Screening of 43 healthy Danish haemophiliacs revealed a significantly lower helper/suppressor (H/S) ratio than in controls. 8 of the haemophiliacs had an H/S ratio less than or equal to 1.0. A significant negative correlation occurred between the total lifetime factor VIII treatment and the H/S ratio. However, high-dose factor VIII treatment given to patients with antibodies against factor VIII was not associated with immunological abnormalities. Children had a significantly higher H/S ratio than the adult haemophiliacs. Patients exclusively treated with Danish cryoprecipitate during the last year had a significantly higher H/S ratio than patients receiving preparations from other sources. This difference might, however, be explained by lower age and lower total lifetime dose in the group receiving Danish preparations. Haemophiliacs treated with American preparations did not differ immunologically from those treated with preparations of other origin. Total serum IgG was increased in 23% of the patients. This parameter was negatively correlated with the H/S ratio. The possible relation of the observed immunological alterations among otherwise healthy haemophiliacs to the acquired immune deficiency syndrome warrants further attention.
Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland; Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland. Electronic address: firstname.lastname@example.org.
Earlier studies have documented an association between cytomegalovirus and cognitive impairment, but results have been inconsistent. Few studies have investigated the association of cytomegalovirus and Epstein-Barr virus with cognitive decline longitudinally. Our aim was to examine whether cytomegalovirus and Epstein-Barr virus are associated with cognitive decline in adults.
The study sample is from the Finnish Health 2000 Survey (BRIF8901, n?=?7112), which is representative of the Finnish adult population. The sample was followed up after 11?years in the Health 2011 Survey. In addition, persons with dementia were identified from healthcare registers.
In the Finnish population aged 30 and over, the seroprevalence of cytomegalovirus was estimated to be 84% and the seroprevalence of Epstein-Barr virus 98%. Seropositivity of the viruses and antibody levels were mostly not associated with cognitive performance. In the middle-aged adult group, cytomegalovirus serointensity was associated with impaired performance in verbal learning. However, the association disappeared when corrected for multiple testing. No interactions between infection and time or between the two infections were significant when corrected for multiple testing. Seropositivity did not predict dementia diagnosis.
The results suggest that adult levels of antibodies to cytomegalovirus and Epstein-Barr virus may not be associated with a significant decline in cognitive function or with dementia at population level.
The study included two clinical materials. First, the frequency of cytomegalovirus and its clinical significance were studied among 661 Swedish children under one year of age admitted to a paediatric hospital. Before the age of one week 4/326 (1%) children excreted virus. At one month the frequency had risen to 6/52 (12%) and after this age the frequency was constant around 20--25%. Sixty per cent of infants born to immigrants were infected after one month of age. One of the four congenitally infected children had symptoms at birth followed by neurological sequelae. The majority of the infections acquired at birth or in early infancy seemed to be subclinical and without sequelae. Second, a retrospective investigation of 18 695 children born during a six-year period was performed. Two cases of virologically confirmed congenital cytomegalic inclusion disease was found. Regarding seven microcephalic patients in the retrospective study congenital CMV-infection could be excluded in four cases. In the remaining three cases the data did not permit any conclusions regarding the etiology.
In a prospective Swedish study started in 1977 and still in progress 10 328 newborn infants in an urban district were investigated for cytomegalovirus (CMV) excretion in the urine by the virus isolation test. Congenital infection was found in 50 cases (0.5%). Of 47 infected infants with known clinical status at birth 9 (19%) had hepatomegaly, splenomegaly, jaundice and/or petechiae. The symptoms were moderate or mild. Of the infants followed up, 2 (25%) of 8 neonatally symptomatic ones and 3 (9%) of 35 asymptomatic ones developed neurologic sequelae. Altogether 5 (12%) of 43 had permanent neurologic symptoms corresponding to 0.06% in the general population. The children ranged in age from 6 months to 4 yr at the last examination. 21 mothers of the 47 infants with known status at birth had a confirmed or presumed primary infection, 15 a confirmed or presumed secondary infection and 11 an undetermined type of infection. Of the 5 infants with neurologic sequelae, 1 with a grave psychomotor retardation and deafness was born to a mother with a primary infection in the 1st trimester; 1 infant with a moderate retardation and 3 deaf infants were all exposed to confirmed or presumed secondary maternal infections. Prospective serological studies of maternal sera in early pregnancy would have suspected only the gravely retarded infant to be at risk.
The nested Polymerase Chain Reaction (PCR) was compared with virus isolation and serology to establish which is the best method for the diagnosis of active cytomegalovirus, (CMV) infection. Samples of blood leucocytes, urine and throat washings from immunosuppressed patients and patients with congenitally acquired CMV infection, as well as from healthy persons, were examined with PCR. CMV DNA was detected in all samples from which CMV could be isolated, but not from any sample from healthy adults, whether CMV seropositive or CMV seronegative. In contrast to the findings in healthy persons, CMV genomes were frequently detected in urine and throat washings from immunosuppressed, CMV-seropositive patients without symptoms of CMV infection. The appearance of CMV genomes in blood cells in immunosuppressed CMV-seronegative patients may be the first sign of primary CMV infection. Congenital CMV infection could be rapidly and safely diagnosed when urine samples were examined by PCR. Nested PCR is a valuable tool for the diagnosis of active CMV infection, when selected materials are used.
Human Cytomegalovirus (CMV) is the most common cause of intrauterine and perinatal infections worldwide. Postnatal CMV transmission has usually no consequences, but in some cases it may produce disease in preterm infants. Literature reports a broad range of breast milk-acquired CMV infections (5.7-58.6%), which depends on the study's design and the treatment of the milk. To evaluate CMV transmission via breast milk, a prospective study using a real-time PCR assay was performed. One hundred and thirty-one mothers (accounting for 160 children) accepted the participation in the study. Urine samples from the infants and breast milk samples from their mothers were collected at 3, 15, 30, 60, and 90 days after delivery. CMV-DNA in breast milk was analysed by quantitative real-time PCR assay Affigene® CMV Trender (Cepheid, Bromma, Sweden). The breast milk samples from 92 mothers (92 of 131, 70.2%) were positive for CMV by PCR. CMV infection was detected in thirteen children by PCR, and four of them (30.7%) had clinical symptoms. There were not significant differences in morbidity between symptomatic and non- symptomatic patients; nonetheless, the average length of hospitalization in symptomatic children was higher than that of non-symptomatic children (P?
The combined effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG, ganciclovir) and hyper immune serum (HIS) was studied in two different rat models. In the first model, a lethal generalized rat cytomegalovirus (RCMV) infection was established in immunosuppressed Brown Norway (BN) rats. Treatment with DHPG or hyper immune serum (HIS) effectively reduced both mortality rate and virus titers in the liver and lungs. By combined treatment the effective dose of both DHPG and HIS was reduced to 25%. The fractionary effective dose was 0.5, indicating a moderate synergistic effect on survival. Combined treatment also established a significant reduction of virus titers in lungs and liver (P
Testing of immunocompromised patients for markers of beta-herpesviruses--human herpesvirus type 6 (HHV-6) and cytomegalovirus (CMV), as well as gamma-herpesvirus--Epstein-Barr virus (EBV), revealed that all mentioned infections are frequently detected, mainlyas mixed infections. Chronic HHV-6 infection was diagnosed in more than half of the patients, whereas markers of acute phase of CMV and EBV infections were detected in 25% and 15% of patients respectively.