Immunogenicity of four Haemophilus influenzae type b conjugate vaccines in 17- to 19-month-old children

OBJECTIVE: To compare the immunogenicity of four Haemophilus influenzae type b (Hib) conjugate vaccines in different populations of 17- to 19-month-old children in the United States. DESIGN: Four immunogenicity trials with sera were assayed in one laboratory. Trials 1 and 2 each compared one vaccine in two regions, and trials 3 and 4 were randomized comparisons of multiple vaccines within a region. SUBJECTS: A convenience sample of 313 healthy children recruited from pediatric practices in Minneapolis, Minn., Dallas and Houston, Tex., and Sellersville, Pa. MEASUREMENTS AND RESULTS: Children with prevaccination antibody greater than 0.15 microgram/ml showed higher antibody responses to vaccination than children with less than or equal to 0.15 microgram/ml (p less than 0.001). Among the former, there were no significant differences in antibody response to vaccination with the different conjugates within any of the trials. Among children with less than or equal to 0.15 microgram/ml of antibody before vaccination, there were no significant differences in the geometric mean antibody responses of children in trial 1 vaccinated with polyribosylribitol phosphate-diphtheria toxoid (PRP-D) in Dallas or in Minneapolis, or of children in trial 3 in Dallas randomly assigned to receive Hib oligosaccharide-CRM197 (HbOC) or PRP-D. In contrast, in trial 2, children given PRP-tetanus toxoid (PRP-T) in Pennsylvania had a significantly higher geometric mean antibody response than children given PRP-T in Houston (13.5 vs 3.0 micrograms/ml; p = 0.005). In trial 4 in Minneapolis, the geometric mean antibody response was highest in children randomly assigned to receive PRP-outer membrane protein (OMP) (9.3 micrograms/ml), followed by PRP-D (5.0 micrograms/ml) and HbOC (2.3 micrograms/ml) (PRP-OMP vs HbOC; p = 0.005). In all four trials, IgG1 responses predominated compared with IgG2 responses. CONCLUSIONS: All four conjugate vaccines are immunogenic in children 17 to 19 months of age. However, the magnitude of the anticapsular antibody response varied by vaccine type, the level of antibody in prevaccination sera, and geographic location.     

Regulation of B Cell:T Cell Interactions: Potential Involvement of an Endogenous B Cell Sialidase

In light of the ability of B cells treated with neuraminidase to interact more effectively with T cells, the increased capacity of activated, but not small resting B cells, to interact with T cells could be associated with the level of sialylation on certain B cell surface molecules which influences the effectiveness of the physical interaction between B and T cells. The purpose of this study was to determine if activation of B cells altered sialylation via an endogenous sialidase which affected both the initial interaction between T and B cells and subsequent B cell-induced T cell proliferation. The competitive neuraminidase inhibitor, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (NeuAc2en), inhibited LPS-mediated enhancement of B cell conjugate formation with Ia-specific T cell clones as well as enhancement of their capacity to stimulate a mixed lymphocyte reaction. The addition of NeuAc2en during LPS stimulation did not affect the surface expression of Ia, LFA-1, ICAM-1 or mB7, suggesting that inhibition of LPS-mediated enhancement by the sialidase inhibitor was not due to changes in the level of expression of the major B cell adhesion or co-stimulatory molecules. Short term stimulation with phorbol myristate acetate (PMA) and ionomycin also enhanced the ability of resting B cells to form antigen specific T:B conjugates. However, activation of B cells with PMA and ionomycin or with LPS did not change the capacity of a sialic acid specific lectin to bind to the B cells, suggesting that activation was not associated with global changes in surface sialic acid content. B cell stimulation did not appear to increase the activity of the most prevalent B cell sialidase activity as measured in an in vitro assay system, suggesting that the major B cell sialidase may not be responsible for the alteration of B cell sialylation levels or the ability of activated B cells to interact more effectively with T cells. The possibility of intracellular compartmentalization of sialidase activity or that a minor B cell sialidase may play a role in the regulation of a B cells ability to interact with T cells are discussed.     

Effects of induced hypotension during experimental vasospasm: a neurological, electrophysiological, and pathological analysis

Vasospasm of the vertebrobasilar system was induced in seven dogs by the intracisternal injection of autologous blood. Somatosensory and brain stem auditory evoked potentials were recorded before and after the induction of angiographically confirmed vasospasm. Additionally, somatosensory evoked potentials were monitored during graded hypotension to 40 mm Hg. There was no significant alteration in the evoked potentials by vasospasm or hypotension. Detailed clinical examination and postmortem histopathological studies did not demonstrate any focal neurological deficit or infarction attributable to vasospasm. Previous studies have noted close correlations between decreased cerebral blood flow and evoked potential alterations. Induced hypotension to a mean arterial pressure of 40 mm Hg in the presence of documented vasospasm was not sufficient to cause evoked potential changes, focal neurological deficit, or pathological evidence of infarction in the canine model.     

Axial diffusion of retinol in isolated frog rod outer segments following substantial bleaches of visual pigment

Partial bleaches of rhodopsin were made in either the proximal or distal halves of isolated Rana pipiens rod outer segments. The fluorescence of all-trans retinol was recorded 15, 60 and 120 min following 17% and 63% bleaches. Some of the retinol that formed remained immobilized in the bleached halves of the outer segments, while another portion was slowly mobilized and diffused along the cell axis.     

Substance abuse and schizophrenia: effect on symptoms but not on neurocognitive function.

The authors compare symptoms and neuropsychological test performance in DSM-III schizophrenic patients who reported prior substance abuse (N = 38) with those in patients who reported no such abuse (N = 25) to determine the impact of substance abuse on the psychopathology of schizophrenia. Positive and negative symptom scores were derived from the Schedule for Affective Disorders and Schizophrenia. Sixty neuropsychological measures drawn from commonly used tests of intelligence, memory, learning, fluency, and problem solving were calculated. Separate analyses were performed on patients in a psychotic episode who were free of neuroleptics (N = 27) and on those taking maintenance neuroleptics (N = 36). Among unmedicated patients, those who reported prior substance abuse had significantly higher thought disorder scores. Among neuroleptic-medicated patients, hallucination and delusion scores were significantly higher in the patients who reported prior substance abuse. The substance abuse followed withdrawal from social relations and preceded the onset of positive symptoms. None of the neuropsychological tests discriminated between abusers and nonabusers.