Autosomal dominant idiopathic scoliosis?
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Biomedical subjects
Publications and source records attributed to M Bell.
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OBJECTIVE: To critically appraise evidence of the effectiveness of continuing medical education (CME) in rheumatic diseases for primary care physicians. METHODS: Three physicians independently applied preset criteria to evaluated CME interventions published between January 1966 and August 1993. RESULT: Eight of 166 articles identified were critically appraised, 7 of which had positive results. Marked heterogeneity in educational interventions, evaluative methods, and outcomes was noted. CONCLUSION: Despite generally positive results, weak methodology precludes drawing firm conclusions about the effectiveness of CME in rheumatic diseases.
This paper explores recent attempts to improve the effectiveness of environmental health programmes and projects by reference to the International Drinking Water Supply and Sanitation Decade (1980-1990) and beyond. Reference is made to how water and sanitation as technical interventions have drawn upon the natural sciences, notably concepts of race and sex, and the social sciences including culture and gender, for their authority and legitimacy. A new and apparently progressive movement, the Water Decade sought to challenge the powerful and enduring high tech image of development on which much western environmental and social transformations have been based. Beginning as a critique of modernism with a commitment to basic needs as human rights, it was driven by a recognition that sophisticated technology could not satisfy human health needs. Alternative technologies would, by contrast, cater for a more extensive and varied market and would promote participatory approaches to service delivery. The paper demonstrates how, during the course of the Decade, sections of the aid community began to redefine basic needs as commodities involving the efficient marketing and delivery of a product with minimal state intervention. Within a shifting international political and economic context, it examines the changing role of the expert and the links being forged between large donors, non-governmental organisations and the private sector. The significance of this reformulated progressivism for the development debate is then considered, notably in relation to concepts of citizenship, consumer choice and the role of the state.
Fifty-four nurses and 205 other professionals provided data on their attitudes to the involvement of parents in initial child-protection conferences in a northern English city, and on the preparation and training they had received for it. Data were collected before the local authority involved parents and again 1 year later, after parents had been invited to the conferences in four neighbourhood teams. This paper describes the attitudes and training of the nurse respondents at the two points in time, before the authority involved parents and after, and the degree and nature of the training they received in preparation. Overall, attitudes became more favourable over time. There were, however, some abiding concerns; for example, that discussion might be inhibited, and the interests of the child become less central. There were also differences in attitude by agency which reflected an agency orientation and its commitment to the child-protection task. Social workers were initially the most positive and their attitudes the least likely to change. Teachers and police began with the most negative attitudes, but their attitudes changed the most. The nurse professionals occupied the middle ground. There were also differences by agency and over time in the amount of training and preparation received. Nurses were the most likely to be offered training and teachers the least. Inter-agency training, including input from experienced practitioners, was valued.
R. is a 40-year-old, divorced, White male with a diagnosis of schizophrenia, paranoid type, chronic. Shortly after his entrance into our work rehabilitation program, R. engaged one of the authors (P.L.) in a conversation about the nature of his illness. He reported that his most disabling and pervasive symptom was a persistent inability to pursue any goal in his life. R. recognized that he had other symptoms of psychiatric illness but stated that these did not account for his disability. He explained that the voice of God that counseled him when he felt overwhelmed and his fear that God was about to kill him as punishment for his sins put life in perspective and, consequently, were sometimes as comforting as they were distressing. R. explained that what had altered his life was a process, invisible to others, that left him unable to plan out and pursue a life course. He did not know whether it was a lack of knowledge or lack of motivation and energy that left him without the inner direction he needed. All he knew was that it was "schizophrenia," and it left him unable to work or to function like other people. What R. was describing as the foundation of his illness and his disability appears to be a disturbance of volition. Interestingly, self-understanding is more consistent with several of the early formulations of schizophrenia than it is with current formulations. To explore the merits of R.'s belief about his illness we offer a review of the role that disturbance of volition has played in historical conceptualizations of schizophrenia, the current nosology, and in theories of the negative or deficit syndrome. The history of R.'s illness is then presented. Lastly, we discuss what we learned from R.'s participation in a paid work program.
Previous studies have demonstrated that IL-1 receptor (IL-1R)- and TCR-initiated signals can interact synergistically to increase the rate of transcription of several lymphokine and lymphokine receptor genes during the competence phase of the activation program in T helper lymphocytes. In this report we describe how signals initiated through the type I IL-1R interact with signals from the antigen receptor to synergistically augment the transactivating properties of NF-kappa B. The synergistic antigen receptor initiated signals are mediated through protein kinase C because they can be mimicked by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, but not with calcium ionophores; and are staurosporine sensitive but cyclosporine resistant. Gel shift analyses demonstrate that NF-kappa B nuclear translocation is stimulated primarily by IL-1 rather than by antigen receptor signals. Western blot and phosphorylation analyses demonstrate that the synergistic effect on NF-kappa B functional activity is independent of I kappa B alpha (MAD3)-NF-kappa B dissociation in the cytosol and is not associated with I kappa B nuclear translocation. The IL-1-induced NF-kappa B DNA nuclear localization is transient and can be prolonged either by an antigen receptor-initiated signal or by inhibiting protein synthesis. These results suggest that IL-1 induces both NF-kappa B nuclear translocation and the synthesis of a protein(s) responsible for terminating NF-kappa B-DNA interaction in the nucleus. Antigen receptor signals prolong NF-kappa B-DNA interaction, probably by functionally antagonizing the IL-1-induced synthesis of a protein(s) responsible for the transient NF-kappa B-DNA interaction and consequently synergistically enhance IL-1-induced NF-kappa B-dependent gene transcription.
Research has suggested that impaired insight in patients with schizophrenia is associated with poorer treatment compliance and outcome. Little is known about what forms of treatment can lead to improvements in insight. Research has found that impairments in insight remain stable despite participation in standard treatments. This study examined changes in insight in a sample of 44 subjects with impaired insight who were enrolled in a vocational rehabilitation program. Significant improvements in insight rating were observed for the sample, with a total of 61% of subjects (N = 27) improving. Multiple regression analysis revealed that measures of cognitive impairment (Digit Symbol Subtest Test, Slosson IQ Test, Wisconsin Card Sorting Test) predicted improvement in insight (R2 = .33), with greater levels of cognitive impairments predicting lesser improvement. Psychosocial variables, including concurrent measurements of positive and negative symptoms, were not significant predictors of improvement. These results suggest that vocational rehabilitation can favorably affect insight, particularly for subjects with less severe cognitive deficits.
Interest in negative symptoms as a dimension of schizophrenia has grown dramatically in the last decade. One hypothesized correlate of negative symptoms that has received less attention is deteriorated work function. To address this issue, this study compared biweekly measurements of work performance for 21 patients with prominent negative symptom and 29 patients without prominent negative symptoms enrolled in a 26-week supported work program. Nonparametric analysis indicated that subjects with prominent negative symptoms demonstrated poorer performance than other subjects on task orientation, social skills and personal presentation. No evidence was found that the work performance of either group improved or worsened over time, although a trend suggested that social skills may have improved slightly for both groups across the 26 weeks. These results support hypotheses linking negative symptoms with deteriorated work function.
PROBLEM: Isolation of viable cervical lymphocyte populations and characterization of their function in healthy tissue is necessary to understand immunity in the genital tract. METHODS: Normal, cervical tissue was digested using a multi-enzymatic digestion procedure. Lymphocytes were characterized using FACS analysis and ELISPOT analysis for immunoglobulin secreting cells. RESULTS: Following the digestion procedure, 0.16 x 10(6) +/- 0.8 cells/g of tissue with a viability of 90-98% were isolated from normal cervical tissue. FACS analysis determined that B lymphocytes were the predominant cell type in normal cervical tissue representing a significantly higher percentage than that found in peripheral blood (P = 0.015). T lymphocytes and NK cells represented a significantly lower percentage than that found in peripheral blood (P = 0.0001 and 0.026, respectively). The largest percentage of immunoglobulin secreting cells isolated were secreting IgG followed by IgA. A limited number of IgM secreting cells were detected. IgA2 secreting cells represented 34.46 +/- 4.6% of the total number of IgA plasma cells. CONCLUSION: These studies represent the first analysis of viable mononuclear cells isolated from normal cervical tissue. The results form a baseline from which it will now be possible to compare changes that occur at the cervical squamocolumnar junction in response to infection or neoplasia.
The metabolism of chylomicrons, very-low-density lipoprotein (VLDL), and their remnants in the postprandial state was studied in normolipidemic healthy men by measuring apoB-48 and apoB-100 and retinyl palmitate (RP) in fractions of triglyceride-rich lipoproteins after a mixed meal type of oral fat load supplemented with vitamin A. ApoB-48 was present at low concentrations in the fasting plasma samples in most subjects and increased in response to the test meal in Svedberg's flotation rate (Sf) > 20 lipoprotein fractions. Concomitantly, the level of Sf 60 to 400 apoB-100 (large VLDL) had doubled at 3 hours and returned to baseline at 9 hours. The number of apoB-48-containing lipoprotein particles did not exceed 20% of the total number of apoB-containing lipoproteins contained in Sf 12 to 400 fractions at any time point after fat intake. The peak plasma level of RP was delayed compared with the peak plasma concentration of apoB-48, suggesting that retinyl ester labeling of chylomicrons is questionable as a means of quantifying postprandial triglyceride-rich lipoproteins of intestinal origin. Approximately 2000 and 4000 RP molecules were carried in each chylomicron particle in the 3- and 6-hour samples, respectively, in contrast to the remnant fractions in which 100 to 600 RP molecules were found for each lipoprotein particle. The limited RP exchange between lipoprotein particles indicates that the smaller intestinal lipoproteins do not originate primarily from larger Sf > 400 chylomicron particles but instead are secreted directly into the Sf 20 to 400 fraction and subsequently converted to smaller chylomicron remnants.(ABSTRACT TRUNCATED AT 250 WORDS)
Prenatal care is an important women's health care issue. Numerous studies have shown that early monitoring and continuous care during pregnancy is associated with more favorable birth outcomes. Using data from a survey of service providers, this paper describes innovative service delivery models that are a part of Washington state's new, comprehensive maternity care system. Washington's program departs from traditional medical prenatal care in making both support and case management services available to pregnant women. The services are described, highlighting the roles that social workers play in providing maternity services.
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Although interleukin 1 (IL-1) receptor signaling events in T helper lymphocytes are incompletely characterized, events associated with translocation of the transcription factor NF-kappa B are receptor-proximal assays of ligand-initiated responses. In this report we demonstrate that the transient nature of IL-1-induced NF-kappa B nuclear translocation occurs as a consequence of ligand-induced receptor desensitization. Other receptor-initiated events including induction of I kappa B alpha phosphorylation, expression of c-jun and junB mRNA, and costimulatory effects on IL-2 synthesis also are altered by IL-1 receptor desensitization. IL-1 receptor desensitization is not initiated by tumor necrosis factor, which also stimulates NF-kappa B translocation, and is not a consequence of alterations in either IL-1 receptor expression or binding affinity. In the absence of IL-1, the effects of desensitization are completely reversed within 18 h. Since IL-1 desensitization is initiated under conditions of low receptor occupancy, it is likely that receptor desensitization results from alterations to a receptor-proximal transducer, rather than from direct modification of the IL-1 receptor. These results suggest that the cyclic nature of the events in the T helper lymphocyte activation program can be controlled, in part, by the reversible desensitization of cell surface IL-1 receptors.
We have used the previously described technique of random-breakage mapping to locate the two yeast genes APN1 and YUH1. The APN1 locus is located approximately 235 kb from the left telomere of chromosome XI, and shows weak (approximately 53 cM) genetic linkage to ura1. The YUH1 locus is located approximately 140 kb from the right telomere of chromosome X, and genetically maps 3.6 cM distal to cdc11. In addition, we show by random-breakage mapping that TRP3 is located approximately 45 kb from the left telomere of chromosome XI, whereas FAS1 is approximately 110 kb from the same telomere. This supports a gene order on the left distal portion of chromosome XI that agrees with other physical reports but is inverted with respect to Edition 11 of the published genetic map. This report confirms that random-breakage mapping is a rapid and convenient method of locating cloned genes.
OBJECTIVE: To analyze the effect of sodium nitroprusside, a nitric oxide releaser, on sperm motion and lipid peroxidation-induced membrane damage in cryopreserved human sperm. DESIGN: Post-thaw, cryopreserved, human sperm samples were washed and divided into three aliquots. Each aliquot was incubated with either 0, 50, or 100 nM sodium nitroprusside. INTERVENTIONS: Samples were analyzed for lipid peroxidation (measured by malonaldehyde-thiobarbituric acid reactivity) at 3 hours post-thaw. MAIN OUTCOME MEASURES: Percent viability and motion parameters were assessed at 0, 10, and 30 minutes and 2, 3, 5, and 6 hours post-thaw. RESULTS: All results represent a mean +/- SEM, n = 10. Lipid peroxidation in samples incubated with 50 nM sodium nitroprusside (15.1 +/- 2.1 nM malonaldehyde/10(8) sperm) or 100 nM sodium nitroprusside (13.2 +/- 2.1 nM malonaldehyde/10(8) sperm) was significantly lower than in controls (22.7 +/- 3.1 nM malonaldehyde/10(8) sperm). Percent viability was significantly reduced from 0 minutes (60.6% +/- 3.5%) to 6 hours post-thaw in controls (38.0% +/- 5.1%) but not in 50 nM (46.8% +/- 10.4%) or 100 nM (48.8% +/- 6.5%) sodium nitroprusside-treated samples. Compared with controls (18.3% +/- 3.4%), maintenance of percent motility at 3 hours post-thaw was significantly improved in 50 nM (24.5% +/- 2.9%) and in 100 nM (26.3% +/- 3.2%) sodium nitroprusside-treated samples. Straight line velocity maintenance was significantly improved in 50 nM (37.3 +/- 1.3) and in 100 nM (37.0 +/- 1) sodium nitroprusside-treated samples as compared with controls (30.5 +/- 1.7). Significant improvements in curvilinear velocity maintenance compared with controls (56.3 +/- 2.9) also were observed in 50 nM (65.9 +/- 2.1) and 100 nM (72.1 +/- 4.1) sodium nitroprusside-treated samples. Significant differences in the motion parameters of sodium nitroprusside-treated samples were maintained at 5 and 6 hours post-thaw in comparison to controls. CONCLUSION: These results suggest that sodium nitroprusside is beneficial to the maintenance of post-thaw sperm motion and viability for up to 6 hours and that reduction of lipid peroxidative damage to sperm membranes may be the mechanism for these benefits.
We surveyed 449 parents to assess: (a) the prevalence of different types of physical and emotional punishment during their childhoods: (b) the prevalence of current parental approval of these types of punishments, and (c) risk factors for current approval of physical and emotional punishments. Parents in waiting rooms of pediatric clinics were asked to complete an anonymous questionnaire about their childhood punishment experiences and their current approval of various types of punishment. Reported experiences and approval were as follows: 24% experienced and 6% approved of uncommon punishments (e.g., burned), 45% experienced and 17% approved of common punishments (e.g., shaken), and 94% experienced and 88% approved of very common punishments (e.g., spanked). Having experienced each type of punishment was a highly significant risk factor for currently approving of that type of punishment (p < .01 for each). Race, income, and education were not significant risk factors for approval of different types of punishment. Many parents have experienced harsh types of punishment during their childhoods. Efforts at identifying and educating parents who approve of harsh and/or abusive types of punishment should focus on those who have experienced harsh punishment rather than on particular racial or socioeconomic groups.
Research has suggested that poor insight in patients with schizophrenia is associated with poorer medication compliance and heightened levels of psychopathology. This study examined the relationship of insight to compliance with a work rehabilitation program and with levels of psychopathology and psychosocial functioning. Poor insight was found to be positively associated with fewer weeks of participation and with poorer social skills and personal presentation in the fifth week of work. Poor insight was also associated with cognitive disorganization and a lower intelligence quotient, but not with heightened levels of psychopathology. Results suggest that poor insight may predict noncompliance with psychosocial treatment and may be related to a constellation of cognitive deficits.
Structure-function studies of the MHC class II alpha chain have been performed by constructing a panel of A alpha k cDNA genes with one or more d allele substitutions at each polymorphic residue of the alpha 1 domain. The altered genes (A alpha k*) were transfected into a B lymphoma cell line (BKO), which is deficient in A alpha mRNA but retains constitutive wild-type A beta k mRNA expression. Cytofluorometric analysis of cell surface A alpha k* Ak beta molecules was used to map the polymorphic alpha chain residues comprising four serologic epitopes. A alpha k-reactive mAbs 1E9, 2A2, and 3F12 recognize an epitope that includes the polymorphic residue 44 of the A alpha k polypeptide, and the A alpha k-reactive antibody, K24-199, recognizes a conformationally determined epitope influenced by residues from all three polymorphic regions. In addition, we confirmed previous studies demonstrating that la.19 and la.2 mAbs bind to epitopes adjacent to residue 75 in A alpha k. A cell surface negative expression variant also was identified in the panel of mutant cell lines and biochemically characterized. Substitution of six d allele polymorphic residues at positions 11, 14, 28, 69, 70, and 75 in the A alpha k polypeptide (T.EG A alpha k* A beta k*) results in an A alpha k* polypeptide that associates with the A alpha k polypeptide but does not associate with the li polypeptide. This defect in li-A alpha k A beta k interaction is associated with a conformational change in the alpha 1 beta 1 domain that was identified by altered reactivity of the T.EG complex with conformationally dependent anti-alpha and anti-beta mAbs.(ABSTRACT TRUNCATED AT 250 WORDS)