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The safety and immunogenicity of various doses of trivalent cold-adapted influenza vaccine (CAIV-T) administered intranasally by drops or spray to children aged 18-71 months was examined. CAIV-T containing A/Johannesburg/33/94 (H3N2), B/Panama/45/90, and A/Texas/36/91 (H1N1) was safe and well-tolerated. At the highest CAIV-T dose, 90%, 50%, and 16% of initially seronegative subjects seroconverted to the H3N2, B, and H1N1 antigens, respectively. The lower immunologic response to the H1N1 vaccine strain compared with the other strains was associated with a low frequency of H1N1 shedding. No statistically significant differences in reactogenicity or immunogenicity were detected between subjects who received CAIV-T by drops or spray. In conclusion, this CAIV-T was safe and induced acceptable immunologic responses to 2 of the 3 vaccine strains. Studies are needed to confirm previous observations that receipt of two doses of this vaccine results in immunologic responses that confer protection to all 3 circulating influenza virus strains.

Because hippocampal neurons are quite vulnerable to the anoxic brain injury that sometimes occurs in aortic arch surgery in humans, hippocampal ischemia should be a sensitive indicator of global cerebral ischemia. It was concluded that the hypothermic retrograde cerebral circulation technique for aortic arch surgery could not only be performed safely with respect to the brain, but could also increase blood flow to the hippocampal areas, probably as a result of restoration of blood flow in the thoracic aorta.

Eight hundred and twelve children, 12 months to 3.5 years of age, were enrolled in two clinical studies to evaluate the safety and immunogenicity of a live, attenuated combination vaccine for measles, mumps, rubella, and varicella (MMRV). Children were enrolled in one of two randomized, multicenter studies, involving administration of (1) MMRV and placebo vs. measles, mumps, and rubella vaccine (M-M-R(II)) and varicella-zoster virus vaccine (VARIVAX), given at separate anatomic sites at the same office visit; or (2) MMRV, DTaP (diphtheria, tetanus, and acellular pertussis vaccine) and OPV (oral polio vaccine) vs. M-M-R(II), DTaP, and OPV, with VARIVAX given 6 weeks later. All vaccine regimens were generally well tolerated. More than 95% of vaccinees seroconverted for measles, mumps, rubella, and varicella, regardless of the vaccine or regimen used. In each study, the level of antibody titer to varicella virus was significantly lower in vaccinees receiving MMRV than in those who received VARIVAX in a separate syringe.

To approximate the effect of prolonged storage on safety and immunogenicity, healthy children were given a single dose of the currently marketed live attenuated varicella vaccine (3625 pfu) or of a partially heat-inactivated vaccine (1125 or 439 pfu). The 3 doses had similar antigen content (attenuated plus inactive virus particles). The vaccine was well tolerated. No significant differences in adverse reactions were observed. Although the seroconversion rates were excellent at each dose (> or = 98%), the higher doses resulted in significantly greater geometric mean antibody titers at 6 weeks (10.5 and 10.6 ELISA U/mL) compared with the 439 pfu dose (5.7 ELISA U/mL), P < or = .01. One year after immunization, differences in antibodies were similar to the 6-week postimmunization results. Results indicate that until the date of expiry, the vaccine's immunogenicity will be preserved and there will be no clinically important changes in type or frequency of adverse events.

A comparison was made of antibody responses generated to live varicella (Oka/Merck) vaccine (Varivax) produced during three different manufacturing campaigns to evaluate the quality of the antibody responses and demonstrate consistency of the manufacturing process. Anti-varicella zoster virus (VZV) antibody titers were measured by an enhanced neutralization assay and VZV glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). For sera taken from children who had received one dose of vaccine an excellent linear concordance in titers was observed between the two assays. Sera from adults who had received two doses demonstrated continuing increased neutralization at high gpELISA titers. The immunogenicity measured by the two assays demonstrates that the overall performance of the vaccine was very similar over the three production series.

Objective: To compare the safety and immunogenicity of a one- vs. two-dose regimen of Oka/Merck varicella vaccine in approximately 2000 healthy children 12 months to 12 years of age., Methodology: Subjects with a negative history of varicella were randomized to receive either one or two injections of the vaccine given 3 months apart and were followed for clinical reactions and serologic response (glycoprotein-based enzyme-linked immunosorbent assay)., Results: Both one- and two-dose vaccine regimens were generally well-tolerated. The incidences of varicelliform rash and fever were less frequent after the second injection. However, a slight increase in the incidence of injection site reactions was noted after the second injection; these were generally mild. Seroconversion rates by glycoprotein-based enzyme-linked immunosorbent assay were 98.2% (1700 of 1731) after one injection and 99.9% (717 of 718) after two injections. A significant (P < 0.001) boost in geometric mean titers was observed in children who received a second injection of vaccine 3 months after the first injection. Of the children who seroconverted at 6 weeks postregimen (one or two doses as assigned), 99.8% (528 of 529) of the one-dose group and 99.8% (473 of 474) of the two-dose group maintained antibody to varicella at 1 year with geometric mean titers of 19.5 and 31.2, respectively., Conclusions: Administration of a one- or two-dose regimen of the live Oka/Merck varicella vaccine (VARIVAX) is immunogenic and is generally well-tolerated in healthy children 1 to 12 years old. Antibody to varicella persists in > 99% of vaccinees 1 year after vaccination regardless of a one- or two-dose regimen. Long-term follow-up studies of this cohort of children may determine whether a two-dose regimen offers superior protection against chickenpox.

We used in situ hybridization combined with immunocytochemistry, cell sorting, and the polymerase chain reaction (PCR) to investigate clinical events in three asymptomatic carriers of human T lymphotrophic virus type-1 (HTLV-1) and ten patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The objective was to determine which T cell subset of peripheral blood mononuclear cells (PBMC), CD4 or CD8, were infected by HTLV-1 and the manner in which HTLV-1 proviral DNA was expressed at the level of the single cell. Both CD4-positive and CD8-positive cells of the PBMC from five patients with HAM/TSP were infected with HTLV-1. The proportion of HTLV-1-infected cells was 2.5-40% in the CD4-positive subset and 1.0-65% in the CD8- positive subset, when quantified by PCR using HTLV-1-infected MT2 cells as a positive standard. Proviral DNA of HTLV-1 was expressed in both CD4-positive cells and CD8-positive cells of the PBMC from six patients with HAM/TSP and three asymptomatic HTLV-1 carriers. In patients with HAM/TSP, the proportion of the cells expressing HTLV-1 proviral DNA was 0.02-0.1% in both subsets. In asymptomatic carriers, the expression of HTLV-1 proviral DNA was 0.01-0.02% in the CD4-positive subset and 0.01% in the CD8-positive subset. Therefore, HTLV-1 possessed similar in vivo cellular tropism for both CD4-positive cells and CD8-positive cells and HTLV-1 proviral DNA was expressed in vivo in both circulating T cell subsets.(ABSTRACT TRUNCATED AT 250 WORDS)

A multicenter clinical trial was conducted among 757 healthy adolescents and adults, 13-54 years, to compare two regimens of Oka/Merck varicella vaccine with respect to safety, tolerability, and immunogenicity. Participants were randomized to receive two injections of vaccine either four or eight weeks apart and were followed for clinical reactions and serologic response. The two vaccine regimens were equally well tolerated. The seroconversion rates (gpELISA) four weeks after injection 1 and 2 were 72 and 99%, respectively, for those who received vaccine four weeks apart and 78 and 99%, respectively, for those who received vaccine eight weeks apart. The differences in seroconversion rates were not statistically significant. However, delaying the second dose to eight weeks resulted in a higher antibody titer one month after the second injection. Administration of a two-dose regimen of varicella vaccine to susceptible adolescents and adults is well tolerated and highly immunogenic.

Objective: To prospectively characterize varicella occurring in children previously immunized with a live attenuated varicella vaccine (breakthrough varicella) through daily observation by medical personnel and to compare it with natural varicella followed in the same manner., Design: A blinded clinical survey., Setting: Four pediatric practices (two private; two hospital-based)., Participants: Healthy 12-month-old through 17-year-old children with chickenpox were studied; 92 had natural varicella and 58 had breakthrough varicella. SELECTION PROCEDURES AND INTERVENTIONS: Study personnel, unaware of vaccination status, documented the clinical characteristics of each patient in the office or at the patient's home each day from enrollment until the day after the total number of lesions increased less than 10%. A standard form documenting number and description of lesions, temperature, duration of illness, and associated clinical complaints was completed each day by the same study personnel. Acute and convalescent sera were obtained on breakthrough cases., Measurements and Results: Antibody to varicella-zoster virus was measured by the glycoprotein-based enzyme-linked immunosorbent assay. Of those with sera available, 85% were serologically confirmed. Eighty-seven percent of enrollees had a known exposure to chickenpox, with at least two thirds of each group having a greater than 4-hour or a household exposure. The numbers of total and vesicular lesions were significantly higher in the natural varicella group, regardless of exposure status (P = .021 to < .001). The group with breakthrough varicella had a significantly lower incidence of fever (P < .001) and a significantly shorter duration of illness (P < .001). Other associated constitutional complaints and complications were not significantly different between groups., Conclusion: Varicella in vaccine recipients is clinically modified and significantly less severe than natural disease.

The ocular manifestation of human T-cell lymphotropic virus type I (HTLV-I) infection has been recognized as a new clinical entity termed HTLV-I uveitis. In order to determine whether HTLV-I uveitis is associated with lymphocyte alveolitis, bronchoalveolar lavage (BAL) was carried out in 11 patients with HTLV-I uveitis, five asymptomatic HTLV-I carriers, 11 HTLV-I-negative patients with ocular sarcoidosis, and nine normal control subjects seronegative for HTLV-I. Six of the 11 patients with HTLV-I uveitis showed increased total cell counts, and T-lymphocytosis in BAL fluid. CD4+/CD8+ ratios of T-lymphocytes were decreased in three of these patients, and normal in three other patients. Such abnormalities of the lung were not found in asymptomatic HTLV-I carriers, and in normal control subjects. BAL findings in HTLV-I uveitis differed from those of patients with sarcoidosis in terms of the lymphocytic component. Interestingly, it was found that there was an increase of HTLV-I proviral deoxyribonucleic acid (DNA) load in peripheral blood mononuclear cells (PBMC) from seven patients with HTLV-I uveitis, and in the BAL cells from four patients with pulmonary involvement. These results provide further evidence in terms of HTLV-I tropism for the lung, and suggest that a systemic and local increase of HTLV-I proviral DNA load plays an important role in the pathogenesis of lymphocyte alveolitis in patients with HTLV-I uveitis.

It has been shown that T lymphocyte alveolitis occurs in patients with human T lymphotropic virus type-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). To determine whether HTLV-1-specific antibodies were present in bronchoalveolar lavage (BAL) fluid, we investigated 15 patients with HAM/TSP, five HTLV-1 carriers without HAM/TSP, and 10 normal control subjects seronegative for HTLV-1. Studies of BAL showed that 12 of 15 patients with HAM/TSP were associated with bronchoalveolar T lymphocytosis. Such abnormalities of the lung were not found in three other patients with HAM/TSP, non-HAM/TSP carriers, and normal control subjects. Using Western blots, specific IgA antibodies were detected only in BAL fluid from 12 patients with HAM/TSP and with pulmonary involvement. On the other hand, specific IgG antibodies in BAL fluid were positive not only in 12 patients with HAM/TSP and with pulmonary involvement, but also in two of three patients with HAM/TSP and three of five non-HAM/TSP carriers, both of whom showed normal BAL findings. Specific IgM class antibodies in BAL fluid were not detected in any subjects in these three groups. Specific IgA antibodies were found in the sera of 12 patients with HAM/TSP and with BAL lymphocytosis, but not in three patients with HAM/TSP and without BAL lymphocytosis, and five non-HAM/TSP carriers. These results suggest that the production of HTLV-1-specific IgA antibodies is closely related to pulmonary involvement in patients with HAM/TSP.

Beef heart cytochrome c oxidase was labeled at a single sulfhydryl group by treatment with 5 mM N-iodoacetylamidoethyl-1-aminonaphthalene-5-sulfonate (1,5-I-AEDANS) at pH 8.0 for 4 h. Sodium dodecyl sulfate gel electrophoresis revealed that the enzyme was exclusively labeled at subunit III, presumably at Cys-115. The high affinity phase of the electron transfer reaction with horse cytochrome c was not affected by acetylamidoethyl-1-aminonaphthalene-5-sulfonate (AEDANS) labeling. Addition of horse cytochrome c to dimeric AEDANS-cytochrome c oxidase resulted in a 55% decrease in the AEDANS fluorescence due to the formation of a 1:1 complex between the two proteins. Forster energy transfer calculations indicated that the distance from the AEDANS label on subunit III to the heme group of cytochrome c was in the range 26-40 A. In contrast to the results with the dimeric enzyme, the fluorescence of monomeric AEDANS-cytochrome c oxidase was not quenched at all by binding horse heart cytochrome c, indicating that the AEDANS label on subunit III was at least 54 A from the heme group of cytochrome c. These results support a model in which the lysines surrounding the heme crevice of cytochrome c interact with carboxylates on subunit II of one monomer of the cytochrome c oxidase dimer and the back of the molecule is close to subunit III on the other monomer. In order to identify the cysteine residues that ligand copper A, a new procedure was developed to specifically remove copper A from cytochrome c oxidase by incubation with 2-mercaptoethanol followed by gel chromatography. Treatment of the copper A-depleted cytochrome c oxidase preparation with 1,5-I-AEDANS resulted in labeling sulfhydryl groups on subunit II as well as on subunit III. No additional subunits were labeled. This result indicates that the copper A binding site is located at cysteines 196 and/or 200 of subunit II and that removal of copper A exposes these residues for labeling by 1,5-I-AEDANS. Alternative copper A depletion methods involving incubation with bathocuproine sulfonate (Weintraub, S.T., and Wharton, D.C. (1981) J. Biol. Chem. 256, 1669-1676) or p-(hydroxymercuri)benzoate (Li, P.M., Gelles, J., Chan, S.I., Sullivan, R.J., and Scott, R.A. (1987) Biochemistry 26, 2091-2095) were also investigated. Treatment of these preparations with 1,5-I-AEDANS resulted in labeling cysteine residues on subunits II and III. However, additional sulfhydryl residues on other subunits were also labeled, preventing a definitive assignment of the location of copper A using these depletion procedures.

Severe myoclonus, generalized seizures, and marked stupor occurred in a 39-year-old woman with chronic renal insufficiency after one week of moxalactam 2 g iv q8h. Moxalactam serum levels far exceeded the recommended therapeutic range. The drug half-life was 17 hours (normal 1.9). Excessively high levels of moxalactam, which penetrates the blood-brain-barrier relatively easily, may provoke seizures and encephalopathy.

Since controversy continues concerning the value of routine electroencephalographic (EEG) monitoring and selective carotid bypass shunting, we reviewed the neurological morbidity and mortality following elective carotid endarterectomy in 172 patients with symptomatic carotid occlusive disease. The use of EEG monitoring and selective shunting was associated with a reduction in the frequency of carotid shunts (49 to 12%) and a decline in combined major neurological morbidity and mortality (2.3 to 1.1%). We conclude that the routine use of intraoperative EEG monitoring is a valuable procedure, particularly in patients at high risk for perioperative neurological complications.