Biomedical subjects
Publications and source records attributed to C Campbell.
In this further article of the series, Claire Campbell introduces and explores the needs of Health Service employees who care for their own relatives or companions who cannot cope due to sickness, disability or age, why it is important to recognise their needs, what kind of support they need, and how policies can be put in place.
OBJECTIVES: The development of a self-report questionnaire capable of assessing cognitive and interpersonal vulnerability factors for clinical depression is described. The Vulnerability to Depression Questionnaire (VDQ) was developed to provide a brief, economical alternative to the Self-Evaluation and Social Support interview (SESS; O'Connor & Brown, 1984), assessing negative evaluation of self, negative interaction with partner or child and lack of a support figure. DESIGN: The VDQ was tested in a prospective study of community-based women who were contacted on three occasions over the course of approximately 1 year, to: (i) compare the VDQ's capacity to categorize vulnerability compared with the SESS interview, and (ii) to test the VDQ's prediction of onset of clinical depression during the follow-up. METHOD: Selected nondepressed respondents completed the VDQ and were interviewed to determine their vulnerability using the SESS. They were re-interviewed on two further occasions during the follow-up period, and the VDQ was also re-administered at the time of first follow-up. Onset of clinical depression during the follow-up was assessed by interview at each contact. RESULTS: Comparison of VDQ and SESS interview classification of participants' vulnerability at first contact indicated that the questionnaire had good sensitivity and specificity. Test-retest scores for the VDQ indicated satisfactory levels of reliability. VDQ scores also predicted onset of clinical depression in the follow-up period. CONCLUSIONS: Results suggest that the VDQ is an economical and effective means of screening large populations for the purposes of risk assessment, to aid future research into clinical depression and to facilitate the implementation of intervention strategies.
OBJECTIVES: To assess the prevalence of elevated blood lead levels (EBLLs) among children before and after foster care placement, and to compare the prevalence of EBLLs among children in foster care with that of their siblings and the general population. METHODS: We conducted a retrospective cohort study using administrative databases from the Philadelphia Department of Human Services and the Birth Certificate Registry and the Childhood Lead Poisoning Prevention Program at the Philadelphia Department of Public Health. Logistic regression analyses were performed to control for confounding variables, including age, race, gender, and the year, seasonal timing, and source (capillary vs venous) of test. RESULTS: From June 1992 to May 1997, there were 1824 children in foster care with available blood lead results in the Childhood Lead Poisoning Prevention Program database. Of these, 519 (28%) had initial lead screening before foster care placement and 654 (36%) after placement. There were 821 siblings and 73 608 children in the general population with available blood lead results. Before entering foster care, children were nearly twice as likely to have EBLLs as their siblings (adjusted odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.4, 2.0), those in placement (adjusted OR = 1.9; 95% CI = 1.6, 2.2), and the general population (adjusted OR = 1.7; 95% CI = 1.5, 2.0). At the highest point prevalence, 50% of children before placement had lead levels >/=20 microg/dL, and nearly 90% had levels >/=10 microg/dL. For all age categories, siblings of children in foster care placement had a higher prevalence of EBLLs than did the general population. After placement, children in foster care were nearly half as likely as the other groups to have EBLLs. CONCLUSIONS: Our findings suggest that children are at high risk for lead poisoning before entering foster care and that placement in foster care may have a beneficial effect on lead exposure. Children before foster care placement are nearly twice as likely to have EBLLs compared with children in foster care placement, the general population, and their siblings. Furthermore, siblings of children in foster care are at high risk for lead poisoning. Children receiving social services in their own homes and children suffering from abuse and neglect should be actively screened for lead poisoning. Greater efforts at preventing lead poisoning among these children must be made.
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OBJECTIVES: This microqualitative case study of a community-based peer education program led by sex workers at a South African mine examined the role of grassroots participation in sexual health promotion. METHODS: The study involved in-depth interviews with 30 members of the target community. The interviews were analyzed in terms of social capital, empowerment, and identity. RESULTS: The study yielded a detailed analysis of the way in which community dynamics have shaped the peer education program's development in a deprived, violent community where existing norms and networks are inconsistent with ideal criteria for participatory health promotion. CONCLUSIONS: Much remains to be learned about the complexities of translating theoretically and politically vital notions of "community participation" into practice among hard-to-reach groups. The fabric of local community life is shaped by nonlocal structural conditions of poverty and sexual inequality in ways that challenge those seeking to theorize the role of social capital in community development in general and in sexual health promotion in particular.
Certain risk factors result in a higher incidence of delayed-onset hearing loss. Ten subjects who passed auditory brainstem response birth screenings and later returned with bilateral sensorineural hearing loss are examined in this report. Although not all subjects in this report had respiratory distress, this study reveals a high correlation between mechanical ventilation and delayed-onset hearing loss.
Compared with rural soils, urban soils in Aberdeen city possessed obviously different microbial features: higher in microbial basal respiration strength, and microbial ecophysiological parameters Cmic/Corg and qCO2, but lower in microbial biomass, also much more rapid in consuming carbon sources deduced from Biolog data. Urban soils showed different characteristics in heavy metals as well. Apparent accumulation of Pb, Zn, Cu, Ni were observed, in which Pb mainly related with iron oxides, Ni, Zn existed in residual forms, Cu exhibited same importance of different chemical forms but for soluble forms. Principal component analysis results reflected the overwhelming factor to control the difference of microbial features between urban and rural soils was soluble Pb, then soluble Zn, soluble and organic bonded Cu and Ni also contributed in some degree.
Fanconi anemia (FA) is a genetic disorder associated with genomic instability and cancer predisposition. Cultured cells from FA patients display a high level of spontaneous chromosome breaks and an increased frequency of intragenic deletions, suggesting that FA cells may have deficiencies in properly processing DNA double strand breaks. In this study, an in vitro plasmid DNA end joining assay was used to characterize the end joining capabilities of nuclear extracts from diploid FA fibroblasts from complementation groups A, C, and D. The Fanconi anemia extracts had 3-9-fold less DNA end joining activity and rejoined substrates with significantly less fidelity than normal extracts. Wild-type end joining activity could be reconstituted by mixing FA-D extracts with FA-A or FA-C extracts, while mixing FA-A and FA-C extracts had no effect on end joining activity. Protein expression levels of the DNA-dependent protein kinase (DNA-PK)/Ku-dependent nonhomologous DNA end-joining proteins Xrcc4, DNA ligase IV, Ku70, and Ku86 in FA and normal extracts were indistinguishable, as were DNA-dependent protein kinase and DNA end binding activities. The end joining activity as measured by the assay was not sensitive to the DNA-PK inhibitor wortmannin or dependent on the nonhomologous DNA end-joining factor Xrcc4. However, when DNA/protein ratios were lowered, the end joining activity became wortmannin-sensitive and no difference in end joining activity was observed between normal and FA extracts. Taken together, these results suggest that the FA fibroblast extracts have a deficiency in a DNA end joining process that is distinct from the DNA-PK/Ku-dependent nonhomologous DNA end joining pathway.
BACKGROUND: Case series and reviews have suggested the effectiveness of zuclopenthixol acetate in the acute management of disturbed behaviour caused by serious mental illnesses. This review investigates the trial-based evidence for these suggestions. METHODS: All randomized clinical trials comparing zuclopenthixol acetate to other 'standard' treatments for the acute management of those with serious mental illnesses were identified and, if possible, their results summated. RESULTS: Six trials were identified. All had methodological problems and one did not meet the minimal methodological inclusion criteria. The summary data do not demonstrate that zuclopenthixol acetate is better than 'standard care' for altering behaviour, decreasing the need for supplementary medication, avoiding side-effects, or postponing early discharge against medical advice. One trial, however, presented data that suggested an earlier, more intense level of sedation. CONCLUSIONS: Recommendations of reviews and open studies for the use of zuclopenthixol acetate in preference to 'standard' treatments in the psychiatric emergency are not supported by evidence from randomized controlled trials.
Hamster EM9 cells, which lack Xrcc1 protein, have reduced levels of DNA ligase III and are defective in nuclear base excision repair. The Xrcc1 protein stabilizes DNA ligase III and may even play a direct role in catalyzing base excision repair. Since DNA ligase III is also thought to function in mitochondrial base excision repair, it seemed likely that mitochondrial DNA ligase III function would also be dependent upon Xrcc1. However, several lines of evidence indicate that this is not the case. First, western blot analysis failed to detect Xrcc1 protein in mitochondrial extracts. Second, DNA ligase III levels present in mitochondrial protein extracts from EM9 cells were indistinguishable from those seen in similar extracts from wild-type (AA8) cells. Third, the mitochondrial DNA content of both cell lines was identical. Fourth, EM9 cells displayed no defect in their ability to repair spontaneous mitochondrial DNA damage. Fifth, while EM9 cells were far more sensitive to the cytotoxic effects of ionizing radiation due to a defect in nuclear DNA repair, there was no apparent difference in the ability of EM9 and AA8 cells to restore their mitochondrial DNA to pre-irradiation levels. Thus, mitochondrial DNA ligase III function is independent of the Xrcc1 protein.
Mammalian mitochondrial DNA end-binding activity is nearly indistinguishable from that of nuclear Ku. This observation led to the hypothesis that mitochondrial DNA end-binding activity is in part dependent upon Ku80 gene expression. To test this hypothesis, we assayed for Ku activity in mitochondrial extracts prepared from the xrs-5 hamster cell line that lacks Ku80 mRNA expression. Mitochondrial protein extracts prepared from this cell line lacked the DNA end-binding activity found in similar extracts prepared from wild-type cells. Azacytidine-reverted xrs-5 cells that acquired nuclear DNA end-binding activity also acquired mitochondrial DNA end-binding activity. Western blot analysis of human mitochondrial protein extracts using a monoclonal antibody specific for an N-terminal epitope of Ku80 identified a protein with an apparent molecular weight of 68 kDa. This mitochondrial protein was not detected by a monoclonal antibody specific for an epitope at the C-terminal end of Ku80. Consistently, while both the N- and C-terminal Ku80 monoclonal antibodies supershifted the nuclear DNA end-binding complex on an electrophoretic mobility shift assay, only the N-terminal monoclonal antibody supershifted the mitochondrial DNA end-binding complex. To confirm that the 68 kDa Ku protein was not a consequence of nuclear protein contamination of mitochondrial preparations, highly purified intact nuclei and mitochondria were treated with proteinase K which traverses the pores of intact nuclei but gains limited access into intact mitochondria. Ku80 in purified intact nuclei was sensitive to treatment with this protease, while the 68 kDa Ku protein characteristic of purified intact mitochondria was resistant. Further, immunocytochemical analysis revealed the co-localization of the N-terminal specific Ku80 monoclonal antibody with a mitochondrial-targeted green fluorescence protein. Mitochondrial localization of the C-terminal Ku80 monoclonal antibody was not observed. These data are consistent with the hypothesis that a C-terminally truncated form of Ku80 is localized in mammalian mitochondria where it functions in a DNA end-binding activity.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
To enhance the potency of 1,2-dibenzamidobenzene-derived inhibitors of factor Xa (fXa), an amidine substituent was incorporated on one of the benzoyl side chains to interact with Asp189 in the S1 specificity pocket. Lead molecule 1 was docked into the active site of fXa to facilitate inhibitor design. Subsequently, iterative SAR studies and molecular modeling led to a 1000-fold increase in fXa affinity and a refined model of the new inhibitors in the fXa active site. Strong support for the computational model was achieved through the acquisition of an X-ray crystal structure using thrombin as a surrogate protein. The amidines in this series show high levels of selectivity for the inhibition of fXa relative to other trypsin-like serine proteases. Furthermore, the fXa affinity of compounds in this series (K(ass) = 50-500 x 10(6) L/mol) translates effectively into both anticoagulant activity in vitro and antithrombotic activity in vivo.
Respiratory support using negative extrathoracic pressure or high-frequency chest wall oscillation was used to treat 3 infants with cystic fibrosis and respiratory failure who had not responded to maximal medical therapy. Beneficial clinical effects were noted in all three cases. Pulmonary function testing was performed in 2 cases, and measures of compliance increased.