PubMed HealthSearch

Biomedical subjects

L Diller

Publications and source records attributed to L Diller.

At least 19 recordsLinked to original sources

Antibody responses to polysaccharide and polysaccharide-conjugate vaccines after treatment of Hodgkin disease.

OBJECTIVE: To compare the immunogenicity of polysaccharide-conjugate vaccines with that of polysaccharide vaccines in patients previously treated for Hodgkin disease. DESIGN: All patients were immunized with Haemophilus influenzae type b (HIB)-conjugate and 4-valent meningococcal polysaccharide vaccines. Subgroups of patients were randomly assigned to receive either 23-valent pneumococcal polysaccharide vaccine or a 7-valent pneumococcal-conjugate vaccine that links seven pneumococcal serotypes to the outer membrane protein complex of Neisseria meningitidis. PATIENTS: 144 patients who had completed treatment for Hodgkin disease, which had been diagnosed at least 2 years before the study. MEASUREMENTS: Antigen-specific antibody concentrations before and 3 to 6 weeks after immunization; number of persons who achieved anti-HIB antibody concentrations considered to be in the protective range. RESULTS: The geometric mean anti-HIB antibody concentration increased from 1.79 micrograms/mL before immunization to 54.1 micrograms/mL after; the percentage of persons with antibody concentrations in the protective range increased from 62% before immunization to 99% after. Patients immunized with 23-valent pneumococcal vaccine had a geometric mean pneumococcal antibody concentration after immunization (9.15 micrograms/mL) that was similar to that of healthy controls (10.0 micrograms/mL) for the seven serotypes measured. In contrast, patients who received 7-valent pneumococcal-conjugate vaccine had a significantly lower mean response compared with patients who received 23-valent; their geometric mean antibody concentration after immunization was 4.95 micrograms/mL (P = 0.005). CONCLUSION: A single dose of HIB-conjugate vaccine was immunogenic in patients who had completed treatment for Hodgkin disease diagnosed at least 2 years before immunization. In addition, responses to the 23-valent pneumococcal and 4-valent meningococcal vaccines were equivalent to those seen in healthy controls. Finally, patients had a significantly lower response to a single dose of 7-valent pneumococcal-conjugate vaccine than to 23-valent vaccine.

Bacterial Capsules

Germline p53 mutations are frequently detected in young children with rhabdomyosarcoma.

We investigated the possibility that a proportion of children with sporadic rhabdomyosarcoma (RMS) carry constitutional mutations of the p53 tumor suppressor gene. 33 patients with sporadic RMS at two large outpatient pediatric oncology clinics submitted blood samples. Genomic DNA was extracted from peripheral blood leukocytes and PCR was used to amplify exons 2-11 of the p53 gene. Amplified genomic DNA was screened for the presence of germline p53 mutations using single-strand conformation polymorphism (SSCP) analysis. The DNA sequence of those samples that showed aberrant migration of bands on SSCP analysis was determined to identify the precise nature of the gene mutations. Patient records were reviewed to assess clinical correlates of the mutant p53 carrier state. Heterozygous constitutional mutations were detected in 3/33 patient samples screened. Two of these missense mutations are located in exon 7 and one in exon 8 of the p53 gene. The presence of mutations was not correlated with tumor histology, stage, or site. However, an association between young age at diagnosis and presence of a constitutional p53 mutation was noted: 3/13 children under the age of 3 yr at diagnosis carried mutations, whereas none of 20 children over 3 yr of age at diagnosis harbored a detectable constitutional mutation. These results in children with RMS corroborates previous findings in other clinical settings suggesting that the mutant p53 carrier state may predispose individuals to malignancy at an early age. Although this study did not assess whether the mutations were preexisting or new germline alterations, assessment of close relatives of RMS patients for cancer risk and predictive genetic testing may be indicated.

Adolescent

Structure and expression of the Xenopus retinoblastoma gene.

We have cloned a Xenopus homology (XRb1) of the human retinoblastoma susceptibility gene. DNA sequence analysis shows that the XRb1 gene product is highly conserved in many regions. The leucine repeat motif and many of the potential cdc2 phosphorylation sites, as well as potential sites for other kinases, are retained. The region of the protein homologous to the SV40 T antigen binding site and the basic region directly C-terminal to the E1A binding site are all conserved. XRb1 gene expression at the RNA level was studied by Northern blot analysis. Transcripts of 4.2 and 10-kb are present as maternal RNA stores in the oocyte. While the 4.2-kb product is stable until at least the mid-blastula stage, the 10-kb transcript is selectively degraded. Between stages 11 and 13 the 10-kb transcript reappears and also a minor product of approximately 11 kb becomes apparent. Both the 4.2- and the 10-kb transcripts remain present until later stages of development and are also present in all adult tissues examined, although at differing levels. Antibodies raised against human p105Rb which recognize the protein product of the XRb1 gene, pXRb1, detect the Xenopus 99-kDa protein prior to the mid-blastula stage, but at lower levels than at later stages in development.

Amino Acid Sequence

Stress, appraisal, and coping in mothers of disabled and nondisabled children.

The cognitive-behavioral model of stress and coping provided the framework for this study of mothers of physically disabled children (n = 69) and mothers of nondisabled children (n = 63). The first aim was to test for differences between groups in responses to stressful parenting events. As hypothesized, mothers of disabled children reported higher levels of depressive symptomatology. Differences in psychological distress and health status approached significance. The second aim was to explore the mediating influences of coping strategies and cognitive appraisals. As predicted, emotion-focused coping was related to increased psychological distress in mothers of disabled children whereas problem-focused coping was associated with decreased distress. Both relationships were significant even after controlling for differences in type of parenting stressor. Hierarchical regressions showed that 58 and 25% of the variance in psychological distress was explained by the independent variables; however, the predictors were different for the two groups of mothers. Factors that may explain the differential effectiveness of coping and appraisal, and clinical implications of this study are discussed.

Adaptation, Psychological

Rhabdomyosarcoma and other soft tissue sarcomas of childhood.

Childhood rhabdomyosarcoma and the other soft tissue sarcomas of childhood are a heterogeneous group of tumors with many histologic subtypes, affecting multiple anatomic locations and requiring the care of subspecialists from a variety of disciplines. Epidemiologic studies of childhood sarcomas indicate that a familial predisposition to malignancy may contribute to tumorigenesis in a proportion of patients. Diagnosis of these tumors may be difficult; immunohistochemical and cytogenetic analysis is clearly important. Large cooperative group studies have answered important treatment questions in past years; these studies are now being analyzed for clues to effective treatment of specific histologic and anatomic subgroups. The Intergroup Rhabdomyosarcoma Study IV is now open and the questions addressed are reviewed. New developments in late effects of therapy for childhood sarcoma are considered.

Adult

Identification of cancer-prone individuals: p53 and family cancer syndromes.

Progress in prevention of any disease is enhanced by the identification of a group of individuals who are at increased risk to develop the disease. The ability to detect families with evident predisposition to malignancy provides a unique opportunity to study high-risk groups. Recent studies of the p53 gene have suggested that heritable mutations in this gene may predispose affected individuals to the development of a wide variety of tumors. In this article, evidence for the involvement of p53 in inheritable cancers is assessed, and the implications for future studies are discussed.

Genes, p53

p53 functions as a cell cycle control protein in osteosarcomas.

Mutations in the p53 gene have been associated with a wide range of human tumors, including osteosarcomas. Although it has been shown that wild-type p53 can block the ability of E1a and ras to cotransform primary rodent cells, it is poorly understood why inactivation of the p53 gene is important for tumor formation. We show that overexpression of the gene encoding wild-type p53 blocks the growth of osteosarcoma cells. The growth arrest was determined to be due to an inability of the transfected cells to progress into S phase. This suggests that the role of the p53 gene as an antioncogene may be in controlling the cell cycle in a fashion analogous to the check-point control genes in Saccharomyces cerevisiae.

Amino Acid Sequence

A preliminary comparison of flat affect schizophrenics and brain-damaged patients on measures of affective processing.

Flat affect is a major component of schizophrenia and is often also seen in neurological disorders. A preliminary set of comparisons were conducted to delineate neuropsychological mechanisms underlying flat affect in schizophrenia, and new measures are described for the assessment of affective deficits in clinical populations. Subjects were schizophrenic with flat affect (SZs), right brain-damaged (RBD), Parkinson's Disease (PDs), and normal control (NC) right-handed adults. Subjects were administered affective measures of expression and perception in both facial and vocal channels. For both perceptual and expressive tasks the SZs performed significantly less accurately than the NCs and the PDs but did not differ from the RBDs. This was the case for both face and voice. This finding lends support to the speculation that right hemisphere mechanisms, especially cortical ones, may be compromised among schizophrenics with flat affect.

Adult

First year after stroke: tracking cognitive and affective deficits.

A total of 58 cerebrovascular accident (CVA) rehabilitation inpatients with lateralized brain damage were assessed at two time points (T1 = admission to rehabilitation facility, about 7 weeks post-CVA, and T2 = 10 months post-CVA) in the following domains: hemispatial neglect, reaction time, depression, and affect comprehension. Performance was compared with 22 age-matched control subjects. Repeated measures ANOVAs were performed with patients subdivided into groups by laterality of lesion and visual field status (a strong predictor of psychometric performance, particularly in the hemispatial-neglect domain). During this initial year after stroke onset, significant improvements were observed in hemispatial neglect and affect comprehension in the two right-brain-damaged groups, but not the left-brain-damaged group. There was also a trend for improvement in observer rating of depression in all three groups. However, there was poor resolution of reaction time and self-reported depression in all three groups. These findings suggest that these latter domains should be targeted for more aggressive therapeutic intervention. An important component of such intervention, in addition to direct treatment of deficits, should be education of both patient and family as to the nature of deficits, expectations regarding resolution, and appropriate attributions of changed behavior after stroke.

Affect

Relationship among CT scans, neurological exam, and neuropsychological test performance in right-brain-damaged stroke patients.

Right-hemisphere stroke rehabilitation inpatients were assessed by: (1) CT scans; (2) neurological exam; and (3) cognitive and affective psychometric measures. Damage to temporal, parietal, and occipital regions was associated with visual-spatial impairments. Surprisingly, parietal damage was no more related than temporal and occipital damage to severity of visual inattention. While the neurologist's ratings of lability and depression were related to CT-scan measures, patients' self-report of depression was not so related. These findings support a less specific and probably greater interlobule organization of the right, as compared with left, hemisphere, and highlight the need for multifaceted affective assessment in such a brain-damaged group.

Brain

Proper and common nouns: form class judgments in Broca's aphasia.

Studies of agrammatic Broca's aphasics' comprehension of sentences containing articles have demonstrated profound deficits. It has not been clear whether the impairments are due to an inability to isolate the article in the stream of speech, or to difficulty in the construction and/or interpretation of various syntactic, semantic, or pragmatic levels of representation. This paper reports three experiments on Broca's aphasics' ability to distinguish between common nouns (e.g., "a rose") and proper nouns (e.g., "Rose"). This grammatical form class decision is signaled by the presence or absence of an article, and is represented at the lexical node level of linguistic analysis. The three experiments demonstrated that Broca's aphasics point to pictures representing classes of objects when asked to point to "the X" and point to pictures representing unique individuals when asked to point to "X". Thus, they were shown to be able to use the presence or absence of an article to determine lexical category. Their performance was especially accurate in an oral language context which was highly redundant and in a written language context where patients themselves could control the rate of information flow. They were quantitatively impaired, relative to controls, in a third study, which made higher information processing demands. Moreover, in this third study nonsense syllables preceding the noun which are phonologically similar to a known article were much more likely to evoke the misclassification of its noun as common than were phonologically distinct nonsense syllables. These data indicate that Broca's aphasics indeed have some difficulty isolating the article in the stream of speech. Nevertheless, detailed analyses of aphasics' performance revealed their ability to distinguish between common nouns and proper nouns even under these demanding conditions. Taken together, the three studies show that insofar as agrammatic patients are able to keep track of the presence or absence of articles, they can make a grammatical decision at the lexical node level of linguistic analysis. We conclude, then, that agrammatic Broca's aphasics are particularly impaired in the use of articles to construct and/or interpret phrasal constituents.

Adult

Exploratory eye movements and visual hemi-neglect.

The severity of visual hemineglect (VHN), as defined by a VHN Index from scores obtained on letter cancellation and visual matching tests, was compared to eye movement behavior during a visual searching task in a group of right-hemisphere stroke patients and a group of age-matched normal controls. A strong negative correlation was obtained between the VHN Index and eye movement Exploration Time of the left visuospatial field for the stroke patients, but not for the control subjects. Further analyses failed to discriminate Exploration Time performance of stroke patients with mild VHN from the performance of control subjects, but did discriminate stroke patients with marked VHN from each of these two groups. Covarying for the presence of a left-visual-field sensory defect slightly reduced the significance level of this finding. The results and questions raised by this study are discussed in the context of developing an operational definition for VHN using the method of directly monitoring eye movement.

Aged

Perceptual remediation in patients with right brain damage: a comprehensive program.

This study provided a comprehensive program to treat visual perceptual disturbances associated with right brain damage (RBD). Three types of previously evaluated perceptual remediation were integrated into a sequentially administered remediation program: basic visual scanning, somatosensory awareness and size estimation training, and complex visual perceptual organization. The purpose of the study was to evaluate the immediate (at rehabilitation discharge) and long-term (four months after discharge) effects of this treatment program on patients with RBD. The effects of treatment on ADL and mood state were also examined. Seventy-seven RBD stroke rehabilitation inpatients were studied--including 48 Experimental (E) and 29 Control (C). At rehabilitation discharge, the E group relative to the C group showed greater gains in all three types of perceptual functioning. Four months after discharge from rehabilitation, the C group continued to show gains in perceptual functioning while the E group had reached a plateau. Longitudinal decreases in levels of self-reported anxiety and hostility, but not depression, were noted only for the E group.

Activities of Daily Living

Treating perceptual organization deficits in nonneglecting RBD stroke patients.

Thirty-five right brain-damaged (RBD) stroke patients, enrolled in active rehabilitation programs, participated in this study. Patients were selected on the basis of their evidenced deficits in performing complex visuo-cognitive tasks and the absence of overt evidence of unilateral visual-spatial neglect. Seventeen of the 35 patients were randomly chosen to receive a training program (lasting approximately 1 month) designed to establish a systematic strategy of organizing complex visual material. The remaining 18 patients were re-examined after 1 month, and served as controls. The design of the treatment program was based on the hypothesis that nonneglected RBD patients fail to appreciate and synthesize elements of complex visual material due to a breakdown in compensation for a persistent lateral bias in visual-spatial attention. Upon posttesting, it was found that those patients who received training exhibited significantly improved performance, as compared to controls, on a subgroup of visuo-cognitive tasks. These results are discussed in terms of: (1) offering indirect support for the argument that pathological asymmetries in attention play a significant role in the failure of RBD patients on many visuo-cognitive tasks; and, (2) offering a basis for extending the treatment of perceptual problems in RBD patients.

Attention