemia or non-Hodgkin's lymphoma. Sixteen children had initial antibody titers that were not detectable at a serum dilution of 1:8 and were considered to be susceptible to varicella. Thirty-one patients had initial serum VZ antibody titers of 1:16 or greater, while three had levels of 1:8. The serum antibody titer was 1:8 or greater in 16 children with a history of varicella. Seven episodes of localized herpes zoster were observed in children whose VZ titer was 1:8 or greater prior to onset. Two nonfatal infections with primary varicella developed in children with leukemia in remission whose initial titers were less than 1:8 and were associated with a convalescent rise in VZ antibody to levels greater than 1:16. Three susceptible children received zoster immune plasma or zoster immune globulin for varicella exposure, causing a transient rise in serum VZ titer. The assessment of serum VZ titer by this immunofluorescent antibody technique combined with the prior varicella history is useful in defining the population of children with leukemia and non-Hodgkin's lymphoma who are susceptible to primary varicella.

This study examines the relationship between age and mitogen-induced lymphocyte blastogenesis. Lymphocytes were stimulated with PHA; Concanavalin A (Con A), and PWM in 156 normal, healthy subjects ranging in age from birth to 75 years. The findings indicate a gradual but significant decrease in PHA- and Con A-induced blastogenesis with increasing age. The decrease in Con A and PHA induced in vitro lymphocyte function begins in early childhood and young adulthood, respectively, and continues throughout the age range studied. In addition, there appears to be a decreased range of lymphocyte functional capacity among the 50-75-year-old subjects. The clinical and laboratory implications of these observations are discussed.

This study examines the relationship between percent recovery of lymphocytes and T- and B-cell typing results. Lymphocytes were recovered from heparinized whole blood by density gradient centrifugation. T- and B-cells were enumerated by spontaneous sheep rosetting and direct fluorescent antibody staining for surface immunoglobulin, respectively. The findings indicate that at low recovery levels ( less than 80%) there is a significant increase in variability of lymphocyte typing results and a significant increase in IgG-bearing B-lymphocytes. Possible explanations for these findings are discussed. These results suggest that lymphocyte typing results should be interpreted in relation to recovery level and that recovery levels of greater than or equal to 80% are desirable.

Cytomegalovirus (CMV) infection in heart and heart-lung transplant recipients represents a serious if not mortal complication. This study reviews the beneficial effects of 9-(1,3-dihydroxy-2-proproxymethyl) guanine (DHPG), an experimental antiviral agent, in patients with CMV infections. Thirteen of 76 heart and heart-lung transplant patients treated with cyclosporine have developed CMV. Nine of 13 patients developed infections since DHPG has been available. Seven patients received hearts, and two received heart and lungs. Six patients were treated, four heart and two heart-lung recipients; five of six had negative CMV serology before surgery, and all had CMV positive donors. Of the patients not treated, one died at home from disseminated CMV; two had resolution of symptoms and were discharged before the diagnosis was made. In the treated group, three patients had gastrointestinal ulcerative disease, two in the stomach and one in the cecum. The other three patients had CMV pneumonia. DHPG was effective in resolving patient symptoms in five of six patients. The patient who did not respond had a cecal ulcer, multiorgan failure, multiple infections, and died. Two patients with abdominal pain had gastric ulcers that were proved with endoscopy. CMV-induced ulcer disease was diagnosed within 2 hours by fluorescent antibody staining, and resolution was documented by endoscopy. Three patients with CMV pneumonia were treated; two were heart-lung transplant recipients. All started to respond within 72 hours. One heart-lung transplant recipient has had a 9-month course of DHPG because of recurrence of infection when the drug was stopped. The usual dosage was 10 mg/kg/day over 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

A male infant infected in utero with Epstein-Barr virus (EBV) demonstrated a syndrome of multiple congenital anomalies (micrognathia, cryptorchidism, central cataracts), hypotonia, thrombocytopenia, persistent monocytosis, proteinuria, and multiple areas of metaphysitis at birth. Lymphocytes were Epstein-Barr nuclear antigen (EBNA) positive (18%) and persisted in culture for three months. He had antibody to early antigen (anti-EA), IgM-viral capsid (anti-VCA), and EBNA (anti-EBNA) detectable at 22 days of age. All attempts to isolate infectious agents or to serologically identify other infectious causes for his syndrome were negative.

A 55-year-old man had a myelopathic syndrome and serologic evidence of Epstein-Barr virus infection. The patient's age and the neurologic and serologic findings suggested reactivation of a latent virus with direct invasion of the CNS. Epstein-Barr virus may exist in a latent state within the nervous system, and should be considered in myelopathic syndromes, even in older patients.

Nine patients with an initial onset of symptoms of acute arthritis within the preceding four weeks were enrolled in a prospective serological study with clinical follow-up for six months to two years. Four adults with chronic rheumatoid arthritis and ten healthy adults were similarly studied. Serial titers measured included antibodies to Epstein-Barr virus (EBV) antigens, group B coxsackieviruses, rubella virus, cytomegalovirus, and herpes simplex virus. Serological evidence of active EBV infection was found in four of the patients with acute arthritis, none of the patients with chronic arthritis, and one of the ten healthy adults. There was no similar correlation between acute disease and presence of antibodies to the other viruses tested. We suggest that EBV may cause acute rheumatic illnesses more commonly than is currently appreciated but is probably not involved in the etiology of typical chronic rheumatoid arthritis.

The effect of Bordetella bronchiseptica upper airway colonization on the clinical, radiographic, serologic, pathologic, and pulmonary function changes caused by canine parainfluenza-2 virus (CPIV-2) infection was studied in 24 purebred Beagle pups (10.5 +/- 1.4 weeks old). Eight control dogs (group I) were not colonized or inoculated with CPIV-2. Of the 12 noncolonized dogs inoculated with CPIV-2 (group II), 9 developed antibody titers to CPIV-2 and 10 had clinical signs of infectious canine tracheobronchitis (kennel cough). Group I and group II dogs did not differ in radiographic findings or pulmonary function. Four group II dogs necropsied 1 to 5 days after clinical signs developed had laryngotracheobronchitis and bronchiolar inflammation not present at necropsy on 2 group I dogs. Four dogs had B bronchiseptica upper airway colonization and were inoculated with CPIV-2 (group III). All 4 group III dogs developed positive antibody titers, had clinical signs of kennel cough, and had radiographic changes. Pulmonary dynamic compliance was lower in group III than in group I or group II animals. Respiratory rate and tidal volume did not differ among the 3 groups. The 1 group III dog that was necropsied had changes similar to group II dogs with the addition of lobar bronchopneumonia. The present study indicates that asymptomatic B bronchiseptica colonization may effect the clinical, radiographic, and pulmonary function changes produced by CPIV-2 respiratory tract infections.

Cytomegalovirus (CMV) causes major morbidity in organ transplant recipients. Gastrointestinal disease was the most prominent manifestation of CMV infection in a population of heart and heart-lung transplant patients, with an incidence of 9.9%, compared with pneumonitis (4.0%) and retinitis (0%), and occurred most frequently in CMV-seronegative recipients of organs from CMV-seropositive donors. Clinical manifestations included gastritis (nine patients), gastric ulceration (four patients), duodenitis (three patients), esophagitis (one patient), pyloric perforation (one patient), and colonic hemorrhage (one patient). Patients with gastrointestinal CMV infection were treated with intravenous ganciclovir sodium therapy, 5 mg/kg twice daily, for 2 to 8 weeks, with positive clinical, endoscopic, histologic, and virologic responses. Relapses occurred in four of nine patients who were followed up for a median period of 18 months. Retreatment resulted in healing of endoscopic lesions and in viral clearing. We conclude that early endoscopic evaluation for CMV is indicated in heart and heart-lung transplant patients with gastrointestinal symptoms. This study further suggests that intravenous ganciclovir therapy is effective for the treatment of gastrointestinal CMV in these patients.

To determine if parainfluenza type II (P2) virus infections in dogs could be used as a model for viral airways disease in children, we studied pulmonary function and histopathology in 12 P2-infected and 8 control beagle dogs. Ten infected animals developed symptoms of cough and rhinitis within 9 days of virus exposure. Histologic changes in infected dogs included ciliated epithelial denudation and peribronchial and peribronchiolar lymphocytic infiltrates involving airways of all sizes; most notably, 19 to 57% of nonrespiratory airways less than 1 mm in diameter were affected. Two weeks after the onset of symptoms, infected dogs were asymptomatic, but they had lower functional residual capacities (p less than 0.05) and lower specific lung conductance (p less than 0.05) than control dogs. Additionally, dynamic compliance did not increase with lung growth in infected dogs as it did in control dogs. These results suggest that parainfluenza type II infections can be experimentally produced in dogs (without concomitant bacterial infection), that these viral infections are similar to human viral lower respiratory tract illnesses, and that such viral infections may alter lung development in rapidly growing dogs.