Working status among Dutch patients with rheumatoid arthritis: work disability and working conditions.

OBJECTIVES: To assess work disability and variables associated with work disability among Dutch patients with rheumatoid arthritis (RA). METHODS: A questionnaire on working status was filled out by 296 patients of working age. Employment and work disability rates adjusted for age and sex from the Dutch population were determined using indirect standardization. Cox proportional hazard analysis was used to assess baseline predictors of work disability in a subgroup of patients (n = 195). RESULTS: After a mean disease duration of 4.3 yr, patients had a 0.78 (95% CI 0.67-0.88) chance of being employed and a 2.14 (95% CI 1.75-2.54) risk of being work disabled when compared with the Dutch population. Functional disability and job type at the start of the disease were predictors of future work disability. In total, 48 (37%) currently employed patients had changed their working conditions, of which reduced working hours (46%), reduced pacing of work (42%) and help from colleagues (49%) were the most important alterations. Of the 60 work disabled patients without a paid job, only 11 patients (18%) would be willing to work again. CONCLUSION: This study shows that the adjusted employment rates were lower and that work disability rates were higher in patients with RA when compared with the general Dutch population. In addition, a substantial number of employed patients had to change their working conditions due to RA. Only a minority of work disabled RA patients was willing to return to the paid labour force.

Quantifying the process and outcomes of person-centered planning.

Although person-centered planning is a popular approach in the field of developmental disabilities, there has been little systematic assessment of its process and outcomes. To measure person-centered planning, we developed three instruments designed to assess its various aspects. We then constructed variables comprising both a Process and an Outcome Index using a combined rational-empirical method. Test-retest reliability and measures of internal consistency appeared adequate. Variable correlations and factor analysis were generally consistent with our conceptualization and resulting item and variable classifications. Practical implications for intervention integrity, program evaluation, and organizational performance are discussed.

Comparison among the perforation rates of Maloney, balloon, and savary dilation of esophageal strictures.

BACKGROUND: Traditionally, mercury-filled rubber bougies are used for dilation of simple or mild-to-moderate esophageal strictures, whereas through-the-scope balloon dilators and wire-guided polyvinyl bougies have become standard for more complex strictures. Because few comparative trials are available, the choice of dilator and technique is largely based on the training and experience of the operator. METHODS: We reviewed 348 esophageal dilation procedures performed on a total of 142 patients over a 4-year period (January 1, 1993, to January 1, 1997). The location and cause of stricture, the maximum diameter of the instrument used per session, the rate of perforation, and the rate of fluoroscopy use were recorded. RESULTS: Maloney, balloon (hydrostatic and pneumatic type), and Savary dilations were performed in 102, 156, and 90 sessions, respectively. Perforations occurred in 4 patients. All of these perforations occurred when Maloney dilators were passed blindly into complex strictures (Fisher's exact test, p = 0.011, two-tailed). Three of these four patients had undergone endoscopy with conscious sedation immediately before the dilation. The immediate outcome of surgery was good in all 4 patients with no deaths. CONCLUSION: Perforation was most commonly associated with the blind passage of Maloney bougies into complex strictures.

System and cost research issues in treatments for people with autistic disorders.

Parents of children with autism and pervasive developmental disorder and educational and clinical practitioners providing services to them regularly confront a wide range of service selection and financial decisions that are not as yet effectively addressed by applied research. Relevant systems issues span a very broad range of concerns: (a) systems delivery models and issues (e.g., costs of services, implementation of intensive intervention, and teacher or therapist training); (b) how best to integrate treatments; (c) providing treatment to those with limited monetary resources; (d) cost and cost/benefit analyses; (e) how to educate adult psychiatrists (as well as other practitioners and personnel) regarding autism; and (f) gaps between research and practice.

Early intensive behavioral intervention: emergence of a consumer-driven service model.

Parents are becoming influential stimulators and shapers of public policy in regard to educational services for their children. Increasingly, this advocacy has created a controversy about the role of applied behavior analysis as a foundation for early intensive behavioral intervention in autism. Uncertainties exist in policy regarding the role of behavior analysis in early intervention and the capacity of behavior analysis to field a trained work force. Based on contacts with parents of children with autism and information available in a variety of forms on the Internet, there is a rising demand for fundamentally better early intervention services that are available and accessible, provide active intervention, and are based on principles of behavior analysis. Contemporary movements in special and early education, however, appear to be nonconducive to scientifically based treatments, and school districts seem hostile to an increasing role for behavior analysis and to the establishment of services that are responsive to changing parental priorities for the education of their children with autism and related disorders.

Psychological services utilization: relationship to severity of behaviour problems in intellectual disability services.

Using the Developmental Disabilities Profile, a population service registry, the present study gives an analysis of the relationship between the rated frequency of contact with psychology specialists and a composite rating of 13 behaviour problems in intellectual disability services. An analysis of information on 45,810 adults with intellectual disability indicated that, when the population was divided into quintile groups based on behaviour severity, distinctively different distributions of rated contacts with psychologists were discernible. The people rated in the highest quintile for severity of maladaptive behaviour constituted especially high utilizers of psychology services. About 37% of participants had had no contact with psychologists during the past year, whereas 26% had such contact weekly or more frequently. The findings are introduced and discussed in the context of psychological practice in intellectual disability services and trends toward managed health and behavioural health care in the USA.

p53 abnormalities in primary prostate cancer: single-strand conformation polymorphism analysis of complementary DNA in comparison with genomic DNA. The Cooperative Prostate Network.

BACKGROUND: The reported frequency of mutation of the p53 tumor suppressor gene (also known as TP53) in human carcinomas of the prostate has varied widely, ranging from 3% to 42%. This variability may be a consequence of tumor heterogeneity and/or the use of different methods of analysis. Since p53 mutation has been associated with clinical outcome for a number of cancer types, determination of its true frequency in primary carcinomas of the prostate is important. PURPOSE: The principal aims of this study were as follows: 1) to validate the utility of detecting p53 gene mutations by means of polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis of complementary DNA (cDNA) (synthesized from prostate tissue RNA and 2) to study the concordance of RNA- and DNA-based PCR-SSCP assays in detecting p53 mutations in individual tumor fragments. METHODS: RNA and genomic DNA were isolated by means of standard techniques from specimens of 19 carcinomas of the prostate, selected on the basis of p53 data obtained in a previous analysis of cDNA (indicating that 14 were mutant and five were wild-type). RNA was converted into cDNA by means of reverse transcription (RT); the cDNA was then amplified by means of nonisotopic (i.e., nonradioactive) PCR, and the PCR products were subjected to SSCP analysis in polyacrylamide gels (RT-PCR-SSCP analysis). Genomic DNA was examined by means of SSCP analysis of isotopically labeled (32PO4) PCR products (DNA-PCR-SSCP analysis). In both approaches, the protein coding region of the p53 gene was divided into multiple, smaller fragments for study. PCR products exhibiting abnormal migration in SSCP gels were subjected to direct nucleotide sequencing or to cloning and sequencing of multiple clones. RESULTS: RT-PCR-SSCP and DNA-PCR-SSCP identified p53 gene abnormalities in 15 of the 19 selected carcinomas, including one previously reported to be wild-type for p53. Overall, PCR-SSCP analysis identified 18 p53 fragments with abnormalities; three carcinomas showed two abnormalities each. Six (33%) of the 18 abnormalities were detected by both RT-PCR-SSCP and DNA-PCR-SSCP, 10 (56%) were detected by RT-PCR-SSCP alone, and two (11%) were detected by DNA-PCR-SSCP alone. The 18 abnormalities were caused by 20 changes in the sequence of the p53 gene; in one carcinoma, double mutations in two individual p53 exons were identified. CONCLUSIONS AND IMPLICATIONS: PCR-SSCP analysis of both RNA and DNA allows the detection of more mutations than the analysis of either alone. Some primary carcinomas of the prostate contain more than one altered p53 gene, consistent with the possibility of intratumoral heterogeneity of mutation of this gene. For comprehensive analysis of p53 mutations in carcinomas of the prostate, and perhaps in other tumor tissues, SSCP analysis of cDNA should be used in combination with SSCP analysis of genomic DNA.

Insertion of the retroposable element, jockey, near the Adh gene of Drosophila melanogaster is associated with altered gene expression.

The alcohol dehydrogenase (Adh) gene of Drosophila melanogaster is well suited to be a gene expression reporter system. Adh produces a measurable phenotype at both the enzyme and mRNA levels. We recovered a spontaneous transposable element (TE) insertion mutation near the Adh gene. The insertion is a truncated retroposable element, jockey, inserted upstream of the adult Adh enhancer region. Comparisons between the Adhjockey allele and its direct wild-type ancestral allele were made in an isogenic background (i.e. identical cis and trans factors). Differences in Adhjockey expression compared with the wild-type can be attributed solely to the presence of the jockey element. This jockey insertion results in a decrease in adult mRNA transcript levels in the Adhjockey homozygous lines relative to the wild-type counterpart and accounts for a correlated decrease in alcohol dehydrogenase (ADH) enzyme activity. The larval ADH activity levels are not detectably different.

Molecular analysis of a spontaneous insertion mutation near the alcohol dehydrogenase gene of Drosophila melanogaster.

The structural integrity of the Adh gene in several isogenic lines of Drosophila melanogaster was tested by Southern blot analysis using a 4.75 kilobase (kb) genomic clone of Alcohol dehydrogenase (Adh) as a probe. One line, RI22, III, showed evidence of a spontaneous insertion mutation 5' to the adult enhancer in an area previously indicated as a putative larval enhancer region. The inserted allele was present at an approximate frequency of 50% in relation to the uninserted wildtype allele. Isogenic lines were constructed of both homozygous mutant and wildtype flies, allowing the comparison of a spontaneous insertion mutant allele and it's direct wildtype ancestral allele. The inserted sequence is a 296 basepair (bp) truncated jockey retroposable element. The sequence and distribution of the element as well as it's proximity to the Adh gene are discussed.

Identification, cloning, and sequencing of DNA essential for encapsulation of Streptococcus pneumoniae.

This paper reports the cloning and sequencing of a region of DNA from Streptococcus pneumoniae serotype 3 surrounding transposon Tn916, insertion of which was previously shown to result in lack of expression of the extracellular capsule. Sequence analysis revealed that the transposon inserted into a consensus insertion site 71 bp from the 5' end of the cloned fragment. Within the clone, 3' downstream regions from two different pneumococcal lytA genes were identified, as well as a putative 194 AA open reading frame (ORF1). Moreover, two copies of the repeat element BOX, oriented in opposite directions, were located immediately 3' of orf1. Within the region bounded by the first pair of internal sequencing primers, analysis revealed that the fragment amplified by PCR was always of the same size. Moreover, Southern blotting showed that for all serotypes examined to date, homology exists with the cloned fragment. These results indicate that this region of the chromosome is highly conserved and, taken together with other independently derived data, suggest that interruptions or deletions within this DNA lead to unencapsulation.

The source of messages produced during facilitated communication with a boy with autism and severe mental retardation: a case study.

Assessed the source of messages produced through facilitated communication with a youth with autism and severe mental retardation using message-passing and picture-naming procedures. Results indicated that the facilitator was the source of the communications produced during the assessment; correct responding occurred only when the facilitator had knowledge of the correct answer. These findings are consistent with the results of other research demonstrating cuing, influence, or control of facilitated communications by the individuals providing assistance (facilitators). Implications for ethical practices by professionals in the context of facilitated communications are briefly discussed.

A brief history of the pneumococcus in biomedical research: a panoply of scientific discovery.

Because of its prominence as a cause of disease in humans, Streptococcus pneumoniae has been the subject of intensive investigation at both the clinical level and the basic scientific level during the past century. In a number of instances, these studies have resulted in important progress toward the comprehension of basic biological principles. The areas advanced by studies of the pneumococcus include an understanding of the concept of pathogenesis of infectious disease; the development of Gram's stain for identification of bacteria in specimens from patients; the elucidation of the role of the bacterial capsule in resistance to phagocytosis by cells of the host's immune system; the demonstration that molecules other than proteins are capable of eliciting the host's humoral immune responses and later, by extension, that isolated bacterial exopolysaccharides can be used safely and effectively as vaccines in humans; the documentation of the efficacy of penicillin; the collection of conclusive evidence that DNA encodes genetic information; and the investigation of putative proteinaceous virulence factors.

The association between psychiatric diagnoses and severe behavior problems in mental retardation.

To investigate the relationship between psychiatric disorders and severe behavior problems in mental retardation, statewide client databases from developmental disabilities services in California (N = 89,419) and New York (N = 45,683) were analyzed and juxtaposed. The study focussed on nine major DSM-III-R psychiatric categories (or their equivalents), and severe forms of aggressive behavior, property destruction, self-injurious behavior, and stereotyped behavior in individuals 45 years old and younger with mental retardation of all levels of severity. In California, 3.9% had at least one psychiatric diagnosis; in New York, 5.4%. The rate of specific psychiatric diagnoses was variable across states, suggesting local preferences in diagnostic practices. Severe behavior problems occurred in 22.1% in California and in 41.4% in New York. This difference in rates can be attributed in part to different recording criteria for behavior problems. With regard to the association between psychiatric diagnoses and problem behaviors the results were consistent across databases: No compelling correlations were found. This means that neither aggression, self-injury, destruction, nor stereotypies determine whether a person receives a psychiatric diagnosis or not.

Evaluating facilitated communications of people with developmental disabilities.

A quasi-experimental message-passing procedure was used to assess the validity of the facilitated communication (FC) by people with autism and mental retardation or with mental retardation. The 23 participants were classified as having intellectual skills within the range of severe to profound mental retardation. Message-passing consisted of showing and verbally labeling a picture of a familiar object with the facilitator absent, and subsequent facilitation to generate a label or description of the object. Three-trial blocks were conducted with each participant on two different days. Blocks were conducted in the participants' normal FC setting, with their facilitators of choice, and no special apparatus was used. No participant was able to accurately label or describe the object shown to them with facilitation. Possible reasons for findings set forth by proponents of FC and findings from the emerging quantitative literature on FC are considered.

Evolution of the chordate muscle actin gene.

The ascidians Styela plicata, S. clava, and Mogula citrina are urochordates. The larvae of urochordates are considered to morphologically resemble the ancestral vertebrate. We asked whether larval and adult ascidian muscle actin sequences are nonmusclelike as in lower invertebrates, musclelike as in vertebrates, or possess characteristics of both. Nonmuscle and muscle actin cDNA clones from S. plicata were sequenced. Based on 27 diagnostic amino acids, which distinguish vertebrate muscle actin from other actins, we found that the deduced protein sequences of ascidian muscle actins exhibit similarities to both invertebrate and vertebrate muscle actins. A comparison to muscle actins from different vertebrate and invertebrate phylogenetic groups suggested that the urochordate muscle actins represent a transition from a nonmusclelike sequence to a vertebrate musclelike sequence. The ascidian adult muscle actin is more similar to skeletal actin and the larval muscle actin is more similar to cardiac actin, which indicates that the divergence of the skeletal and cardiac isoforms occurred before the emergence of urochordates. The muscle actin gene may be a powerful probe for investigating the chordate lineage.

An experimental assessment of facilitated communication.

This report presents a quantitative study of facilitated communication. Participants were 12 people living at an institutional autism program and 9 people who provided them with facilitated communication support. These subjects were the 12 most competent producers of facilitated communication in the program. They were shown pictures of familiar objects and asked to type the names of the objects under three conditions: (a) assisted typing with facilitators unaware of the content of the stimulus picture, (b) unassisted typing, and (c) a condition in which the participants and facilitators were each shown pictures at the same time. In this last condition the paired pictures were either the same or different, and the participant's typing was facilitated to label or describe the picture. These participants were unable to succeed in the tasks without facilitator assistance. On trials when the facilitators and participants had different pictures, the only "correct" labels were for pictures shown to the facilitators and not shown to the participants. This finding demonstrates that the facilitators were unknowingly determining what was typed.

Who is treated using restrictive behavioral procedures? A population perspective.

Considerable controversy surrounds the continued use of restrictive behavioral procedures in the treatment of destructive behaviors, such as self-injury, aggression, and property damage, displayed by some people with mental retardation. This study reports on the extent that pharmacological and behavioral consequences occur in response to these behaviors within a population of 31,000 people in one state's developmental services system. Data on these individuals are analyzed to determine the degree to which intellectual level, residential setting type, type and extent of problem behaviors, and age are related to the prescriptive use of pharmacologic and behavioral consequences. These variables appear to bear a significant relationship on the extent to which consequences are applied as part of treatment. Furthermore, although pharmacologic and several behavior consequences are applied at similar rates, it was found that generally timeout, as a specific treatment procedure, was applied at rates considerably less than those for psychoactive medication in each population sub-group that was examined.