Cytomegalovirus vaccine. Specific humoral and cellular immune responses in human volunteers.

Four seronegative adult male volunteers were immunized with Towne strain cytomegalovirus (CMV) vaccine. The only reaction was transient pain and swelling at the inoculation site. Viral cultures were performed during the first 12 weeks after immunization, and CMV was not recovered from throat, urine, or peripheral blood mononuclear cells. Both CMV-specific humoral and cellular immunity developed within three weeks of vaccination. Whereas humoral antibody titers declined steadily with time, the cellular immune responses seemed biphasic. An early peak in lymphocyte proliferation to CMV antigen occurred three to six weeks after immunization. Responses then diminished but increased again six to ten months after immunization. This study in a small group of normal male volunteers indicated that CMV vaccine was safe and immunogenic. That CMV vaccine elicited CMV-specific humoral and cell-mediated immunity is important, because there is evidence that both are necessary for protection from CMV infections.

A trial of vidarabine for cytomegalovirus infection in renal transplant patients.

Vidarabine was evaluated in renal transplant patients as a potential therapeutic agent in cytomegalovirus (CMV) infection. Four patients received vidarabine on an open protocol, then ten additional patients were enrolled in a double-blind protocol. Among the nine patients who received vidarabine, no notable clinical improvement occurred in either the vidarabine- or placebo-treated groups. Thus, vidarabine showed no therapeutic effect in the treatment of CMV infections at the dosages used. Four patients showed dramatic CNS deterioration within several days of the onset of vidarabine therapy. Tremors and myoclonus were common, and one patient had unusual brain pathologic changes with widespread neuronal chromatolysis. The pathologic findings in the brain in the other three patients were complex and included intracerebral hemorrhage, Fabry's disease, coccidioidomycosis meningitis, and cerebral vascular occlusion. Thus, there was no conclusive proof that vidarabine contributed to the sudden neurologic deterioration of these patients.

Visual attention and aging.

The present review of visual attentional processes and aging focuses on definitions of attention that emphasize some aspect of the control of information processing (selective attention) or the processing resources needed to drive these control processes (attentional capacity). Emphasis is placed on how increased adult age affects attentional mechanisms and how these age differences in attention affect overall information processing. Past research has emphasized that selective attention appears to be resistant to age-related decline. Age-related deficits in attentional capacity or processing resources, however, have been found. A review of more recent psychological research demonstrates the extension of the investigation of attention with emphasis on further defining what is selected in selective attention, and on reexamining the processing resources or capacity issue. Finally, developments in cognitive neuroscience are reviewed in terms of their relevance to attention and aging.

Influence of age and processing stage on visual word recognition.

The authors used a lexical-decision task in 3 different experiments to examine whether age differences in word recognition were consistent across processing stage. In all experiments, word frequency and length were manipulated. In Experiments 1 and 2, encoding difficulty was varied, and in Experiment 3, response selection difficulty was varied. In all 3 experiments, there were no age differences for word frequency. However, in Experiments 1 and 2, older adults showed a larger decrement for encoding. In Experiment 3, age differences were larger when response selection load increased. These results suggest that age differences in word recognition occur because older adults exhibit primarily peripheral-rather than central-processing decrements. The implications of these data for generalized and localized slowing models are discussed.

RA27/3 rubella vaccine. A four-year follow-up.

RA27/3 rubella vaccine was given to 418 subjects aged 1 to 17 years in 1974, 201 of whom participated in a four-year follow-up study. Two vaccine-associated complications were reported. A 5-year-old boy had transient arthritis of the hip, and a 1-year-old boy had a pigmented macule at the inoculation site. Rubella reinfection was uncommon, occurring at most in three of our subjects. All of the 186 susceptible children seroconverted, and 182 had hemagglutination-inhibiting (HI) titers of 8 or greater at four-year follow-up (geometric mean titer, 30.3). In the four children whose HI titers declined to undetectable levels, both HI and neutralizing (Nt) antibodies had developed immediately postimmunization, and two had Nt titers at follow-up despite loss of HI antibodies. RA27/3 vaccine boosted HI titers in 15 seropositive subjects, but titers returned to preimmunization levels four years later. We concluded that RA27/3 vaccine produced durable immunity with very low rates of rubella reinfection and secondary vaccine failure during the four years since immunization.

Influence of response selection and noise similarity on age differences in the redundancy gain.

We examined the impact of target redundancy for target-plus-noise (TPN) and target-only (TO) trials. Experiment 1 manipulated response selection load (two-choice vs go/no-go) and Experiment 2 (all two-choice) varied noise redundancy (single or cumulative noise letters) on a visual search, divided attention task in which target letters were presented in one, two, or three corners of a four-corner display. Half of the trials also included noise letters. For Experiment 1, there was a definite redundancy gain for TO trials. Furthermore, older adults, relative to young adults, evidenced an even larger redundancy gain for TO trials than for TPN trials, although response selection load did not interact with age. These results are consistent with the notion that older adults exhibit a processing resources decrement. For Experiment 2, older adults evidenced a relatively larger redundancy gain for TPN trials than for TO trials, and this was especially the case for TPN trials in which all nontarget locations were filled with noise letters. Experiment 2 results are consistent with the notion that older adults also exhibit a selective attention decrement.

Impact of age, redundancy, and perceptual noise on visual search.

We examined adult age differences in the impact of redundancy and perceptual noise during visual search. Using a two-choice, visual search task, subjects responded to letters presented in one to four corners of an imaginary display square. On each trial, one, two, or three instances of a given target letter were presented. In the target-plus-noise condition, all nontarget corners of the imaginary square were filled with distractor (i.e., noise) letters. In the target-only condition, all nontarget corners were left blank. The results indicated that older adults showed relatively greater redundancy benefits than the young adults for the target-plus-noise trials than for the target-only trials. These results are interpreted within an internal noise framework.

Impact of adult age and Alzheimer's disease on levels of neural noise for letter matching.

We tested healthy young and older adults as well as higher-scoring (Mini-Mental State Exam, MMSE, scores between 14-20) and lower-scoring patients diagnosed with probable Alzheimer's disease (AD) on a letter-matching task. Subjects were instructed to respond "same" if two simultaneously presented letters were identical, or "different" if the letters did not match. Healthy older adults showed a larger "fast-same" effect than healthy young adults. Also, higher-scoring AD patients showed a large "false-different" effect for errors, but lower-scoring AD patients showed a large "false-same" effect. These data indicate that older adults exhibit higher neural noise levels than younger adults. The cross-over error pattern for AD suggests that moderately demented AD patients show evidence of forming degraded visual percepts whereas more severely demented AD patients show evidence of forming incomplete percepts.

Rubella viraemia and antibody responses after rubella vaccination and reimmunization.

Eleven 4-13 year old schoolgirls, who were seronegative by haemagglutination inhibition (HI) and radioimmunoassay (RIA) tests despite having been given HPV77-DE5 vaccine 3-9 years previously, were revaccinated with RA27/3. They showed evidence of residual immunity since they had accelerated immune responses, little or no rubella-specific IgM, no viraemia, and no vaccine-induced reactions. In contrast, all but one of the five adult women who were primary vaccinees showed a more delayed immune response. Three of four women tested had viraemia and two had vaccine-induced reactions. Enhanced HI and enhanced RIA showed that many of the schoolgirls had antibody before challenge, as did a fifth adult, who also showed an accelerated immune response, yet became viraemic.

Acyclovir therapy for mucocutaneous herpes simplex infections in immunocompromised patients.

11 of 24 immunocompromised patients with mucocutaneous herpes simplex virus (HSV) infections were given intravenous acyclovir in a randomised double-blind placebo-controlled study. Patients receiving acyclovir experienced no major adverse effects. The median times to cessation of new lesion formation, lesion crusting, lesion healing, cessation of pain, and termination of viral shedding were shorter in the acyclovir-treated group than in the placebo group. The time-to-event probability curves for the acyclovir and placebo groups were significantly different for cessation of pain (p=0.032) and termination of viral shedding (p=0.004). The median times to termination of viral shedding were also statistically different (p=0.045). Acyclovir seems to be a non-toxic and effective treatment for mucocutaneous HSV infections in immunocompromised patients.

Evaluation of zoster immune plasma. Treatment of cutaneous disseminated zoster in immunocompromised patients.

Zoster immune plasma (ZIP) was evaluated for treatment of cutaneous disseminated zoster in immunocompromised hosts. Twenty patients were studied: 13 were enrolled in a double-blind protocol, five received ZIP under an open protocol, and two were observed without receiving a transfusion. In the double-blind study, eight patients actually received ZIP; five were given plasma lacking varicella-zoster virus antibodies (control plasma). The clinical course of zoster in the group given ZIP was the same as that of patients given control plasma or no transfusions. Because ZIP did not alter the clinical course of zoster and because zoster patients produced high-antibody titers without ZIP, we concluded that ZIP is not useful for treatment of cutaneous disseminated zoster and should be reserved for prevention or modification of varicella in exposed, susceptible immunocompromised patients.

Prevention or modification of varicella using zoster immune plasma.

Zoster immune plasma (ZIP) was given to 31 susceptible immunocompromised children one to seven days (median, two days) following household, playmate, or hospital exposures to varicella. The average amount of ZIP transfused was 7 ml/kg. Twenty-one children did not develop varicella or persistent antibodies to varicella-zoster virus (VZV). Eight (26%) of the 31 contracted clinical varicella. Seven cases were mild, but in one child, who was given ZIP seven days after exposure, visceral disease developed and the child died. Two children had subclinical varicella that was documented by persistence of VZV antibodies for at least ten months after passive immunization. Because none of the 30 children given ZIP one to six days following exposure had severe varicella, we conclude that ZIP is effective in preventing or modifying varicella in immunocompromised patients if given shortly after exposure.